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Sample records for bone marrow transplants

  1. BONE MARROW TRANSPLANTATION

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. BONE MARROW TRANSPLANTATION. AUTOLOGOUS TRANSPLANTS: Oct 1986 - Dec 2007. Multiple Myeloma 90. NHL 39. Hodgkins lymphoma 19. AML 36. APML 9. ALL 2. Amyloidosis 2. Granulocytic Sarcoma 1.

  2. Bone Marrow Transplantation

    Science.gov (United States)

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains immature cells, called stem cells. The ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a ...

  3. Bone marrow transplant - discharge

    Science.gov (United States)

    ... lymphoblastic leukemia (ALL) Acute myeloid leukemia - adult Aplastic anemia Bone marrow transplant Chronic lymphocytic leukemia (CLL) Chronic myelogenous leukemia (CML) Graft-versus-host disease Hodgkin lymphoma Multiple myeloma Non-Hodgkin lymphoma Patient ...

  4. Bone marrow transplantation

    International Nuclear Information System (INIS)

    Storb, R.; Santos, G.W.

    1979-01-01

    Bone marrow transplantation has been increasingly used to treat patients with severe combined immunodeficiency diseases, severe aplastic anemia, and malignant hematologic diseases, especially leukemia. At the Workshop a number of problems were discussed, e.g., conditioning regimens aimed at overcoming the problem of marrow graft rejection and reducing the incidence of recurrent leukemia, prevention of graft-versus-host disease (GVHD), possible mechanisms involved in stable graft-host tolerance, graft-versus-leukemia effect in mice, and finally, the possible use of autologous marrow transplantation

  5. Blood and Bone MarrowTransplant?

    Science.gov (United States)

    ... Topics / Blood and Bone Marrow Transplant Blood and Bone Marrow Transplant Also known as Hematopoietic Stem Cell Transplant , Hematopoietic Cell Transplant , Autologous Transplant , Allogeneic Transplant A blood or bone marrow ...

  6. HLA in bone marrow transplantation

    International Nuclear Information System (INIS)

    Tsuji, Kimiyoshi

    1989-01-01

    It has been well understood that human major histocompatibility antigen system, HLA is the most important role in the allo transplantation. Therefore, the structure of HLA genes was presented by the recent information (1987). Moreover, their functions in vitro and in vivo also were described. Finally, bone marrow transplantation and HLA network system in Japan against HLA mismatched case was proposed. It is eagerly expected that functional and clinical bone marrow transplantation in Japan could be succeeded. (author)

  7. Bone marrow transplant

    Science.gov (United States)

    ... cure your illness. If the transplant is a success, you can go back to most of your ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  8. Bone marrow transplantation after irradiation

    International Nuclear Information System (INIS)

    Koch, M.; Blaha, M.; Merka, V.

    1990-01-01

    Bone marrow transplantation after irradiation is successful in only a part of the affected patients. The Chernobyl accident added to our knowledge: BMT can save life after whole-body irradiation with a dose exceeding 7-8 Gy. A timely decision on transplantation after a nuclear accident is difficult to make (rapid determination of homogeneity and type of radiation and the total dose. HL-A typing in lymphopenia, precise identification of radiation damage to other target organs, etc.). Further attention is to be paid to the treatment. Transplantations in case of malignities (especially hematologic ones) and other diseases will add to our knowledge and will lead to more simple procedures. (author). 3 figs., 1 tab., 12 refs

  9. Allogeneic and Autologous Bone-Marrow Transplantation

    OpenAIRE

    Deeg, H. Joachim

    1988-01-01

    The author of this paper presents an overview of the current status of bone marrow transplantation, including indications, pre-transplant considerations, the transplant procedure, acute and delayed transplant-related problems, results currently attainable, and a short discussion of possible future developments.

  10. Legal issues in bone marrow transplantation.

    OpenAIRE

    Holder, A. R.

    1990-01-01

    The article discusses some of the more common legal issues involved in bone marrow transplantation. These include malpractice claims, testing prospective donors for AIDS, sale of bone marrow, informed consent for both donor and recipient, and questions that arise when the donor is a child.

  11. Bone marrow transplantation: current results in leukemia.

    OpenAIRE

    Santos, G. W.

    1982-01-01

    Bone marrow transplantation offers two potential therapeutic advantages over more conventional therapy of leukemia. It allows more intensive treatment to be given without regard to marrow toxicity and allows in the case of allogeneic marrow an additional immunotherapeutic effect through graft-versus-host disease (GVHD). Initially, allogeneic transplants in HLA matched sibling donors were only employed in end-stage patients. Although there were encouraging results in terms of long-term therape...

  12. Bone marrow transplantation. [Mice, gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Storb, R.; Santos, G.W.

    1979-03-01

    Bone marrow transplantation has been increasingly used to treat patients with severe combined immunodeficiency diseases, severe aplastic anemia, and malignant hematologic diseases, especially leukemia. At the Workshop a number of problems were discussed, e.g., conditioning regimens aimed at overcoming the problem of marrow graft rejection and reducing the incidence of recurrent leukemia, prevention of graft-versus-host disease (GVHD), possible mechanisms involved in stable graft-host tolerance, graft-versus-leukemia effect in mice, and finally, the possible use of autologous marrow transplantation.

  13. Tetanus after allogeneic bone-marrow transplantation

    International Nuclear Information System (INIS)

    Kendra, J.R.; Halil, O.; Barrett, A.J.; Selwyn, S.

    1982-01-01

    A brief report is presented of a case of tetanus after allogeneic bone-marrow transplantation complicated by radiation-induced pneumonitis. A 30-year-old army sergeant received a bone-marrow transplant from his brother for the treatment of a granulocytic sarcoma after local radiotherapy to the tumour. Six years earlier he had sustained an open, compound fracture of the left tibia and fibula while on army exercise. At the time a pin and plate had been inserted and booster anti-tetanus administered. Bone-marrow transplantation was performed after total body irradiation. Cyclosporin A was given against graft-versus-host disease. Fifty four days after transplantation tetanus was diagnosed and death followed 14 days later. Necropsy disclosed radiation-induced pneumonitis, but no organisms were cultured from the lungs or the old fracture site. It is suggested that spores were incorporated into the wound site before surgery and that oxygenation around the plate became compromised after transplantation, permitting germination of dormant spores, immunosuppression allowing development of the disease. (U.K.)

  14. Tetanus after allogeneic bone-marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kendra, J.R.; Halil, O.; Barrett, A.J.; Selwyn, S. (Westminster Medical School, London (UK))

    1982-11-13

    A brief report is presented of a case of tetanus after allogeneic bone-marrow transplantation complicated by radiation-induced pneumonitis. A 30-year-old army sergeant received a bone-marrow transplant from his brother for the treatment of a granulocytic sarcoma after local radiotherapy to the tumour. Six years earlier he had sustained an open, compound fracture of the left tibia and fibula while on army exercise. At the time a pin and plate had been inserted and booster anti-tetanus administered. Bone-marrow transplantation was performed after total body irradiation. Cyclosporin A was given against graft-versus-host disease. Fifty four days after transplantation tetanus was diagnosed and death followed 14 days later. Necropsy disclosed radiation-induced pneumonitis, but no organisms were cultured from the lungs or the old fracture site. It is suggested that spores were incorporated into the wound site before surgery and that oxygenation around the plate became compromised after transplantation, permitting germination of dormant spores, immunosuppression allowing development of the disease.

  15. Psychiatric disorders in bone marrow transplant patients

    International Nuclear Information System (INIS)

    Khan, A.G.; Irfan, M.; Shamsi, T.S.; Hussain, M.

    2007-01-01

    To identify the psychiatric illnesses in patients with hematological/oncological disorders encountered during blood and bone marrow transplantation. All consecutive patients, aged 15 years and above, who fulfilled inclusion and exclusion criteria and underwent blood and bone marrow transplantation, were enrolled in this study. Psychiatric assessment comprised of a semi-structured interview based on Present Status Examination (PSE). The psychiatric diagnosis was made on the basis of International Classification of Diseases (ICD-10) system of classification devised by W.H.O. Eighty patients, who fulfilled the inclusion criteria, were inducted in this study. Thirty (37.5%) cases were found to have psychiatric disorders. Out of the total, 60 (75%) were males and 20 (25%) females. Adjustment disorder was the most frequent diagnosis (n=12), followed by major depression (n=7). Rest of the diagnoses made were generalized anxiety disorder, acute psychotic disorder, delirium and depressive psychosis. High psychiatric morbidity associated with blood and bone marrow transplantation was observed. It indicates the importance of psychiatric intervention during the isolation period of BMT as well as pre-transplant psychiatric assessment and counseling regarding procedure. (author)

  16. BONE MARROW TRANSPLANTATION CMC (Oct 1986 – Dec 2007)

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. BONE MARROW TRANSPLANTATION CMC (Oct 1986 – Dec 2007). Allogeneic transplants. Total Transplant 717. I – Transplant 683. II – Transplant 31. III – Transplant 3. Autologous transplants (1992-2007) 198. (Autologous failure proceeded to Allogeneic transplant ...

  17. Bone marrow transplantation for childhood malignancies

    International Nuclear Information System (INIS)

    Toyoda, Yasunori

    1992-01-01

    As of June 30, 1991, 1013 pediatric patients had registrated to The Bone Marrow Transplantation Committee of the Japanese Society of Pediatric Hematology. Bone marrow transplantation (BMT) from HLA-matched siblings is now reasonably safe and an established method of treatment in acute leukemia. Total body irradiation, which is major part of preparative regimen for BMT, affect endocrine function, subsequent growth, gonadal function, development of secondary malignancies. We propose the indication of TBI for children and young adults as follows; those who are at high risk for leukemic relapse after BMT such as Phl-positive-All, leukemia-lymphoma syndrome, AML with monocytic component, BMT in elapse, BMT from other than HLA-matched siblings. (author)

  18. Colonic complications following human bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Paulino Martínez Hernández-Magro

    2015-01-01

    Full Text Available Background: Human bone marrow transplantation (BMT becomes an accepted treatment of leukemia, aplastic anemia, immunodeficiency syndromes, and hematologic malignancies. Colorectal surgeons must know how to determine and manage the main colonic complications. Objective: To review the clinical features, clinical and pathological staging of graft vs host disease (GVHD, and treatment of patients suffering with colonic complications of human bone marrow transplantation. Patients and methods: We have reviewed the records of all patients that received an allogeneic bone marrow transplant and were evaluated at our Colon and Rectal Surgery department due to gastrointestinal symptoms, between January 2007 and January 2012. The study was carried out in patients who developed colonic complications, all of them with clinical, histopathological or laboratory diagnosis. Results: The study group was constituted by 77 patients, 43 male and 34 female patients. We identified colonic complications in 30 patients (38.9%; five patients developed intestinal toxicity due to pretransplant chemotherapy (6.4%; graft vs. host disease was present in 16 patients (20%; 13 patients (16.8% developed acute colonic GVHD, and 3 (3.8% chronic GVHD. Infection was identified in 9 patients (11.6%. Conclusions: The three principal colonic complications are the chemotherapy toxicity, GVHD, and superinfection; the onset of symptoms could help to suspect the type of complication (0–20 day chemotherapy toxicity, 20 and more GVHD, and infection could appear in any time of transplantation. Resumo: Experiência: O transplante de medula óssea humana (MOH passou a ser um tratamento adotado para leucemia, anemia aplástica, síndromes de imunodeficiência e neoplasias hematológicas. Cirurgiões colorretais devem saber como determinar e tratar as principais complicações do cólon. Objetivo: Revisar as características clínicas, estadiamentos clínico e patológico da doença do enxerto

  19. Intractable diseases treated with intra-bone marrow-bone marrow transplantation

    OpenAIRE

    Li, Ming; Guo, Kuquan; Ikehara, Susumu

    2014-01-01

    Bone marrow transplantation (BMT) is used to treat hematological disorders, autoimmune diseases (ADs) and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT) has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells (HSCs) but also mesenchymal stromal cells (MSCs). MSCs are multi-potent stem cells that can be isolated from bone marrow (BM), umbilical co...

  20. Hemolytic uremic syndrome after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Ayako; Sakamaki, Hisashi; Tanikawa, Shu [Tokyo Metropolitan Komagome Hospital (Japan)] [and others

    1998-06-01

    One hundred and thirteen patients who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic uremic syndrome (HUS). HUS developed in seven patients (four males and three females, five acute lymphocytic leukemia (ALL), one acute myelogenous leukemia, one non-Hodgkin`s lymphoma) between 36-196 days after BMT. Four patients were recipients of autologous BMT and three were those of allogeneic BMT. Six patients were preconditioned with the regimens including fractionated total body irradiation (TBI). ALL and preconditioning regimen with TBI were suspected to be the risk factors for the development of HUS. Cyclosporin A (CSP) administration was discontinued in three patients who had been given CSP for graft-versus-host disease prophylaxis. Predonisolone was given to the three patients and plasma exchange was performed in one patient. Both hemolytic anemia and thrombocytopenia were resolved in virtually all patients, while creatinine elevation has persisted along with hypertension in one patient. (author)

  1. Hemorrhagic cytitis after bone marrow transplantation.

    Science.gov (United States)

    Padilla-Fernandez, Barbara; Bastida-Bermejo, J M; Virseda-Rodriguez, A J; Labrador-Gomez, J; Caballero-Barrigon, D; Silva-Abuin, J M; San Miguel-Izquierdo, J F; Lorenzo-Gomez, M F

    2014-03-01

    Hemorrhagic cystitis (HC) presenting with gross hematuria, bladder pain and urinary frequency develops in 13-38% of patients following bone marrow transplantation (BMT). The objective of the study was to study the characteristics of patients suffering hemorrhagic cystitis after hematopoietic stem cell transplantation in our center. We conducted a retrospective chart review of all patients who underwent BMT at our institution between January 1996 and August 2012. We recorded the age, sex, diagnosis, conditioning regimen, interval between BMT and development of symptoms of cystitis and treatment instituted. Five hundred patients underwent BMT in the period of time studied. 52 of them developed hemorrhagic cystitis. The mean age of the affected patients was 39 years; there were 34 males and 18 females. The diagnoses include AML (n=11), ALL (n=8), CML (n=6), MDS (n=11), CLL (n=5), NHL (n=1), HD (n=5), MM (n=2), Medular aplasia((n=3). HC appeared 59.48 days after BMT. There were no differences between sexes. Mortality among the 52 patients was 51.14% but HC was not the cause of death in any patient. Polyomaviruses were detected in the urine of 78.94 % of survivors. Polyomavirus infection with BK and JC types is usually acquired in infancy and the virus remains latent in renal tissue. Immunosuppression facilitates reactivation of the renal infection and replication of the virus responsible for the clinical manifestations of HC. The differential diagnoses include other urinary infections, lithiasis, thrombocytopenia and adverse effects of pharmacological agents. The urologist plays a limited role in the management of this disease.

  2. The Bone Marrow Transplantation Center of the National Cancer Institute - its resources to assist patients with bone marrow failure

    International Nuclear Information System (INIS)

    Tabak, Daniel

    1997-01-01

    This paper describes the bone marrow transplantation center of the brazilian National Cancer Institute, which is responsible for the cancer control in Brazil. The document also describes the resources available in the Institute for assisting patients presenting bone marrow failures. The Center provides for allogeneic and autologous bone marrow transplants, peripheral stem cell transplants, umbilical cord collections and transplants, and a small experience with unrelated bone marrow transplants. The Center receives patient from all over the country and provides very sophisticated medical care at no direct cost to the patients

  3. Bone marrow transplantation and other treatment after radiation injury

    International Nuclear Information System (INIS)

    Balner, H.

    1977-01-01

    This review deals mainly with current concepts about bone marrow transplantation as therapy for serious radiation injury. Such injury can be classified according to the following broadly defined dose ranges: (1) the supralethal range, leading mainly to the cerebral and intestinal syndromes; (2) the potentially lethal or therapeutic range which causes the bone marrow syndrome, and (3) the sublethal range which rarely leads to injury requiring therapy. The bone marrow syndrome of man and animals is discussed in detail. The optimal therapy for this syndrome is bone marrow transplantation in conjunction with conventional supportive treatment. The principal complications of such therapy are Graft versus Host Disease and a slow recovery of the recipient's immune system. Concerted research activities in a number of institutions have led to considerable progress in the field of bone marrow transplantation. Improved donor selection, new techniques for stem-cell separation and preservation, as well as effective barrier-nursing and antibiotic decontamination, have made bone marrow transplantation an accepted therapy for marrow depression, including the aplasia caused by excessive exposure to radiation. The review also contains a number of guidelines for the handling of serious radiation accidents. (Auth.)

  4. Immunological aspects of unrelated bone marrow transplantation: alloreactivity and immunoreconstitution

    Directory of Open Access Journals (Sweden)

    Madrigal J. Alejandro

    2001-01-01

    Full Text Available The main complications after bone marrow transplantation (BMT are graft versus host disease (GvHD, post-transplant viral infections and disease relapse. The underlying causes of these problems are the degree of HLA matching between donor and patient and the rate of immune reconstitution.

  5. Intractable Diseases Treated with Intra-Bone Marrow-Bone Marrow Transplantation

    Directory of Open Access Journals (Sweden)

    Ming eLi

    2014-09-01

    Full Text Available Bone marrow transplantation (BMT is used to treat hematological disorders, autoimmune diseases and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells but also mesenchymal stem cells (MSMCs. MSMCs are multi-potent stem cells that can be isolated from bone marrow, umbilical cord blood, and adipose tissue. MSMCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSMCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of bone marrow-derived- MSMCs, and the treatment of intractable diseases such as rheumatoid arthritis and malignant tumors with IBM-BMT.

  6. Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation.

    Science.gov (United States)

    Hisatomi, Toshio; Sonoda, Koh-hei; Ishikawa, Fumihiko; Qiao, Hong; Nakazawa, Takahiro; Fukata, Mitsuhiro; Nakamura, Toru; Noda, Kousuke; Miyahara, Shinsuke; Harada, Mine; Kinoshita, Shigeru; Hafezi-Moghadam, Ali; Ishibashi, Tatsuro; Miller, Joan W

    2007-04-01

    To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC). Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild-type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy. To investigate bone marrow derived cell recruitment under inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in transplanted mice. GFP positive cells were distributed in the entire sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)% (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC transplantation. Transmission and scanning electron microscopy revealed antigen presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of GFP (+) cells developed into the sclera. We have provided direct and novel evidence for the migration of bone marrow and HSC cells into the sclera differentiating into macrophages and dendritic cells. Vast infiltration of bone marrow and HSC cells was found to be part of the inflammatory process in EAU.

  7. Total lymphatic irradiation and bone marrow in human heart transplantation

    International Nuclear Information System (INIS)

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-01-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem

  8. Successful nonsibling bone marrow transplantation in severe combined immunodeficiency

    DEFF Research Database (Denmark)

    Ramsøe, K; Skinhøj, P; Andersen, V

    1978-01-01

    Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA...

  9. Bone marrow transdifferentiation in brain after transplantation: a retrospective study.

    Science.gov (United States)

    Cogle, Christopher R; Yachnis, Anthony T; Laywell, Eric D; Zander, Dani S; Wingard, John R; Steindler, Dennis A; Scott, Edward W

    2004-05-01

    End-organ repair by adult haemopoietic stem cells is under great scrutiny with investigators challenging the notion of these cells' plasticity. Some investigations of animals and short-term human bone marrow transplants suggest that bone marrow can repair brain. We looked for evidence of clinically relevant marrow-derived restorative neurogenesis: long-term, multilineage, neural engraftment that is not the result of cell-fusion events. We examined autopsy brain specimens from three sex-mismatched female bone-marrow-transplantation patients, a female control, and a male control. We did immunohistochemistry, fluorescence in-situ hybridisation, and tissue analysis to look for multilineage, donor-derived neurogenesis. Hippocampal cells containing a Y chromosome were present up to 6 years post-transplant in all three patients. Transgender neurons accounted for 1% of all neurons; there was no evidence of fusion events since only one X chromosome was present. Moreover, transgender astrocytes and microglia made up 1-2% of all glial cells. Postnatal human neuropoiesis happens, and human haemopoietic cells can transdifferentiate into neurons, astrocytes, and microglia in a long-term setting without fusing. Transplantable human haemopoietic cells could serve as a therapeutic source for long-term regenerative neuropoiesis.

  10. Treatment of Radiation Induced Biological Changes by Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    El-Missiry, M.A.; Shehata, G.; Roushdy, H.M; Fayed, Th.A.

    1999-01-01

    Preventing the propagation of radiation induced oxidative damage has been a subject of considerable investigations. The ultimate goal of the present study is to use bone marrow cells to ameliorate or to treat the radiation sickness. Transplantation of bone marrow cell has shown promising results in the present experimental radiation treatment. In this report, suspension of bone marrow cells was injected into rats 12 h. after exposure to 4.5 Gy whole body gamma irradiation. Significant results were recorded on the successful control of the radiation induced disorders in a number of biochemical parameters including certain enzymatic and nonenzymatic antioxidants (superoxide dismutase and glutathione) and certain parameters related to kidney function including creatinine, urea as well as Atpase Activity in blood serum, urine and kidney tissue

  11. Late renal dysfunction in adult survivors of bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, C.A.; Cohen, E.P.; Barber-Derus, S.W.; Murray, K.J.; Ash, R.C.; Casper, J.T.; Moulder, J.E. (Medical College of Wisconsin Affiliated Hospitals, Milwaukee (USA))

    1991-06-01

    Until recently long-term renal toxicity has not been considered a major late complication of bone marrow transplantation (BMT). Late renal dysfunction has been described in a pediatric population status post-BMT which was attributable to the radiation in the preparatory regimen. A thorough review of adults with this type of late renal dysfunction has not previously been described. Fourteen of 103 evaluable adult patients undergoing allogeneic (96) or autologous (7) bone marrow transplantation, predominantly for leukemia and lymphomas, at the Medical College of Wisconsin (Milwaukee, WI) have had a syndrome of renal insufficiency characterized by increased serum creatinine, decreased glomerular filtration rate, anemia, and hypertension. This syndrome developed at a median of 9 months (range, 4.5 to 26 months) posttransplantation in the absence of specific identifiable causes. The cumulative probability of having this renal dysfunction is 20% at 1 year. Renal biopsies performed on seven of these cases showed the endothelium widely separated from the basement membrane, extreme thickening of the glomerular basement membrane, and microthrombi. Previous chemotherapy, antibiotics, and antifungals as well as cyclosporin may add to and possibly potentiate a primary chemoradiation marrow transplant renal injury, but this clinical syndrome is most analogous to clinical and experimental models of radiation nephritis. This late marrow transplant-associated nephritis should be recognized as a potentially limiting factor in the use of some intensive chemoradiation conditioning regimens used for BMT. Some selective attenuation of the radiation to the kidneys may decrease the incidence of this renal dysfunction.

  12. What Is a Bone Marrow Transplant?

    Science.gov (United States)

    ... however you can Daughter's dying wish became mother's motivation Be The Match Blog Stories Anna, transplant recipient ... Jobs Job application FAQs E-Verify Career events Employee benefits About us Bea, transplant recipient Be The ...

  13. Disseminated cutaneous trichosporonosis in an adult bone marrow transplant patient

    Directory of Open Access Journals (Sweden)

    A. M. Y. Yong

    2017-01-01

    Full Text Available The Trichosporon species are yeast-like opportunistic pathogens in immunocompromised patients. Trichosporon asahii infections have been reported in pediatric bone marrow transplant (BMT patients. However, its incidence is low in the adult literature. A 52-year-old Chinese woman who was diagnosed with acute myeloid leukemia received induction chemotherapy and underwent allogenic bone marrow transplant, which was complicated by a relapse and required salvage chemotherapy. She developed persistent non-neutropenic fever secondary to presumed hepatosplenic candidiasis. Antifungal therapy with fluconazole and anidulafungin was administered. She remained febrile and tender dusky nodules appeared over all the four limbs. Histopathological examination and fungal culture identified T. asahii. Oral voriconazole was initiated with complete resolution of her lesions. The Trichosporon species is a frequently isolated yeast species from cancer patients. Voriconazole has become the first choice agent against Trichosporon. We highlight the increased awareness and clinical suspicion required for diagnosis and subsequent management in similar adult patients.

  14. Serum carnitine levels in bone marrow transplant recipients.

    Science.gov (United States)

    Kirvelä, O; Antila, H; Heinonen, O; Toivanen, A

    1990-12-01

    This study investigated plasma carnitine levels in patients undergoing allogenic bone marrow transplantation. The patients received fat-based TPN (50% fat, 50% CHO; calorie: nitrogen ratio 125:1) for an average of 33 +/- 7.5 days. TPN was started before transplantation and stopped when patients were able to eat. Caloric needs were estimated using the Harris-Benedict equation; 150% of the estimated BEE was given for the first two weeks after transplantation. The amount of TPN was gradually decreased as patients resumed their oral intake. All patients had low-normal serum carnitine levels before transplantation. There was no significant change in total or free serum carnitine levels during the course of TPN. However, in patients who had symptoms of graft vs. host reaction (GVH), the highest carnitine values during GVH (total 72.3 +/- 6.5 and free 61.2 +/- 12.4 mumol/l) were significantly higher (p < 0.001) than the baseline values (total 27.1 +/- 9.3 and free 24.9 +/- 9.6 mumol/l) or the highest non GVH values after transplantation (total 32.0 +/- 10.7 and free 29.0 +/- 10.7 mumol/l, respectively). The serum triglyceride, total cholesterol, and HDL cholesterol remained within normal range. In conclusion, bone marrow transplant patients receiving fat-based TPN have normal circulating levels of carnitine. GVH reaction caused an increase in the carnitine levels, which was probably due to increased tissue catabolism.

  15. Bone marrow transplant – children - discharge

    Science.gov (United States)

    American Academy of Pediatric Dentistry. Guideline on dental management of pediatric patients receiving chemotherapy, hematopoietic cell transplantation, and/or radiation. Pediatr Dent . 2013 Sep- ...

  16. Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

    Directory of Open Access Journals (Sweden)

    Itır Sirinoglu Demiriz

    2012-01-01

    Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

  17. Quantitative magnetic resonance imaging in autologous bone marrow transplantation for Hodgkin's disease.

    OpenAIRE

    Smith, S. R.; Williams, C. E.; Edwards, R. H.; Davies, J. M.

    1989-01-01

    Fifteen consecutive patients with refractory or relapsed Hodgkin's disease (HD) referred for autologous bone marrow transplantation (ABMT) underwent quantitative magnetic resonance (MR) studies of the lumbar vertebral bone marrow. Markedly elevated lumbar vertebral marrow T1 values suggestive of bone marrow involvement with HD were seen in four patients, two of whom had no evidence of HD on bilateral iliac crest bone marrow biopsy. Serial studies showed normalisation of T1 values in the post-...

  18. Factors controlling the engraftment of transplanted dog bone marrow cells

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Klapwyk, W.M.; Heidt, P.J.; Hogeweg, B.; Zurcher, C.; Bekkum, D.W. van

    1982-01-01

    The LD50 of total body irradiation (TBI) for the bone marrow (BM) syndrome and the gastrointestinal (GI) syndrme was determined in dogs as 3.7 Gy, and 8.5 Gy respectively. Five Gy TBI was adequate conditioning for BM cells of littermate donors identical for the major histocompatibility comples (MHC). The maximum tolerated TBI (about 7.5 Gy) caused more side effects than 5.0 Gy TBI and was insufficient for engraftment of realistic numbers of BM cells of MHC mismatched donors. In autologous and MHC matched transplants, the rateof hemopoietic recovery correlated with the number of BM cells given. Approximtely 2 x 10 7 autologous and 1 x 10 8 MHC identical BM cells.kg -1 were needed for radiation protection. Platelet recovery was significantly more rapid in allogeneic combinations in comparison to autologous transplants. Low numbers of autologous cryopreserved bone marrow cells were as effective as fresh bone marrow cells in rescuing animals after lethal TBI. Other factors that influence BM cell engraftment were confirmed (prior sensitization of the recipient, donor selection) or identified (purification of BM cells on density gradient and selective gastrointestinal decontamination of the recipient). Consistent engraftment of gradient separated, MHC identical, BM cells was found after conditioning with two fractions of 6.0 Gy TBI, separated by 72 h. One MHC haplotype mismatched marrow did engraft after two TBI fractions of 6.0 Gy. Engraftment no longer occurred with gradient purified bone marrow cells from this type of donor. Late effects of TBI were early greying in all animals, and secondary uterine inertia in female dogs after 7.5 GY TBI. Fertility in males or females was not changed by radiation. An increase of pancreas fibrosis was noted in dogs receiving fractions of 6.0 Gy TBI. (author)

  19. Growth in children following irradiation for bone marrow transplantation

    International Nuclear Information System (INIS)

    Bushhouse, S.; Ramsay, N.K.; Pescovitz, O.H.; Kim, T.; Robison, L.L.

    1989-01-01

    Longitudinal height data from 46 pediatric bone marrow transplant (BMT) patients, including 18 with aplastic anemia (AA), 19 with acute nonlymphoblastic leukemia (ANLL), and 9 with acute lymphoblastic leukemia (ALL), were analyzed to assess growth posttransplantation. Patients were prepared for BMT with high-dose cyclophosphamide followed by 7.5 Gy single-dose irradiation; AA patients received total lymphoid irradiation (TLI), and leukemia patients received total body irradiation (TBI). AA patients demonstrated reduced height posttransplant as reflected in a negative mean standard deviation score. The observed reduction was statistically significant only at 3 years following transplant. In contrast, leukemia patients showed a significant loss in relative height that was first visible at 1 year post-BMT and continued until at least 4 years post-BMT. Mean growth velocities in the leukemia patients were significantly below median for the 3 years following transplant. With a median follow-up of 4 years, antithymocyte globulin plus steroids in combination with methotrexate as graft vs. host prophylaxis was associated with less severe growth suppression than methotrexate alone, while there were no significant associations between growth during the first 2 years following transplant and prepubertal status at transplant (as defined by age), graft vs. host disease, thyroid or gonadal function, or previous therapies received by the leukemia patients. Children undergoing marrow transplantation, particularly those receiving TBI, are at significant risk of subsequent growth suppression

  20. Osteonecrosis of the femoral head after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Mi; Jun, Jeong Su; Park, Chang Suk; Kim, Yong Sik; Kwon, Soon Yong; Kim, Yoo Jin; Kim, Chun Choo [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2003-07-01

    To retrospectively review findings of osteonecrosis of the femoral head after bone marrow transplantation. We reviewed the clinical and MR findings of osteonecrosis of the femoral head in 23 of 1112 patients who underwent marrow transplantation during a five-year follow-up period lasting from 1996 to 2000. Mean age at the time of diagnosis was 31 (range, 20-47) years, and the mean time from transplant to diagnosis was 17 months. All patients developed variable graft-versus-host disease and seventeen were treated with high-dose prednisolone and/or cysclosporin for severe acute or extensive chronic graft versus host disease. Osteonecrosis was diagnosed by magnetic resonance (MR) imaging, which allowed early detection of disease assessment of its stage. At the time of diagnosis, 15 hips were at stage I, 28 at stage II, two at stage III, and none at stage IV, according to the international ARCO classification system. Osteonecrosis of femoral diaphyses, the lower lumbar spine, or pelvic bones in the MR field was also found to have occurred in 11 patients. Initial treatment was conservative: 21 hips underwent surgery [core decompression (n=10), vascularized fibular bone graft (n=5), and joint replacement (n=6)]. In patients receiving high-dose steroids for the treatment of graft-versus-host disease, MR screening might help detect osteonecrosis at an early stage.

  1. Osteonecrosis of the femoral head after bone marrow transplantation

    International Nuclear Information System (INIS)

    Park, Jeong Mi; Jun, Jeong Su; Park, Chang Suk; Kim, Yong Sik; Kwon, Soon Yong; Kim, Yoo Jin; Kim, Chun Choo

    2003-01-01

    To retrospectively review findings of osteonecrosis of the femoral head after bone marrow transplantation. We reviewed the clinical and MR findings of osteonecrosis of the femoral head in 23 of 1112 patients who underwent marrow transplantation during a five-year follow-up period lasting from 1996 to 2000. Mean age at the time of diagnosis was 31 (range, 20-47) years, and the mean time from transplant to diagnosis was 17 months. All patients developed variable graft-versus-host disease and seventeen were treated with high-dose prednisolone and/or cysclosporin for severe acute or extensive chronic graft versus host disease. Osteonecrosis was diagnosed by magnetic resonance (MR) imaging, which allowed early detection of disease assessment of its stage. At the time of diagnosis, 15 hips were at stage I, 28 at stage II, two at stage III, and none at stage IV, according to the international ARCO classification system. Osteonecrosis of femoral diaphyses, the lower lumbar spine, or pelvic bones in the MR field was also found to have occurred in 11 patients. Initial treatment was conservative: 21 hips underwent surgery [core decompression (n=10), vascularized fibular bone graft (n=5), and joint replacement (n=6)]. In patients receiving high-dose steroids for the treatment of graft-versus-host disease, MR screening might help detect osteonecrosis at an early stage

  2. Late taste disorders in bone marrow transplantation: clinical evaluation with taste solutions in autologous and allogeneic bone marrow recipients.

    Science.gov (United States)

    Marinone, M G; Rizzoni, D; Ferremi, P; Rossi, G; Izzi, T; Brusotti, C

    1991-01-01

    The aim of this work was to determine the type and the significance of taste disorders in allogeneic bone marrow transplanted patients. In a retrospective study the taste threshold of a cohort of 15 allogeneic bone marrow transplanted patients, 4-51 months after transplantation (mean: 30.6 +/- 15.8), was compared to the taste threshold of 8 autologous bone marrow recipients, 4-48 months after transplantation (mean: 24.12 +/- 12.18), and to the taste threshold of a group of 20 consecutive normal subjects. Allogeneic bone marrow transplanted patients showed a significant hypogeusia for salt (Pearson's chi square p = 0.0002; Yates' correction p = 0.0007) and sour (Pearson's chi square p = 0.001; Yates' correction p = 0.008). No significant variations were observed for sweet and bitter. Autologous bone marrow recipients did not show any significant variation of taste acuity for sweet, salt or sour; a constant reduction of the taste threshold for bitter was observed, but the values were not significantly different from normal (Pearson's chi square p = 0.47; Yates' correction p = 0.83). So, late and selective taste disorders are observed in allogeneic bone marrow transplanted patients. Since the severity of the disorders is not strictly related to the severity of chronic oral G.V.H.D., taste analysis could discover the slightest, clinically undetectable cases of chronic oral G.V.H.D. The mechanism of immune aggression on the sensorial taste cells is poorly understood. Further trials are needed to define variations of taste acuity not only after allogeneic bone marrow transplantation, but also in systemic immune diseases.

  3. Muscle-specific kinase antibody associated myasthenia gravis after bone marrow transplantation.

    Science.gov (United States)

    Heidarzadeh, Zeinab; Mousavi, Seyyed-Asadollah; Ostovan, Vahid Reza; Nafissi, Shahriar

    2014-02-01

    Myasthenia gravis is a rare complication of bone marrow transplantation and graft versus host disease. We report a 30-year-old woman presented with oculobulbar and proximal limb weakness after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Also, she developed graft versus host disease following bone marrow transplantation. Investigations led to the diagnosis of muscle specific kinase antibody related myasthenia gravis. There have been only two case reports of muscle specific kinase antibody positive myasthenia gravis after bone marrow transplantation in the literature, but none of the previously reported cases had graft versus host disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia

    International Nuclear Information System (INIS)

    Gratwohl, A.; Hermans, J.; Biezen, A.V.

    1996-01-01

    A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incident at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy. (Author)

  5. Autologous bone marrow mononuclear cells transplant in patients with critical leg ischemia: preliminary clinical results.

    Science.gov (United States)

    Li, Min; Zhou, Hua; Jin, Xing; Wang, Mo; Zhang, Shiyi; Xu, Lei

    2013-10-01

    Stem cell transplant can induce vasculogenesis and improve the blood supply to an ischemic region, offering hope for chronic lower extremity ischemic diseases. Bone marrow mononuclear cells are one of the sources for stem cell transplants. We sought to observe the safety and efficacy of autologous bone marrow mononuclear cells transplant for treating critical limb ischemia. Eligible patients were randomized 1:1 to receive placebo (0.9% NaCl) or 1 × 107 piece/mL bone marrow mononuclear cell transplant. For 6 months, patients' skin ulcers, ankle-brachial index, and rest pain were examined and recorded before and after treatment. Six months after the bone marrow mononuclear cells transplant, clinical symptoms like rest pain and skin ulcers gradually abated (P transplant (P Autologous bone marrow mononuclear cells transplant for treatment of patients with chronic limb ischemia is safe, effective, and feasible.

  6. Bone marrow transplantation for patients with chronic myeloid leukemia

    International Nuclear Information System (INIS)

    Goldman, J.M.; Apperley, J.F.; Jones, L.

    1986-01-01

    Between February 1981 and December 1984 we treated 52 patients with chronic myeloid leukemia in the chronic phase and 18 patients with more advanced disease by high-dose chemoradiotherapy followed by allogeneic bone marrow transplantation using marrow cells from HLA-identical sibling donors. In addition, the 40 patients who had not previously undergone splenectomy received radiotherapy to the spleen. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with donor marrow depleted of T cells. Of the 52 patients treated in the chronic phase, 38 are alive after a median follow-up of 25 months (range, 7 to 50); the actuarial survival at two years was 72%, and the actuarial risk of relapse was 7%. Of the 18 patients with more advanced disease, 4 have survived; the actuarial two-year survival was 18%, and the actuarial risk of relapse was 42%. We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase of chronic myeloid leukemia. T-cell depletion may have reduced the incidence and severity of graft versus host disease. The value of irradiation to the spleen before transplantation has not been established

  7. Infection in the bone marrow transplant recipient and role of the microbiology laboratory in clinical transplantation.

    OpenAIRE

    LaRocco, M T; Burgert, S J

    1997-01-01

    Over the past quarter century, tremendous technological advances have been made in bone marrow and solid organ transplantation. Despite these advances, an enduring problem for the transplant recipient is infection. As immunosuppressive regimens have become more systematic, it is apparent that different pathogens affect the transplant recipient at different time points in the posttransplantation course, since they are influenced by multiple intrinsic and extrinsic factors. An understanding of ...

  8. Remodeling of the thoracic aorta after bone marrow cell transplantation

    OpenAIRE

    Felix, Alyne; Monteiro, Nemesis; Rocha, Vinícius Novaes; Oliveira, Genilza; Moraes, Alan Cesar; Andrade, Cherley; Nascimento, Ana Lucia; de Carvalho, Laís; Thole, Alessandra; Carvalho, Jorge

    2014-01-01

    Stem cells are characterized by their ability to differentiate into multiple cell lineages and display the paracrine effect. The aim of this work was to evaluate the effect of therapy with bone marrow cells (BMCs) on blood glucose, lipid metabolism and aortic wall remodeling in mice through the administration of a high fat diet and subsequent BMCs transplantation. C57BL/6 mice were fed a control diet (CO group) or an atherogenic diet (AT group). After 16 weeks, the AT group was divided into f...

  9. Pulmonary complications after bone marrow transplantation in chest radiography

    International Nuclear Information System (INIS)

    Schuster, J.; Sailer, M.; Schmeiser, T.; Schumacher, K.A.; Heit, W.; Ulm Univ.

    1988-01-01

    In a retrospective study chest radiographs of 87 bone marrow transplant recipients were analysed. 36 patients had pulmonary complications with lung opacifications. Interstitial changes were more frequent than air-space pneumonias. The latter were caused by bacteria and fungi only. The most common cause of pulmonary complications was cytomegalovirus pneumonia. It was characterised uniformly by a bilateral diffuse interstitial pattern. Idiopathic interstitial pneumonias were indistinguishable from CMV infection. Pneumonias caused by Epstein-Barr virus and protozoa, diffuse radiation pneumonitis and leukaemic infiltrates were rare and also associated with interstitial changes. (orig.) [de

  10. Graves-Basedow disease after allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Jakubas, B.; Kostecka-Matyja, M.; Darczuk, A.; Gil, J.

    2006-01-01

    One severe aplastic anaemia case who presented autoimmune thyroid disease after allogeneic bone marrow transplantation (alloBMT) is described. A 19 year old Polish girldeveloped Graves' hyperthyroidisms 19 months after allogeneic BMT for severe aplastic anaemia (SAA) donated from her brother. Her serum was positive for thyroid stimulating antibody (TSAb) and anti-thyroid peroxidase autoantibodies (aTPO) while her brother remained euthyroid, seronegative for TSAb, and showed no clinical signs of thyroid pathology. The genetic studies of lymphocytes FISH (fluorescence in situ hybridization) and analysis of STR (short tandem repeated) fragments suggested, that lymphocytes responsible for hyperthyroidisms were of donor origin. (author)

  11. [Experimental study on bone defect treated by combined autologous bone marrow transplantation, cuttlebone, and sodium hyaluronate].

    Science.gov (United States)

    Yi, Hong-cheng; Tang, Liang-hua; Zhang, Xue-peng

    2011-08-01

    To study the feasibility of repairing bone defect by combined autologous bone marrow transplantation, cuttebone, and sodium hyaluronate. Forty-eight New Zealand rabbits were randomly divided into four groups. The 10-mm bone defect of the radial shaft animal model was established, with the periosteum remained. Rabbits of Group A were treated by autologous bone marrow transplantation, cuttlebone, and sodium hyaluronate. Those of Group B were treated by autologous bone marrow transplantation and cuttlebone. Rabbits of Group C were implanted with cuttlebone and sodium hyaluronate. And rabbits of Group D were taken as the blank control. There were twelve rabbits in each group. All rabbits were sacrificed, and the general histological examination, X-ray test, the pathohistological observation and scoring, the new born formation area measurement were performed at 2-week, 4-week, 8-week, and 12-week after transplantation respectively. The capacities for bone transplantation and defect repairing were compared and analyzed as well. The bone defect of Group A was completely repaired at week 12. The comprehensive indices at each time point were superior to those of the rest groups, showing statistical significance (Pbone repair in Group B and Group C were somewhat poor, with the repairing effect inferior to that of Group A. The bone repairing was better in Group B than in Group C. Most portion of the bone defect in Group D was filled with fibrous tissue and muscular tissue, with little bone repairing. The combined autologous bone marrow transplantation, cuttlebone, and sodium hyaluronate showed obviously synergistically bone forming capacities. It could be taken as a substitute material for transplantation.

  12. Megakaryocytopoiesis and the number of thrombocytes after bone marrow cell transplantation in lethally irradiated mice

    International Nuclear Information System (INIS)

    Viktora, L.; Hermanova, E.; Zoubkova, M.

    1977-01-01

    Changes were studied in the number of thrombocytes in the peripheral blood and megakaryocytes in the bone marrow and spleen in lethally irradiated mice after the transplantation of bone marrow cells. It was found that the thrombocytes increased in dependence on time after transplantation with the maximal values around the 20th day. An increased megakaryocytopoiesis was observed not only in the bone marrow but also in the spleen. These ascertainments suggest the importance of the transplantation of bone marrow cells and the role of thrombocytes for the survival of the organism after irradiation. (author)

  13. Total body irradiation as a form of preparation for bone marrow transplantation

    International Nuclear Information System (INIS)

    Inoue, Toshihiko

    1987-01-01

    The history of total body irradiation and bone marrow transplantation is surprisingly old. Following the success of Thomas et al. in the 1970s, bone marrow transplantation appeared to be the sole curative treatment modality for high-risk leukemia. A supralethal dose of total body irradiation was widely accepted as a form of preparation for bone marrow transplantation. In this paper, I described the present status of bone marrow transplantation for leukemia patients in Japan based on the IVth national survey. Since interstitial pneumonitis was one of the most life threatening complications after bone marrow transplantation, I mentioned the dose, dose-rate and fraction of total body irradiation in more detail. In addition, I dealt with some problems of the total body irradiation, such as dose prescription, compensating contour as well as inhomogeneity, and shielding for the highrisk organs. (author) 82 refs

  14. MICA, MICB, and MHC beta block matching in bone marrow transplantation: relevance to transplantation outcome.

    Science.gov (United States)

    Kitcharoen, K; Witt, C S; Romphruk, A V; Christiansen, F T; Leelayuwat, C

    2006-03-01

    Genetic testing of the MHC is required for selection of donors for bone marrow transplantation. The outcome of related bone marrow transplantation is usually superior to that of unrelated bone marrow transplantation. This may be the result of inaccurate or incomplete genetic testing employed for selection of donor for transplantation. Based on MHC haplotype matching, MHC block matching has been developed for selection of potential unrelated donor. Block matching has been shown previously to improve outcome when added to the conventional method of human leukocyte antigen (HLA) typing for selection of donors. In this study, we have retrospectively analyzed 44 donor recipient pairs from the Australian Bone Marrow Donor Registry Repository with respect to matching of HLA-B and HLA-Cw by sequence-based typing and MICA and MICB by polymerase chain reaction-sequence specific primer and MHC beta block matching and correlated these results with survival. Beta block matching was correlated with MIC matching (p matching. Patients who were HLA-B and -Cw matched had significantly improved survival when they were additionally matched for MHC beta block (p(c) = 0.04) or MIC (p(c) = 0.05).

  15. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid

    International Nuclear Information System (INIS)

    Ambrus, C.M.; Ambrus, J.L.

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole-body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colony-forming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls

  16. Bone marrow transplantations to study gene function in hematopoietic cells

    NARCIS (Netherlands)

    de Winther, Menno P. J.; Heeringa, Peter

    2011-01-01

    Immune cells are derived from hematopoietic stem cells in the bone marrow. Experimental replacement of bone marrow offers the unique possibility to replace immune cells, to study gene function in mouse models of disease. Over the past decades, this technique has been used extensively to study, for

  17. Social functioning of children surviving bone marrow transplantation.

    Science.gov (United States)

    Vannatta, K; Zeller, M; Noll, R B; Koontz, K

    1998-06-01

    To evaluate the behavioral reputation and peer acceptance of pediatric bone marrow transplant (BMT) survivors. Forty-eight BMT survivors (8-16 years of age) were compared to 48 nonchronically ill, same-classroom, same-gender comparison peers (COMP). Peer, teacher, and self-report data were collected. Relative to COMP, BMT survivors had fewer friends and were described by peers, but not teacher or self-report, as more socially isolated. In addition, peers described BMT survivors as being less physically attractive and athletically skilled. Further analyses suggested that these nonsocial attributes (physical appearance and athletic ability) and treatment variables (whether cranial irradiation was received) mediated the social difficulties of BMT survivors. These data are suggestive of an unremitting pattern of difficulties with peers that has the potential to disrupt normal social and emotional development. Differences between peer, teacher and self-reports highlight the need for multiple informants in future work.

  18. MRI of intracranial toxoplasmosis after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Dietrich, U.; Doerfler, A.; Forsting, M. [Department of Neuroradiology, University Hospital, Essen (Germany); Maschke, M. [Department of Neurology, University Hospital Essen (Germany); Prumbaum, M. [Department of Bone Marrow Transplantation, University Hospital Essen (Germany)

    2000-01-01

    Toxoplasma encephalitis was confirmed by biopsy in three patients with bone marrow (BMT) or peripheral blood stem-cell transplantation (PBSCT). All had MRI before antimicrobial therapy. The intensity of contrast enhancement was very variable. One patient had one large, moderately enhancing cerebral lesion and several smaller almost nonenhancing lesions. The second had small nodular and haemorrhagic lesions without any enhancement. The third had late cerebral toxoplasmosis and showed multiple lesions with marked contrast enhancement. The moderate or absent contrast enhancement in the two patients in the early phase of cerebral toxoplasmosis may be related to a poor immunological response, with a low white blood cell count in at least one patient. Both received higher doses of prednisone than the patient with late infection, leading to a reduced inflammatory response. In patients with a low leukocyte count and/or high doses of immunosuppressive therapy, typical contrast enhancement may be absent. (orig.)

  19. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation.

    Science.gov (United States)

    Zhou, Ya-Jing; Liu, Jian-Min; Wei, Shu-Ming; Zhang, Yun-Hao; Qu, Zhen-Hua; Chen, Shu-Bo

    2015-08-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  20. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Science.gov (United States)

    Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats. PMID:26487860

  1. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    Directory of Open Access Journals (Sweden)

    Raphael P H Meier

    Full Text Available Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow and 10 days (kidney capsule. Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  2. Acquisition of vernal and atopic keratoconjunctivitis after bone marrow transplantation.

    Science.gov (United States)

    Tabbara, Khalid F; Nassar, Amr; Ahmed, Syed Osman; Al Mohareb, Fahad; Aljurf, Mahmoud

    2008-09-01

    Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) result from genetic and environmental factors. We present patients who had no history of atopic disorders before bone marrow transplantation (BMT) and who seem to have acquired VKC or AKC from their donors, who had atopic disorders. Observational case series. The patients in this study were part of a cohort of patients who had undergone allogeneic hemapoietic stem cell transplantation (HSCT) from January 1997 through December 2007. Of 621 HSCT recipients, four recipients who were free of allergic disorders acquired VKC or AKC from their afflicted donors after HSCT. Each patient underwent complete ophthalmologic examination, determination of the total serum immunoglobulin (Ig) E, and conjunctival scrapings. Four (0.64%) of 621 patients who had undergone HSCT acquired VKC or AKC after BMT. The donors had VKC or atopic dermatitis. In addition, in two of these four patients, asthma developed. One patient had elevated total serum IgE. Conjunctival scrapings of all four patients revealed the presence of eosinophils. One patient had concurrent graft-versus-host disease. VKC and AKC are systemic allergic disorders characterized by local ocular manifestations. This report suggests the possibility of the acquisition of VKC or AKC after BMT by adoptive transfer.

  3. Cataract after total body irradiation and bone marrow transplantation: degree of visual impairment

    NARCIS (Netherlands)

    van Kempen-Harteveld, M. Loes; Struikmans, Henk; Kal, Henk B.; van der Tweel, Ingeborg; Mourits, Maarten P.; Verdonck, Leo F.; Schipper, Jan; Battermann, Jan J.

    2002-01-01

    PURPOSE: To assess the degree of visual impairment as a result of cataract formation after total body irradiation (TBI) for bone marrow transplantation. METHODS AND MATERIALS: The data from 93 patients who received TBI in 1 or 2 fractions as a part of their conditioning regimen for bone marrow

  4. Remodeling of the thoracic aorta after bone marrow cell transplantation

    Science.gov (United States)

    Felix, Alyne; Monteiro, Nemesis; Rocha, Vinícius Novaes; Oliveira, Genilza; Moraes, Alan Cesar; Andrade, Cherley; Nascimento, Ana Lucia; de Carvalho, Laís; Thole, Alessandra; Carvalho, Jorge

    2014-01-01

    Stem cells are characterized by their ability to differentiate into multiple cell lineages and display the paracrine effect. The aim of this work was to evaluate the effect of therapy with bone marrow cells (BMCs) on blood glucose, lipid metabolism and aortic wall remodeling in mice through the administration of a high fat diet and subsequent BMCs transplantation. C57BL/6 mice were fed a control diet (CO group) or an atherogenic diet (AT group). After 16 weeks, the AT group was divided into four groups: an AT 14 days group and AT 21 days group, that were given an injection of vehicle and sacrificed at 14 and 21 days after, respectively; AT-BMC 14 days group and AT-BMC 21 days group that was given an injection of BMCs and sacrificed at 14 and 21 days after. The CO group was sacrificed along with other groups. The BMCs transplant had reduced blood glucose, triglycerides and total cholesterol. The Qa (1/mm2) was quantitatively reduced in AT 14 days group, AT 21 days group and was high in AT-BMC 21 days group. The AT 21 days group exhibited increased tunica media and elastic system fibers. The immunolabeling for α-SMA and VEGF showed less immunolabeling in transplanted groups with BMCs. The immunostaining for PCNA seems to be more expressive in the group AT-BMC 21 days group. To conclude, our results support the concept that in mice, the injection of BMCs improve glucose levels, lipid metabolism and remodeling of the aortic wall in animals using atherogenic diet. PMID:25337194

  5. [Varicella zoster virus infection after bone marrow transplant. Unusual presentation and importance of prevention].

    Science.gov (United States)

    Ladrière, M; Bibes, B; Rabaud, C; Delaby, P; May, T; Canton, P

    Leukemeia and lymphoproliferative disease are associated with a high risk of varicela-zoster virus (VZV) infection. Although infrequent, visceral involvement can be fatal. We report two cases of patients presenting severe VZV infection after bone marrow transplantation. The first patient was a 42-year old man who received an allogeneic bone marrow transplantation for chronic myelogenous leukemia. A severe graft-versus-host reaction occurred. Three months after discontinuing VZV prophylaxis, VZV transverse myelitis was diagnosed, leading to death despite prompt treatment with acyclovir. The second patient was a 42-year-old woman treated with autologous bone marrow transplantation for lymphoma. She developed acute viral pancreatitis one month after discontinuing VZV prophylaxis. Recovery was achieved with intravenous treatment. These two cases illustrate the potential gravity of VZV infection after bone marrow transplantation. These observations point to the need for revisiting the duration of VZV prophylaxis.

  6. Late-onset persistent retinal microvascular changes after bone marrow transplantation: 3-year follow-up

    Directory of Open Access Journals (Sweden)

    Muccioli Cristina

    2002-01-01

    Full Text Available Purpose: To describe a case of persistent retinopathy after bone marrow transplantation in the absence of radiation therapy. Methods: Case Report. Results: A 42 year-old man developed bilateral visual loss 15 months after receiving a bone marrow transplant for acute leukemia. The patient was treated with a high dose of cyclosporin A and oral corticosteroids. No radiation therapy was given. Late-onset, multiple, bilateral cotton-wool spots developed 15 months after the bone marrow transplantation and still persist. After three years other cotton-wool spots arose in the absence of any immunosuppressive therapy. Conclusions: Bone marrow transplantation microvasculopathy of the retina may be related to certain combinations of chemotherapy drugs or immunosuppression itself and may persist in the absence of these immunosuppressive drugs.

  7. Radiobiological studies on target cell populations in murine bone marrow transplantation recipients.

    NARCIS (Netherlands)

    van Os, Ronald Peter

    1994-01-01

    The experiments presented in this thesis were designed to investigate the role of total body irradiation (TBI) in conditioning murine recipients of syngeneic and allogeneic bone marrow transplantation (BMT). ... Zie: Summary

  8. Bone marrow aspiration

    Science.gov (United States)

    Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

  9. Differentiating Functional Roles of Gene Expression from Immune and Non-immune Cells in Mouse Colitis by Bone Marrow Transplantation

    Science.gov (United States)

    Koon, Hon Wai; Ho, Samantha; Cheng, Michelle; Ichikawa, Ryan; Pothoulakis, Charalabos

    2012-01-01

    To understand the role of a gene in the development of colitis, we compared the responses of wild-type mice and gene-of-interest deficient knockout mice to colitis. If the gene-of-interest is expressed in both bone marrow derived cells and non-bone marrow derived cells of the host; however, it is possible to differentiate the role of a gene of interest in bone marrow derived cells and non- bone marrow derived cells by bone marrow transplantation technique. To change the bone marrow derived cell genotype of mice, the original bone marrow of recipient mice were destroyed by irradiation and then replaced by new donor bone marrow of different genotype. When wild-type mice donor bone marrow was transplanted to knockout mice, we could generate knockout mice with wild-type gene expression in bone marrow derived cells. Alternatively, when knockout mice donor bone marrow was transplanted to wild-type recipient mice, wild-type mice without gene-of-interest expressing from bone marrow derived cells were produced. However, bone marrow transplantation may not be 100% complete. Therefore, we utilized cluster of differentiation (CD) molecules (CD45.1 and CD45.2) as markers of donor and recipient cells to track the proportion of donor bone marrow derived cells in recipient mice and success of bone marrow transplantation. Wild-type mice with CD45.1 genotype and knockout mice with CD45.2 genotype were used. After irradiation of recipient mice, the donor bone marrow cells of different genotypes were infused into the recipient mice. When the new bone marrow regenerated to take over its immunity, the mice were challenged by chemical agent (dextran sodium sulfate, DSS 5%) to induce colitis. Here we also showed the method to induce colitis in mice and evaluate the role of the gene of interest expressed from bone-marrow derived cells. If the gene-of-interest from the bone derived cells plays an important role in the development of the disease (such as colitis), the phenotype of the

  10. Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. II. Renal allographs

    International Nuclear Information System (INIS)

    Myburgh, J.A.; Smit, J.A.; Hill, R.R.H.; Browde, S.

    1980-01-01

    A modified regimen of fractionated total lymphoid irradiation and allogeneic bone marrow (BM) injection in chacma baboons produced transplantation tolerance for allografted kidneys from the BM donors, and substantial chimerism without evidence of graft-versus-host disease. Increasing the dose of nucleated BM cells injected 4-fold over that used in liver transplantation resulted consistently in normal graft function in the early weeks after transplantation. Bone marrow injection and challenge with renal allografts could be delayed for at least 3 weeks after completion of irradiation. If it can be shown that this period can be extended even further, the protocols will be relevant to the circumstances of clinical cadaveric renal transplantation

  11. Radiation nephritis following total-body irradiation and cyclophosphamide in preparation for bone marrow transplantation

    International Nuclear Information System (INIS)

    Bergstein, J.; Andreoli, S.P.; Provisor, A.J.; Yum, M.

    1986-01-01

    Two children prepared for bone marrow transplantation with total-body irradiation and cyclophosphamide developed hypertension, microscopic hematuria, proteinuria, diminished renal function, and anemia six months after transplantation. Light microscopy of the kidneys revealed mesangial expansion, glomerular capillary wall thickening, and lumenal thrombosis. Electron microscopy demonstrated widening of the subendothelial space due to the deposition of amorphous fluffy material. In one patient, immunofluorescence microscopy revealed glomerular capillary wall deposition of fibrin and immunoglobulins. The clinical and histologic findings support the diagnosis of radiation nephritis. Patients prepared for bone marrow transplantation with total-body irradiation and cyclophosphamide should be followed closely after transplantation for the development of hypertension, proteinuria, and renal insufficiency

  12. Pneumatosis intestinalis in children after allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Yeager, A.M.; Kanof, M.E.; Lake, A.M.; Kramer, S.S.; Jones, B.; Saral, R.; Santos, G.W.

    1987-01-01

    Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or highgrade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT. (orig.)

  13. Pneumatosis intestinalis in children after allogeneic bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Yeager, A.M.; Kanof, M.E.; Lake, A.M.; Kramer, S.S.; Jones, B.; Saral, R.; Santos, G.W.

    1987-01-01

    Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or highgrade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT.

  14. Endocrine dysfunction after total body irradiation and bone marrow transplantation

    International Nuclear Information System (INIS)

    Feyer, P.; Titlbach, O.; Hoffmann, F.A.; Kubel, M.; Helbig, W.; Leipzig Univ.

    1989-01-01

    Data regarding changes of endocrine parameters after total body irradiation (TBI) and bone marrow transplantation (BMT) are described. Endocrine glands are usually resistant to irradiation under morphological aspects. But new methods of determination and sensitive tests were developed in the last few years. Now it is possible to detect already small functional changes. Endocrine studies in the course of the disease were followed serially in 16 patients with TBI and BMT. Pretransplant conditioning consisted of single-dose irradiation combined with a high-dose, short-term chemotherapy. Reactions of the endocrine system showed a defined temporary order. Changes of ACTH and cortisol were in the beginning. The pituitary-adrenal cortex system responds in a different way. The pituitary-thyroid system develops a short-term 'low-T 3 -syndrome' reflecting the extreme stress of the organism. At the same time we obtained an increase of thyroxine. Testosterone and luteotropic hormone, the sexual steroids showed levels representing a primary gonadal insufficiency. The studies in the posttransplant period yielded a return to the normal range at most of the hormonal levels with the exception of the sexual steroids. Sterility is one of the late effects of TBI. A tendency towards hypothyroidism could be noticed in some cases being only subclinical forms. Reasons and possible therapy are discussed. (author)

  15. Autologous Bone Marrow Mononuclear Cells Intrathecal Transplantation in Chronic Stroke

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2014-01-01

    Full Text Available Cell therapy is being widely explored in the management of stroke and has demonstrated great potential. It has been shown to assist in the remodeling of the central nervous system by inducing neurorestorative effect through the process of angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, the effect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs is analyzed on the recovery process of patients with chronic stroke. 24 patients diagnosed with chronic stroke were administered cell therapy, followed by multidisciplinary neurorehabilitation. They were assessed on functional independence measure (FIM objectively, along with assessment of standing and walking balance, ambulation, and hand functions. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. Further factor analysis was done. Patients of the younger groups showed higher percentage of improvement in all the areas. Patients who underwent cell therapy within 2 years after the stroke showed better changes. Ischemic type of stroke had better recovery than the hemorrhagic stroke. This study demonstrates the potential of autologous BMMNCs intrathecal transplantation in improving the prognosis of functional recovery in chronic stage of stroke. Further clinical trials are recommended. This trial is registered with NCT02065778.

  16. Administration of RANKL boosts thymic regeneration upon bone marrow transplantation.

    Science.gov (United States)

    Lopes, Noella; Vachon, Hortense; Marie, Julien; Irla, Magali

    2017-06-01

    Cytoablative treatments lead to severe damages on thymic epithelial cells (TECs), which result in delayed de novo thymopoiesis and a prolonged period of T-cell immunodeficiency. Understanding the mechanisms that govern thymic regeneration is of paramount interest for the recovery of a functional immune system notably after bone marrow transplantation (BMT). Here, we show that RANK ligand (RANKL) is upregulated in CD4 + thymocytes and lymphoid tissue inducer (LTi) cells during the early phase of thymic regeneration. Importantly, whereas RANKL neutralization alters TEC recovery after irradiation, ex vivo RANKL administration during BMT boosts the regeneration of TEC subsets including thymic epithelial progenitor-enriched cells, thymus homing of lymphoid progenitors, and de novo thymopoiesis. RANKL increases specifically in LTi cells, lymphotoxin α, which is critical for thymic regeneration. RANKL treatment, dependent on lymphotoxin α, is beneficial upon BMT in young and aged individuals. This study thus indicates that RANKL may be clinically useful to improve T-cell function recovery after BMT by controlling multiple facets of thymic regeneration. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  17. Bone marrow transplantation for thalassemia: a global perspective

    Directory of Open Access Journals (Sweden)

    Mohamed Hamed Hussein

    2013-03-01

    Full Text Available Even though severe thalassemia is a preventable disease, over 100,000 new cases are born yearly, particularly in the Middle East and South-East Asia. Most of these children may not reach adulthood because long-term appropriate supportive care is either inaccessible or unaffordable. Bone marrow transplantation (BMT remains the only available definitive cure and success rates can be very high in appropriately selected patients, i.e. low-risk younger children with a matched family donor. In these circumstances BMT may be justified medically, ethically as well as financially, in fact, the cost of low-risk BMT is equivalent to that of a few years of non-curative supportive. This manuscript will briefly review the current status of bone marrow transplantation for thalassemia major with particular emphasis on a global prospective and present the experience of the Cure2Children Foundation supporting sustainable and scalable start up BMT programs in low-resource settings. The initial twelve consecutive patients managed in two start up BMT units in Pakistan (Children’s Hospital of the Pakistan Institute of Medical Sciences, Islamabad and India (South East Asia Institute for Thalassemia, Jaipur were included in this analysis. These initial six patients per each institution where purposely chosen as the focus of this report because they represent the steepest phase of the learning curve. The median age at transplant was 3.9 years, range 0.9 to 6.0, liver was no greater than 2 cm from costal margin, and all received matched related BMT. A structured on-site focused training program as well as ongoing intensive on-line cooperation was provided by the Cure2Children team of professionals. At a median follow-up of 7.5 months (range 3.5 to 33.5 months both thalassemia-free and overall survival are 92%, one patient died of encephalitis-meningitis of unknown cause. No rejections where observed. Neutrophil recovery occurred at a median of 15.5 days (range 13

  18. [Etiopathogenesis of aplastic anemia and of the severe form treated with immunosuppression and bone marrow transplantation].

    Science.gov (United States)

    Dulley, F L; Lotério, H A; Massumoto, C M; Llacer, P E; Chamone, D de A

    1989-01-01

    Aplastic anemia is a condition characterized by bone marrow hipoplasia and pancytopenia. Various etiologic agents are related to the acquired form of this disease but in many cases the causative agents remain obscure. Severe aplastic anemia has been treated by immunosuppression and allogeneic marrow transplantation.

  19. Osteopetrose maligna: transplante de medula óssea Malignant osteopetrosis: bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Maria L. Borsato

    2008-04-01

    bone re-absorption also leads to macrocephaly, frontal bossing, hypertelorism, exophthalmos, increased intracranial pressure, retarded tooth eruption, retarded linear growth and psychomotor delay. Death occurs within the first years of life. The only curative therapy is allogeneic bone marrow transplantation with a HLA-identical donor, which restores hematopoiesis, monocyte-macrophage function and bone recovery, but there is no sensorial deficit restoration once present. The authors report two cases of allogeneic bone marrow transplant for infantile malignant osteopetrosis. The first child, on day 1260 after bone marrow transplantation (BMT, showed radiologic bone recovery and no progression of neurological deficits with a bone biopsy showing no signs of osteopetrosis. The second child showed signs of bone re-absorption and no progression of neurological deficits on day 700. The authors emphasize the importance of early diagnosis of osteopetrosis and the necessity of bone marrow transplantation before neurological deficits have begun.

  20. Minor histocompatibility antigens on transfused leukoreduced units of red blood cells induce bone marrow transplant rejection in a mouse model

    OpenAIRE

    Desmarets, Maxime; Cadwell, Chantel M.; Peterson, Kenneth R.; Neades, Renee; Zimring, James C.

    2009-01-01

    When successful, human leukocyte antigen (HLA)–matched bone marrow transplantation with reduced-intensity conditioning is a cure for several nonmalignant hematologic disorders that require chronic transfusion, such as sickle cell disease and aplastic anemia. However, there are unusually high bone marrow transplant (BMT) rejection rates in these patients. Rejection correlates with the number of transfusions before bone marrow transplantation, and it has been hypothesized that preimmunization t...

  1. Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Vriesendorp, H.M.; Halliwell, R.E.; Johnson, P.M.; Fey, T.A.; McDonough, C.M.

    1985-06-01

    The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated.

  2. Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Halliwell, R.E.; Johnson, P.M.; Fey, T.A.; McDonough, C.M.

    1985-01-01

    The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated

  3. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Seyed Mojtaba Hosseini

    2015-01-01

    Full Text Available Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the fluorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These findings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.

  4. Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction

    International Nuclear Information System (INIS)

    Sawyers, C.L.; Timson, L.; Clark, S.S.; Witte, O.N.; Champlin, R.; Kawasaki, E.S.

    1990-01-01

    Relapse of chronic myelogenous leukemia after bone marrow transplantation can be detected by using clinical, cytogenetic, or molecular tools. A modification of the polymerase chain reaction can be used in patients to detect low levels of the BCR-ABL-encoded mRNA transcript, a specific marker for chronic myelogenous leukemia. Early detection of relapse after bone marrow transplantation could potentially alter treatment decisions. The authors prospectively evaluated 19 patients for evidence of molecular relapse, cytogenetic relapse, and clinical relapse after bone marrow transplantation. They used the polymerase chain reaction to detect residual BCR-ABL mRNA in patients followed up to 45 months after treatment and found 4 patients with BCR-ABL mRNA expression following bone marrow transplantation. Fifteen patients did not express detectable BCR-ABL mRNA. All 19 patients remain in clinical remission. In this prospective study of chronic myelogenous leukemia patients treated with bone marrow transplantation, molecular relapse preceded cytogenetic relapse in those patients who persistently express BCR-ABL mRNA. They recommend using standard clinical and cytogenetic testing to make patient care decisions until further follow-up determines the clinical outcome of those patients with residual BCR-ABL mRNA transcripts detected by polymerase chain reaction

  5. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    OpenAIRE

    Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-l...

  6. Infected bone inactivation combined with transplantation of autologous platelet-rich plasma and bone marrow for treatment of chronic osteomyelitis.

    Science.gov (United States)

    Wang, J-H; Zhao, K; Liu, H-L; Zhao, H-M; Yang, J; Sun, X-K

    2015-12-01

    Here we tested the therapeutic efficacy of infected bone inactivation combined with transplantation of autologous platelet-rich plasma and bone marrow in chronic osteomyelitis. 64 patients with chronic osteomyelitis were randomly divided into two groups. Patients in control group received conventional antibiotic and surgical treatments, while patients in the experimental treatment group underwent infected bone inactivation combined with transplantation of autologous platelet-rich plasma and bone marrow. The X-ray, histological, and biochemical (alkaline phosphatase) changes were assessed at 4, 8, 12 and 16 weeks after the treatment. At all tested study points, X-ray and histological scores, and alkaline phosphatase levels were significantly better in patients of the experimental treatment group. Infected bone inactivation combined with transplantation of autologous platelet-rich plasma and bone marrow achieves beneficial therapeutic results in chronic osteomyelitis.

  7. Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Wang FJ

    2015-12-01

    Full Text Available Mesenchymal stromal cells (MSCs have shown promise as treatment for graft-versus-host disease (GvHD following allogeneic bone marrow transplantation (alloBMT. Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs were injected via carotid artery (IA or tail vein (TV into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole–body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.

  8. Bone marrow-derived mononuclear cell transplantation in spinal cord injury patients by lumbar puncture.

    Science.gov (United States)

    Suzuki, Yoshihisa; Ishikawa, Namiko; Omae, Kaoru; Hirai, Tatsuya; Ohnishi, Katsunori; Nakano, Norihiko; Nishida, Hidetaka; Nakatani, Toshio; Fukushima, Masanori; Ide, Chizuka

    2014-01-01

    This study was conducted to assess the safety and feasibility of intrathecal transplantation of autologous bone marrow-derived mononuclear cells for the treatment of patients with spinal cord injury. Ten patients were included in the study. Approximately 120 ml of bone marrow aspirate was obtained from bilateral iliac bone of patients with spinal cord injury. Isolation of mononuclear cells was performed using Ficoll density-gradient centrifugation. Bone marrow mononuclear cells were transplanted into cerebrospinal fluid by lumbar puncture. Functional tests were performed prior to the cell transplantation and six months after cell transplantation. The patients were carefully observed for up to six months. In 5 patients with AIS A prior to cell transplantation, 1 patient converted to AIS B six months after cell transplantation. In 5 patients with AIS B, 1 patient converted to AIS D and 2 patients to AIS C. MRI did not show any complication. Two patients showed slight anemia after aspiration of bone-marrow cells, which returned to normal level within a several weeks. The results of this study suggest that this method may be safe and feasible.

  9. Enhancement of the grafting efficiency by the new method of fetal liver-bone marrow scheduled transplantation

    International Nuclear Information System (INIS)

    Xiang Yingsong; Yang Rujun; Yang Ping; Cai Jianming; Min Rui

    2000-01-01

    To enhance the grafting efficiency of bone marrow transplantation, lethally Irradiated recipient Kunming mice were transplantation with fetal liver-bone marrow scheduled transplantation. (FL-BMST) The numbers of WBC, nucleated cells were near to normal level 17 d after irradiation in FL-BMST group transplantation with 1 x 10 6 bone marrow cells, the indexes of CFU-E, CFU-GM, CFU-F, CFU-S, were returned to normal; the degree of GVHD in the FL-BMST group was slighter than that in sing bone marrow transplantation group; and the survival rate of mice was 60%, which was significantly higher than that of routine single bone marrow transplantation group. 'Niches' vacated each time could be fully used and be improved, be increased by fetal liver-bone marrow scheduled transplantation, so the homing of stem cells was increased, and the number of transplanted bone marrow cells could be decreased. So this new method was a better method than routine bone singe marrow transplantation

  10. Autologous bone marrow mononuclear cell transplant and surgical decompression in a dog with chronic spinal cord injury.

    Science.gov (United States)

    Tamura, Katsutoshi; Harada, Yasuji; Kunimi, Maki; Takemitsu, Hiroshi; Hara, Yasushi; Nakamura, Tatsuo; Tagawa, Masahiro

    2015-02-01

    In dogs with deep analgesia caused by acute spinal cord injury from thoracolumbar disk herniation, autologous bone marrow mononuclear cell transplant may improve recovery. The purpose of the present study was to evaluate autologous bone marrow mononuclear cell transplant in a dog that had paraplegia and deep analgesia caused by chronic spinal cord injury. Autologous bone marrow mononuclear cell transplant was performed in a dog having paraplegia and analgesia for 3 years that was caused by a chronic spinal cord injury secondary to Hansen type I thoracolumbar disk herniation. Functional recovery was evaluated with electrophysiologic studies and the Texas Spinal Cord Injury Scale. Somatosensory evoked potentials were absent before transplant but were detected after transplant. Functional improvement was noted (Texas Spinal Cord Injury Scale: before transplant, 0; after transplant, 6). No adverse events were observed. Autologous bone marrow mononuclear cell transplant into the subarachnoid space may be a safe and beneficial treatment for chronic spinal cord injury in dogs.

  11. Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury

    OpenAIRE

    Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal ...

  12. Success Stories in Radiotherapy Development Projects: Optimizing Total Body Irradiation for Bone Marrow Transplants in Bulgaria. Chapter 28.3

    International Nuclear Information System (INIS)

    Rosenblatt, E.; Gocheva-Petkova, L.

    2017-01-01

    Each year, hundreds of cancer patients in Bulgaria receive bone marrow transplants as treatment for haematological malignancies such as leukaemia, lymphoma and multiple myeloma, or for solid tumours such as neuroblastoma, one of the more common cancers in infancy. To undergo a bone marrow transplant, patients must first go through a preparatory process that conditions the body for the transplant. This involves a special radiotherapy technique called total body irradiation (TBI). TBI helps to make space for the transplanted marrow, destroys any malignant cells that may be left in the bone marrow after chemotherapy and suppresses the immune system to help prevent rejection of the transplant. To avoid complications, patients must also receive irradiated cellular blood components during the preparatory process. The IAEA assisted medical professionals in Bulgaria in optimizing bone marrow transplants by providing the equipment and building the capabilities necessary to carry out TBI. The IAEA also offered very specialized radiotherapy training to the medical staff, including blood irradiation.

  13. Bone marrow transplantation for research and regenerative therapies in the central nervous system.

    Science.gov (United States)

    Díaz, David; Alonso, José Ramón; Weruaga, Eduardo

    2015-01-01

    Bone marrow stem cells are probably the best known stem cell type and have been employed for more than 50 years, especially in pathologies related to the hematopoietic and immune systems. However, their potential for therapeutic application is much broader (because these cells can differentiate into hepatocytes, myocytes, cardiomyocytes, pneumocytes or neural cells, among others), and they can also presumably be employed to palliate neural diseases. Current research addressing the integration of bone marrow -derived cells in the neural circuits of the central nervous system together with their features and applications are hotspots in current Neurobiology. Nevertheless, as in other leading research lines the efficacy and possibilities of their therapeutic application depend on the technical procedures employed, which are still far from being standardized. In this chapter we shall explain one of these procedures in depth, namely the transplantation of whole bone marrow from harvested bone marrow stem cells for subsequent integration into the encephalon.

  14. The effect of thymus cells on bone marrow transplants into sublethally irradiated mice

    International Nuclear Information System (INIS)

    Kruszewski, J.A.; Szcylik, C.; Wiktor-Jedrzejczak, W.

    1984-01-01

    Bone marrow cells formed similar numbers of 10-days spleen colonies in sublethally (6 Gy) irradiated C57B1/6 mice as in lethally (7.5 Gy) irradiated mice i.e. approximately 20 per 10 5 cells. Numbers of 10 day endogenous spleen colonies in sublethally irradiated mice (0.2 to 0.6 per spleen) did not differ significantly from the numbers in lethally irradiated mice. Yet, transplants of 10 7 coisogenic marrow cells into sublethally irradiated mice resulted in predominantly endogenous recovery of granulocyte system as evidenced by utilization of ''beige'' marker for transplanted cells. Nevertheless, transplanted cells engrafted into sublethally irradiated mice were present in their hemopoietic tissues throughout the observation period of 2 months never exceeding 5 to 10% of cells. Thymus cells stimulated endogenous and exogenous spleen colony formation as well as endogenous granulopoietic recovery. Additionally, they increased both the frequency and absolute numbers of graft-derived granulocytic cells in hemopoietic organs of transplanted mice. They failed, however, to essentially change the quantitative relationships between endogenous and exogenous hemopoietic recovery. These results may suggest that spleen colony studies are not suitable for prediction of events following bone marrow transplant into sublethally irradiated mice. Simultaneously, they have strengthened the necessity for appropriate conditioning of recipients of marrow transplants. (orig.) [de

  15. Visceral Leishmaniasis: A Differential Diagnosis to Remember after Bone Marrow Transplantation

    Directory of Open Access Journals (Sweden)

    Margarida Dantas Brito

    2014-01-01

    Full Text Available Leishmania infection in immunocompromised hosts is reported in the literature, mostly concerning human immunodeficiency virus infected patients. It is not well characterized in the context of stem cell transplantation. We report a rare case clinical case of visceral leishmaniasis after allogeneic bone marrow transplantation. A 50-year-old Caucasian male was referred to allogeneic bone marrow transplantation with a high-risk acute lymphoblastic B leukemia in first complete remission. Allogeneic SCT was performed with peripheral blood stem cells from an unrelated Portuguese matched donor. In the following months, patient developed mild fluctuating cytopenias, mostly thrombocytopenia (between 60 and 80∗109/L. The only significant complaint was intermittent tiredness. The common causes for thrombocytopenia in this setting were excluded—no evidence of graft versus host disease, no signs of viral or bacterial infection, and no signs of relapsed disease/dysplastic changes. The bone marrow smear performed 12 months after transplantation revealed an unsuspected diagnosis: a massive bone marrow infiltration with amastigotes.

  16. Palmar Eccrine Hidradenitis Secondary to Trauma from Computer Gaming in an Adolescent After Bone Marrow Transplantation.

    Science.gov (United States)

    Lee, Lynette Ying; Koh, Mark Jean-Aan

    2017-09-01

    A 14-year-old boy who had undergone a matched sibling bone marrow transplant for acute lymphoblastic leukemia presented with painful nodules on his palms after prolonged gaming on his computer and mobile phone. Histology showed a neutrophilic inflammatory infiltrate surrounding the acrosyringium and eccrine sweat coils in the deep dermis. The lesions resolved spontaneously with conservative management. © 2017 Wiley Periodicals, Inc.

  17. The twitcher mouse. Central nervous system pathology after bone marrow transplantation

    NARCIS (Netherlands)

    Suzuki, K.; Hoogerbrugge, P. M.; Poorthuis, B. J.; Bekkum, D. W.

    1988-01-01

    Effects of bone marrow transplantation (BMT) on the pathology of the central nervous system were evaluated, at light and electron microscope levels, in the homozygous twitcher mouse (twi/twi), an authentic murine model of globoid cell leukodystrophy (GLD, Krabbe disease) in humans. In the twitcher

  18. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subcla...

  19. Bone Marrow Transplantation Confers Modest Benefits in Mouse Models of Huntington’s Disease

    Science.gov (United States)

    Kwan, Wanda; Magnusson, Anna; Chou, Austin; Adame, Anthony; Carson, Monica J.; Kohsaka, Shinichi; Masliah, Eliezer; Möller, Thomas; Ransohoff, Richard; Tabrizi, Sarah J.; Björkqvist, Maria; Muchowski, Paul J.

    2013-01-01

    Huntington’s disease (HD) is caused by an expanded polyglutamine tract in the protein huntingtin (htt). Although HD has historically been viewed as a brain-specific disease, htt is expressed ubiquitously, and recent studies indicate that mutant htt might cause changes to the immune system that could contribute to pathogenesis. Monocytes from HD patients and mouse models are hyperactive in response to stimulation, and increased levels of inflammatory cytokines and chemokines are found in pre-manifest patients that correlate with pathogenesis. In this study, wild-type (WT) bone marrow cells were transplanted into two lethally irradiated transgenic mouse models of HD that ubiquitously express full-length htt (YAC128 and BACHD mice). Bone marrow transplantation partially attenuated hypokinetic and motor deficits in HD mice. Increased levels of synapses in the cortex were found in HD mice that received bone marrow transplants. Importantly, serum levels of interleukin-6, interleukin-10, CXC chemokine ligand 1, and interferon-γ were significantly higher in HD than WT mice but were normalized in mice that received a bone marrow transplant. These results suggest that immune cell dysfunction might be an important modifier of pathogenesis in HD. PMID:22219276

  20. Bone marrow concentrate for autologous transplantation in minipigs. Characterization and osteogenic potential of mesenchymal stem cells.

    Science.gov (United States)

    Herten, M; Grassmann, J P; Sager, M; Benga, L; Fischer, J C; Jäger, M; Betsch, M; Wild, M; Hakimi, M; Jungbluth, P

    2013-01-01

    Autologous bone marrow plays an increasing role in the treatment of bone, cartilage and tendon healing disorders. Cell-based therapies display promising results in the support of local regeneration, especially therapies using intra-operative one-step treatments with autologous progenitor cells. In the present study, bone marrow-derived cells were concentrated in a point-of-care device and investigated for their mesenchymal stem cell (MSC) characteristics and their osteogenic potential. Bone marrow was harvested from the iliac crest of 16 minipigs. The mononucleated cells (MNC) were concentrated by gradient density centrifugation, cultivated, characterized by flow cytometry and stimulated into osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated by histological and immunohistological staining of relevant lineage markers. The proliferation capacity was determined via colony forming units of fibroblast and of osteogenic alkaline-phosphatase-positive-cells. The MNC could be enriched 3.5-fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry analysis revealed a positive signal for the MSC markers. Cells could be differentiated into the three lines confirming the MSC character. The cellular osteogenic potential correlated significantly with the percentage of newly formed bone in vivo in a porcine metaphyseal long-bone defect model. This study demonstrates that bone marrow concentrate from minipigs display cells with MSC character and their osteogenic differentiation potential can be used for osseous defect repair in autologous transplantations.

  1. Hematopoiesis Stimulating Role of IL-12 Enabling Bone Marrow Transplantation in Irradiated Rats

    International Nuclear Information System (INIS)

    Ashry, O.M.; Abd el Sammad, H.; El Shahat, M.; Abou el Khier, I.

    2012-01-01

    Severe myelosuppression is a common side effect of radiotherapy or chemotherapy. As a mean to stimulate the full-lineage blood cell recovery from severe myelosuppression, sublethally irradiated animals were used to evaluate immunological effect of interleukin IL-12 in bone marrow transplanted animals. Isologous bone marrow (BM), from the same inbred strain, were given to male rats, 1 hour post whole body gamma irradiation at a single dose level of 5 Gy and subcutaneous injection of 100 ng/ml IL-12. Irradiation induced a significant drop in haematological values, blood glutathione(GSH) as well as bone marrow viability associated with a significant elevation of serum malondialdehyde (MDA). Related to immunological data, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) also recorded a significant depression. Irradiated animals receiving BM and IL-12 showed significantly elevated body and spleen weights, erythrocytes count (RBCs), hemoglobin content (Hb) and hemotocrit value (Hct %) besides, white blood cells (WBCs)and its differential count, as well as GSH, while MDA was significantly depressed as compared to the irradiated group. Bone marrow viability was significantly increased while IL-6 and TNF-α were normalized. The curative action of IL-12 enforcing significant innate response could trigger and augment adaptive immune response by bone marrow transplantation, hence improving oxidative stress. IL-12 administration is proposed as a complementary strategy to treat radiation-induced path-physiology and trapping free radicals accumulations after irradiation.

  2. Visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury.

    Science.gov (United States)

    Zhang, Rui-Ping; Xu, Cheng; Liu, Yin; Li, Jian-Ding; Xie, Jun

    2015-03-01

    An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T7-8. Superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cord via the subarachnoid space. An outer magnetic field was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesenchymal stem cells reached the lesion site in these rats than in those without magnetic guidance or superparamagnetic iron oxide labeling, and immunofluorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan (BBB) locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guidance. Our data confirm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic field guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively tracked in vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury.

  3. Experimental study of low dose radiation stimulate the haematogenesis reconstitution of the recipient after bone marrow transplantation in mice

    International Nuclear Information System (INIS)

    Zhang Liyuan; Yang Shun; Zhang Ye; Zhang Mingzhi; Jiang Jiagui; Jiang Jianping

    2007-01-01

    Objective: To investigate if low dose radiation can stimulate the haematogenesis reconstitution of the recipient after bone marrow transplantation in mice. Methods: Bone marrow cells were irradiated in vitro by different low dose radiation and then cultured in vitro. 3 H-TdR incorporation was used to measure the reproductive activity of cells, and then the radiation dose with the best stimulating effect was determined. The donator myeloid cells were exposed to low dose radiation before the recipient mice received bone marrow transplantation; then the irradiated myeloid cells were infused to the recipient; and lastly, the counts of peripheral blood cells (PBC) and bone marrow mononuclear cells (BMMNC) were monitored in order to observe the effect of low dose radiation on haematogenesis reconstitution of the recipient animal after bone marrow transplantation. Results: The reproductive activity of the bone marrow cells irradiated by 6 and 8 cGy could be improved significantly in vitro. When the recipient mice received bone marrow transplantation of the myeloid cells after low dose radiation, the counts of BMMNC and PBC were higher than those in the control group (P<0.05). Conclusions: Low dose radiation can stimulate the haematogenesis reconstitution of the recipient after bone marrow transplantation. (authors)

  4. Simultaneous occurrence of osteosarcoma and osteochondroma following treatment of neuroblastoma with chemotherapy, radiotherapy, and bone marrow transplantation

    International Nuclear Information System (INIS)

    Poustchi-Amin, M.; Leonidas, J.C.; Elkowitz, S.S.

    1996-01-01

    Radiation-induced bone changes and second malignancies, as well as benign tumors, following bone marrow transplantation are being reported with increasing frequency. An osteosarcoma of the fourth right rib and an osteochondroma of the left scapula developed in a long-term survivor of abdominal neuroblastoma treated with chemotherapy, local radiation, and bone marrow transplantation. All these treatment modalities are known to induce neoplasia. (orig.). With 3 figs

  5. Homing regularity of different doses bone marrow transplantation in allogeneic hosts

    International Nuclear Information System (INIS)

    Sun Suping; Cai Jianming; Xiang Yingsong; Zhao Fang; Huang Dingde; Gao Jianguo; Yang Rujun

    2001-01-01

    Objective: To explore the homing regularity of different doses of bone marrow cell transplantation. Method: An allogeneic mouse model was used. The homing status of different dose groups from the first day to the forth day after transplantation were observed. Results: The rate of positive cells in bone marrow and spleen: differences among four groups was not significant. The rate of positive cells of third day was highest among four days (P<0.01). A phenomenon that homing-mobilization-re-homing could be observed. The homing efficiency: low dose groups were higher than that high dose groups (P<0.01). Conclusion: The homing efficiency of low dose groups is higher than that of the high dose groups in certain range, the routine method of transplanting a large quantities cells by a single injection may be an waste

  6. Percutaneous autologous bone marrow transplantation for the treatment of delayed union of limb bone in children.

    Science.gov (United States)

    Wu, Jun; Guo, Hongxi; Liu, Xing; Li, Ming; Cao, Yujiang; Qu, Xiangyang; Zhou, Hai; Weng, Liuqi

    2018-01-01

    Percutaneous autologous bone marrow transplantation (PABMT) is a minimally invasive therapeutic strategy for the treatment of delayed bone union in adults, which has been confirmed by many studies. However, there is no report on PABMT application in pediatric orthopedic surgery. The aim of this article was to analyze the therapeutic effect of PABMT in children with delayed union of limb bone and its influence in relation to delayed bone union therapy, transplantation period, patients' sex, fracture location, and fracture fixation. In this study, 53 patients (aged 3-16 years, with an average age of 6.7 years) with delayed union of long bone (20 femurs, 12 tibiae, 10 humeri, 5 radiuses, 5 ulnas, and 1 fibula) were treated using PABMT. Clinical examination and X-ray were integrated to evaluate the therapeutic effect. All 53 patients were followed up for 2-6 years (average time, 3.5 years). Of the 53 patients, 47 (88.7%) were healed, whereas the other 6 (11.3%) were not, and were subsequently treated by autologous bone grafting. In 30 patients who received their first PABMT treatment 6-8 months after fixation, the clinical cure rate, operation times, and healing time were 83.3%, 5.8±0.5 months, and 2.5±0.6, respectively. In the other 23 patients, whose first PABMT treatments were started within 4 to 6 months after fixation, the clinical cure rate, operation times, and healing time were 95.7% ( P =0.167), 3.2±0.3 months ( P =0.001), and 1.3±0.6 ( P =0.001), respectively. The patients' sex, fracture location, and fracture fixation did not have statistical influence on the clinical efficacy. PABMT is a minimally invasive and effective strategy for the treatment of delayed union of limb bone in children. The early surgical treatment facilitates the fracture healing, reduces the number of transplantation, and shortens the course of treatment.

  7. Percutaneous autologous bone marrow transplantation for the treatment of delayed union of limb bone in children

    Directory of Open Access Journals (Sweden)

    Wu J

    2018-02-01

    Full Text Available Jun Wu,* Hongxi Guo,* Xing Liu, Ming Li, Yujiang Cao, Xiangyang Qu, Hai Zhou, Liuqi Weng Department of Orthopaedics, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, People’s Republic of China *These authors contributed equally to this work Background and purpose: Percutaneous autologous bone marrow transplantation (PABMT is a minimally invasive therapeutic strategy for the treatment of delayed bone union in adults, which has been confirmed by many studies. However, there is no report on PABMT application in pediatric orthopedic surgery. The aim of this article was to analyze the therapeutic effect of PABMT in children with delayed union of limb bone and its influence in relation to delayed bone union therapy, transplantation period, patients’ sex, fracture location, and fracture fixation.Methods: In this study, 53 patients (aged 3–16 years, with an average age of 6.7 years with delayed union of long bone (20 femurs, 12 tibiae, 10 humeri, 5 radiuses, 5 ulnas, and 1 fibula were treated using PABMT. Clinical examination and X-ray were integrated to evaluate the therapeutic effect.Results: All 53 patients were followed up for 2–6 years (average time, 3.5 years. Of the 53 patients, 47 (88.7% were healed, whereas the other 6 (11.3% were not, and were subsequently treated by autologous bone grafting. In 30 patients who received their first PABMT treatment 6–8 months after fixation, the clinical cure rate, operation times, and healing time were 83.3%, 5.8±0.5 months, and 2.5±0.6, respectively. In the other 23 patients, whose first PABMT treatments were started within 4 to 6 months after fixation, the clinical cure rate, operation times, and healing time were 95.7% (P=0.167, 3.2±0

  8. The prevention of oral complications in bone-marrow transplantations by means of oral hygiene and dental intervention

    NARCIS (Netherlands)

    Raber-Durlacher, J. E.; Abraham-Inpijn, L.; van Leeuwen, E. F.; Lustig, K. H.; van Winkelhoff, A. J.

    1989-01-01

    Oral complications cause morbidity and mortality in patients, undergoing allogeneic or autologous bone-marrow transplantation. The clinical features and the pathogenesis of the oral sequelae of bone marrow ablative therapy and graft-versus-host disease are discussed. In addition, a preventive oral

  9. Multiple small versus few large amount aspirations for bone marrow harvesting in autologous and allogeneic bone marrow transplantation.

    Science.gov (United States)

    Witt, Volker; Pichler, Herbert; Fritsch, Gerhard; Peters, Christina

    2016-10-01

    For successful bone marrow transplantation it is necessary to obtain enough progenitor cells during the bone marrow (BM) harvesting procedure. Most centers are using multiple aspirations of maximum 2 ml BM (A), while other centers are using few larger amount aspirations for BM harvesting (B). There is still a discussion about possible differences in graft composition between A and B. To evaluate the feasibility in children we evaluated twenty BM harvestings that were performed in 18 donors, 7 autologous (median age 6.93y; 2.48-16.6) and 13 allogeneic donors (median age 19.75y; 6.45-50.7). A and B were performed crosswise by 2 operators starting with A (2 ml) or B (100 ml) changing to B or A, collecting identically amounts with both methods. We found no statistically significant difference between A and B for MNC, T-cells, and CFU (MNC/ml 824572 versus 725000, p = 0.728; MNC/kg 3.1 10 7 versus 2.9 10 7 , p = 0.296; CD3/ml 162500 versus 300000, p = 0.310; CFU/10 5 MNC 1678 versus 1315, p = 0.094), but for CD34+ cells (CD34/kg 2.62 versus 2.09, p = 0.045). BM harvest by the large amount few punctures method (B) is as sufficient as the commonly used small amount frequent punctures method (A), and could be therefore used equally. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation.

    Directory of Open Access Journals (Sweden)

    Amy M Becker

    Full Text Available Specific G protein coupled receptors (GPRs regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation.

  11. Immunological Enhancement of Interferon Alpha Treatment to Allogeneic Bone Marrow Transplantation in Irradiated Rats

    International Nuclear Information System (INIS)

    Hussein, E.M.; Abd El-Naby, Y.H.

    2011-01-01

    The Influence of the biological response modifiers: interferon alpha (IFN-α) and bone marrow transplantation (BMT) on stimulation of blood cell recovery and boosting the immunological response were investigated in this work. Male rats received BMT 3 h post total body ?-irradiation of 5 Gy and were injected with 10 units of IFN-α weekly for 5 weeks. Irradiation induced a significant decrease in blood parameters, reduced glutathione (GSH) as well as bone marrow lymphocyte count and viability. Immunological data revealed that tumour necrosis factor alpha (TNF-α) and interleukin-2 (IL-2) recorded a significant depression while lipid peroxidation (MDA) was conversely elevated. White blood cells (WBC), erythrocytes (RBC), haemoglobin (Hb), haematocrit (Hct), lymphocytes and GSH in irradiated animals receiving BMT and IFN-α, were significantly elevated, while MDA was significantly depressed as compared to the irradiated group. Bone marrow lymphocytic count and viability percentage were significantly increased while IL-2 and TNF-α were normalized. The curative action of IFN-α enforcing significant innate response could trigger and augment adaptive immune response by bone marrow transplantation. Such therapies boosting both components of immunity would be considered a potential strategy for irradiation treatment

  12. Nonspecific suppressor T cells cause decreased mixed lymphocyte culture reactivity in bone marrow transplant patients

    Energy Technology Data Exchange (ETDEWEB)

    Harada, M.; Ueda, M.; Nakao, S.; Kondo, K.; Odaka, K.; Shiobara, S.; Matsue, K.; Mori, T.; Matsuda, T.

    1986-07-15

    Decreased reactivity in mixed lymphocyte culture (MLC) was observed in patients within 1 yr after allogeneic and autologous bone marrow transplantation. Suppressor activity of peripheral blood mononuclear cells (PBMC) from transplant patients was studied by adding these cells as modulator cells to a bidirectional MLC with cells from normal individuals. PBMC from transplant patients markedly suppressed MLC reactivity in a dose-dependent manner. Suppressor activity was present in cells forming rosettes with sheep erythrocytes. Treatment of modulator cells with monoclonal antibodies against T cell differentiation antigens (OKT8, OKIa1) and complement completely abolished suppression of MLC. Suppressor activity was unaffected by 30 Gy irradiation. Suppressor activity declined gradually after transplantation and was inversely correlated with MLC reactivity of each patient at a significant level (p less than 0.01). These observations suggest that OKT8+ Ia+ radioresistant suppressor T cells play a role in the development of decreased MLC reactivity observed during the early post-transplant period.

  13. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Madaric, Juraj, E-mail: jurmad@hotmail.com [National Institute of Cardiovascular Diseases (NUSCH) and Slovak Medical University, Department of Cardiology and Angiology (Slovakia); Klepanec, Andrej [National Institute of Cardiovascular Diseases, Department of Diagnostic and Interventional Radiology (Slovakia); Mistrik, Martin [Clinic of Hematology and Transfusiology, Faculty Hospital (Slovakia); Altaner, Cestmir [Slovak Academy of Science, Institute of Experimental Oncology (Slovakia); Vulev, Ivan [National Institute of Cardiovascular Diseases, Department of Diagnostic and Interventional Radiology (Slovakia)

    2013-04-15

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  14. Progressive neurologic dysfunctions 20 years after allogeneic bone marrow transplantation for Chediak-Higashi syndrome.

    Science.gov (United States)

    Tardieu, Marc; Lacroix, Catherine; Neven, Bénédicte; Bordigoni, Pierre; de Saint Basile, Geneviève; Blanche, Stéphane; Fischer, Alain

    2005-07-01

    Three patients with Chediak-Higashi syndrome underwent allogeneic bone marrow transplantation between the ages of 2 years 9 months and 7 years. The outcome was uneventful, with sustained mixed chimerism. No subsequent recurrent infections or hemophagocytic syndrome were observed. At the age of 22 to 24 years, these 3 patients developed a neurologic deficit combining difficulty walking, loss of balance, and tremor. Neurologic evaluation demonstrated cerebellar ataxia and signs of peripheral neuropathy. Moderate axon loss and rarefaction of large myelinated fibers were observed on semithin sections of peripheral nerve. Cerebellar atrophy was detected by cerebral magnetic resonance imaging in 2 patients. We also reviewed the very long-term outcome of the other 11 patients with Chediak-Higashi syndrome who had received bone marrow transplants at our center since 1981. All displayed neurologic deficits or low cognitive abilities.

  15. Invasive central nervous system aspergillosis in bone marrow transplantation recipients: an overview

    International Nuclear Information System (INIS)

    Guermazi, Ali; Gluckman, Eliane; Tabti, Bachir; Miaux, Yves

    2003-01-01

    Invasive central nervous system aspergillosis is being seen with an increased frequency, particularly due to the increased number of immunosuppressed patients. The major cause of invasive central nervous system aspergillosis is bone marrow transplantation. In most cases, aspergillosis develops in the paranasal sinuses and in the lungs, and secondarily spreads to the brain. Imaging of cerebral aspergillosis may present different patterns depending on the lesion's age and the immunologic status of the patient. Lesions of the spinal cord are far less common but has been encountered in our series. In this article we review the clinical and radiologic features of aspergillosis affecting the central nervous system in patients who underwent bone marrow transplantation. Different CT and MR patterns are presented, including pertinent clinical and pathologic material. Significant morbidity and mortality can be associated with this fungal infection, and it is therefore incumbent upon the radiologist to identify intracranial aspergillosis as early as possible so that appropriate therapy can be administered. (orig.)

  16. Bone Marrow Transplantation in Mice as a Tool to Generate Genetically Modified Animals

    Science.gov (United States)

    Rőszer, Tamás; Pintye, Éva; Benkő, Ilona

    2008-12-01

    Transgenic mice can be used either as models of known inherited human diseases or can be applied to perform phenotypic tests of genes with unknown function. In some special applications of gene modification we have to create a tissue specific mutation of a given gene. In some cases however the gene modification can be lethal in the intrauterine life, therefore we should engraft the mutated cells in the postnatal life period. After total body irradiation transplantation of bone marrow cells can be a solution to introduce mutant hematopoietic stem cells into a mature animal. Bone marrow transplantation is a useful and novel tool to study the role of hematopoietic cells in the pathogenesis of inflammation, autoimmune syndromes and many metabolic alterations coupled recently to leukocyte functions.

  17. Bacteriological findings in patients with bone marrow transplantation (Karl Marx University Leipzig, 1985-1987).

    Science.gov (United States)

    Wonitzki, C; Hoffmann, F A

    1989-01-01

    The results of the bacteriological surveillance cultures for 26 patients with bone marrow transplantation (Karl Marx University Leipzig, G.D.R., 1985-1987) are presented. 5.9% of all surveillance cultures contained facultatively pathogenic germs (with Pseudomonas aeruginosa as the most frequent representative, which was the reason of a sepsis in two patients). Coagulasenegative Staphylococci and other germs with an obscure pathogenicity were isolated upon a large scale, especially from the mucous membrane regions. There are hints, that above all special strains of coagulasenegative Staphylococci "colonize" the patient's body (also for longer periods) and turn into the blood too. During the total decontamination intestinal anaerobic flora is absent. After closing of total decontamination Clostridium perfringens is the first detectable anaerobic species. During the selective decontamination systemic applications of antibiotics are able to obliterate anaerobic findings for certain periods. Recommendations for an effective arrangement of the surveillance cultures of bone marrow transplantation patients are given.

  18. Cytogenetic studies on recipients of allogeneic bone marrow transplants after fractionated total body irradiation

    International Nuclear Information System (INIS)

    Schmitz, N.; Goedde-Salz, E.; Loeffler, H.

    1985-01-01

    Cytogenetic findings from the bone marrow (BM) and the peripheral blood (PB) of nine consecutive patients after allogeneic bone marrow transplantation (BMT) for acute or chronic myelogenous leukaemia are reported. After a conditioning regimen consisting of cyclophosphamide and fractionated total body irradiation (TBI) given in five or six fractions of 2 Gy, persistence of host cells was detected in four out of seven cases with permanent engraftment. While one of these patients relapsed 4 months after host cells had been found in BM and PB, the other patients stayed relapse-free 124, 257 and 347 d after grafting. Before transplantation, the leukaemic cells in all three cases carried unique cytogenetic abnormalities giving the opportunity to distinguish the leukaemic population from chromosomally non-aberrant cells thought to represent residual normal host cells. As the persisting host cells after BMT lacked any cytogenetic abnormalities, it is suggested that they were members of residual normal clones not involved in the leukaemic process. (author)

  19. Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice.

    Directory of Open Access Journals (Sweden)

    Subhrajit Saha

    Full Text Available Nuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS, resulting from direct cytocidal effects on intestinal stem cells (ISC and crypt stromal cells. We examined whether bone marrow-derived adherent stromal cell transplantation (BMSCT could restitute irradiated intestinal stem cells niche and mitigate radiation-induced gastrointestinal syndrome.Autologous bone marrow was cultured in mesenchymal basal medium and adherent cells were harvested for transplantation to C57Bl6 mice, 24 and 72 hours after lethal whole body irradiation (10.4 Gy or abdominal irradiation (16-20 Gy in a single fraction. Mesenchymal, endothelial and myeloid population were characterized by flow cytometry. Intestinal crypt regeneration and absorptive function was assessed by histopathology and xylose absorption assay, respectively. In contrast to 100% mortality in irradiated controls, BMSCT mitigated RIGS and rescued mice from radiation lethality after 18 Gy of abdominal irradiation or 10.4 Gy whole body irradiation with 100% survival (p<0.0007 and p<0.0009 respectively beyond 25 days. Transplantation of enriched myeloid and non-myeloid fractions failed to improve survival. BMASCT induced ISC regeneration, restitution of the ISC niche and xylose absorption. Serum levels of intestinal radioprotective factors, such as, R-Spondin1, KGF, PDGF and FGF2, and anti-inflammatory cytokines were elevated, while inflammatory cytokines were down regulated.Mitigation of lethal intestinal injury, following high doses of irradiation, can be achieved by intravenous transplantation of marrow-derived stromal cells, including mesenchymal, endothelial and macrophage cell population. BMASCT increases blood levels of intestinal growth factors and induces regeneration of the irradiated

  20. Syringomyelia in mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): imaging findings following bone marrow transplantation

    International Nuclear Information System (INIS)

    Hite, S.H.; Krivit, W.; Haines, S.J.; Whitley, C.B.

    1997-01-01

    We present the imaging findings in a patient with mucopolysaccharidosis (MPS) type VI (Maroteaux-Lamy syndrome) who developed holocord syringomyelia. This represents the only reported case of syrinx formation in a child with MPS VI. Clinical, neurologic and spinal magnetic resonance imaging findings are presented. The patient has maintained a stable clinical and neurologic course over the period following allogeneic bone marrow transplant. (orig.). With 3 figs

  1. Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation.

    Science.gov (United States)

    Chen, Yu-Bing; Jia, Quan-Zhang; Li, Dong-Jun; Sun, Jing-Hai; Xi, Shuang; Liu, Li-Ping; Gao, De-Xuan; Jiang, Da-Wei

    2015-01-01

    The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4',6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons.

  2. Overview of marrow transplantation

    International Nuclear Information System (INIS)

    Thomas, E.D.

    1985-01-01

    Bone marrow transplantation is now an accepted form of therapy for many hematologic disorders including aplastic anemia, genetically determined diseases and malignant diseases, particularly leukemia, and for rescue of patients given intensive chemoradiotherapy for malignant disease. The donor may be a healthy identical twin, a family member or even an unrelated person. Selection is made on the basis of human leukocyte antigen tissue typing. Intensive chemoradiotherapy is used to suppress patients' immune systems to facilitate engraftment and destroy diseased marrow. Transfusion of platelets, erythrocytes and granulocytes (or all of these), antibiotic coverage and protection from infection are necessary during the pancytopenic period. Survival rates vary considerably depending on a patient's disease, clinical state and age. Patients with aplastic anemia transplanted early in the course of their disease have a survival rate of approximately 80%. Patients with acute lymphoblastic leukemia are usually transplanted in a second or subsequent remission and have a survival rate of 25% to 40%. Patients with acute nonlymphoblastic leukemia in remission have survivals ranging from 45% to 70%. More than 200 patients in the chronic phase of chronic granulocytic leukemia have been transplanted with survival ranging from 50% to 70%. Complications of marrow transplantation include marrow graft rejection, graft-versus-host disease, immunologic insufficiency and the possibility of recurrence of the leukemia. 14 references

  3. [Long-term results of intracoronary transplantation of autologous bone marrow cells in dilated cardiomyopathy].

    Science.gov (United States)

    Bartolucci, Jorge; Verdugo, Fernando J; Carrion, Flavio; Abarzúa, Ema; Goset, Carlos; Lamich, Rubén; Sanhueza, Patricio; Pedreros, Pablo; Nazzal, Carolina; Khoury, Maroun; Figueroa, Fernando E

    2015-04-01

    Intracoronary delivery of autologous bone marrow mononuclear cells is an interesting therapeutic promise for patients with heart failure of different etiologies. To evaluate the long-term safety and efficacy of this therapy in patients with dilated cardiomyopathy of different etiologies under optimal medical treatment. Prospective, open-label, controlled clinical trial. Of 23 consecutive patients, 12 were assigned to autologous bone marrow mononuclear cell intracoronary transplantation, receiving a mean dose of 8.19 ± 4.43 x 10(6) CD34+ cells. Mortality, cardiovascular readmissions and cancer incidence rate, changes in functional capacity, quality of life questionnaires and echocardiographic measures from baseline, were assessed at long-term follow-up (37.7 ± 9.7 months) in patients receiving or not the cells. No significant differences were observed in mortality, cardiovascular readmissions or cancer incidence rate amongst groups. An improvement in functional class and quality of life questionnaires in the transplanted group was observed (p transplantation of autologous bone marrow mononuclear cells is feasible and safe in patients with dilated cardiomyopathy of diverse etiologies. This therapy was associated to persistent improvements in functional class and quality of life. There was also a non-significant long-term improvement of left ventricular function.

  4. Patient mobility for bone marrow transplant: the experience of the Perugia Hospital, years 2000-2013.

    Science.gov (United States)

    Pierini, E; Pioppo, M; Troiano, G; Casucci, P; Checconi, O; Ruffini, F; Messina, G; Nante, N

    2015-01-01

    Patient mobility, driven by patient preference is an indirect indicator of perception of hospital quality. Patients' choices depend on their previous healthcare experiences, the reputation of the hospital staff and the network of relationships between the patient, hospital doctors, general practitioners/reference specialists, etc. Therefore, the analysis of patient preferences provides an idea of hospital quality as well as qualitative and quantitative lack of services. The aim of the present research was to describe and analyze patient mobility for bone marrow transplantation regarding the Hospital of Perugia, which represents the second most important structure for bone marrow transplant in Italy. Data have been collected from hospital discharge records in the ordinary regime related to the Diagnosis Related Group 481 "bone marrow transplant" since 2000 to 2013. We included autologous and allogenic transplant, in the adult and the child. Analysis of escaped, attracted and resident patients flows was undertaken using Gandy's nomogram which detects, through repeated time investigations, patients' movement inside and outside their catchment area. Between 2000 and 2013, 1782 patients were admitted to hospital with a DRG 481 "bone marrow transplant". Nine hundred and nineteen (51,5%) were resident in Umbria region, 799 (44,8%) in other regions, 64 (0,3%) abroad. Escapes were 158. The high percentage of admissions represented by patients that live out of Umbria, shows a high attractive power of the hospital. For "distant regions" this situation was maintained from 2000 to 2003, with a mild decrease from 2004 and, from 2010, the situation is stable. Only for "bordering regions" the attraction, which was stable up to 2010, seems to decrease. Gandy's nomogram shows also that the hospital was able to satisfy the health needs of the Umbria residents between 2004 and 2009 with a reductions in the escapes; then, in the last four years there is an increase in Umbria residents

  5. EFFECT ON LIFESPAN OF HIGH YIELD NONMYELOABLATING TRANSPLANTATION OF BONE MARROW FROM YOUNG TO OLD MICE

    Directory of Open Access Journals (Sweden)

    Marina eKovina

    2013-08-01

    Full Text Available Tissue renewal is a well-known phenomenon by which old and dying-off cells of various tissues of the body are replaced by progeny of local or circulating stem cells (SC. An interesting question is whether donor stem cells are capable to prolong the lifespan of an ageing organism by tissue renewal.. In this work we investigated the possible use of bone marrow SC for lifespan extension. To this purpose, chimeric C57BL/6 mice were created by transplanting bone marrow from young 1.5-month donors to 21.5-month-old recipients. Transplantation was carried out by means of a recently developed method which allowed to transplant without myeloablation up to 1.5×108 cells, that is, about 25 % of the total BM cells of the mouse. As a result, the mean survival time, counting from the age of 21.5 months, the start of the experiment, was +3.6 and +5.0 (± 0.1 months for the control and experimental groups, respectively, corresponding to a 39% ± 4% increase in the experimental group over the control. In earlier studies on BM transplantation a considerably smaller quantity of donor cells (5×106 was used, about 1 % of the total own BM cells. The recipients before transplantation were exposed to a lethal (for control animals X-ray dose which eliminated the possibility of studying the lifespan extension by this method.

  6. Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury.

    Science.gov (United States)

    Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

    2014-08-15

    Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

  7. Immunohistochemistry analysis of bone marrow biopsies in multiple sclerosis patients undergoing autologous haematopoietic stem cells transplantation.

    Science.gov (United States)

    Carrai, Valentina; Donnini, Irene; Mazzanti, Benedetta; Alterini, Renato; Amato, Maria Pia; Barilaro, Alessandro; Bosi, Alberto; Massacesi, Luca; Portaccio, Emilio; Repice, Anna Maria; Rotunno, Giada; Saccardi, Riccardo

    2013-07-01

    Recently autologous haematopoietic stem cell transplantation (AHSCT) has been introduced for the treatment of severe forms of multiple sclerosis (MS). As little data are available on bone marrow (BM) of MS patients undergoing AHSCT, we investigated the morphological and phenotypic characteristics of MS BM. BM biopsies of 14 MS patients screened for AHSCT and 10 control patients were evaluated to assess cellularity, morphology, immunological profile and bone marrow microenvironment. Immunohistochemistry analysis was performed to evaluate the expression of CD3, CD4, CD8, CD20, CD68, CD45, MMP-9. 8 out of 14 MS (57%) patients showed a reduction of age-related bone marrow cellularity, possibly due to previous immunosuppressive therapies. There were no differences in the T CD3+ lymphocyte expression rate amongst MS and the control patients, the CD4/CD8 ratio (2:1) was maintained as was the rate of B lymphocytes. We found an increased, although not significant, MMP-9 expression (9.2%) in the bone marrow of MS patients, when compared to the control patients (6.3%). The BM of MS patients showed a reduced cellularity and CD45+ cells content in comparison to the controls. A slightly increased expression of MMP-9 was also shown, possibly confirming an involvement of this compartment in the pathogenesis of the disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. The role of iron in patients after bone marrow transplantation.

    NARCIS (Netherlands)

    Witte, T.J.M. de

    2008-01-01

    Haemopoietic stem cell transplantation (HSCT) is an important intervention for malignant and non-malignant blood diseases. However, HSCT is also associated with considerable morbidity and mortality, some of which may be related to iron overload. Levels of serum iron are elevated in patients

  9. Monosomy 7 in donor cell-derived leukemia after bone marrow transplantation for severe aplastic anemia: Report of a new case and review of the literature

    OpenAIRE

    Otero, Luize; de Souza, Daiane Correa; de Cássia Tavares, Rita; Gomes, Bernadete Evangelho; Padilha, Telma França; Bouzas, Luiz Fernando; de Souza Fernandez, Teresa; Abdelhay, Eliana

    2012-01-01

    Monosomy 7 arises as a recurrent chromosome aberration in donor cell leukemia after hematopoietic stem cell transplantation. We report a new case of donor cell leukemia with monosomy 7 following HLA-identical allogenic bone marrow transplantation for severe aplastic anemia (SAA). The male patient received a bone marrow graft from his sister, and monosomy 7 was detected only in the XX donor cells, 34 months after transplantation. The patient's bone marrow microenvironment may have played a rol...

  10. Autologous bone marrow-derived progenitor cell transplantation for myocardial regeneration after acute infarction

    Directory of Open Access Journals (Sweden)

    Obradović Slobodan

    2004-01-01

    Full Text Available Background. Experimental and first clinical studies suggest that the transplantation of bone marrow derived, or circulating blood progenitor cells, may beneficially affect postinfarction remodelling processes after acute myocardial infarction. Aim. This pilot trial reports investigation of safety and feasibility of autologous bone marrow-derived progenitor cell therapy for faster regeneration of the myocardium after infarction. Methods and results. Four male patients (age range 47-68 years with the first extensive anterior, ST elevation, acute myocardial infarction (AMI, were treated by primary angioplasty. Bone marrow mononuclear cells were administered by intracoronary infusion 3-5 days after the infarction. Bone marrow was harvested by multiple aspirations from posterior cristae iliacae under general anesthesia, and under aseptic conditions. After that, cells were filtered through stainless steel mesh, centrifuged and resuspended in serum-free culture medium, and 3 hours later infused through the catheter into the infarct-related artery in 8 equal boluses of 20 ml. Myocardial viability in the infarcted area was confirmed by dobutamin stress echocardiography testing and single-photon emission computed tomography (SPECT 10-14 days after infarction. One patient had early stent thrombosis immediately before cell transplantation, and was treated successfully with second angioplasty. Single average ECG revealed one positive finding at discharge, and 24-hour Holter ECG showed only isolated ventricular ectopic beats during the follow-up period. Early findings in two patients showed significant improvement of left ventricular systolic function 3 months after the infarction. There were no major cardiac events after the transplantation during further follow-up period (30-120 days after infarction. Control SPECT for the detection of ischemia showed significant improvement in myocardial perfusion in two patients 4 months after the infarction

  11. Allotransplantation of the lung without immunosuppression after transplantation. II. Combined autotransplantation of bone marrow and allotransplantation of lung

    International Nuclear Information System (INIS)

    Blumenstock, D.A.; Cannon, F.D.; Franck, W.A.; Hales, C.A.; Kazemi, H.; Ferrebee, J.W.

    1977-01-01

    A series of seven animals underwent allotransplantation of a lung from a donor matched for the recognition of serologically defined (SD) antigens by the use of alloantisera followed by autotransplantation of bone marrow without further immunosuppression. In two animals, the lung was transplanted into the recipient immediately before the administration of total-body irradiation and in five, the lung was transplanted after completion of total-body irradiation. In the first group, one animal is living at 46 months with good function of the transplant. The other was killed at 6 months with chronic rejection. In the second group, three of five animals are alive 46 to 47 months after transplantation. Two others died early, one of cardiac tamponade and the other of diffuse hemorrhage before engraftment of marrow could be accomplished. Significant function of the transplant was demonstrated in all long-term survivors. Four control animals, subjected to marrow harvest and reimplantation of the left lung followed by total-body irradiation and marrow reinfusion, were studied to determine the possible deleterious effects of the total-body irradiation and marrow transplant procedure. Pulmonary function studies showed some reduction in ventilation and perfusion to the upper lobe areas, which was probably related to technical factors but did demonstrate no severe adverse effects to the procedures. Autologous bone marrow reconstitution after total-body irradiation combined withallotransplantation of the lung has allowed long-term survival and function of lung transplants without the necessity for administration of immunosuppressive drugs after the transplantation procedure

  12. MR tomography of bone marrow changes after high-dose chemotherapy and autologous peripheral stem cell transplantation

    International Nuclear Information System (INIS)

    Pereira, P.L.; Schick, F.; Farnsworth, C.T.; Mattke, A.; Duda, S.H.; Claussen, C.D.; Einsele, H.; Kollmansberger, C.

    1999-01-01

    Purpose: Evaluation of MR standard imaging and short time inversion recovery (STIR) imaging to assess changes in red bone marrow cellularity after high-dose chemotherapy (HDC) and peripheral blood stem cells transplantation (PBSCT). Results: STIR sequences demonstrated marked changes in signal intensity not only until the aplasia occurred but also during bone marrow repopulation. An increased signal intensity was observed after HDC in 13/15 patients (87%), followed by a decrease in signal intensity immediately after aplasia in 14/15 patients (93%). Signal intensity further changed parallel to marrow engraftment in 11/15 patients (73%). T 2 -TSE only showed clear changes during repopulation in 8/15 patients (53%). The individual course of the signal in T 1 -TSE was markedly inhomogeneous. Conclusions: STIR sequences show bone marrow edema during aplasia and marrow cellularity during reconstitution and are suitable for characterisation of red bone marrow after HDC and autologous PBSCT. (orig.) [de

  13. Autologous Bone Marrow Transplantation in Multiple Sclerosis: Biomarker Relevance for Patient Recruitment and Follow up.

    Science.gov (United States)

    Londoño, Ana C; Mora, Carlos A

    2016-10-01

    Despite the current availability of disease modifying therapies for the treatment of multiple sclerosis, there are still patients who suffer from severe neurological dysfunction in the relapsing-remitting or early progressive forms of the disease. For these patients autologous hematopoietic stem cell transplant offers an important therapeutic solution to prevent progression to irreversible disability. In spite of multiple studies in the last two decades, patient inclusion criteria, protocols for peripheral blood stem cell mobilization and bone marrow cell conditioning and methodology of follow up for autologous hematopoietic stem cell transplant in multiple sclerosis have not been strictly unified. We reviewed five recent clinical studies that confirmed the positive outcome of transplant in spite of disclosing significant differences in methodology of enrollment including patient disease subtypes, disease duration range, disability, regimens of peripheral blood stem cell mobilization and bone marrow cell conditioning, scheduling of imaging studies after transplant, and absence of laboratory biomarkers consistently applied to these studies. Therapy with autologous hematopoietic stem cell transplant has shown best results among young individuals with severe relapsing-remitting or early progressive disease through its ability to maintain no evidence of disease activity status in a significantly higher proportion of patients after transplant in comparison to patients treated with disease modifying therapies. Important cross-sectional differences in the reviewed studies were found. A specific and careful selection of biomarkers, based on the current physiopathological mechanisms known to result in multiple sclerosis, will contribute to a better and earlier patient selection for autologous hematopoietic stem cell transplant and follow up process. An objective and measurable response could be obtained with the determination of biomarkers at the onset of treatment and

  14. Autologous bone marrow transplantation following chemotherapy and irradiation in dogs with spontaneous lymphomas

    International Nuclear Information System (INIS)

    Bowles, C.A.; Bull, M.; McCormick, K.; Kadin, M.; Lucas, D.

    1980-01-01

    Thirty dogs with spontaneous lymphomas were administered two to six cycles of chemotherapy and were randomized into 3 groups to receive 800 rads of total body irradiation and autologous bone marrow transplantation. Of 10 dogs irradiated after chemotherapy-induced remission and infused with remission marrow (group 1), 8 (80%) had successful grafts and experienced remissions lasting 62 to 1024 days. Of 9 dogs irradiated during remission and infused with remission marrow mixed with autologous tumor cells (group 2), 6 (66%) had remission lasting 15 to 45 days. Eleven dogs with progressive tumor growth (relapse) following chemotherapy were irradiated and infused with remission marrow (group 3). Tumor remission lasting 39 to 350 days was observed in 5 dogs (45%) in this group, and 6 dogs died in less than 30 days. Dogs in groups 1 to 3 had median survival times of 216, 60, and 45 days, respectively. The prolonged survival times for dogs in group 1 compared to dogs in groups 2 and 3 suggest that protocols involving irradiation and autologous marrow grafting in this model would be most effective when these protocols are applied to animals having a minimum tumor burden at the time of irradiation and when the grafting is done with tumor-free autologous marrow

  15. A murine model of graft-versus-host disease induced by allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Hu Jiangwei; Jin Jiangang; Ning Hongmei; Yu Liquan; Feng Kai; Chen Hu; Wang Lisha

    2007-01-01

    Objective: To establish the model of graft-versus-host disease (GVHD) in mice with allogeneic bone marrow transplantation. Methods: Bone marrow cells were combined with spleen cells of male donor C57BL/6 mice according to different proportions, then were transfused into female postradiation recipient BALB/c mice. General state, life span and histopathology of the recipient mice and detected chimera were observed. Results and Conclusion:The recipient mice groups which accepted above 5 x 10 6 donor spleen cells developed acute GVHD after different peroids of time. The GVHD model in mice after allo-BMT was successfully established. The transfusion of 5 x 10 6 -5 x 10 7 spleen cells may be adequate to establish the murine model of GVHD for the prevention and treatment of GVHD. The number of murine spleen cells can be chosen according to the experimental requirement. (authors)

  16. Engraftment failure following bone marrow transplantation in children with thalassemia major using busulfan and cyclophosphamide conditioning.

    Science.gov (United States)

    Solh, H; Rao, K; Martins da Cunha, A; Padmos, A; Giri, N; Spence, D; Clink, H; Ernst, P

    1997-01-01

    Thirteen children older than 3 years of age with beta-thalassemia major underwent allogeneic bone marrow transplantation (BMT) from a full human leukocyte antigen (HLA) matched sibling donor in a single institution. These patients received busulfan (Bu). 16 mg/kg followed by cyclophosphamide (Cy) 200 mg/kg for conditioning. Eight of the 13 patients (Group 1) engrafted and have a median age of 13 years (range 5-15 years). The five patients (Group 2) who failed to engraft have a median age of 6 years (range 3-8 years). The association with the following factors was found to be statistically significant: age (older in Group 1), duration of nadir of white blood count (WBC) of younger children leading to inadequate bone marrow ablation when the standard dose of 16 mg/kg is used.

  17. Bone marrow transplantation in patients with storage diseases: a developing country experience

    Directory of Open Access Journals (Sweden)

    Lange Marcos C.

    2006-01-01

    Full Text Available Bone marrow transplantation (BMT is a therapeutic option for patients with genetic storage diseases. Between 1979 and 2002, eight patients, four females and four males (1 to 13 years old were submitted to this procedure in our center. Six patients had mucopolysaccharidosis (MPS I in 3; MPS III in one and MPS VI in 2, one had adrenoleukodystrophy (ALD and one had Gaucher disease. Five patients had related and three unrelated BMT donor. Three patients developed graft versus host disease (two MPS I and one MPS VI and died between 37 and 151 days after transplantation. Five patients survived 4 to 16 years after transplantation. Three patients improved (one MPS I; one MPS VI and the Gaucher disease patient, one patient had no disease progression (ALD and in one patient this procedure did not change the natural course of the disease (MPS III.

  18. Reduction of acute rejection by bone marrow mesenchymal stem cells during rat small bowel transplantation.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available Bone marrow mesenchymal stem cells (BMMSCs have shown immunosuppressive activity in transplantation. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats.Heterotopic small bowel transplantation was performed from Brown Norway to Lewis rats, followed by infusion of BMMSCs through the superficial dorsal veins of the penis. Controls included rats infused with normal saline (allogeneic control, isogeneically transplanted rats (BN-BN and nontransplanted animals. The animals were sacrificed after 1, 5, 7 or 10 days. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg cells were assessed at each time point.Acute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF-α, and interferon (IFN-γ while upregulating IL-10 and transforming growth factor (TGF-β expression and increasing Treg levels.BMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation.

  19. Transfusion-induced bone marrow transplant rejection due to minor histocompatibility antigens.

    Science.gov (United States)

    Patel, Seema R; Zimring, James C

    2013-10-01

    Traditionally, alloimmunization to transfused blood products has focused exclusively on recipient antibodies recognizing donor alloantigens present on the cell surface. Accordingly, the immunologic sequelae of alloimmunization have been antibody mediated effects (ie, hemolytic transfusion reactions, platelet refractoriness, anti-HLA and anti-HNA effects, etc). However, in addition to the above sequelae, there is also a correlation between the number of antecedent transfusions in humans and the rate of bone marrow transplant (BMT) rejection-under reduced intensity conditioning with HLA-matched or HLA-identical marrow. Bone marrow transplant of this nature is the only existing cure for a series of nonmalignant hematologic diseases (eg, sickle cell disease, thalassemias, etc); however, rejection remains a clinical problem. It has been hypothesized that transfusion induces subsequent BMT rejection through immunization. Studies in animal models have observed the same effect and have demonstrated that transfusion-induced BMT rejection can occur in response to alloimmunization. However, unlike traditional antibody responses, sensitization in this case results in cellular immune effects, involving populations such as T cell or natural killer cells. In this case, rejection occurs in the absence of alloantibodies and would not be detected by existing immune-hematologic methods. We review human and animal studies in light of the hypothesis that, for distinct clinical populations, enhanced rejection of BMT may be an unappreciated adverse consequence of transfusion, which current blood bank methodologies are unable to detect. © 2013.

  20. Autologous bone marrow transplantation in decompensated liver: Systematic review and meta-analysis.

    Science.gov (United States)

    Pankaj, Prasoon; Zhang, Qi; Bai, Xue-Li; Liang, Ting-Bo

    2015-07-28

    To evaluate the efficacy of autologous bone marrow mononuclear cell transplantation in decompensated liver disease. Medline, EMBASE, PubMed, Science Direct, and the Cochrane Library were searched for relevant studies. Retrospective case-control studies were included along with randomized clinical trials. Meta-analysis was performed in line with recommendations from the Cochrane Collaboration software review manager. Heterogeneity was assessed using a random-effects model. Four randomized controlled trials and four retrospective studies were included. Cell transplantation increased serum albumin level by 1.96 g/L (95%CI: 0.74-3.17; P = 0.002], 2.55 g/L (95%CI: 0.32-4.79; P = 0.03), and 3.65 g/L (95%CI: 0.76-6.54; P = 0.01) after 1, 3, and 6 mo, respectively. Patients who had undergone cell transplantation also had a lower level of total bilirubin [mean difference (MD): -1.37 mg/dL; 95%CI: -2.68-(-0.06); P = 0.04] after 6 mo. This decreased after 1 year when compared to standard treatment (MD: -1.26; 95%CI: -2.48-(-0.03); P = 0.04]. A temporary decrease in alanine transaminase and aspartate transaminase were significant in the cell transplantation group. However, after 6 mo treatment, patients who had undergone cell transplantation had a slightly longer prothrombin time (MD: 5.66 s, 95%CI: 0.04-11.28; P = 0.05). Changes in the model for end-stage liver disease score and Child-Pugh score were not statistically significant. Autologous bone marrow transplantation showed some benefits in patients with decompensated liver disease. However, further studies are still needed to verify its role in clinical treatment for end-stage liver disease.

  1. An innovative approach to bone marrow collection and transplantation in a patient with beta-thalassemia major: marrow collection using a perfusion method followed by intra-bone marrow injection of collected bone marrow cells.

    Science.gov (United States)

    Li, Chunfu; He, Yuelin; Feng, Xiaoqin; Inaba, Muneo; Adachi, Yasushi; Takada, Keizo; Zhang, Yuming; Yamamoto, Yoshihisa; Wu, Xuedong; Cui, Yunze; Iwasaki, Masayoshi; Hisha, Hiroko; Hosaka, Naoki; Taira, Mitsuru; Minamino, Keizo; Suzuki, Yasuhiro; Nakano, Keiji; Fukui, Junichi; Ueda, Yusuke; Koike, Yasushi; Tsuda, Masanobu; Ikehara, Susumu

    2007-01-01

    Using small animals (mice and rats) and monkeys, we have found that the combination of bone marrow collection using the perfusion method (PM) and intra-bone marrow-bone marrow transplantation (IBM-BMT) of the collected cells is safe and effective in treating various intractable diseases. Based on these findings, we attempted to apply this method to humans. We report here the first case of a patient (6 years old) with beta-thalassemia major who underwent allogeneic BMT using this new PM + IBM-BMT method. The white blood cell counts of the patient gradually increased to more than 1500/microL by day 47 and continued to increase, reaching the highest level (8600/microL) on day +55. Fluorescence in situ hybridization data on day +33 showed that 98% of the peripheral blood cells were from the donor. Notably, there were no symptoms of graft-versus-host disease (GvHD). However, on day +56, the patient regrettably died of asphyxia resulting from sticky sputum. There was no evidence of infection (in the lung or liver) or GvHD (in the skin) by necropsy. We hope that this case report will help make our new strategies more readily available for the treatment of patients with various intractable diseases.

  2. Imaging characteristics of toxoplasmosis encephalitis after bone marrow transplantation: report of two cases and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Mang, C.; Mang, T.G.; Thurnher, M.M. [University Hospital Vienna, Department of Radiology, Vienna (Austria); Kalhs, P. [University Hospital Vienna, Department of Internal Medicine, Vienna (Austria)

    2006-02-15

    Toxoplasmosis encephalitis is a severe, but often misdiagnosed complication in patients after bone marrow transplantation (BMT). We describe the unique computed tomography (CT) and magnetic resonance (MR) imaging features of cerebral toxoplasmosis in two bone marrow recipients and compare them to the cases in the literature. To our knowledge, this is the first report analyzing the appearance of cerebral toxoplasmosis on diffusion-weighted MR imaging (DWI). (orig.)

  3. Imaging characteristics of toxoplasmosis encephalitis after bone marrow transplantation: report of two cases and review of the literature

    International Nuclear Information System (INIS)

    Mueller-Mang, C.; Mang, T.G.; Thurnher, M.M.; Kalhs, P.

    2006-01-01

    Toxoplasmosis encephalitis is a severe, but often misdiagnosed complication in patients after bone marrow transplantation (BMT). We describe the unique computed tomography (CT) and magnetic resonance (MR) imaging features of cerebral toxoplasmosis in two bone marrow recipients and compare them to the cases in the literature. To our knowledge, this is the first report analyzing the appearance of cerebral toxoplasmosis on diffusion-weighted MR imaging (DWI). (orig.)

  4. Sequential renal and bone marrow transplants in a child with Fanconi anemia.

    Science.gov (United States)

    Vincent, Carol L; Primack, William A; Hipps, John; Kasow, Kimberly A

    2016-02-01

    FA is an autosomal recessive disorder characterized by small stature and renal abnormalities. FA can lead to progressive bone marrow failure, myelodysplastic syndrome, or acute leukemia. Using a multidisciplinary team approach, we managed a 3-yr-old boy with FA who simultaneously developed renal and hematopoietic failure. Because renal function was insufficient to support the conditioning regimen for HCT, we performed a deceased donor renal transplant in December 2012 prior to HCT with the known risk of graft-versus-graft rejection of the donor kidney. Seven months later he underwent allogeneic HCT. He obtained myeloid engraftment on day +11 and peripheral blood chimerism demonstrated all donor by day +21. He developed asymptomatic CMV reactivation and despite antirejection medications, mild skin graft-versus-host disease. He has maintained excellent renal function and remains transfusion independent with full hematopoietic recovery. He has not experienced any renal rejection episodes nor developed donor-specific antibodies toward his renal donor. Peripheral blood chimerism remains completely HCT donor. He is clinically well, now greater than two and a half yr after renal transplant and two yr after HCT. The continuing close collaboration between the Pediatric Nephrology and Bone Marrow Transplant teams is a major factor in this successful outcome. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Clinical and histological study of permanent alopecia after bone marrow transplantation.

    Science.gov (United States)

    Basilio, Flávia Machado Alves; Brenner, Fabiane Mulinari; Werner, Betina; Rastelli, Graziela Junges Crescente

    2015-01-01

    Permanent alopecia after bone marrow transplantation is rare, but more and more cases have been described, typically involving high doses of chemotherapeutic agents used in the conditioning regimen for the transplant. Busulfan, classically described in cases of irreversible alopecia, remains associated in recent cases. The pathogenesis involved in hair loss is not clear and there are few studies available. In addition to chemotherapeutic agents, another factor that has been implicated as a cause is chronic graft-versus-host disease. However, there are no histopathological criteria for defining this diagnosis yet. the study aims to evaluate clinical and histological aspects in cases of permanent alopecia after bone marrow transplantation, identifying features of permanent alopecia induced by myeloablative chemotherapy and alopecia as a manifestation of chronic graft-versus-host disease. data were collected from medical records of 7 patients, with description of the clinical features and review of slides and paraffin blocks of biopsies. Two distinct histological patterns were found: one similar to androgenetic alopecia, non-scarring pattern, and other similar to lichen planopilaris, scarring alopecia. The first pattern corroborates the literature cases of permanent alopecia induced by chemotherapeutic agents, and the second is compatible with manifestation of chronic graft-versus-host disease on scalp, that has never been described yet. The results contribute to the elucidation of the factors involved in these cases, including the development of therapeutic methods.

  6. Clinical and histological study of permanent alopecia after bone marrow transplantation*

    Science.gov (United States)

    Basilio, Flávia Machado Alves; Brenner, Fabiane Mulinari; Werner, Betina; Rastelli, Graziela Junges Crescente

    2015-01-01

    BACKGROUND Permanent alopecia after bone marrow transplantation is rare, but more and more cases have been described, typically involving high doses of chemotherapeutic agents used in the conditioning regimen for the transplant. Busulfan, classically described in cases of irreversible alopecia, remains associated in recent cases. The pathogenesis involved in hair loss is not clear and there are few studies available. In addition to chemotherapeutic agents, another factor that has been implicated as a cause is chronic graft-versus-host disease. However, there are no histopathological criteria for defining this diagnosis yet. OBJECTIVE the study aims to evaluate clinical and histological aspects in cases of permanent alopecia after bone marrow transplantation, identifying features of permanent alopecia induced by myeloablative chemotherapy and alopecia as a manifestation of chronic graft-versus-host disease. METHODS data were collected from medical records of 7 patients, with description of the clinical features and review of slides and paraffin blocks of biopsies. RESULTS Two distinct histological patterns were found: one similar to androgenetic alopecia, non-scarring pattern, and other similar to lichen planopilaris, scarring alopecia. CONCLUSION The first pattern corroborates the literature cases of permanent alopecia induced by chemotherapeutic agents, and the second is compatible with manifestation of chronic graft-versus-host disease on scalp, that has never been described yet. The results contribute to the elucidation of the factors involved in these cases, including the development of therapeutic methods PMID:26734861

  7. Cataract after total body irradiation and bone marrow transplantation degree of visual impairment

    International Nuclear Information System (INIS)

    Kempen-Harteveld, M. Loes van; Struikmans, Henk; Kal, Henk B.; Tweel, Ingeborg van der; Mourits, Maarten P.; Verdonck, Leo F.; Schipper, Jan; Battermann, Jan J.

    2002-01-01

    Purpose: To assess the degree of visual impairment as a result of cataract formation after total body irradiation (TBI) for bone marrow transplantation. Methods and Materials: The data from 93 patients who received TBI in 1 or 2 fractions as a part of their conditioning regimen for bone marrow transplantation were analyzed with respect to the degree of visual impairment as a result of cataract formation. The probability to develop severe visual impairment (SVI) was determined for all patients, and the degree of visual impairment was assessed for 56 patients with stabilized cataract, using three categories: no, mild, or severe. Results: For all 93 patients, the probability of developing a cataract causing SVI was 0.44. For allogeneic patients, it was 0.33 without and 0.71 with steroid treatment (p<0.001). All SVI-free probability curves reached a plateau distinct from the cataract-free curves. Apparently, cataracts developing late in the follow-up period rarely cause SVI. Of the patients with stabilized cataract, 32% had no visual impairment, 16% had mild, and 52% severe impairment. No or mild visual impairment was present in 61% of all patients with stable cataract and no steroid treatment compared with only 13% of the patients treated with steroids (p=0.035). Conclusion: SVI occurs in only some of the patients (52%) with stable cataract after TBI for bone marrow transplantation in 1 or 2 fractions. Steroid treatment markedly increases the probability of developing visual problems as result of a cataract after TBI

  8. Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, M. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, OncoRay - National Center for Radiation Research in Oncology, Dresden (Germany); German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); Haagen, J.; Noack, R.; Siegemund, A.; Gabriel, P. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, OncoRay - National Center for Radiation Research in Oncology, Dresden (Germany); Doerr, W. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiotherapy and Radiation Oncology, OncoRay - National Center for Radiation Research in Oncology, Dresden (Germany); Comprehensive Cancer Center, Medical University/AKH Vienna, Dept. of Radiation Oncology/Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Vienna (Austria)

    2014-04-15

    Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation. Daily fractionated irradiation (5 x 3 Gy/week) was given over 1 (days 0-4) or 3 weeks (days 0-4, 7-11, 14-18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose-effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols. Transplantation of 6 x 10{sup 6}, but not of 3 x 10{sup 6} bone marrow stem cells on day -1, +4, +8, +11 or +15 significantly increased the ED{sub 50} values (dose, at which an ulcer is expected in 50% of the mice); transplantation on day +2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day -1, 2 or +8 significantly, and on day +4 marginally increased the ED{sub 50} values. Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation. (orig.)

  9. Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation

    International Nuclear Information System (INIS)

    Schmidt, M.; Haagen, J.; Noack, R.; Siegemund, A.; Gabriel, P.; Doerr, W.

    2014-01-01

    Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation. Daily fractionated irradiation (5 x 3 Gy/week) was given over 1 (days 0-4) or 3 weeks (days 0-4, 7-11, 14-18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose-effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols. Transplantation of 6 x 10 6 , but not of 3 x 10 6 bone marrow stem cells on day -1, +4, +8, +11 or +15 significantly increased the ED 50 values (dose, at which an ulcer is expected in 50% of the mice); transplantation on day +2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day -1, 2 or +8 significantly, and on day +4 marginally increased the ED 50 values. Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation. (orig.)

  10. Selection of unrelated donors for bone marrow transplantation studied in rhesus monkeys

    International Nuclear Information System (INIS)

    Wagemaker, G.; Bekkum, D.W. van

    Graft versus Host disease (GvHD) remains to be a severe limitation to a more general application of bone marrow transplantation. Clinically acceptable results are restricted to those potential recipients for which a major histocompatibility complex (MHC) identical sibling donor is available. At an average family size of 2 to 3 siblings, the frequency of such donors is not more than approximately 30%. This pre-clinical study in rhesus monkeys is directed at the selection of donors for recipients which lack an MHC identical sibling. (Auth.)

  11. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

    DEFF Research Database (Denmark)

    Nysom, K; Holm, K; Hesse, B

    1996-01-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...... significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated...

  12. The incidence of interstitial pneumonitis: Comparison of total body irradiation schedules for allogenic bone marrow transplantation

    International Nuclear Information System (INIS)

    Bamberg, M.; Molls, M.; Beelen, D.W.; Mahmoud, H.K.; Schaefer, U.W.

    1986-01-01

    Interstitial pneumonitis (IP) is one of the major causes of death following bone marrow transplantation (BMT). This report deals with a comparison between data compiled from six centers concerning the essential factors responsible for the development of IP. Special concern has been paid to the idiopathic form of disease where TBI is thought to be the most important factor in its pathogenesis. Our own experience using different TBI modalities shows that the instantaneous dose rate seems to be an important factor in the development of IIP. Comparing the data from various centers it is not possible at the present time to recommend one optimal modality. (orig.) [de

  13. Rhabdomyolysis Caused by Candida parapsilosis in a Patient with Acute Myeloid Leukemia after Bone Marrow Transplantation.

    Science.gov (United States)

    Kakiuchi, Seiji; Yakushijin, Kimikazu; Yamamoto, Katsuya; Tomioka, Hideo; Inui, Yumiko; Okamura, Atsuo; Kawamoto, Shinichiro; Minami, Yosuke; Murayama, Tohru; Ito, Mitsuhiro; Matsuoka, Hiroshi; Minami, Hironobu

    2015-01-01

    Rhabdomyolysis is characterized by a marked elevation of the creatine kinase (CK) levels and myoglobinuria, thus leading to renal dysfunction. Various viruses or bacteria can be etiologic agents, but mycosis has only rarely been reported to be a cause of rhabdomyolysis. In this report, we describe an adolescent male with acute myeloid leukemia who underwent allogeneic bone marrow transplantation and thereafter developed rhabdomyolysis and Candida parapsilosis fungemia almost at the same time. Following treatment for C. parapsilosis, the transaminase and CK levels both satisfactorily decreased. This case illustrates that C. parapsilosis infection may be a causative agent of rhabdomyolysis in immunocompromised patients.

  14. Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells into the Developing Mouse Eye

    International Nuclear Information System (INIS)

    Lee, Eun-Shil; Yu, Song-Hee; Jang, Yu-Jin; Hwang, Dong-Youn; Jeon, Chang-Jin

    2011-01-01

    Mesenchymal stem cells (MSCs) have been studied widely for their potential to differentiate into various lineage cells including neural cells in vitro and in vivo. To investigate the influence of the developing host environment on the integration and morphological and molecular differentiation of MSCs, human bone marrow-derived mesenchymal stem cells (BM-MSCs) were transplanted into the developing mouse retina. Enhanced green fluorescent protein (GFP)-expressing BM-MSCs were transplanted by intraocular injections into mice, ranging in ages from 1 day postnatal (PN) to 10 days PN. The survival dates ranged from 7 days post-transplantation (DPT) to 28DPT, at which time an immunohistochemical analysis was performed on the eyes. The transplanted BM-MSCs survived and showed morphological differentiation into neural cells and some processes within the host retina. Some transplanted cells expressed microtubule associated protein 2 (MAP2ab, marker for mature neural cells) or glial fibrillary acid protein (GFAP, marker for glial cells) at 5PN 7DPT. In addition, some transplanted cells integrated into the developing retina. The morphological and molecular differentiation and integration within the 5PN 7DPT eye was greater than those of other-aged host eye. The present findings suggest that the age of the host environment can strongly influence the differentiation and integration of BM-MSCs

  15. Constant post-irradiation repopulation rates and linear relationship between cellular blood response and number of transplanted bone marrow cells in inbread mice

    International Nuclear Information System (INIS)

    Petersen, B.H.

    1977-01-01

    Graded doses of syngeneic bone marrow cells were transplanted into lethally irradiated mice. Repopulation curves of peripheral blood granulocytes and platelets were apparently exponential and parallel after doses larger than 5 x 10 5 cells. The blood platelet sub(d) was reduced from 111 h to 53-57 h, and granulocyte Tsub(d) from 57 to 40 h in transplanted groups. The mean blood cell counts were reproducible to be used as a biological assay of the amount of bone marrow cells transplanted. Linear relationship between increment of blood cells up to day 16 and number of bone marrow cells transplanted on day 1 was demonstrated (1,200 granulocytes and 14,300 platelets/μl blood per 10 5 bone marrow cells). The linearity suggested a mean Tsub(d) < 22.5 h of proliferating bone marrow cells, and allowed a rough estimation of mouse bone marrow stem cell radiosensitivity (Dsub(o) 76 rad). (author)

  16. Autologous transplantation of bone marrow adult stem cells for the treatment of idiopathic dilated cardiomyopathy.

    Science.gov (United States)

    Westphal, Ricardo João; Bueno, Ronaldo Rocha Loures; Galvão, Paulo Bezerra de Araújo; Zanis Neto, José; Souza, Juliano Mendes; Guérios, Ênio Eduardo; Senegaglia, Alexandra Cristina; Brofman, Paulo Roberto; Pasquini, Ricardo; Cunha, Claudio Leinig Pereira da

    2014-12-01

    Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. We administered 4,54 x 10(8) ± 0,89 x 10(8) bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation.

  17. Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ricardo João Westphal

    2014-12-01

    Full Text Available Background: Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective: Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods: We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results: During follow-up, six patients (25% improved functional class and eight (33.3% kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018, respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%. Four patients (16.6% had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion: Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation.

  18. Fate of bone marrow mesenchymal stromal cells following autologous transplantation in a rabbit model of osteonecrosis.

    Science.gov (United States)

    Sugaya, Hisashi; Mishima, Hajime; Gao, Ran; Kaul, Sunil C; Wadhwa, Renu; Aoto, Katsuya; Li, Meihua; Yoshioka, Tomokazu; Ogawa, Takeshi; Ochiai, Naoyuki; Yamazaki, Masashi

    2016-02-01

    Internalizing quantum dots (i-QDs) are a useful tool for tracking cells in vivo in models of tissue regeneration. We previously synthesized i-QDs by conjugating QDs with a unique internalizing antibody against a heat shock protein 70 family stress chaperone. In the present study, i-QDs were used to label rabbit mesenchymal stromal cells (MSCs) that were then transplanted into rabbits to assess differentiation potential in an osteonecrosis model. The i-QDs were taken up by bone marrow-derived MSCs collected from the iliac of 12-week-old Japanese white rabbits that were positive for cluster of differentiation (CD)81 and negative for CD34 and human leukocyte antigen DR. The average rate of i-QD internalization was 93.3%. At 4, 8, 12, and 24 weeks after transplantation, tissue repair was evaluated histologically and by epifluorescence and electron microscopy. The i-QDs were detected at the margins of the drill holes and in the necrotized bone trabecular. There was significant colocalization of the i-QD signal in transplanted cells and markers of osteoblast and mineralization at 4, 8, and 12 weeks post-transplantation, while i-QDs were detected in areas of mineralization at 12 and 24 weeks post-transplantation. Moreover, i-QDs were observed in osteoblasts in regenerated tissue by electron microscopy, demonstrating that the tissue was derived from transplanted cells. These results indicate that transplanted MSCs can differentiate into osteoblasts and induce tissue repair in an osteonecrosis model and can be tracked over the long term by i-QD labeling. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  19. Migration of labeled bone marrow MSCs and skin fibroblasts after systemic and local transplantation in rat burn wound model

    Directory of Open Access Journals (Sweden)

    Shchegelskaya E. A.

    2015-10-01

    Full Text Available Aim. To study migration of syngeneic bone marrow MSCs and skin fibroblasts (FB, labeled by fluorochromes, after intravenous (IV and local transplantation in a rat burn wound model (BWM. Methods. Rats were divided into 3 groups: C – without burn + IV injection of labeled MSCs and FBs mixture; O1 – BWM + IV injection of labeled MSCs and FBs mixture; O2 – BWM + fibrin matrix filled with labeled cell mixture. MSCs were labeled by green fluorochrome, and fibroblasts – by red one. The presence of labeled cells in cryocuts of the skin, liver, kidney and bone marrow was assessed on the 3 and 7 days after transplantation. Results. Skin FBs selective migration to the regenerating burn wound and MSCs accumulation in the kidneys were found in rats of group O1 on day 7 after the IV injection. The labeled cells proliferated in the transplanted fibrin matrix and participated in the wound regeneration. MSCs partly migrated to the bone marrow after the IV injections. Conclusions. IV transplanted syngeneic bone marrow MSCs and skin FBs (passage 0 migrate to the burn wound and participate in the healing. Migration of bone marrow MSCs in the kidneys can prevent kidney failure after burn.

  20. Bone Marrow Versus Peripheral Blood Stem Cell Transplant in Lymphoma: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Jiang, Yanxia; Zhen, Yue; Xu, Qian; He, Dong; Chen, Guoan; Chen, Yan

    2017-12-18

    The choice of whether to use bone marrow or peripheral blood in autologous transplantation remains controversial. Posttransplant relapse and long-term survival are critical issues. Studies that compared bone marrow transplant versus peripheral blood stem cell transplant in lymphoma patients were searched. Our search resulted in 15 studies. Pooled data showed contradictory results with no conclusive differences in overall survival (for randomized controlled trials vs nonrandomized controlled trials: hazard ratio = 0.69 vs 1.17; 95% confidence interval, 0.44-1.10 vs 0.90-1.51; and P = .12 vs P = .25), progression-free survival (for randomized controlled trials vs nonrandomized controlled trials: hazard ratio = 0.89 vs 1.14; 95% confidence interval, 0.57-1.38 vs 0.82-1.58; and P = .60 vs P = .43), and relapse rates. However, we observed an overall trend toward lower relapse rate after bone marrow transplant. Lower relapse rate was likely associated with better progression-free survival (P = .052), and lower transplant-related mortality was associated with better overall survival (P = .043). Autologous bone marrow transplant with mobilization should be reconsidered for lymphoma patients to reduce recurrence and improve quality of life. More powered randomized controlled trials are warranted to update our findings.

  1. Prognostic value of bone marrow microvessel density and angiogenic cytokines in patients with multiple myeloma undergoing autologous stem cell transplant.

    Science.gov (United States)

    Sucak, Gülsan Türköz; Aki, Sahika Zeynep; Yüzbaşioğlu, Bilgehan; Akyürek, Nalân; Yağci, Münci; Bağriaçik, Umit; Haznedar, Rauf

    2011-07-01

    Angiogenesis is important for the proliferation and metastasis of most malignant neoplasms including multiple myeloma (MM). The aim of this study was to evaluate the role of bone marrow angiogenesis and angiogenic cytokines in patients with MM prior to and after autologous stem cell transplant (ASCT). Twenty-nine patients with MM who underwent ASCT had serial samples of serum and bone marrow biopsies at diagnosis, prior to ASCT, and at the 3rd and 6th months post-transplant. Besides bone marrow microvessel density (MVD), serum angiogenic cytokines including vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) and markers of disease activity such as interleukin-6 (IL-6), IL-1β, C-reactive protein (CRP), β(2)-microglobulin, and bone marrow plasma cells (BMPCs) were also determined. Bone marrow MVD, serum levels of IL-6, CRP, and β(2)-microglobulin, and BMPCs decreased significantly from diagnosis to the 6th month post-transplant (p transplant, however lost this significance at the 6th month. Serum VEGF levels did not vary significantly during follow-up. MVD, serum angiogenic cytokine levels, and parameters reflecting disease activity were similar in responders and non-responders to induction chemotherapy. Cytokines and MVD both at diagnosis and prior to transplant did not show any correlation with overall survival (OS) and progression-free survival (PFS) after a median follow-up of 55 months after transplant (p > 0.05). Our findings suggest that bone marrow MVD decreases significantly with ASCT in MM, however without an impact on OS and PFS.

  2. Central venous access through the external jugular vein in children submitted to bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    José Luiz de Godoy

    2005-01-01

    Full Text Available Establishment of long-term central venous access is a sine qua non step for bone marrow transplantation in children. Most frequently, long-term central venous access has been obtained via blind percutaneous cannulation of subclavian and internal jugular veins or via internal jugular vein cutdown. In order to avoid some potential minor and major complications associated with the subclavian or internal jugular approaches, the authors describe an easy, simple and safe method for central venous access through an external jugular vein cutdown that should be of interest to readers involved in the field of bone marrow transplantation. It should be also considered for children as well as adults needing central venous access via an external catheter - or totally implantable port - for reasons other than bone marrow transplantation, such as total parenteral nutrition and administration of chemotherapeutic agents.O estabelecimento de um acesso venoso central de longa duração é uma condição sine qua non para realizar o transplante de medula óssea em crianças. Com frequência, este acesso tem sido obtido através da punção percutânea das veias subclávia e jugular interna ou via dissecção da jugular interna. Com o objetivo de evitar algumas complicações maiores e menores associadas com a subclávia e a jugular interna, os autores descrevem um método simples, fácil e seguro para o acesso venoso central através de dissecção da veia jugular externa. Este método deveria ser de interesse dos leitores envolvidos com o transplante de medula óssea e ser considerado também para crianças e/ou adultos que necessitem de cateter venoso central de longa permanência (externo ou totalmente implantável devido a outras razões, como a nutrição parenteral ou a administração de agentes quimioterápicos.

  3. Transplantation of mononuclear cells from bone marrow in a rat model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Serrano T

    2016-12-01

    Full Text Available Teresa Serrano,1 Paula Pierozan,2 Esteban Alberti,1 Lisette Blanco,1 Karelys de la Cuétara Bernal,1 María E González,1 Nancy Pavón,1 Lourdes Lorigados,1 María A Robinson-Agramonte,1 Jorge A Bergado1 1International Center for Neurological Restoration (CIREN, La Habana, Cuba; 2Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil Abstract: This article investigates the possible effects of transplantation of mononuclear bone marrow cells (mBMCs to ameliorate or prevent the behavioral impairments and the cellular damage observed in a quinolinic acid (QA model of Huntington’s disease. mBMCs were isolated using a standard procedure and implanted within the QA-lesioned striatum. Behavior was explored using motor (beam test and memory (object recognition and Morris water maze tests. Morphology was evaluated using conventional histology (cresyl violet, bisbenzimide (to evaluate cell vitality, and immunohystochemistry to identify neurons or glia. mBMC-transplanted animals showed improvements in motor coordination (beam test. Regarding memory, object recognition was significantly improved in transplanted animals, while spatial memory (Morris water maze test was not severely affected by QA and, therefore, the results after transplantation were significant only in the probe-trial retention test. In samples taken from the animals that participated in the behavioral tests, a preserved morphology of striatal neurons and a reduced glial reaction indicated a possible neuroprotective effect of the transplanted mBMCs. A parallel study confirmed that the transplanted mBMCs have a long survival period (1 year follow-up. The results presented confirm the possibility that mBMC transplantation may be a viable therapeutic option for Huntington’s disease. Keywords: mononuclear bone marrow cells, Huntington’s disease, quinolinic acid, transplant, Fluoro-Jade C

  4. Experimental observation of human bone marrow mesenchymal stem cell transplantation into rabbit intervertebral discs.

    Science.gov (United States)

    Tao, Hao; Lin, Yazhou; Zhang, Guoqing; Gu, Rui; Chen, Bohua

    2016-09-01

    Allogeneic bone marrow mesenchymal stem cell (BMSC) transplantation has been investigated worldwide. However, few reports have addressed the survival status of human BMSCs in the intervertebral discs (IVDs) in vivo following transplantation. The current study aimed to observe the survival status of human BMSCs in rabbit IVDs. The IVDs of 15 New Zealand white rabbits were divided into three groups: Punctured blank control group (L1-2); punctured physiological saline control group (L2-3); and punctured human BMSCs transfected with green fluorescent protein (GFP) group (L3-4, L4-5 and L5-6). One, 2, 4, 6 and 8 weeks after transplantation the IVDs were removed and a fluorescence microscope was used to observe the density of GFP-positive human BMSCs. The results indicated that in the sections of specimens removed at 1, 2, 4, 6 and 8 weeks post-transplantation, no GFP-positive cells were observed in the control groups, whereas GFP-positive cells were apparent in the nucleus pulposus at all periods in the GFP-labeled human BMSCs group, and the cell density at 6 and 8 weeks was significantly less than that at 1, 2 and 4 weeks post-transplantation (P<0.001). Thus, it was identified that human BMSCs were able to survive in the rabbit IVDs for 8 weeks.

  5. Treatment of chronic hepatic cirrhosis with autologous bone marrow stem cells transplantation in rabbits

    International Nuclear Information System (INIS)

    Zhu Yinghe; Xu Ke; Zhang Xitong; Han Jinling; Ding Guomin; Gao Jue

    2008-01-01

    Objective: To evaluate the feasibility of treatment for rabbit model with hepatic cirrhosis by transplantation of autologous bone marrow-derived stem cells via the hepatic artery and evaluate the effect of hepatocyte growth-promoting factors (pHGF) in the treatment of stem cells transplantation to liver cirrhosis. To provide empirical study foundation for future clinical application. Methods: Chronic hepatic cirrhosis models of rabbits were developed by subcutaneous injection with 50% CCl 4 0.2 ml/kg. Twenty-five model rabbits were randomly divided into three experimental groups, stem cells transplant group (10), stem cells transplant + pHGF group (10) and control group (5). Autologous bone marrow was harvested from fibia of each rabbit, and stem cells were disassociated using density gradient centrifugation and transplanted into liver via the hepatic artery under fluoroscopic guidance. In the stem cells transplant + pHGF group, the hepatocyte growth-promoting factor was given via intravenous injection with 2 mg/kg every other day for 20 days. Liver function tests were monitored at 4, 8,12 weeks intervals and histopathologic examinations were performed at 12 weeks following transplantation. The data were analyzed using analysis of variance Results: Following transplantation of stern cells, the liver function of rabbits improved gradually. Twelve weeks after transplantation, the activity of ALT and AST decreased from (73.0±10.6) U/L and (152.4± 22.8) U/L to (48.0±1.0) U/L and (86.7±2.1) U/L respectively; and the level of ALB and PTA increased from (27.5±1.8) g/L and 28.3% to (33.2±0.5) g/L and 44.1% respectively. The changes did not have statistically significant difference when compared to the control group (P>0.05). However, in the stem cellstransplant + pHGF group, the activity of ALT and AST decreased to (43.3±0.6) U/L and (78.7±4.0) U/L respectively and the level of ALB and PTA increased to (35.7±0.4) g/L and 50.5% respectively. The difference was

  6. Transfusion-independent β(0)-thalassemia after bone marrow transplantation failure: proposed involvement of high parental HbF and an epigenetic mechanism

    NARCIS (Netherlands)

    Paciaroni, Katia; Lucarelli, Guido; Martelli, Fabrizio; Migliaccio, Anna Rita; von Lindern, Marieke; Borg, Joseph; Gillemans, Nynke; van Dijk, Thamar B.; Philipsen, Sjaak

    2014-01-01

    Currently, bone marrow transplantation is the only curative treatment for β-thalassemia and sickle cell disease. In rare cases, sustained and full fetal hemoglobin production was observed in patients after failure of bone marrow transplantation. This rendered the patients transfusion-free, despite

  7. Invasive central nervous system aspergillosis in bone marrow transplantation recipients: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Guermazi, Ali [Department of Radiology, University of California, San Francisco, 350 Parnassus Avenue, Suite 150, San Francisco, CA 94117 (United States); Department of Radiology, Saint-Louis Hospital, AP-HP, Paris (France); Gluckman, Eliane [Department of Bone Marrow Transplantation, Saint-Louis Hospital, AP-HP, Paris (France); Tabti, Bachir [Department of Radiology, Saint-Louis Hospital, AP-HP, Paris (France); Miaux, Yves [Department of Radiology, University of California, San Francisco, 350 Parnassus Avenue, Suite 150, San Francisco, CA 94117 (United States)

    2003-02-01

    Invasive central nervous system aspergillosis is being seen with an increased frequency, particularly due to the increased number of immunosuppressed patients. The major cause of invasive central nervous system aspergillosis is bone marrow transplantation. In most cases, aspergillosis develops in the paranasal sinuses and in the lungs, and secondarily spreads to the brain. Imaging of cerebral aspergillosis may present different patterns depending on the lesion's age and the immunologic status of the patient. Lesions of the spinal cord are far less common but has been encountered in our series. In this article we review the clinical and radiologic features of aspergillosis affecting the central nervous system in patients who underwent bone marrow transplantation. Different CT and MR patterns are presented, including pertinent clinical and pathologic material. Significant morbidity and mortality can be associated with this fungal infection, and it is therefore incumbent upon the radiologist to identify intracranial aspergillosis as early as possible so that appropriate therapy can be administered. (orig.)

  8. Feasibility and safety of intrathecal transplantation of autologous bone marrow mesenchymal stem cells in horses.

    Science.gov (United States)

    Maia, Leandro; da Cruz Landim-Alvarenga, Fernanda; Taffarel, Marilda Onghero; de Moraes, Carolina Nogueira; Machado, Gisele Fabrino; Melo, Guilherme Dias; Amorim, Rogério Martins

    2015-03-15

    Recent studies have demonstrated numerous biological properties of mesenchymal stem cells and their potential application in treating complex diseases or injuries to tissues that have difficulty regenerating, such as those affecting the central and peripheral nervous system. Thus, therapies that use mesenchymal stem cells are promising because of their high capacity for self-regeneration, their low immunogenicity, and their paracrine, anti-inflammatory, immunomodulatory, anti-apoptotic and neuroprotective effects. In this context, the purpose of this study was to evaluate the feasibility and safety of intrathecal transplantation of bone marrow-derived mesenchymal stem cells in horses, for future application in the treatment of neurological diseases. During the neurological evaluations, no clinical signs were observed that were related to brain and/or spinal cord injury of the animals from the control group or the treated group. The hematological and cerebrospinal fluid results from day 1 and day 6 showed no significant differences (P > 0.05) between the treated group and the control group. Additionally, analysis of the expression of matrix metalloproteinase (MMP) -2 and -9 in the cerebrospinal fluid revealed only the presence of pro-MMP-2 (latent), with no significant difference (P > 0.05) between the studied groups. The results of the present study support the hypothesis of the feasibility and safety of intrathecal transplantation of autologous bone marrow-derived mesenchymal stem cells, indicating that it is a promising pathway for cell delivery for the treatment of neurological disorders in horses.

  9. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury

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    Zurab Kakabadze

    2016-01-01

    Full Text Available Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50% cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA scale, 7 (78% out of the 9 patients observed an improvement by one grade, while two cases (22% saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury.

  10. Transfer of accelerated presbycusis by transplantation of bone marrow cells from senescence-accelerated mice.

    Science.gov (United States)

    Baba, Susumu; Iwai, Hiroshi; Inaba, Muneo; Kawamoto, Kohei; Omae, Mariko; Yamashita, Toshio; Ikehara, Susumu

    2006-11-20

    Until now, there has been no effective therapy for chronic sensorineural hearing impairment. This study investigated the role of bone marrow cells (BMCs) in cochlear dysfunction. BALB/c mice (2 months of age), a non-presbycusis-prone mouse strain, were lethally irradiated and then transplanted with BMCs from SAMP1 mice (2 months of age), a presbycusis-prone mouse strain. Acceleration of age-related hearing loss, early degeneration of spiral ganglion cells (SGCs) and impairment of immune function were observed in the recipient mice as well as in the SAMP1 mice. However, no spiral ganglion cells of donor (SAMP1) origin were detected in the recipient mice. These results indicated that accelerated presbycusis, cochlear pathology, and immune dysfunction of SAMP1 mice can be transferred to BALB/c recipient mice using allogeneic bone marrow transplantation (BMT). However, although the BMCs themselves cannot differentiate into the spiral ganglion cells (SGCs), they indirectly cause the degeneration of the SGCs. Further studies into the relationship between the inner ear cells and BMCs are required.

  11. High-dose melphalan total body irradiation with bone marrow transplantation for refractory malignancies

    International Nuclear Information System (INIS)

    Spitzer, G.; Jagannath, S.; Dicke, K.A.; Nebraska Univ., Omaha

    1986-01-01

    Nineteen adult patients with relapsed disease, 15 of them having hematologic malignancies, were treated with high-dose melphalan (100 mg/m 2 -140 mg/m 2 ) divided over 2 consecutive days followed by a rest period of 4 days before receiving total body irradiation, 850 rad administered in five fractionated doses over 3 days. Subsequently 11 patients received autologous, seven allogeneic and one syngeneic, bone marrow transplantation. All patients had severe myelosuppression and the major extramedullary toxicity was mucositis. There were three early deaths, two related to septicemia and one to graft-versus-host disease with associated cytomegalovirus pneumonitis. All patients were heavily pretreated, and 16 were demonstrating progressive disease on alternative salvage therapies at the time of bone marrow transplantation. Two of the 16 evaluable patients (12.5%) achieved complete remissions, and 10 (63%) achieved partial remissions for a total response rate of 75%. One patient is a long-term disease-free survivor (over 1 yr). The combination of melphalan, an alternative alkylating agent to cyclophosphamide and total body irradiation are associated with moderate gastrointestinal toxicity in heavily pretreated adult patients. (author)

  12. The availability of full match sibling donors and feasibility of allogeneic bone marrow transplantation in Brazil

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    Eid K.A.B.

    2003-01-01

    Full Text Available The feasibility of allogeneic bone marrow transplantation (alloBMT in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years, 684 (60.1% were males and 454 (39.9% were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8% candidates had full match donors; 352/1138 (30.8% were eligible for alloBMT. Only 235 of 352 (66.7% were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3%; monthly family income ranged from US$60 (7% to more than US$400 (36%. Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30%, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil.

  13. Inhibition of Autoimmune Chagas-Like Heart Disease by Bone Marrow Transplantation

    Science.gov (United States)

    Guimaro, Maria C.; Alves, Rozeneide M.; Rose, Ester; Sousa, Alessandro O.; de Cássia Rosa, Ana; Hecht, Mariana M.; Sousa, Marcelo V.; Andrade, Rafael R.; Vital, Tamires; Plachy, Jiří; Nitz, Nadjar; Hejnar, Jiří; Gomes, Clever C.; L. Teixeira, Antonio R.

    2014-01-01

    Background Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory. Methods/Principal Findings To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb) minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR) technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8β+ effector cells that expressed TCRγδ, vβ1 and vβ2 receptors, which infiltrated the adult hearts and the reporter heart grafts. Conclusions/Significance Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease. PMID:25521296

  14. Comparative analysis of curative effect of bone marrow mesenchymal stem cell and bone marrow mononuclear cell transplantation for spastic cerebral palsy.

    Science.gov (United States)

    Liu, Xuebin; Fu, Xiaojun; Dai, Guanghui; Wang, Xiaodong; Zhang, Zan; Cheng, Hongbin; Zheng, Pei; An, Yihua

    2017-02-24

    Bone marrow mesenchymal stem cells (BMMSCs) and bone marrow mononuclear cells (BMMNCs) are both used to treat spastic cerebral palsy. However, the differences in therapeutic effect remain unknown. A total of 105 patients with spastic cerebral palsy were enrolled and randomly assigned to three groups: the BMMSC group, the BMMNC group and the control group. Patients in both transplantation groups received four intrathecal cell injections. Patients in the control group received Bobath therapy. The gross motor function measure (GMFM) and the fine motor function measure (FMFM) were used to evaluate the therapeutic efficacy before transplantation and 3, 6, and 12 months after transplantation. Three months after cell transplantation, scores in the A dimension of GMFM and the A and C dimensions of FMFM scores in the BMMSC group are all higher than those of the BMMNC and the control groups (P < 0.05). Six months after cell transplantation, scores in the A, B dimensions of GMFM and the A, B, C, D, and E dimensions of FMFM scores in the BMMSC group are higher than those of the BMMNC and the control groups (P < 0.05). Twelve months after cell transplantation, scores in the A, B, and C dimensions of GMFM and the A, B, C, D, and E dimensions of FMFM scores in the BMMSC group are all higher than those of the BMMNC and the control groups (P < 0.05). No obvious adverse effects were investigated during follow-up. BMMSC transplantation for the treatment of cerebral palsy is safe and feasible, and can improve gross motor and fine motor function significantly. In addition, compared with BMMNC, the motor function of children improved significantly in terms of gross motor and fine motor functions.

  15. Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors

    Science.gov (United States)

    Kan, Fangyu; Woo Ahn, Kwang; Spellman, Stephen R.; Aljurf, Mahmoud; Ayas, Mouhab; Burke, Michael; Cairo, Mitchell S.; Chen, Allen R.; Davies, Stella M.; Frangoul, Haydar; Gajewski, James; Gale, Robert Peter; Godder, Kamar; Hale, Gregory A.; Heemskerk, Martin B.A.; Horan, John; Kamani, Naynesh; Kasow, Kimberly A.; Chan, Ka Wah; Lee, Stephanie J.; Leung, Wing H.; Lewis, Victor A.; Miklos, David; Oudshoorn, Machteld; Petersdorf, Effie W.; Ringdén, Olle; Sanders, Jean; Schultz, Kirk R.; Seber, Adriana; Setterholm, Michelle; Wall, Donna A.; Yu, Lolie; Pulsipher, Michael A.

    2010-01-01

    Although some trials have allowed matched or single human leukocyte antigen (HLA)–mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs) for pediatric bone marrow transplantation in early-stage hematologic malignancies, whether mmRD grafts lead to similar outcomes is not known. We compared patients < 18 years old reported to the Center for International Blood and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and 2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic-matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied. Multivariate analysis showed that recipients of MSD transplants had less transplantation-related mortality, acute graft-versus-host disease (GVHD), and chronic GVHD, along with better disease-free and overall survival than the URD and mmRD groups. No differences were observed in transplant-related mortality, acute and chronic GVHD, relapse, disease-free survival, or overall survival between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes are similar, whereas MSD outcomes are superior to the other 2 sources. Whether allele level typing could identify mmRD recipients with better outcomes will not be known unless centers alter practice and type mmRD at the allele level. PMID:20671124

  16. Effect of intravenous transplantation of bone marrow mesenchymal stem cells on neurotransmitters and synapsins in rats with spinal cord injury.

    Science.gov (United States)

    Chen, Shaoqiang; Wu, Bilian; Lin, Jianhua

    2012-07-05

    Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3-5 bone marrow mesenchymal stem cells were transplanted into rats with traumatic spinal cord injury via the caudal vein. Basso-Beattie-Bresnahan scores indicate that neurological function of experimental rats was significantly improved over transplantation time (1-5 weeks). Expressions of choline acetyltransferase, glutamic acid decarboxylase and synapsins in the damaged spinal cord of rats was significantly increased after transplantation, determined by immunofluorescence staining and laser confocal scanning microscopy. Bone marrow mesenchymal stem cells that had migrated into the damaged area of rats in the experimental group began to express choline acetyltransferase, glutamic acid decarboxylase and synapsins, 3 weeks after transplantation. The Basso-Beattie- Bresnahan scores positively correlated with expression of choline acetyltransferase and synapsins. Experimental findings indicate that intravenously transplanted bone marrow mesenchymal stem cells traverse into the damaged spinal cord of rats, promote expression of choline acetyltransferase, glutamic acid decarboxylase and synapsins, and improve nerve function in rats with spinal cord injury.

  17. Effect of intravenous transplantation of bone marrow mesenchymal stem cells on neurotransmitters and synapsins in rats with spinal cord injury

    Science.gov (United States)

    Chen, Shaoqiang; Wu, Bilian; Lin, Jianhua

    2012-01-01

    Bone marrow mesenchymal stem cells were isolated, purified and cultured in vitro by Percoll density gradient centrifugation combined with the cell adherence method. Passages 3–5 bone marrow mesenchymal stem cells were transplanted into rats with traumatic spinal cord injury via the caudal vein. Basso-Beattie-Bresnahan scores indicate that neurological function of experimental rats was significantly improved over transplantation time (1–5 weeks). Expressions of choline acetyltransferase, glutamic acid decarboxylase and synapsins in the damaged spinal cord of rats was significantly increased after transplantation, determined by immunofluorescence staining and laser confocal scanning microscopy. Bone marrow mesenchymal stem cells that had migrated into the damaged area of rats in the experimental group began to express choline acetyltransferase, glutamic acid decarboxylase and synapsins, 3 weeks after transplantation. The Basso-Beattie- Bresnahan scores positively correlated with expression of choline acetyltransferase and synapsins. Experimental findings indicate that intravenously transplanted bone marrow mesenchymal stem cells traverse into the damaged spinal cord of rats, promote expression of choline acetyltransferase, glutamic acid decarboxylase and synapsins, and improve nerve function in rats with spinal cord injury. PMID:25657678

  18. Addition of exogenous cytokines in mixed lymphocyte culture for selecting related donors for bone marrow transplantation

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    Jeane Eliete Laguila Visentainer

    Full Text Available CONTEXT: Mixed lymphocyte culturing has led to conflicting opinions regarding the selection of donors for bone marrow transplantation. The association between a positive mixed lymphocyte culture and the development of graft-versus-host disease (GVHD is unclear. The use of exogenous cytokines in mixed lymphocyte cultures could be an alternative for increasing the sensitivity of culture tests. OBJECTIVE: To increase the sensitivity of mixed lymphocyte cultures between donor and recipient human leukocyte antigen (HLA identical siblings, using exogenous cytokines, in order to predict post-transplantation GVHD and/or rejection. TYPE OF STUDY: Prospective study. SETTING: Bone Marrow Transplantation Unit, Universidade Estadual de Campinas. PARTICIPANTS: Seventeen patients with hematological malignancies and their respective donors selected for bone marrow transplantation procedures. PROCEDURES: Standard and modified mixed lymphocyte culturing by cytokine supplementation was carried out using donor and recipient cells typed for HLA. MAIN MEASUREMENTS: Autologous and allogenic responses in mixed lymphocyte cultures after the addition of IL-4 or IL-2. RESULTS: In comparison with the standard method, average responses in the modified mixed lymphocyte cultures increased by a factor of 2.0 using IL-4 (p < 0.001 and 6.4 using IL-2 (p < 0.001, for autologous donor culture responses. For donor-versus-recipient culture responses, the increase was by a factor of 1.9 using IL-4 (p < 0.001 and 4.1 using IL-2 (p < 0.001. For donor-versus-unrelated culture responses, no significant increase was observed using IL-4, and a mean response inhibition of 20% was observed using IL-2 (p < 0.001. Neither of the cytokines produced a significant difference in the unrelated control versus recipient cell responses. CONCLUSION: IL-4 supplementation was the best for increasing the mixed lymphocyte culture sensitivity. However, IL-4 also increased autologous responses, albeit less

  19. Predictive value of post-transplant bone marrow plasma cell percent in multiple myeloma patients undergone autologous transplantation.

    Science.gov (United States)

    Hwang, In Hye; Chung, Joo Seop; Shin, Ho Jin; Choi, Young Jin; Song, Moo Kon; Seol, Young Mi; Cho, Goon Jae; Choi, Bo Gwang; Choi, Mun Ki; Choi, Bo Kyung; Ahn, Kang Hee; Shin, Kyung Hwa; Lee, Hee Sun; Nam, Hyung Seok; Hwang, Jong Min

    2011-03-01

    Autologous stem cell transplantation (ASCT) has become the treatment of choice for patients with multiple myeloma (MM). Studies have shown that maintenance treatment with interferon-alpha is associated with improved survival rates following ASCT. However, despite these recent advances in regimes, relapses are inevitable; thus, the prediction of relapse following ASCT requires assessment. We retrospectively analyzed 39 patients who received ASCT between 2003 and 2008. All patients received chemotherapy with vincristine, adriamycin, and dexamethasone (VAD), and ASCT was performed following high-dose melphalan conditioning therapy. We evaluated the influence of the post-transplant day +14 (D+14) bone marrow plasma cell percent (BMPCp) (≥ 2 vs. transplant D+14 were correlated with PFS and OS. A multivariate analysis revealed that a post-transplant D+14 BMPCp ≥ 2% (PFS, hazard ratio [HR] = 4.426, p = 0.008; OS, HR = 3.545, p = 0.038) and CR after 3 cycles of VAD therapy (PFS, HR = 0.072, p = 0.014; OS, HR = 0.055, p = 0.015) were independent prognostic parameters. Post-transplant D+14 BMPCp is a useful parameter for predicting the outcome for patients with MM receiving ASCT.

  20. Autologous Bone Marrow Mononuclear Cell Transplantation Delays Progression of Carotid Atherosclerosis in Rabbits.

    Science.gov (United States)

    Cui, Kefei; Ma, Xiao; Yu, Lie; Jiang, Chao; Fu, Chao; Fu, Xiaojie; Yu, Xiaofang; Huang, Yuanjing; Hou, Suyun; Si, Caifeng; Chen, Zhengguang; Yu, Jing; Wan, Jieru; Wang, Jian

    2016-09-01

    Bone marrow mononuclear cells (BMMNCs) can counteract oxidative stress and inhibit the inflammatory response in focal ischemic stroke models. However, the effect of BMMNC transplantation on carotid atherosclerosis needs to be determined. The carotid atherosclerotic plaque model was established in New Zealand White rabbits by balloon injury and 8 weeks of high-fat diet. Rabbits were randomized to receive an intravenous injection of autologous bromodeoxyuridine (BrdU)-labeled BMMNCs or an equal volume of phosphate-buffered saline. Plaques were evaluated for expression of proinflammatory and anti-inflammatory cytokines, anti-oxidant proteins, and markers of cell death. BMMNCs migrated into atherosclerotic plaque on the first day after cell transplantation. BMMNC-treated rabbits had smaller plaques and more collagen deposition than did the vehicle-treated controls on day 28 (p Autologous BMMNC transplantation can suppress the process of atherosclerotic plaque formation and is associated with enhanced anti-oxidative effect, reduced levels of inflammatory cytokines and cleaved caspase-3, and increased expression of insulin-like growth factor-1 and its receptor. BMMNC transplantation represents a novel approach for the treatment of carotid atherosclerosis.

  1. Preliminary study of autologous bone marrow nucleated cells transplantation in children with spinal cord injury.

    Science.gov (United States)

    Jarocha, Danuta; Milczarek, Olga; Kawecki, Zdzislaw; Wendrychowicz, Anna; Kwiatkowski, Stanislaw; Majka, Marcin

    2014-03-01

    The objective of this study was to assess the safety and efficacy of transplanting bone marrow nucleated cells (BMNCs) to treat children with complete interruption of spinal cord (SC) continuity. The present study was conducted from 2005 to 2011. The inclusion criteria were a magnetic resonance imaging-confirmed complete interruption of SC continuity and no improvement in neurological status within 6 months after standard therapy. Bone marrow was isolated from the iliac ala and submitted to BMNC isolation. Subsequently, the cell suspension was administered into the SC cavity and intravenously. In total, 18 of 19 intraspinal and intravenous BMNC transplantation procedures performed caused no adverse events. One case was connected with transient bradycardia. The experimental therapy showed no late complications in the 1- to 6-year follow-up evaluation period. Neurological improvement was observed in two patients who received multiple implantations. One patient demonstrated improved superficial sensation from Th3 to Th12/L1 and a restored bladder-filling sensation. In the other case, superficial sensation was improved from C2 to C5, and the respiratory drive, the swallowing reflex, and tongue movements were restored. Spasticity and quality of life were improved in three of five patients. In addition, skin pressure ulcers healed and did not recur. Our preliminary results demonstrate the safety and feasibility of BMNC transplantation in children with complete SC injury. The results indicate that a certain degree of neurological and quality-of-life improvement can be attained by children with chronic complete SC injury who receive multiple BMNC implantations.

  2. Genetic variants of human granzyme B predict transplant outcomes after HLA matched unrelated bone marrow transplantation for myeloid malignancies.

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    Luis J Espinoza

    Full Text Available Serine protease granzyme B plays important roles in infections, autoimmunity, transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant that encodes three amino substitutions (Q48R, P88A, and Y245H has been reported to have altered biological functions. In the polymorphism rs8192917 (2364A>G, the A and G alleles represent wild type QPY and RAH mutant variants, respectively. In this study, we analyzed the impact of granzyme B polymorphisms on transplant outcomes in recipients undergoing unrelated HLA-fully matched T-cell-replete bone marrow transplantation (BMT through the Japan Donor Marrow Program. The granzyme B genotypes were retrospectively analyzed in a cohort of 613 pairs of recipients with hematological malignancies and their unrelated donors. In patients with myeloid malignancies consisting of acute myeloid leukemia and myelodysplastic syndrome, the donor G/G or A/G genotype was associated with improved overall survival (OS; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41-0.89; P = 0.01 as well as transplant related mortality (TRM; adjusted HR, 0.48; 95% CI, 0.27-0.86, P = 0.01. The recipient G/G or A/G genotype was associated with a better OS (adjusted HR, 0.68; 95% CI, 0.47-0.99; P = 0.05 and a trend toward a reduced TRM (adjusted HR, 0.61; 95% CI, 0.35-1.06; P = 0.08. Granzyme B polymorphism did not have any effect on the transplant outcomes in patients with lymphoid malignancies consisting of acute lymphoid leukemia and malignant lymphoma. These data suggest that there is an association between the granzyme B genotype and better clinical outcomes in patients with myeloid malignancies after unrelated BMT.

  3. Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis.

    Science.gov (United States)

    Bai, Yang-Qiu; Yang, Yu-Xiu; Yang, Ya-Ge; Ding, Song-Ze; Jin, Fang-Li; Cao, Ming-Bo; Zhang, Yan-Rui; Zhang, Bing-Yong

    2014-07-14

    To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis. A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial, including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment, and 15 patients receiving medical treatment only as controls. Forty-three of 47 patients were infected with hepatitis B virus. Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period. Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion. Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L (P = 0.047); albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L (P = 0.002); total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L (P = 0.048); prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s (P = 0.046); prothrombin activity 84.3% ± 14.3% vs 74.4% ± 17.8% (P = 0.046); fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L (P = 0.017); and platelet count 74.5 ± 15.7 × 10(9)/L vs 63.3 ± 15.7 × 10(9)/L (P = 0.027) in the treatment group and control group, respectively. Differences were statistically significant. The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group. Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls. However, these improvements disappeared 24 mo after transplantation. BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis. It also decreases the incidence of serious complications.

  4. A case of severe aplastic anemia transplanted with allogeneic bone marrow following premedication by cyclophosphamide and subtotal lymphoid irradiation

    International Nuclear Information System (INIS)

    Kato, Koji; Yoshida, Miyako; Iwamura, Haruki; Mizuno, Tomohisa; Matsuoka, Hiroshi; Hotta, Tomomitsu; Kodera, Yoshihisa

    1985-01-01

    A one-year old girl was admitted to the Okayama Red Cross Hospital on August 22, 1984 with fever and multiple furuncles. She was pale; peripheral blood examination revealed pancytopenia, and bone marrow aspiration showed a very hypoplastic marrow with only 4.5 percent of hematopoietic cells. Immediately anabolic steroid was administered but it failed to improve her hematological condition. She had a HLA identical brother and was transferred to the Department of Pediatrics of Nagoya University Hospital for bone marrow transplantation. After gut sterilization and an intravenous catheter were prepared, she received 500 mg of cyclophosphamide for successive 4 days followed by 750 rads of subtotal lymphoid irradiation, and 5 x 10 9 bone marrow cells were infused from her brother. Bone marrow aspiration on day 13 showed an increase in hematopoietic cells, and engraftment was confirmed by examinations of red blood cell type and sex chromosome. Hepatic transaminase increased from day 19, but was normalized by cessation of methotrexate and administration of betamethasone. Decreased immunoglobulin level after transplantation has recovered, and inverted OKT 4/8 ratio has also been normalized. After one year from transplantation, she is in a good hematological condition and is enjoying her life without any complication. (author)

  5. Bone marrow transplantation as an established approach for understanding the role of macrophages in atherosclerosis and the metabolic syndrome

    NARCIS (Netherlands)

    Aparicio-Vergara, Marcela; Shiri-Sverdlov, Ronit; Koonen, Debby P. Y.; Hofker, Marten H.

    Purpose of review Bone marrow transplantation (BMT) technology is a firmly established tool for studying atherosclerosis. Only recently it is helping us to understand the inflammatory mechanisms leading to the development of obesity, insulin resistance and type 2 diabetes. Here we review the use of

  6. The entry of the prothymocyte into the thymus after lethal irradiation and bone marrow transplantation. 2

    International Nuclear Information System (INIS)

    Mulder, A.H.; Visser, J.W.M.; Zoetelief, J.; Bekkum, D.W. van

    1988-01-01

    The time of entry of prothymocytes into the thymus after lethal irradiation and bone marrow transplantation (BMT) was determined by exposing the thymus only or the whole body with the thymus shielded to a second irradiation after different intervals. The repopulation of the thymus by donor type cells was determined by a thymus repopulation assay using donor specific markers. Reirradiation of the thymus kills the prothymocytes that have entered the thymus during the interval. It was found that reirradiation of the thymus from 48 hours after BMT onwards increasingly delayed thymus regeneration. This shows that donor prothymocytes do not enter the thymus until about 2 days after BMT and that they continue to do so during at least 3 subsequent days. In the second reirradiation protocol thymus regeneration occurred earlier in the shielded thymus than in thymuses of whole body irradiated mice. Earlier thymus regeneration was not seen in mice that were reirradiated at 24 hours after BMT, but occurred only when irradiation took place at 48 hours and later. These data are consistent with those obtained in the first protocol. The results are in contradiction with results of direct homing experiments, which showed entrance of donor cells within 3 hours after BMT. A functional assay demonstrated that the early appearing cells cannot be prothymocytes. In retransplantation experiments it was shown that the bone marrow may indeed be the initial homing site of prothymocytes. 14 refs.; 5 figs.; 1 table

  7. Successful repigmentation of vitiligo after allogeneic bone marrow transplantation for Hodgkin′s lymphoma by autologous noncultured melanocyte-keratinocyte transplantation

    Directory of Open Access Journals (Sweden)

    Huijuan Tang

    2015-01-01

    Full Text Available The treatment of vitiligo is derisory since the pathogenesis of vitiligo is not clear at present. Most conservative treatments are difficult to approach satisfactory therapy. So transplantation is the only way left when the disease becomes insensitive to those conservative treatments. Here we describe an 18-year-old patient who developed vitiligo, which was triggered by graft-versus-host disease after a allogeneic bone marrow transplantation for the treatment of Hodgkin′s lymphoma from his sister. In the following treatment to vitiligo, the patient successfully performed the transplantation of autologous uncultured melanocyte on the premise of poor reaction to other conservative methods. We infer that transplantation can be a treatment of the vitiligo after allogeneic bone marrow transplantation.

  8. Irradiated or aseptically prepared frozen dairy desserts: acceptability to bone marrow transplant recipients

    International Nuclear Information System (INIS)

    Dong, F.M.; Hashisaka, A.E.; Rasco, B.A.; Einstein, M.A.; Mar, D.R.; Aker, S.N.

    1992-01-01

    Sterile ice cream and frozen yogurt were offered to immunosuppressed patients recovering from bone marrow transplantation. To obtain sterile products, two of the dairy desserts (prepackaged ice cream and frozen yogurt bars) were exposed to 40 kGy of cobalt 60 irradiation. Four different flavors of ice cream were aseptically prepared under a laminar airflow hood using commercially sterilized ingredients. A commercially sterile, frozen milk-based drink on the low-microbial menu served as the control. Ratings of the seven products by 17 patients indicated that a frozen vanilla milk-based drink and aseptically prepared chocolate ice cream were highly acceptable to recovering immunosuppressed patients who have difficulty eating most foods. However, the seven desserts received higher ratings from a sensory panel of healthy individuals than from the patient panel, confirming that new foods for the low-microbial diet should be ''market-tested'' by the targeted patient population before inclusion in the menu

  9. Noninvasive investigation of diffuse pulmonary abnormalities in autologous bone marrow transplants

    International Nuclear Information System (INIS)

    Bergin, C.; Ravin, C.E.; Herfkens, R.J.; Peters, W.

    1987-01-01

    Pulmonary complications were assessed in 70 patients with autologous bone marrow transplants. Pulmonary edema complicated the clinical course of 25 patients. Frequently cardiogenic edema could not be reliably distinguished from noncardiogenic edema from chest radiographs alone, and because of susceptibility to bleeding and infection in this population, invasive methods are used with caution. However, in seven patients CT was useful in distinguishing cardiogenic edema from noncardiogenic pulmonary abnormalities induced by drug toxicity. In addition, cine gradient refocused MR imaging disclosed myocardial signal inhomogeneity and decreased ejection fractions in four patients with cyclophosphamide-induced cardiogenic edema. The authors conclude that CT and MR imaging proves useful in distinguishing cardiogenic from noncardiogenic diffuse parenchymal abnormalities in this patient population

  10. Irradiated or aseptically prepared frozen dairy desserts: acceptability to bone marrow transplant recipients.

    Science.gov (United States)

    Dong, F M; Hashisaka, A E; Rasco, B A; Einstein, M A; Mar, D R; Aker, S N

    1992-06-01

    Sterile ice cream and frozen yogurt were offered to immunosuppressed patients recovering from bone marrow transplantation. To obtain sterile products, two of the dairy desserts (prepackaged ice cream and frozen yogurt bars) were exposed to 40 kGy of cobalt 60 irradiation. Four different flavors of ice cream were aseptically prepared under a laminar airflow hood using commercially sterilized ingredients. A commercially sterile, frozen milk-based drink on the low-microbial menu served as the control. Ratings of the seven products by 17 patients indicated that a frozen vanilla milk-based drink and aseptically prepared chocolate ice cream were highly acceptable to recovery immunosuppressed patients who have difficulty eating most foods. However, the seven desserts received higher ratings from a sensory panel of healthy individuals than from the patient panel, confirming that new foods for the low-microbial diet should be "market-tested" by the targeted patient population before inclusion in the menu.

  11. [Estimating the grade of patient satisfaction at the bone marrow transplantation department in Florence hospitals].

    Science.gov (United States)

    Marsullo, M; Tozzi, S; Biagini, S; Rinaldi, L

    2000-01-01

    The satisfaction of the patients admitted to the bone marrow transplant unit of Careggi Hospital was evaluated by the nursing team. The aim of the evaluation was to measure the level of satisfaction for the nursing care and services and the areas of improvement. The questionnaire, with 23 questions referring to 5 areas (hotel care, Nurses' reliability, Ability to reassure, to answer to patients' needs and Empathy) derived from the conceptual model of Servqual. Ninety patients were given (or mailed) the questionnaire during a follow-up visit. Patients were asked to answer the questions evaluating each aspect on a scale from 1 (falls short of expectation) to 10 (exceeds all expectations). The answers show a very high satisfaction (> 8) for all the areas except for the food that reported a medium score of 5.2. Further analysis will allow a better understanding of the causes of dissatisfaction.

  12. Autologous bone marrow cell transplantation in acute spinal cord injury--an Indian pilot study.

    Science.gov (United States)

    Chhabra, H S; Sarda, K; Arora, M; Sharawat, R; Singh, V; Nanda, A; Sangodimath, G M; Tandon, V

    2016-01-01

    Phase- I/II, prospective, randomized, single-blind, controlled pilot study. To determine the safety and feasibility of autologous bone marrow transplantation in patients with acute spinal cord injury (SCI) via two routes of transplantation as compared with controls. Indian Spinal Injuries Center, New Delhi. Twenty-one subjects with acute, American Spinal Injury Association Impairment Scale (AIS) A (complete), traumatic SCI with neurological level T1-T12, were recruited and randomized into three groups of seven subjects each. Two groups underwent cell transplantation through the intrathecal or intralesional route, whereas the third served as control. Participants were assessed at baseline and followed up at 6 months and 12-months post enrollment. Safety and tolerability were evaluated by monitoring for any adverse events. Efficacy was assessed through neurological, functional and psychological evaluation, as well as through electrophysiological studies and urodynamics. Surgery was tolerated well by all participants. There were no significant adverse events attributable to the procedure. There was no significant improvement in the neurological, electrophysiological or urodynamic efficacy variables. A statistically significant improvement in functional scores as evaluated by the Spinal Cord Independence Measure and International Spinal Cord Injury Scale was observed in all groups. The procedure is safe and feasible in AIS A participants with thoracic-level injuries at 12-months follow-up. No efficacy could be demonstrated that could be attributed to the procedure.

  13. Data mining in bone marrow transplant records to identify patients with high odds of survival.

    Science.gov (United States)

    Taati, Babak; Snoek, Jasper; Aleman, Dionne; Ghavamzadeh, Ardeshir

    2014-01-01

    Patients undergoing a bone marrow stem cell transplant (BMT) face various risk factors. Analyzing data from past transplants could enhance the understanding of the factors influencing success. Records up to 120 measurements per transplant procedure from 1751 patients undergoing BMT were collected (Shariati Hospital). Collaborative filtering techniques allowed the processing of highly sparse records with 22.3% missing values. Ten-fold cross-validation was used to evaluate the performance of various classification algorithms trained on predicting the survival status. Modest accuracy levels were obtained in predicting the survival status (AUC = 0.69). More importantly, however, operations that had the highest chances of success were shown to be identifiable with high accuracy, e.g., 92% or 97% when identifying 74 or 31 recipients, respectively. Identifying the patients with the highest chances of survival has direct application in the prioritization of resources and in donor matching. For patients where high-confidence prediction is not achieved, assigning a probability to their survival odds has potential applications in probabilistic decision support systems and in combination with other sources of information.

  14. Transplantation of neuronal-primed human bone marrow mesenchymal stem cells in hemiparkinsonian rodents.

    Directory of Open Access Journals (Sweden)

    Melissa L M Khoo

    Full Text Available Bone marrow-derived human mesenchymal stem cells (hMSCs have shown promise in in vitro neuronal differentiation and in cellular therapy for neurodegenerative disorders, including Parkinson' disease. However, the effects of intracerebral transplantation are not well defined, and studies do not agreed on the optimal neuronal differentiation method. Here, we investigated three growth factor-based neuronal differentiation procedures (using FGF-2/EGF/PDGF/SHH/FGF-8/GDNF, and found all to be capable of eliciting an immature neural phenotype, in terms of cell morphology and gene/protein expression. The neuronal-priming (FGF-2/EGF method induced neurosphere-like formation and the highest NES and NR4A2 expression by hMSCs. Transplantation of undifferentiated and neuronal-primed hMSCs into the striatum and substantia nigra of 6-OHDA-lesioned hemiparkinsonian rats revealed transient graft survival of 7 days, despite the reported immunosuppressive properties of MSCs and cyclosporine-immunosuppression of rats. Neither differentiation of hMSCs nor induction of host neurogenesis was observed at injection sites, and hMSCs continued producing mesodermal fibronectin. Strategies for improving engraftment and differentiation post-transplantation, such as prior in vitro neuronal-priming, nigral and striatal grafting, and co-transplantation of olfactory ensheathing cells that promote neural regeneration, were unable to provide advantages. Innate inflammatory responses (Iba-1-positive microglia/macrophage and GFAP-positive astrocyte activation and accumulation were detected around grafts within 7 days. Our findings indicate that growth factor-based methods allow hMSC differentiation toward immature neuronal-like cells, and contrary to previous reports, only transient survival and engraftment of hMSCs occurs following transplantation in immunosuppressed hemiparkinsonian rats. In addition, suppression of host innate inflammatory responses may be a key factor for

  15. Pulmonary function changes in long-term survivors of bone marrow transplantation

    International Nuclear Information System (INIS)

    Gore, Elizabeth M.; Lawton, Colleen A.; Ash, Robert C.; Lipchik, Randolph J.

    1996-01-01

    Purpose: This study was undertaken to evaluate long-term pulmonary function changes in patients undergoing bone marrow transplantation (BMT), to assess their clinical significance, and to identify factors influencing these changes. Methods and Materials: Pulmonary function tests (PFT) were evaluated before and after BMT in 111 adult patients undergoing BMT between 1985 and 1991. Forced expiratory volume at 1 s (FEV 1 ), forced vital capacity (FVC), diffusing capacity (DLCO), and total lung capacity (TLC) were evaluated. One hundred and three patients (92.8%) received total body irradiation (TBI) to a total dose of 14 Gy in nine equal fractions. The lung dose was restricted to 1 , FVC, and TLC were lower than pre transplant values (p 1 did not fall significantly in patients without acute or chronic GVHD and recovered earlier than in patients without post transplant pulmonary infection. Recovery of FVC, TLC, and DLCO was also delayed in patients with acute and chronic GVHD and post transplant pulmonary infection. Multiple regression analysis revealed an association between a higher radiation dose to the lungs, and decreased FVC at 2 years (p = 0.01). Progressive obstructive pulmonary disease was not observed. Conclusions: An initial decline in PFTs with subsequent recovery was observed. Factors associated with delayed recovery and incomplete recovery of PFTs were GVHD, post transplant pulmonary infection, and higher radiation dose to the lungs. The conditioning regimen used at Medical College of Wisconsin, including relatively high TBI doses with partial transmission pulmonary shielding, appears to be well tolerated by the lungs in long-term survivors. No progressive decline in PFTs or symptomatic decline in pulmonary function was observed during the time interval studied

  16. Application of cell sheet technology to bone marrow stromal cell transplantation for rat brain infarct.

    Science.gov (United States)

    Ito, Masaki; Shichinohe, Hideo; Houkin, Kiyohiro; Kuroda, Satoshi

    2017-02-01

    Bone marrow stromal cells (BMSC) transplantation enhances functional recovery after cerebral infarct, but the optimal delivery route is undetermined. This study was aimed to assess whether a novel cell-sheet technology non-invasively serves therapeutic benefits to ischemic stroke. First, the monolayered cell sheet was engineered by culturing rat BMSCs on a temperature-responsive dish. The cell sheet was analysed histologically and then transplanted onto the ipsilateral neocortex of rats subjected to permanent middle cerebral artery occlusion at 7 days after the insult. Their behaviours and histology were compared with those in the animals treated with direct injection of BMSCs or vehicle over 4 weeks post-transplantation. The cell sheet was 27.9 ± 8.0 μm thick and was composed of 9.8 ± 2.4 × 10 5 cells. Cell sheet transplantation significantly improved motor function when compared with the vehicle-injected animals. Histological analysis revealed that the BMSCs were densely distributed to the neocortex adjacent to the cerebral infarct and expressed neuronal phenotype in the cell sheet-transplanted animals. These findings were almost equal to those for the animals treated with direct BMSC injection. The attachment of the BMSC sheet to the brain surface did not induce reactive astrocytes in the adjacent neocortex, although direct injection of BMSCs profoundly induced reactive astrocytes around the injection site. These findings suggest that the BMSCs in cell sheets preserve their biological capacity of migration and neural differentiation. Cell-sheet technology may enhance functional recovery after ischaemic stroke, using a less invasive method. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Transplantation of human bone marrow stromal cell-derived neuroregenrative cells promotes functional recovery after spinal cord injury in mice.

    Science.gov (United States)

    Mannoji, Chikato; Koda, Masao; Kamiya, Koshiro; Dezawa, Mari; Hashimoto, Masayuki; Furuya, Takeo; Okawa, Akihiko; Takahashi, Kazuhisa; Yamazaki, Masashi

    2014-01-01

    Transplantation of bone marrow stromal cells (BMSCs) for spinal cord injury (SCI) has been shown to improve functional outcome. BMSCs can be easily obtained from bone marrow aspirate and have fewer problems in the clinical application for human SCI from the ethical and legal points of view. Recently, we produced cells with neural stem and/or progenitor cell property and neural regeneration supporting capacity from human bone marrow stromal cells (human bone marrow stromal cell-derived neuroregenerative cells: hBMSC-NRs). The aim of the present study was to clarify the effectiveness of transplantation of hBMSC-NRs to injured spinal cord of severe combined immunodeficiency (NOD/SCID) mice. Neurite outgrowth assay of PC-12 cells was performed. One week after a T9-level contusion SCI, hBMSCs or hBMSC-NRs were transplanted into the spinal cord. After the transplantation, functional and histological examinations were performed. Conditioned media of hBMSC-NRs significantly promoted the neurite outgrowth of PC-12 cells in vitro. Transplanted hBMSC-NRs survived in the injured spinal cord 8 weeks after SCI. Immunohistochemistry revealed that the density of serotonin-positive fibers of the transplanted group was significantly higher than that of the control group at the epicenter and caudal segment to the injured site. The recovery of hind limb function of the hBMSC-NRs group was significantly better than that of the control group. In conclusion, hBMSC-NRs can be one of the realistic candidates for cell transplantation therapy for human SCI.

  18. Autologous bone marrow transplantation in acute myeloid leukemia: the university of minnesota experience

    International Nuclear Information System (INIS)

    Dusenbery, Kathryn E.; Steinbuch, Michael; McGlave, Philip B.; Ramsay, Norma K.C.; Blazar, Bruce R.; Neglia, Joseph P.; Litz, Craig; Kersey, John H.; Woods, William G.

    1996-01-01

    Purpose: To report the outcome of autologous bone marrow transplantation for patients with acute myeloid leukemia (AML) in first or greater complete remission (CR) treated by autologous bone marrow transplantation using two different preparatory regimens. Methods and Materials: Between September 1986 and August 1993, 75 patients with AML ranging in age from 6 months to 58 years underwent autologous bone marrow transplantation using previously harvested and frozen unpurged (n = 6) or 4-hydroperoxycyclophosphamide purged marrows (n = 69). Patients were in first CR (n = 44) or beyond first CR (n 31). The preparative regimen consisted of 120 mg/kg of cyclophosphamide (CY) and 1320 cGy total body irradiation (TBI) in eight fractions over 4 days (CY/TBI) in 29 patients; and 16 mg/kg of Busulfan (BU) and 200 mg/kg of CY (BU/CY) in 46 patients. Thirty-five of these 75 patients (18 CY/TBI and 17 BU/CY) were part of a randomized trial comparing the two preparative regimens. Results: At 2 years, overall survival and disease-free survival (DFS) were 49% [95% confidence interval (C.I.) 37-61%] and 43% (95% C.I. 32-55%), respectively. Patients in first CR had a significantly better outcome than patients beyond first CR with an estimated 2-year DFS of 59% (95% C.I. 44-74%) vs. 21% (95% C.I. 5-36%, log-rank p = 0.0001), respectively. For patients conditioned with CY/TBI, the estimated 2-year DFS was 52% compared to 39% for BU/CY (log-rank p = 0.35). Estimated 2-year relapse rates were 44% vs. 56% (log-rank p = 0.40), respectively. For patients in first CR, no differences in DFS were observed between the two regimens (2-year estimates 69% vs. 55% log-rank p = 0.52). Patients beyond first CR had a significantly improved DFS with the CY/TBI regimen (2-year estimates of 38% vs. 7%, log-rank p = 0.04). No differences were found between the two regimens in terms of time to WBC engraftment, absolute neutrophil count of gr 500, incidence of bacteremias, or median time to hospital

  19. Transplantation of islet cells across major histocompatibility barriers after total lymphoid irradiation and infusion of allogeneic bone marrow cells

    International Nuclear Information System (INIS)

    Britt, L.D.; Scharp, D.W.; Lacy, P.E.; Slavin, S.

    1982-01-01

    Diabetic Lewis rats (AgB1/L) were evaluated as recipients of allogeneic Wistar-Furth (AgB2/2) isolated adult islets without the use of standard recipient immunosuppression. One group was treated with fractionated total lymphoid irradiation (TLI) and Wistar-Furth bone marrow cell reconstitution to proven chimerism prior to islet transplantation. This group returned to a prediabetic state following Wistar-Furth islet transplantation without any evidence of rejection for 100 days posttransplant. A second group of Lewis rats received only TLI without bone marrow treatment. They gave a varying result following islet transplantation with one recipient showing evidence of prolonged islet survival. A third chimeric control group did not receive isolated islets and did not alter their diabetic state. A fourth group was not given TLI nor donor bone marrow cells and uniformly rejected their allogeneic islets by 7 days. Thus, allogeneic adult islets will survive across major rat histocompatibility barriers using TLI and donor bone marrow chimerism as the only form of immunosuppression

  20. Electrophysiological functional recovery in a rat model of spinal cord hemisection injury following bone marrow-derived mesenchymal stem cell transplantation under hypothermia.

    Science.gov (United States)

    Wang, Dong; Zhang, Jianjun

    2012-04-05

    Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours (mild hypothermia). Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells (bromodeoxyuridine-positive cells), better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury.

  1. Bone marrow concentrated cell transplantation: rationale for its use in the treatment of human osteochondral lesions.

    Science.gov (United States)

    Cavallo, C; Desando, G; Cattini, L; Cavallo, M; Buda, R; Giannini, S; Facchini, A; Grigolo, B

    2013-01-01

    Bone marrow is one of the best characterized stem cell microenvironments that contains Mesenchymal Stem Cells (MSCs), a rare population of non-hematopoietic stromal cells. MSCs have been indicated as a new option for regenerative medicine because of their ability to differentiate into various lineages such as bone, cartilage and adipose tissue. However, isolation procedures are crucial for the functional activity of the transplanted cells. The use of concentrated bone marrow cells (BMCs) enables a cell population surrounded by its microenvironment (niche) to be implanted while avoiding all the complications related to the in vitro culture. The cells of the niche are able to regulate stem cell behavior through direct physical contact and secreting paracrine factors. The aim of this study was to characterize BMCs in vitro to evaluate their ability to differentiate toward mature cells and try to understand whether there are differences in the chondrogenic and osteogenic potential of cells from patients of different ages. Mononuclear Cells (MNCs) isolated by Ficoll were used as control. Both cell populations were grown in monolayers and differentiated with specific factors and analyzed by histological and molecular biology assays to evaluate the expression of some specific extracellular matrix molecules. The present investigations revealed the ability of BMCs to act as isolated cells. They are able to form colonies and differentiate toward chondrogenic and osteogenic lineages, the latter pathway appearing to be influenced by donor age. The results obtained by this study support the use of BMCs in clinical practice for the repair of osteochondral damage, which might be particularly useful for the one-step procedure allowing cells to be directly implanted in operating room.

  2. Monosomy 7 in donor cell-derived leukemia after bone marrow transplantation for severe aplastic anemia: report of a new case and review of the literature

    Directory of Open Access Journals (Sweden)

    Luize Otero

    2012-01-01

    Full Text Available Monosomy 7 arises as a recurrent chromosome aberration in donor cell leukemia after hematopoietic stem cell transplantation. We report a new case of donor cell leukemia with monosomy 7 following HLA-identical allogenic bone marrow transplantation for severe aplastic anemia (SAA. The male patient received a bone marrow graft from his sister, and monosomy 7 was detected only in the XX donor cells, 34 months after transplantation. The patient's bone marrow microenvironment may have played a role in the leukemic transformation of the donor hematopoietic cells.

  3. Origin of Enriched Regulatory T Cells in Patients Receiving Combined Kidney-Bone Marrow Transplantation to Induce Transplantation Tolerance.

    Science.gov (United States)

    Sprangers, B; DeWolf, S; Savage, T M; Morokata, T; Obradovic, A; LoCascio, S A; Shonts, B; Zuber, J; Lau, S P; Shah, R; Morris, H; Steshenko, V; Zorn, E; Preffer, F I; Olek, S; Dombkowski, D M; Turka, L A; Colvin, R; Winchester, R; Kawai, T; Sykes, M

    2017-08-01

    We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney-bone marrow transplantation (CKBMT) that led to transient chimerism under a previously published nonmyeloablative conditioning regimen (Immune Tolerance Network study 036). Polychromatic flow cytometry and high-throughput sequencing of T cell receptor-β hypervariable regions of DNA from peripheral blood regulatory T cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of Tregs (CD3 + CD4 + CD25 high CD127 low Foxp3 + ) in blood that resulted from peripheral proliferation (Ki67 + ), possibly new thymic emigration (CD31 + ), and, in one tolerant subject, conversion from non-Tregs. Among recovering conventional T cells, central memory CD4 + and CD8 + cells predominated. A large proportion of the T cell clones detected in posttransplantation biopsy specimens by T cell receptor sequencing were detected in the peripheral blood and were not donor-reactive. Our results suggest that enrichment of Tregs by new thymic emigration and lymphopenia-driven peripheral proliferation in the early posttransplantation period may contribute to tolerance after CKBMT. Further, most conventional T cell clones detected in immunologically quiescent posttransplantation biopsy specimens appear to be circulating cells in the microvasculature rather than infiltrating T cells. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Bone Marrow Mononuclear Cell Transplantation Restores Inflammatory Balance of Cytokines after ST Segment Elevation Myocardial Infarction.

    Directory of Open Access Journals (Sweden)

    Kirsi Alestalo

    Full Text Available Acute myocardial infarction (AMI launches an inflammatory response and a repair process to compensate cardiac function. During this process, the balance between proinflammatory and anti-inflammatory cytokines is important for optimal cardiac repair. Stem cell transplantation after AMI improves tissue repair and increases the ventricular ejection fraction. Here, we studied in detail the acute effect of bone marrow mononuclear cell (BMMNC transplantation on proinflammatory and anti-inflammatory cytokines in patients with ST segment elevation myocardial infarction (STEMI.Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI were randomly assigned to receive either BMMNC or saline as an intracoronary injection. Cardiac function was evaluated by left ventricle angiogram during the PCI and again after 6 months. The concentrations of 27 cytokines were measured from plasma samples up to 4 days after the PCI and the intracoronary injection.Twenty-six patients (control group, n = 12; BMMNC group, n = 14 from the previously reported FINCELL study (n = 80 were included to this study. At day 2, the change in the proinflammatory cytokines correlated with the change in the anti-inflammatory cytokines in both groups (Kendall's tau, control 0.6; BMMNC 0.7. At day 4, the correlation had completely disappeared in the control group but was preserved in the BMMNC group (Kendall's tau, control 0.3; BMMNC 0.7.BMMNC transplantation is associated with preserved balance between pro- and anti-inflammatory cytokines after STEMI in PCI-treated patients. This may partly explain the favorable effect of stem cell transplantation after AMI.

  5. Rapid ultrastructural detection of success or failure after bone marrow transplantation in the Chediak-Higashi syndrome.

    Science.gov (United States)

    White, James G; Hess, Richard A; Gahl, William A; Introne, Wendy

    2013-01-01

    The present study has used electron microscopic techniques to rapidly detect the success or failure of bone marrow transplantation in three patients with the Chediak-Higashi Syndrome (CHS). The most rapid procedure was the whole mount technique to determine the presence or absence of dense bodies, which are inherently electron-opaque, serotonin-containing storage organelles in platelets. Dense bodies were present in normal numbers in platelets from two patients with successful transplantation and absent in thrombocytes from another patient in whom the transplant had failed.

  6. Evaluation of stem cell reserve using serial bone marrow transplantation and competitive repopulation in a murine model of chronic hemolytic anemia

    International Nuclear Information System (INIS)

    Maggio-Price, L.; Wolf, N.S.; Priestley, G.V.; Pietrzyk, M.E.; Bernstein, S.E.

    1988-01-01

    Serial transplantation and competitive repopulation were used to evaluate any loss of self-replicative capacity of bone marrow stem cells in a mouse model with increased and persistent hemopoietic demands. Congenic marrows from old control and from young and old mice with hereditary spherocytic anemia (sphha/sphha) were serially transplanted at 35-day intervals into normal irradiated recipients. Old anemic marrow failed or reverted to recipient karyotype at a mean of 3.5 transplants, and young anemic marrow reverted at a mean of 4.0 transplants, whereas controls did so at a mean of 5.0 transplants. In a competitive assay in which a mixture of anemic and control marrow was transplanted, the anemic marrow persisted to 10 months following transplantation; anemic marrow repopulation was greater if anemic marrow sex matched with the host. It is possible that lifelong stress of severe anemia decreases stem cell reserve in the anemic sphha/sphha mouse marrow. However, marginal differences in serial transplantation number and the maintenance of anemic marrow in a competition assay would suggest that marrow stem cells, under prolonged stress, are capable of exhibiting good repopulating and self-replicating abilities

  7. Detection of invasive aspergillosis in bone marrow transplant recipients using real-time PCR

    Directory of Open Access Journals (Sweden)

    Mojtaba Nabili

    2013-01-01

    Full Text Available Objective: The invasive aspergillosis (IA is a serious opportunistic infection caused by various species of Aspergillus in immunocompromised individuals. Basically, rapid and early diagnosis prevents IA progression. In this study we performed a Real Time PCR/ Fluorescence Resonance Energy Transfer (FRET for diagnosis of IA in hematologic malignancies and bone marrow transplant recipients. Materials and Methods: Sixty two patients with hematologic malignancies and marrow transplant recipients were evaluated for IA in Sari and Tehran from 2009 to 2010. The primer and hybridization probe were designed to amplify the specific sequence of 18S rRNA genes using Light Cycler system and FRET. Galactomannan (GM assay was performed on serums which obtained from selected patients using the Platelia Aspergillus kit. Results: According to the criteria defined by the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG for IA, 18 (29% patients out of 62 patients were stratified into probable and possible groups. The female-to-male ratio was 1:2; the mean age of the patients was 36 years. The most common malignancies in these patients were acute lymphoblastic leukemia (38.9%. The minimum detection limit was 10 conidia (10 1 CFU/ml equivalents (100 fg per PCR reaction. GM assay was positive in 20.9% and real-time PCR probe set assay were positive in 17.7% patients who had clinical signs and host factor according to the mentioned criteria. Conclusion: Using the Real-Time PCR/FRET assay in whole blood specimens seems to be a promising method for diagnosis of IA, especially when used in combination with the GM detection test.

  8. [Effect of intracoronary autologous bone marrow mononuclear cells transplantation on arrhythmia in canines].

    Science.gov (United States)

    Tang, J; Sun, G Y; Chen, T; Wang, Y D; Zhang, J; Qi, X Q

    2016-12-24

    Objective: To observe the survival and the differentiation of grafted bone marrow cells (BM-MNCs) in host myocardium. To observe whether BM-MNCs transplantation can potentially cause arrhythmia and whether the BM-MNCs transplantation can alter the spatial distribution of connexins, important mediator for arrhythmia genesis after myocardial infarction. Methods: Acute myocardial infarction (AMI) was induced by left anterior descending coronary artery (LAD) ligation in hybrid canine. BM-MNCs suspension was prepared by density centrifugation. The BM-MNCs were labeled with CM-DiI. Sixteen hybrid canines were randomly divided into transplantation group and control group. BM-MNCs (transplantation group, n =10) or saline (control group, n =6) were intracoronarily infused into infarction related artery at 2 hours after AMI. At 6 weeks after AMI, ventricular fibrillation (VF) was induced in infarct area and periinfarct area. The effective refractive period (ERP) of different areas in myocardium was assessed and the expression of connexin 43 (Cx43) was assessed by immunohistochemical staining. Results: Six weeks after the BM-MNCs transplantation, CM-DiI labeled BM-MNCs were mainly located within periinfarct and infarct area. Some BM-MNCs were positive for Cx43. Combined" CM-DiI and FITC" in images were observed. VF was induced in 2 out of the 10 canines in transplantation group and in 2 out of the 6 canines in control group in infarct area. VF was not induced in periinfarct area of both groups. The ERP of infarct area ((85.0±9.3) ms vs. (90.0±7.1)ms, P >0.05), periinfarct area (87.8±9.4 vs. 90.0±7.1, P >0.05) and normal area (85.0±12.0 vs. 88.3±9.4, P >0.05) was similar between transplantation group and control group. The expression of Cx43 in normal area was similar between transplantation group and control group (3 543.7±446.0 vs. 3 431.7±421.5, P >0.05). The expression of Cx43 in periinfarct area of transplantation group was significantly higher than that in

  9. Role of bone marrow transplantation for correcting hemophilia A in mice

    Science.gov (United States)

    Follenzi, Antonia; Raut, Sanj; Merlin, Simone; Sarkar, Rita

    2012-01-01

    To better understand cellular basis of hemophilia, cell types capable of producing FVIII need to be identified. We determined whether bone marrow (BM)–derived cells would produce cells capable of synthesizing and releasing FVIII by transplanting healthy mouse BM into hemophilia A mice. To track donor-derived cells, we used genetic reporters. Use of multiple coagulation assays demonstrated whether FVIII produced by discrete cell populations would correct hemophilia A. We found that animals receiving healthy BM cells survived bleeding challenge with correction of hemophilia, although donor BM-derived hepatocytes or endothelial cells were extremely rare, and these cells did not account for therapeutic benefits. By contrast, donor BM-derived mononuclear and mesenchymal stromal cells were more abundant and expressed FVIII mRNA as well as FVIII protein. Moreover, injection of healthy mouse Kupffer cells (liver macrophage/mononuclear cells), which predominantly originate from BM, or of healthy BM-derived mesenchymal stromal cells, protected hemophilia A mice from bleeding challenge with appearance of FVIII in blood. Therefore, BM transplantation corrected hemophilia A through donor-derived mononuclear cells and mesenchymal stromal cells. These insights into FVIII synthesis and production in alternative cell types will advance studies of pathophysiological mechanisms and therapeutic development in hemophilia A. PMID:22368271

  10. Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Su Mi; Choi, Ihl Bohng; Kang, Ki Mun; Kim, In Ah; Shinn, Kyung Sub; Kim, Choon Choo; Kim, Dong Jip [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1994-06-15

    Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6 fractions/3 days (6 patients) or 1320 cGy/8 fractions/4 days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase.

  11. Living related liver transplantation in an adult patient with hepatocellular adenoma and carcinoma 13 years after bone marrow transplantation for Fanconi anemia : A case report

    NARCIS (Netherlands)

    Colle, Isabelle; Laureys, Geneviève; Raevens, Sarah; Libbrecht, Louis; Leroy, Juliaan G; Reyntjens, Koen; Geerts, Anja; Rogiers, Xavier; Troisi, Roberto I; Hoehn, Holger; Schindler, Detlev; Hanenberg, Helmut; De Wilde, Vincent; Van Vlierberghe, Hans

    Fanconi anemia (FA) is an inherited bone marrow failure syndrome due to defective DNA inter-strand cross-link repair. Hematopoietic stem cell transplantation (HSCT) is curative for pancytopenia, but may not prevent the development of non-hematological malignancies. We describe a 26-year-old male

  12. Third Party Cord Blood Transplant Boosts Autologous Hematopoiesis in a Case of Persistent Bone Marrow Aplasia after Double Transplant Failure for B-Thalassemia Major

    OpenAIRE

    Visani, Giuseppe; Picardi, Paola; Guiducci, Barbara; Loscocco, Federica; Giardini, Claudio; Lucesole, Moira; Barulli, Sara; Ricciardi, Teresa; Isidori, Alessandro

    2013-01-01

    A 9-year-old female received an allogeneic stem cell transplant (SCT) from an ABO-incompatible HLA-matched sibling for ?-thalassemia major, without achieving a complete donor chimerism. Subsequently, the patient received five donor lymphocyte infusions, without increasing donor chimerism, and autologous SCT. Due to the persistent bone marrow aplasia, the patient received a second allogeneic SCT from the same donor without obtaining any engrafment. After the double transplant failure, we perfo...

  13. Safety Assessment of Human Bone Marrow-derived Mesenchymal Stromal Cells Transplantation in Wistar Rats.

    Science.gov (United States)

    Aithal, Ashwini P; Bairy, Laxminarayana Kurady; Seetharam, Raviraja N

    2017-09-01

    Bone Marrow-derived Mesenchymal Stromal Cells (BM-MSCs) are multipotent stem cells isolated from adult human bone marrow. Properties of MSCs make them potentially ideal candidates for regenerative medicine. The preclinical data available in the literature regarding the safety assessment of MSCs at different dosage group is scanty. To evaluate the safety of BM-MSCs transplantation in Wistar rats. Eighteen adult female Wistar rats were used in the study. They were randomly divided into normal control, low dose MSCs and high dose MSCs groups. Low dose group received 3.25 million BM-MSCs/kg body weight; high dose group received 9.75 million BM-MSCs/kg body weight intravenously. Body weight, food and water intake of each rat were measured statistically using SPSS version 16.0; animals were observed for changes in behaviour, general clinical signs, presence of any abnormal response, mortality for thirty days. Repeated measures ANOVA indicated a significant increase in body weight, food, and water intake of all animals at all weeks of the study period compared to week zero (pfood and water intake in MSCs group when compared to normal control. All the animals survived for the entire duration of the study. Further, there was no change in the behaviour of the animals, no adverse clinical signs or complications following the MSCs treatment. Results indicate that administration of BM-MSCs is safe when given by a slow intravenous infusion as it did not alter the food and water intake behaviour of the animals and did not have any negative effect on its body weight.

  14. Selective engraftment of the granulocyte compartment after allogeneic bone marrow transplantation in a patient with severe aplastic anemia.

    Science.gov (United States)

    Barriga, F J; Legues, M E; Bertin, P

    1996-05-01

    We present a patient with severe aplastic anemia who had partial engraftment with full chimerism after allogeneic bone marrow transplantation from an HLA identical sibling. A 3-year-old girl with severe aplastic anemia (SAA) received a bone marrow transplantation (BMT) from an HLA identical brother 9 months after her diagnosis. Before BMT she was red blood cell tranfusion dependent, had an absolute neutrophil count (ANC) of 1,000-1,500 x 10(9)/1 and a platelet count of 15-19,000 x 10(9)/1. She was conditioned with 800 cGy total body irradiation (TBI) and cyclophosphamide and received 3X10(8) nucleated cells/kg. She reached an ANC of 1500 x 10(9)/1 on day +35 but her reticulocyte and platelet counts did not recover. A bone marrow aspirate and biopsy post BMT showed hypoplasia with marked decrease in megakaryocyte and red blood cell precursors. The granulocyte compartment showed a left shift with predominance of promyelocytes and myelocytes. The karyotype showed full chimerism (46,XY) with no 46,XX metaphases. This case illustrates the possibility of a bone marrow microenvironment defect as the cause of SAA.

  15. Splenic hemochromatosis incidentally found on Tc-99m MDP bone scan in a chronic myelogenous leukemia patient who received bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol; Seo, Ji Hyoung; Bae, Jin Ho; Jeong, Sin Young; Lee, Jae Tae; Lee, Kyu Bo [School of Medicine, Kyungpook National Univ., Daegu (Korea, Republic of)

    2004-02-01

    Tc-99m MDP bone scan was performed to evaluate a generalized bone pain in a 24-year-old male chronic myelogenous leukemia patient who received bone marrow transplantation at 7 months ago. The patient had received large amounts of blood transfusion for managing symptoms related to anemia. Bone scan revealed substantial splenic tracer uptake. Magnetic resonance image and laboratory evidence of hemochromatosis suggests that the presence of large quantities of iron in the spleen of this patient may have been responsible for the splenic uptake of the bone scanning agent. The authors report a c ase of splenic hemochromatosis incidentally found on Tc-99m MDP bone scan.

  16. Changes in hemopoiesis of dying and surviving mice after fractionated irradiation and repeated bone marrow transplantation

    International Nuclear Information System (INIS)

    Tkadlecek, L.; Viklicka, S.; Hofer, M.; Karpfel, Z.

    1990-01-01

    Mice received doses of 3 Gy of 60 Co-gamma rays total body irradiation at four-day intervals up to a total dose of 24 Gy. After each dose per fraction half of the animals were injected with 10 6 bone marrow cells. At four- and nine-day intervals evaluations were made of the blood count, bone marrow and spleen cellularities, and spleen mass. In animals subjected only to irradiation the damage of hemopoietic organs was becoming deeper until the end of observation; the majority of these mice died by nine days after the irradiation with the last dose per fraction (by 37 days of the experiment). The authors consider anemia as the main cause of their death. All of the mice that were given bone marrow injections survived; nine days after the last dose of irradiation the mean cellularities of their bone marrows and spleens were 76.8% and 112.3% of the unirradiated controls respectively. In general, regeneration of erythropoiesis was quite successful, the number of thrombocytes was positively influenced, and the number of leukocytes nearly unchanged in bone marrow recipients when compared with the only irradiated mice. We observed two periods of maximum and one of minimum bone marrow and spleen regeneration, which were not synchronized. These results deny an unrepairable damage to the hemopoietic microenvironment in conditions of our experiment. This paper follows up with our preceding work describing results of an experiment which ended on day 24. (orig.) [de

  17. Bone Marrow Diseases

    Science.gov (United States)

    ... that help with blood clotting. With bone marrow disease, there are problems with the stem cells or ... marrow makes too many white blood cells Other diseases, such as lymphoma, can spread into the bone ...

  18. Restoration of Respiratory Gases and Acid-base Balance of Blood of Gamma Irradiated Rats Through Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    Eissa, S.M.; Roushdy, H.M.; Khamis, F. I.; Abu-Zeid, N.M.

    2000-01-01

    The present investigation aimed at elucidating the role played by bone marrow transplantation as a biological treatment against the deleterious effect of ionizing radiation. The parameters tested were PO2; PCO2; TCO2 and acid base balance encountering pH and (HCO3) in blood. Investigations were conducted 1,3,7,14 and 21 days post whole body gamma exposure at the dose levels 2 and 6 Gy. The data obtained showed highly significant changes in all tested parameters after whole body gamma irradiation. A higher depressant effect was more pronounced after exposure to higher radiation dose. Bone marrow transplantation to irradiated rats resulted in partial restoration or the radiation induced changes in both PO2 and PCO2 as recorded on the first week post treatment and succeeded to ameliorate the radiation induced changes in pH values and (HCO3) in blood

  19. Imaging findings in a child with calcineurin inhibitor-induced pain syndrome after bone marrow transplant for beta thalassemia major

    Energy Technology Data Exchange (ETDEWEB)

    Ayyala, Rama S.; Arnold, Staci D.; Bhatia, Monica; Dastgir, Jahannaz [Columbia University Medical Center, Morgan Stanley Children' s Hospital, Department of Radiology, New York, NY (United States)

    2016-10-15

    Calcineurin inhibitor-induced pain syndrome is an entity recognized in patients on immunosuppressive therapy after transplantation. Diagnosis is characterized by onset of pain beginning in the setting of an elevated calcineurin-inhibitor trough level. Reducing the medication dose relieves symptoms. Imaging findings can be nonspecific, including bone marrow edema and periosteal reaction. We present the unique case of calcineurin inhibitor-induced pain syndrome in a child and review the imaging findings. (orig.)

  20. Imaging findings in a child with calcineurin inhibitor-induced pain syndrome after bone marrow transplant for beta thalassemia major

    International Nuclear Information System (INIS)

    Ayyala, Rama S.; Arnold, Staci D.; Bhatia, Monica; Dastgir, Jahannaz

    2016-01-01

    Calcineurin inhibitor-induced pain syndrome is an entity recognized in patients on immunosuppressive therapy after transplantation. Diagnosis is characterized by onset of pain beginning in the setting of an elevated calcineurin-inhibitor trough level. Reducing the medication dose relieves symptoms. Imaging findings can be nonspecific, including bone marrow edema and periosteal reaction. We present the unique case of calcineurin inhibitor-induced pain syndrome in a child and review the imaging findings. (orig.)

  1. Prospective neurodevelopmental studies of two children treated with total body irradiation and bone marrow transplantation for acute leukemia in infancy

    International Nuclear Information System (INIS)

    Kaleita, T.; Tesler, A.; Feig, S.A.

    1987-01-01

    Five-year neurodevelopmental studies of two infants with acute leukemia are presented. Both patients underwent bone marrow transplantation (BMT) after conditioning with cyclophosphamide and total body irradiation (TBI). Neither patient was treated with intrathecal chemotherapy. Their outcome is remarkable for normal development of intelligence, language, perception, and motor coordination. These results suggest that TBI and BMT should be considered in future therapeutic studies of infants with acute leukemia, who are at great risk for failure of conventional therapy

  2. An asymptomatic 61-year-old man with BCR-ABL-positive bone marrow following autologous transplantation for multiple myeloma

    Science.gov (United States)

    Roper, Nitin; Deangelo, Daniel; Kuo, Frank; Cin, Paola dal; Ghobrial, Irene; Aster, Jon C.

    2010-01-01

    A 61-year-old man treated with an autologous transplant for multiple myeloma was incidentally found to have a high level of BCR-ABL fusion gene-positive cells in his bone marrow. We describe the clinical decision-making process that led us to initiate therapy with imatinib, despite the absence of any clinical evidence of chronic myelogenous leukemia or other BCR-ABL associated hematologic malignancy. PMID:20730794

  3. Incidence of interstitial pneumonia after hyperfractionated total body irradiation before autologous bone marrow/stem cell transplantation

    International Nuclear Information System (INIS)

    Lohr, F.; Schraube, P.; Wenz, F.; Flentje, M.; Kalle, K. von; Haas, R.; Hunstein, W.; Wannenmacher, M.

    1995-01-01

    Purpose/Objectives Interstitial pneumonia (IP) is a severe complication after allogenic bone marrow transplantation (BMT) with incidence rates between 10 % and 40 % in different series. It is a polyetiologic disease that occurs depending on age, graft vs. host disease (GvHD), CMV-status, total body irradiation (TBI) and immunosuppressive therapy after BMT. The effects of fractionation and dose rate are not entirely clear. This study evaluates the incidence of lethal IP after hyperfractionated TBI for autologous BMT or stem cell transplantation. Materials and Methods Between 1982 and 1992, 182 patients (60 % male, 40 % female) were treated with hyperfractionated total body irradiation (TBI) before autologous bone marrow transplantation. Main indications were leukemias and lymphomas (53 % AML, 21 % ALL, 22 % NHL, 4 % others) Median age was 30 ys (15 - 55 ys). A total dose of 14.4 Gy was applied using lung blocks (12 fractions of 1.2 Gy in 4 days, dose rate 7-18 cGy/min, lung dose 9 - 9.5 Gy). TBI was followed by cyclophosphamide (200 mg/kg). 72 % were treated with bone marrow transplantation, 28 % were treated with stem cell transplantation. Interstitial pneumonia was diagnosed clinically, radiologically and by autopsy. Results 4 patients died most likely of interstitial pneumonia. For another 12 patients interstitial pneumonia was not the most likely cause of death but could not be excluded. Thus, the incidence of lethal IP was at least 2.2 % but certainly below 8.8 %. Conclusion Lethal interstitial pneumonia is a rare complication after total body irradiation before autologous bone marrow transplantation in this large, homogeously treated series. In the autologous setting, total doses of 14.4 Gy can be applied with a low risk for developing interstitial pneumonia if hyperfractionation and lung blocks are used. This falls in line with data from series with identical twins or t-cell depleted marrow and smaller, less homogeneous autologous transplant studies. Thus

  4. Persistent bone marrow edema after osteochondral autograft transplantation in the knee joint

    International Nuclear Information System (INIS)

    Nemec, Stefan Franz; Marlovits, Stefan; Trattnig, Siegfried

    2009-01-01

    Background and objective: The assessment of bone marrow edema-like signal intensity in magnetic resonance imaging (MRI) in patients after osteochondral autograft transplantation (OCT) in the knee joint is a parameter of yet indefinite value. This study determines the prevalence of persistent edema-like signal intensity in OCT patients and evaluates the correlation between edema and morphological imaging findings of the graft and clinical pain symptoms. Materials and methods: In this longitudinal observational study, 10 patients after OCT were followed by MRI prospectively 1 month, 3 months, 6 months, 12 months, and 24 months post-operatively. All MR examinations were performed on a 1.0 T MR unit with the same protocol using a modified scoring system (magnetic resonance observation of cartilage repair tissue-MOCART) for evaluation. Edema-like signal intensity in and beneath the osteochondral graft was assessed in its prevalence and graded using a coronal short tau inversion recovery fast spin echo (STIR-FSE) sequence: grade 1, normal; grade 2, moderate (diameter 2 cm). The finding of edema-like signal intensity was correlated with graded parameters describing the morphology of the repair tissue assessed in a sagittal dual FSE sequence including: (a) surface of repair tissue: grade 1, intact; grade 2, damaged. (b) Cartilage interface: grade 1, complete; grade 2, incomplete. (c) Bone interface: grade 1, complete; grade 2, delamination. The finding of edema-like signal intensity was also correlated with the KOOS pain score assessing knee pain after 12 months. Results: Initially, after 1 month the prevalence of edema-like signal intensity was 70% (7/10 patients) and finally after 24 months 60% (6/10 patients). We found no significant relationship between the prevalence and degree of edema-like signal intensity and parameters describing the morphology of the repair tissue. Also the clinical pain score did not show significant correlation with edema. Conclusion

  5. Living-Donor Lung Transplantation After Bone Marrow Transplantation for Chediak-Higashi Syndrome.

    Science.gov (United States)

    Yamada, Tetsu; Chen-Yoshikawa, Toyofumi F; Oh, Shigeharu; Ito-Taniguchi, Rieko; Gochi, Fumiaki; Sato, Masaaki; Aoyama, Akihiro; Date, Hiroshi

    2017-03-01

    An 8-year-old girl with Chediak-Higashi syndrome (CHS) had pulmonary complications after hematopoietic stem cell transplantation (HSCT) for hemophagocytic lymphohistiocytosis (HLH) and eventually underwent single living-donor lobar lung transplantation (LDLLT). Electron micrographic findings showed vagus nerve tissue in extracted lung having granular inclusions, which are pathognomonic for CHS. Because her mother was the donor for both hematopoietic stem cell and lung transplantations, she was weaned from immunosuppression and is doing well 3 years after lung transplantation. Furthermore, an induced pluripotent stem (iPS) cell line was established from her skin fibroblasts for investigation and potential future treatment for CHS. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Allotransplantation of lung without immunosuppression after transplantation. I. Staged transplantation of bone marrow and lung

    International Nuclear Information System (INIS)

    Blumenstock, D.A.; Kazemi, H.; Hales, C.A.; Cannon, F.D.; Zumwalt, R.; Ferrebee, J.

    1974-01-01

    Six of 12 animals are alive 8 to 22 months after transplantation. Five of these animals and one which died of streptococcal pneumonia after pulmonary function testing demonstrated adequate pulmonary function in the transplant. One living recipient has not been studied. Four animals died of a ''wasting syndrome'' thought to be related to radiation damage to the pancreas rather than graft-versus-host reaction. One animal was killed with a severe skin eruption of unknown cause

  7. Concise Review: Bone Marrow Mononuclear Cells for the Treatment of Ischemic Syndromes: Medicinal Product or Cell Transplantation?

    Science.gov (United States)

    Rico, Laura; Herrera, Concha

    2012-01-01

    In November of 2011, the Committee for Advanced Therapies (CAT) of the European Medicines Agency (EMA) published two scientific recommendations regarding the classification of autologous bone marrow-derived mononuclear cells (BM-MNCs) and autologous bone marrow-derived CD133+ cells as advanced therapy medicinal products (ATMPs), specifically tissue-engineered products, when intended for regeneration in ischemic heart tissue on the basis that they are not used for the same essential function (hematological restoration) that they fulfill in the donor. In vitro and in vivo evidence demonstrates that bone marrow cells are physiologically involved in adult neovascularization and tissue repair, making their therapeutic use for these purposes a simple exploitation of their own essential functions. Therefore, from a scientific/legal point of view, nonsubstantially manipulated BM-MNCs and CD133+ cells are not an ATMP, because they have a physiological role in the processes of postnatal neovascularization and, when used therapeutically for vascular restoration in ischemic tissues, they are carrying out one of their essential physiological functions (the legal definition recognizes that cells can have several essential functions). The consequences of classifying BM-MNCs and CD133+ cells as medicinal products instead of cellular transplantation, like bone marrow transplantation, in terms of costs and time for these products to be introduced into clinical practice, make this an issue of crucial importance. Therefore, the recommendations of EMA/CAT could be reviewed in collaboration with scientific societies, in light of organizational and economic consequences as well as scientific knowledge recently acquired about the mechanisms of postnatal neovascularization and the function of bone marrow in the regeneration of remote tissues. PMID:23197819

  8. [National care logbook for patients undergoing autologous hematopoietic cell transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

    Science.gov (United States)

    Porcheron, Sophie; Balcaen, Sandie; Cardinael, Nathalie; Courbon, Corinne; Dendoncker, Caroline; Faivre-Lescat, Hélène; François, Ghislaine; Gilis, Lila; Guiraud, Myriam; Schmitt, Stéphanie; Vercasson, Marlene; Adam, Catherine; Yakoub-Agha, Ibrahim

    2017-12-01

    In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its seventh annual workshop series in September 2016 in Lille. This event brought together practitioners from across the country. Our workshop discusses the creation of a patient care logbook for patients undergoing autologous hematopoietic cell transplantation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  9. Modulation of Radiation Injury in Pregnant Rats by Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    Hussein, E.M.; Abd Rabu, M.A.

    2011-01-01

    This Work aims to point out the influence of bone marrow transplantation (BMT) in protection of irradiated pregnant rats and suppression of oxidative stress. BMT was administered to rats, 1 h post gamma irradiation at the dose level of 2 Gy given at the 7th or 14th day of gestation. Rats were examined after 20 days from gestation to detect the physiological parameters of the mother and number of implantation sites and resorption as well as length of foetuses and tails. Pregnant rats irradiated at the 7th and 14th day of gestation showed reduction in live foetuses and length of foetuses and their tails and significant decrease in erythrocytes (RBCs), leucocytes (WBCs), haemoglobin content (Hb), and hematocrit percentage (Ht). Irradiation-induced an elevation in aldosterone and a drop in calcium (Ca). Glutathione levels showed significant decreases in blood while the content of serum thiobarbituric acid reactive substance (TBARS) showed significant increases. Lipid profile exhibited an increase in the concentrations of total cholesterol (TC), triglycerides (TG) and low lipoproteins cholesterol (LDL-C) with a significant decrease in high lipoproteins cholesterol (HDL-C) in both groups. BMT to irradiated pregnant rats induced significant amelioration in radiation- induced changes. BMT was shown to be effective in reducing physiological disorders and oxidative stress in pregnant rats reflected on minimizing embryonic injuries

  10. The central nervous system complications of bone marrow transplantation in children

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Shoko; Hayakawa, Katsumi; Yamamoto, Akira [Kyoto City Hospital, Department of Radiology, Kyoto (Japan); Kuroda, Hiroshi; Imashuku, Shinsaku [Kyoto City Hospital, Department of Pediatrics, Kyoto (Japan)

    2008-10-15

    Bone marrow transplantation (BMT) is widely performed for both neoplastic and non-neoplastic disease. Before BMT, patients are prepared with high-dose chemotherapy, frequently associated with total-body radiation, to destroy residual malignant cells and to reduce immunologic resistance. BMT is associated with several central nervous system (CNS) complications secondary to underlying disease, prolonged myelosuppression, and the use of immunosuppressive drugs. These complications include infections, vascular disease, drug-induced neurotoxicity, metabolic disturbance, and post-BMT carcinogenesis. The immune status of children after BMT can be divided into three phases: the pre-engraftment period (days 0-30 after BMT), the post-engraftment period (days 30-100), and the late phase (after day 100). The timing of CNS complications that occur after BMT, as for complications in other organs, can be described with reference to these three phases of immune status. It is essential that radiologists become familiar with the relationships between the immune status of the recipient and the times of onset of these disorders, and with the neuroimaging patterns associated with the various complications. CNS complications can be life-threatening for immunosuppressed children, so accurate diagnosis is important for prompt and appropriate treatment. (orig.)

  11. Therapeutic effect of bone marrow transplantation plue previous blood transfusion on rats with total body irradiation

    International Nuclear Information System (INIS)

    Yan Yongtang; Ran Xinze; Wei Shuqing

    1988-01-01

    Therapeutic effect of bone marrow transplantation (BMT) and blood transfusion on different groups of rats subjected to various doses of total body irradiation (TBI) was studied. In the control group, 80 rats that received TBI of 8,9,10,11 and 12 Gy died between 3∼14 days. In the second group, 67 rats that received the same doses of irradiation were treated with BMT. Except that 8 rats died from lung hemorrhages at 4∼6 days after TBI. 85% of these animals (500/59) showed hemopoietic engraftment. The survival rates of 8, 9, 10, 11 and 12 Gy subgroups at 90 days after BMT were 90%, 56%, 56%, 25% and 0% respectively. In the third group, 82 rats receive TBI and blood transfusion prior to BMT. Except that 8 rats subjected to 11∼12 Gy irradiation died from lung hemorrhage at 4∼6 days after BMT, 97% of these animals (72/74) showed hemopoietic engraftment. The 90-day survival rates of 8, 9, 10, 11 and 12 Gy subgroups were 93%, 80%, 80%, 60% and 6% respectively. The 90-day survival rate of 50 rats subjected to 9∼11 Gy TBI and treated with blood transfusion and BMT, was 72%, while that 47 rats treated simply with BMT was only 42%. These results showed clearly that previous blood transfusion could increase the rate of hemopoietic engraftment, reduce the incidence if rejection, and raise the survival rate

  12. Involved field radiation therapy for Hodgkin's disease autologous bone marrow transplantation regimens

    International Nuclear Information System (INIS)

    Pezner, Richard D.; Nademanee, Auayporn; Niland, Joyce C.; Vora, Nayana; Forman, Stephen J.

    1995-01-01

    From 1986 through 1992, involved-field radiation therapy (IF-RT) was administered to 29 of 86 patients with recurrent Hodgkin's disease (HD) who received a high-dose cyclophosphamide/etoposide regimen with autologous bone marrow transplantation (A-BMT). Patients without a significant history of prior RT received total body irradiation (TBI), initially as a single dose 5-7.5 Gy, and subsequently with fractionated TBI (F-TBI) delivering 12 Gy. Previously irradiated patients received a high-dose BCNU regimen instead of TBI. IF-RT was employed selectively, usually for sites of bulky disease (> 5 cm). IF-RT doses were typically 20 Gy at 2 Gy per fraction for TBI patients and 30-40 Gy at 1.8-2.0 Gy per fraction for non-TBI Patients. Fatal complications developed in four patients while second malignancies have developed in two. The region which received IF-RT was the site of first recurrence in only two cases (7%). With a median follow-up of 28 months, the two-year disease-free survival rate was 44%. For the 22 patients treated by either F-TBI or high-dose BCNU, the 2-year disease-free survival rate was 50% with a median follow up of 29 months. Selective use of IF-RT may increase the chances of complete remission and disease free survival in HD patients with a history of bulky disease

  13. Cryotherapy effect on oral mucositis severity among recipients of bone marrow transplantation: a literature review.

    Science.gov (United States)

    Tayyem, Abdel-Qader Mahmoud

    2014-08-01

    Oral mucositis is a distressing toxic effect of cancer therapy and one of the major side effects of the myeloablative conditioning used to prepare patients for bone marrow transplantation (BMT). Oral cryotherapy is one of the recent modalities used to prevent and manage oral mucositis. The purpose of this review is to clarify the cryotherapy effect on oral mucositis severity among patients receiving myeloablative conditioning followed by BMT. A literature search was performed using six different electronic databases: CINAHL®, MEDLINE®, Nursing Ovid, PubMed, Springer, and Science Direct. Six articles were deemed relevant and included in this review. Oral mucositis increases mortality rate, length of hospital stay, opioid use, and the need for parenteral nutrition usage. It also decreases patient's quality of life and his or her desire to complete treatment. However, oral cryotherapy significantly minimizes the incidence and severity of oral mucositis and decreases secondary oral mucositis complications. Using oral cryotherapy concurrently with a regular oral care protocol can improve its efficacy for preventing and managing oral mucositis. Additional studies should be conducted to create standard oral cryotherapy protocols.

  14. Pulmonary infections in the late period after allogeneic bone marrow transplantation: chest radiography versus computed tomography

    International Nuclear Information System (INIS)

    Schueller, Gerd; Matzek, Wolfgang; Kalhs, Peter; Schaefer-Prokop, Cornelia

    2005-01-01

    Purpose: To analyze the capabilities of chest roentgenogram (CXR) and computed tomography (CT) in the evaluation of pulmonary infectious disease in the late period (>100 days) after allogeneic bone marrow transplantation (BMT). Methods: Ninety-four matched CXR and CT examinations were performed for clinical suspicion of infectious lung disease. The time gap between CXR and CT was 48 h at maximum. The image pairs were correlated with the patients' clinical course and with the results of diagnostic bronchoalveolar lavage (BAL). An unremarkable clinical course over the subsequent seven days after imaging and/or negative microbiological culture served as the basis for excluding infectious lung disease. Positive microbiological culture and/or improvement of symptoms after antibiotic therapy were considered as evidence of infectious disease. Results: The correlation with the clinical course and/or BAL revealed a significantly higher sensitivity, negative predictive value, and accuracy for CT than for CXR (89% versus 58%, P < 0.0001; 78% versus 47%, P < 0.0001; 90% versus 68%, P < 0.0001, respectively). CT was significantly more diagnostic in BAL verified fungal and bacterial infections (P < 0.05). Conclusion: CT is significantly superior to CXR in the evaluation of infectious pulmonary disease in the late phase after BMT. Therefore, an unremarkable CXR should be followed by a CT scan to reliably detect or to accurately exclude early pulmonary infection in these patients

  15. Meaning in bone marrow transplant nurses' work: experiences before and after a "meaning-centered" intervention.

    Science.gov (United States)

    Leung, Doris; Fillion, Lise; Duval, Stéphane; Brown, Jocelyn; Rodin, Gary; Howell, Doris

    2012-01-01

    When a clinical culture emphasizes cure, as in bone marrow transplantation (BMT) services, BMT nurses commonly experience enormous stress when patients are suffering or dying. In this context, it is unclear what meanings BMT nurses experience in their work and how they find meaning and sustain hope, given conflicting responsibilities to patients. This study aimed to explore BMT nurses' experiences of meaning and hope and the effects of a meaning-centered intervention (MCI) on these experiences using qualitative methodology. Fourteen BMT nurses engaged in a 5-session MCI, with 7 members each participating in 2 groups. Semistructured qualitative interviews were conducted at 1 month before and after the intervention. Interpretive phenomenology guided data analysis. The BMT nurses in the Princess Margaret Hospital experienced meaning in their involvement with their patients' suffering. The MCI seemed to inspire participants to engage more with patients and their suffering. Three subthemes reflected this influence: (a) greater awareness of boundaries between their personal and professional involvement, (b) enhanced empathy from an awareness of a shared mortality, and (c) elevated hope when nurses linked patients' suffering with meaning. This study confirms that patients' suffering constitutes nurses' search for meaning and hope in their work. The MCI offers a way in which to actively support nurses in this process. Nurses can learn to be more responsive to patients' suffering beyond limits of cure. A minimal intervention, such as the MCI, supports BMT nurses in finding positive personal meaning and purpose in their otherwise highly stressful work culture.

  16. Bone marrow transplantation modulates tissue macrophage phenotype and enhances cardiac recovery after subsequent acute myocardial infarction.

    Science.gov (United States)

    Protti, Andrea; Mongue-Din, Heloise; Mylonas, Katie J; Sirker, Alexander; Sag, Can Martin; Swim, Megan M; Maier, Lars; Sawyer, Greta; Dong, Xuebin; Botnar, Rene; Salisbury, Jon; Gray, Gillian A; Shah, Ajay M

    2016-01-01

    Bone marrow transplantation (BMT) is commonly used in experimental studies to investigate the contribution of BM-derived circulating cells to different disease processes. During studies investigating the cardiac response to acute myocardial infarction (MI) induced by permanent coronary ligation in mice that had previously undergone BMT, we found that BMT itself affects the remodelling response. Compared to matched naive mice, animals that had previously undergone BMT developed significantly less post-MI adverse remodelling, infarct thinning and contractile dysfunction as assessed by serial magnetic resonance imaging. Cardiac rupture in male mice was prevented. Histological analysis showed that the infarcts of mice that had undergone BMT had a significantly higher number of inflammatory cells, surviving cardiomyocytes and neovessels than control mice, as well as evidence of significant haemosiderin deposition. Flow cytometric and histological analyses demonstrated a higher number of alternatively activated (M2) macrophages in myocardium of the BMT group compared to control animals even before MI, and this increased further in the infarcts of the BMT mice after MI. The process of BMT itself substantially alters tissue macrophage phenotype and the subsequent response to acute MI. An increase in alternatively activated macrophages in this setting appears to enhance cardiac recovery after MI. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Lung damage following bone marrow transplantation after hyperfractionated total body irradiation

    International Nuclear Information System (INIS)

    Latini, Paolo; Aristei, Cynthia; Checcaglini, Franco; Maranzano, Ernesto; Panizza, B.M.; Perrucci, Elisabetta; Aversa, Franco; Martelli, M.F.; Raymondi, Carlo

    1991-01-01

    From July 1985 to December 1989, 72 evaluable patients aged 6-51 (median age 27) suffering from hematological malignancies received allo-geneic bone marrow transplant (BMT) depleted of T-lymphocytes to reduce risks of graft-versus-host-disease (GvHD); 57 were matched and 15 mis-matched. Three different conditioning regiments were used in an effort to enhance cytoreduction without increase extramedullary toxicity. Mis-matched patients were treated with more immunosuppressive regimens. Total body irradiation (TBI) was given in 3 doses/day, 5 h apart over 4 days for a total of 12 fractions. The dose to the lungs was 14.4, 15.6 and 9 Gy according to the conditioning regimen. The incidence of inter-stitial pneumonia (IP) was 12.3 percent in matched and 46.7 in mis-matched patients. The results seem to indicate that lung toxicity is correlated with the intensity of the conditioning regimen, the stage of disease and, in mismatched patients, with the degree of human leucocyte antigen (HLA) disparity and the poor post-BMT reconstitution, rather than the radiotherapy dose delivered to the lungs. On the contrary, the hyperfractionated scheme adopted, the absence of GvHD and, perhaps, the post-TBI administration of cyclophosphamide all seem to have contributed to the low incidence of IP in the matched patients. (author). 30 refs.; 5 figs.; 1 tab

  18. Hyperfractionated total body irradiation for bone marrow transplantation: early results in leukemia patients

    International Nuclear Information System (INIS)

    Shank, B.; Hopfan, S.; Kim, J.H.

    1981-01-01

    Bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide has previously been shown to be of value in treating refractory leukemias. Major problems, however, have been fatal interstitial pneumonitis and leukemic relapse. In an attempt to minimize these problems, we initiated a new hyperfractionated regimen for total body irradiation, with partial lung sparing. From May 1979 through July 1980, we treated 48 leukemia patients according to this regimen, varying in age from 1.5 to 42 years old (mean age: 18 y). Analysis in September 1980, with follow-up from 2 to 16 months, showed that we have a significantly reduced incidence of interstitial pneumonitis compared with single dose (1000 rad) irradiation (33 vs 70%), as well as decreased deaths attributable to interstitial pneumonitis (23 vs 50%). This is reflected in the survival curves, with loss of the early drop in survival previously observed with single dose irradiation. One year actuarial survival was 65% for acute lymphocytic leukemia (n = 16) and 72% for actue non-lymphocytic leukemia (n = 29). This compares with only 17% for acute non-lymphocytic leukemia patients (n = 12) on our previous single dose regimen. Age was also found to be an important parameter for both survival and interstitial pneumonitis

  19. Bone marrow MR imaging as predictors of outcome in hemopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Shen, Jun; Cheng, Li-Na; Duan, Xiao-Hui; Liang, Bi-Ling; Griffith, James F.; Xu, Hong-Gui

    2008-01-01

    The purpose of this study is to investigate the role of femoral marrow MR imaging as predictor of outcome for hemopoietic stem cell transplantation (HSCT) in beta-thalassemia major. MR imaging of the proximal femur, including T1- and T2-weighted spin echo and short-tau inversion recovery and in-phase and out-of-phase fast field echo images, was prospectively performed in 27 thalassemia major patients being prepared for HSCT. The area of red marrow and its percentage of the proximal femur were measured, and the presence of marrow hemosiderosis was assessed. Age-adjusted multivariate logistic regression was used to determine the relationship between red marrow area percentage and marrow hemosiderosis and HSCT outcome. Red area percentage were less in patients with successful (90.25±4.14%) compared to unsuccessful transplants (94.54% ±2.93%; p=0.01). Red marrow area percentage correlated positively with duration of symptoms(r=0.428, p=0.026) and serum ferritin (r=0.511, p=0.006). In multivariate-adjusted logistic regression analyses, red marrow area percentage was significantly inversely associated with successful HSCT (OR=1.383, 95% CI: 1.059-1.805, p=0.005). Marrow hemosidersosis and duration of sympotms and serum ferritin were not associated with HSCT outcome(p=0.174, 0.974, 0.762, respectively). Red marrow area percentage of proximal femur on MR imaging is a useful predictor of HSCT outcome. (orig.)

  20. Bone marrow MR imaging as predictors of outcome in hemopoietic stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Jun; Cheng, Li-Na; Duan, Xiao-Hui; Liang, Bi-Ling [Sun Yat-sen University, Department of Radiology, Guangzhou, Guangdong (China); Second Affiliated Hospital, Guangzhou, Guangdong (China); Griffith, James F. [Chinese University of Hong Kong, Prince of Wales Hospital, Department of Diagnostic Radiology and Organ Imaging, Shatin, Hong Kong SAR (China); Xu, Hong-Gui [Sun Yat-sen University, Department of Pediatrics, Guangzhou, Guangdong (China); Second Affiliated Hospital, Guangzhou, Guangdong (China)

    2008-09-15

    The purpose of this study is to investigate the role of femoral marrow MR imaging as predictor of outcome for hemopoietic stem cell transplantation (HSCT) in beta-thalassemia major. MR imaging of the proximal femur, including T1- and T2-weighted spin echo and short-tau inversion recovery and in-phase and out-of-phase fast field echo images, was prospectively performed in 27 thalassemia major patients being prepared for HSCT. The area of red marrow and its percentage of the proximal femur were measured, and the presence of marrow hemosiderosis was assessed. Age-adjusted multivariate logistic regression was used to determine the relationship between red marrow area percentage and marrow hemosiderosis and HSCT outcome. Red area percentage were less in patients with successful (90.25{+-}4.14%) compared to unsuccessful transplants (94.54% {+-}2.93%; p=0.01). Red marrow area percentage correlated positively with duration of symptoms(r=0.428, p=0.026) and serum ferritin (r=0.511, p=0.006). In multivariate-adjusted logistic regression analyses, red marrow area percentage was significantly inversely associated with successful HSCT (OR=1.383, 95% CI: 1.059-1.805, p=0.005). Marrow hemosidersosis and duration of sympotms and serum ferritin were not associated with HSCT outcome(p=0.174, 0.974, 0.762, respectively). Red marrow area percentage of proximal femur on MR imaging is a useful predictor of HSCT outcome. (orig.)

  1. Enteral nutrition during bone marrow transplantation in patients with pediatric cancer: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Adriana Garófolo

    Full Text Available CONTEXT AND OBJECTIVE: Cancer patients undergoing bone marrow transplantation (BMT often require nutritional therapy due to treatment toxicities. The aim here was to evaluate the use of tube feeding and its applicability, indications, contraindications and complications in these patients. DESIGN AND SETTING: Prospective observational study conducted at a public university in São Paulo between January 2002 and August 2007. METHODS: The patients were followed up daily in the BMT unit by a research dietitian. Tube feeding was indicated when oral supplementation proved to be insufficient, when the patient had severe malnutrition or there was an impediment to use of oral feeding. It was contraindicated in the presence of gastrointestinal toxicity of grade 3 and 4 or other conditions that implied a risk or hindered its use or placement. Complications of tube feeding were divided into minor and major, according to whether they had life-threatening implications. RESULTS: Forty-two (47.2% patients had indications for tube feeding: the main reasons were transplantation inadequate food and supplement intake, insufficient intake with malnutrition or weight loss, severe malnutrition or need for oral fasting. Thirty-one (73.8% received tube feeding: 11 autologous and 20 allogenic patients (P = 0.04. The main contraindications were severe gastrointestinal toxicities and sinusitis. Minor complications from tube feeding were more prevalent in patients with allogenic BMT, but no major complications were observed. CONCLUSION: Enteral nutrition is a feasible procedure in patients undergoing BMT and should be encouraged. The main difficulty in BMT patients, in relation to tube feeding, is gastrointestinal toxicities.

  2. Intrathecal Transplantation of Autologous Adherent Bone Marrow Cells Induces Functional Neurological Recovery in a Canine Model of Spinal Cord Injury.

    Science.gov (United States)

    Gabr, Hala; El-Kheir, Wael Abo; Farghali, Haithem A M A; Ismail, Zeinab M K; Zickri, Maha B; El Maadawi, Zeinab M; Kishk, Nirmeen A; Sabaawy, Hatem E

    2015-01-01

    Spinal cord injury (SCI) results in demyelination of surviving axons, loss of oligodendrocytes, and impairment of motor and sensory functions. We have developed a clinical strategy of cell therapy for SCI through the use of autologous bone marrow cells for transplantation to augment remyelination and enhance neurological repair. In a preclinical large mammalian model of SCI, experimental dogs were subjected to a clipping contusion of the spinal cord. Two weeks after the injury, GFP-labeled autologous minimally manipulated adherent bone marrow cells (ABMCs) were transplanted intrathecally to investigate the safety and efficacy of autologous ABMC therapy. The effects of ABMC transplantation in dogs with SCI were determined using functional neurological scoring, and the integration of ABMCs into the injured cords was determined using histopathological and immunohistochemical investigations and electron microscopic analyses of sections from control and transplanted spinal cords. Our data demonstrate the presence of GFP-labeled cells in the injured spinal cord for up to 16 weeks after transplantation in the subacute SCI stage. GFP-labeled cells homed to the site of injury and were detected around white matter tracts and surviving axons. ABMC therapy in the canine SCI model enhanced remyelination and augmented neural regeneration, resulting in improved neurological functions. Therefore, autologous ABMC therapy appears to be a safe and promising therapy for spinal cord injuries.

  3. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation.

    Science.gov (United States)

    Xue, Feng; Wu, Er-Jun; Zhang, Pei-Xun; Li-Ya, A; Kou, Yu-Hui; Yin, Xiao-Feng; Han, Na

    2015-01-01

    We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial fibrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  4. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Directory of Open Access Journals (Sweden)

    Feng Xue

    2015-01-01

    Full Text Available We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker and glial fibrillary acidic protein (glial cell marker at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  5. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Science.gov (United States)

    Xue, Feng; Wu, Er-jun; Zhang, Pei-xun; Li-ya, A; Kou, Yu-hui; Yin, Xiao-feng; Han, Na

    2015-01-01

    We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial fibrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury. PMID:25788929

  6. Transplant of stem cells derived from bone marrow and granulocytic growth factor in acute and chronic ischemic myocardiopathy

    International Nuclear Information System (INIS)

    Senior Juan M; Cuellar Francisco; Velasquez Oscar; Velasquez Margarita; Navas Claudia M; Ortiz Sergio; Delgado Juan A; Guillerrno, Blanco; Londono Juan L; Coronado Manuel A; Gomez Francisco; Alzate, Fernando Leon; Zuluaga Alejandra

    2007-01-01

    Recent studies have shown the safety and efficacy of the stem cells derived from bone marrow (BMC) implant with concomitant administration of stimulating factor of granulocyte colonies in patients with acute myocardial infarction with ST segment elevation and in chronic ischemic cardiopathy. An open prospective (before and after) design was made to evaluate the safety and efficacy of cell therapy associated to growth factor administration. The first experience with this kind of therapy is reported. Methodology: this is a 6 months follow-up report of patients with acute and chronic ischemic cardiopathy to who transplant of stem cells derived from bone marrow mobilized with granulocyte colonies growth stimulating factor via coronary arteries or epicardium was realized. Two groups of patients were included: Ten patients with anterior wall infarct and 2. Five patients with chronic ischemic cardiopathy, all with extensive necrosis demonstrated by absence of myocardial viability through nuclear medicine and ejection fraction of less than 40%. Results: significant improvement of ejection fraction from 29.44 ± 3.36 to 37.6 ± 5.3 with p<0.001 and decrease of ventricular systolic and diastolic volume without statistical significance (p =0.31 and 0.4 respectively) were demonstrated. Exercise capacity evidenced by increment in the six minutes test, exercise time and the MET number achieved, increased in a significant way. There were significant changes in the perfusion defect from the second follow-up month and no complications directly related to the stem cells derived from bone marrow transplant or the use of stimulating granulocyte colony factor were presented. Conclusions: this is the first experience of stem cells derived from bone marrow transplant associated to the administration of stimulating granulocyte growth colony factor in which recovery of left ventricular function was demonstrated, as well as improvement in exercise capacity and in the perfusion defect

  7. Multiple Autologous Bone Marrow-Derived CD271+Mesenchymal Stem Cell Transplantation Overcomes Drug-Resistant Epilepsy in Children.

    Science.gov (United States)

    Milczarek, Olga; Jarocha, Danuta; Starowicz-Filip, Anna; Kwiatkowski, Stanislaw; Badyra, Bogna; Majka, Marcin

    2018-01-01

    There is a need among patients suffering from drug-resistant epilepsy (DRE) for more efficient and less toxic treatments. The objective of the present study was to assess the safety, feasibility, and potential efficacy of autologous bone marrow cell transplantation in pediatric patients with DRE. Two females and two males (11 months to 6 years) were enrolled and underwent a combined therapy consisting of autologous bone marrow nucleated cells (BMNCs) transplantation (intrathecal: 0.5 × 10 9 ; intravenous: 0.38 × 10 9 -1.72 × 10 9 ) followed by four rounds of intrathecal bone marrow mesenchymal stem cells (BMMSCs) transplantation (18.5 × 10 6 -40 × 10 6 ) every 3 months. The BMMSCs used were a unique population derived from CD271-positive cells. The neurological evaluation included magnetic resonance imaging, electroencephalography (EEG), and cognitive development assessment. The characteristics of BMMSCs were evaluated. Four intravenous and 20 intrathecal transplantations into the cerebrospinal fluid were performed. There were no adverse events, and the therapy was safe and feasible over 2 years of follow-up. The therapy resulted in neurological and cognitive improvement in all patients, including a reduction in the number of epileptic seizures (from 10 per day to 1 per week) and an absence of status epilepticus episodes (from 4 per week to 0 per week). The number of discharges on the EEG evaluation was decreased, and cognitive improvement was noted with respect to reactions to light and sound, emotions, and motor function. An analysis of the BMMSCs' characteristics revealed the expression of neurotrophic, proangiogenic, and tissue remodeling factors, and the immunomodulatory potential. Our results demonstrate the safety and feasibility of BMNCs and BMMSCs transplantations and the considerable neurological and cognitive improvement in children with DRE. Stem Cells Translational Medicine 2018;7:20-33. © 2017 The Authors Stem Cells Translational Medicine

  8. Effect of autologous transplantation of bone marrow cells concentrated with the MarrowXpress system in patients with critical limb ischemia.

    Science.gov (United States)

    Maione, C; Botti, C; Coppola, C A; Silvestroni, C; Lillo, S; Schiavone, V; Sica, G; Sica, V; Kumar, V; Cobellis, G

    2013-01-01

    Critical limb ischemia (CLI), a vascular disease affecting lower limbs, with high morbidity and mortality, is becoming a challenge due to the aging of the population. Patients without direct revascularization options have the worst outcomes. To date, 25% to 40% of CLI patients are not candidates for surgical or endovascular approaches, facing a major amputation as the ultimate option. This study sought to assess the safety and efficacy of transplantation of autologous bone marrow concentrates in "no-option" patients to restore blood perfusion by collateral flow and limb salvage. We performed a nonrandomized, noncontrolled pilot study for no-option CLI patients using intra-arterial infusion of autologous bone marrow concentrate. Variation of blood perfusion parameters, evaluated by laser doppler flowmetry after 6 and 12 months, was set as primary endpoint. Thirteen enrolled patients showed improvements in objective measurements of perfusion. This uncontrolled study provided evidence that transplantation of autologous bone marrow concentrates was well tolerated by CLI patients without significant adverse effects, demonstrating improved perfusion, confirming the feasibility and safety of the procedure. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. [Bone marrow transplant in patients with sickle cell anaemia. Experience in one centre].

    Science.gov (United States)

    García Morin, Marina; Cela, Elena; Garrido, Carmen; Bardón Cancho, Eduardo; Aguado Del Hoyo, Alejandra; Pascual, Cristina; Pérez-Corral, Ana; Beléndez, Cristina

    2017-03-01

    Sickle cell disease (SCD), despite the improvement in the medical management, is still associated with severe morbidity and decreased survival. Allogenic hematopoietic stem cell transplantation (Allo-HSCT) currently provides the only curative therapy. A report is presented on our experience in children with SCD, who underwent Allo-HSCT in a single centre. A single centre descriptive study was conducted on patients with SCD who underwent a bone marrow transplant from an HLA-identical sibling donor between January 2010 and December 2014. Epidemiological, clinical and analytical parameters were collected with a follow-up to December 2015. Data are presented as frequencies, percentages, and medians (range). Allo-HCST was performed in 11 patients (8 males) with a median age of 7 years (2-13), all of them with comorbidity prior to the HCST. A stable graft was achieved in 10 out of 11 patients, 9 of them with complete donor chimerism, and one patient with stable mixed chimerism after 1 year of allo-HSCT. One patient has secondary graft failure with re-appearance of symptoms associated with SCD on day 180. Complications of Allo-HSCT are: arterial hypertension 7/11, acute renal failure 3/11, CMV reactivation 9/11, neurological complications 4/11 (subarachnoid haemorrhage, seizure), and acute graft versus host disease (aGVHD) of the skin 6/11, one of whom developed grade iv intestinal aGVHD, causing his death (day 51). None of the patients developed chronic GVHD. The overall survival and event-free survival was 90.9% and 81.9%, respectively, with a median follow-up of 3.1 (1-5.7) years. Allo-HSCT, the only curative therapy, remains associated with morbidity. There was a transplant related mortality in our study, consistent with multicentre studies (1/11), and with aGVHD being the main cause. Other problems still include graft failure (1/11), and neurological complications (4/11), although the permanent sequelae are mild. Copyright © 2016 Asociación Española de Pediatr

  10. The immunodeficiency of bone marrow-transplanted patients. II. CD8-related suppression by patient lymphocytes of the response of donor lymphocytes to mitogens, antigens, and allogeneic cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jacobsen, N

    1987-01-01

    Lymphocytes from 21 patients sampled 1-6 months after bone marrow transplantation (BMT) were tested for functional suppressor activity against marrow-donor lymphocytes in the lymphocyte transformation test. Suppression of donor responses to allogeneic (i.e. mixed lymphocyte reaction, MLR...

  11. Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Lapidot, T.; Singer, T.S.; Salomon, O.; Terenzi, A.; Schwartz, E.; Reisner, Y.

    1988-01-01

    Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection

  12. T cell repertoire expression in murine recipients of bone marrow transplant after LF 08-0299 (Tresperimus) administration.

    Science.gov (United States)

    Annat, J; Dutartre, P

    1998-12-01

    LF 08-0299 (Tresperimus), a novel immunosuppressive compound, has been previously shown to prevent graft-versus-host disease in murine models. In this study, we investigated the influence of LF 08-0299 on the TCR Vbeta repertoire of irradiated F1 recipient mice reconstituted with either syngeneic or parental bone marrow cells. We showed that a partial blockade of thymic differentiation occurred in normal mice under treatment at the transition CD4-/CD8- to CD4+/CD8+, and that this blockade was fully reversible. Despite the effect on the thymus, normal T cell repertoire negative selection was preserved following syngeneic bone marrow transplantation. We further assessed whether LF 08-0299 administration could modify Vbeta T cell expression in irradiated recipients reconstituted with parental bone marrow cells. In our murine parental to F1 transplant model, abnormal TCR Vbeta3, Vbeta5, Vbeta6 and Vbeta11 expression was demonstrated in peripheral lymph nodes of irradiated recipients. Moreover, Vbeta6 and Vbeta3 T cell populations were overexpressed. Administration of LF 08-0299 modified the pattern of Vbeta T cell expression. The expansion of Vbeta6 T cells was selectively inhibited under LF 08-0299 therapy and, in contrast, Vbeta5 T cells were overexpressed. Lymph node histological analysis showed that LF 08-0299 administration fully prevented the graft-versus-host reaction occurring in untreated recipient mice.

  13. The Japan Marrow Donor Program, 25 years of experience in achieving 20,000 bone marrow transplantations: organization structure, activity, and financial basis.

    Science.gov (United States)

    Saito, Hidehiko; Ito, Masaharu; Kato, Shunichi; Kodera, Yoshihisa; Okamoto, Shinichiro; Taniguchi, Shuichi; Takanashi, Minoko; Kanamori, Heiwa; Masaoka, Toru; Takaku, Fumimaro

    2018-01-24

    The Japan Marrow Donor Program (JMDP), established in 1991, has continued to grow in its capacity to facilitate unrelated bone marrow (BMT) and peripheral blood stem cell transplantation (PBSCT) for the past 25 years in Japan. The current donor pool is 463,465 (as of 31 December 2016) and 20,237 transplants were performed with the help of the Japanese Red Cross, government, and supporters. As JMDP introduced PBSCT in 2010, the vast majority of transplants are BMT. All donors are fully typed for HLA-A, B, C, and DR. The peak age of registered donors is around 40 years. The 8/8 HLA-matched donors are found in our registry for 96% of the patients and 54% of the patients receive a transplant. The median time between the initiation of donor search and the transplantation is approximately 122 days. The median interval between the initiation of donor search and identification of the first potential donor is 40 days. The most common diseases for which unrelated BMT/PBSCT is indicated are acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), and malignant lymphoma. In recent years we have seen a marked increase in elderly patients who received BMT.

  14. Effects of X-rays and γ-rays on reconstitution of hematopoiesis and immunity after allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Pan Bin; Zeng Lingyu; Cheng Hai; Song Guoliang; Jia Lu; Yan Zhiling; Chen Chong; Xu Kailin

    2011-01-01

    Objective: To determine the conditioning regimen suitable for mice allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Twelve BALB/c mice were randomly divided into 2 equal groups to undergo X-ray irradiation by linear accelerator at the dose of 7.0 Gy (pure X-ray group) or 60 Co source irradiation at the dose of 7.0 Gy (pure γ-ray group). Thirty mice were randomly divided into 2 equal groups to undergo X-ray irradiation and then infusion of bone marrow from donor mice via caudal vein (X-ray + transplantation group) or γ-ray and then infusion of bone marrow via caudal vein (γ-ray + transplantation group). 3, 5, 7, 10, 15, 20, and 30 d later peripheral blood samples were collected to calculate the number of white blood cells (WBCs) and detect the chimeric rates of lymphocytes by flow cytometry. 5, 10, and 20 d after irradiation 15 mice were killed with their lung, liver, small intestine, spleen, and femurs taken out to undergo pathological examination. Results: The survival rates during the period 5-15 days of the γ-ray + transplantation group were all significantly higher than those of the X-ray + transplantation group. The pathological changes of organs of the X-ray + transplantation group were all more severe than those of the γ-ray + transplantation group. Since the fifth day after transplantation cells originating from the donor began to appear in the peripheral blood. The chimeric rate of the γ-ray + transplantation group 10 days after transplantation was (95.53± 2.57) %. The chimeric rates 5, 10, and 20 days after transplantation of the γ-ray + transplantation group were all significantly higher than those of the X-ray + transplantation group (t=15.263, 3.256, P<0.05). The WBC count of both irradiation groups decreased to the lowest level 5 d later and began to increase 10 days after transplantation and the WBC counts of the γ-ray + transplantation group 10 and 20 days after transplantation were both significantly higher than

  15. Transplantation of autologous bone marrow stromal cells (BMSC for CNS disorders – Strategy and tactics for clinical application

    Directory of Open Access Journals (Sweden)

    Satoshi Kuroda

    2010-01-01

    Full Text Available Background – There is increasing evidence that the transplanted bone marrow stromal cells (BMSC significantly promote functional recovery after central nervous system (CNS damage in the animal models of various kinds of CNS disorders, including cerebral infarct, brain contusion and spinal cord injury. However, there are several shortages of information when considering clinical application of BMSC transplantation for patients with neurological disorders. In this paper, therefore, we discuss what we should clarify to establish cell transplantation therapy in clinical situation and describe our recent works for this purpose.Methods and Results – The BMSC have the ability to alter their gene expression profile and phenotype in response to the surrounding circumstances and to protect the neurons by producing some neurotrophic factors. They also promote neurite extension and rebuild the neural circuits in the injured CNS. Using optical imaging and MRI techniques, the transplanted BMSC can non-invasively be tracked in the living animals for at least 8 weeks after transplantation. Functional imaging such as PET scan may have the potential to assess the beneficial effects of BMSC transplantation. The BMSC can be expanded using the animal protein-free culture medium, which would maintain their potential of proliferation, migration, and neural differentiation.Conclusion – It is urgent issues to develop clinical imaging technique to track the transplanted cells in the CNS and evaluate the therapeutic significance of BMSC transplantation in order to establish it as a definite therapeutic strategy in clinical situation in the future

  16. Allotransplantation of the lung without immunosuppression after transplantation. II. Combined autotransplantation of bone marrow and allotransplantation of lung. [Gamma radiation, beagles

    Energy Technology Data Exchange (ETDEWEB)

    Blumenstock, D.A.; Cannon, F.D.; Franck, W.A.; Hales, C.A.; Kazemi, H.; Ferrebee, J.W.

    1977-09-01

    A series of seven animals underwent allotransplantation of a lung from a donor matched for the recognition of serologically defined (SD) antigens by the use of alloantisera followed by autotransplantation of bone marrow without further immunosuppression. In two animals, the lung was transplanted into the recipient immediately before the administration of total-body irradiation and in five, the lung was transplanted after completion of total-body irradiation. In the first group, one animal is living at 46 months with good function of the transplant. The other was killed at 6 months with chronic rejection. In the second group, three of five animals are alive 46 to 47 months after transplantation. Two others died early, one of cardiac tamponade and the other of diffuse hemorrhage before engraftment of marrow could be accomplished. Significant function of the transplant was demonstrated in all long-term survivors. Four control animals, subjected to marrow harvest and reimplantation of the left lung followed by total-body irradiation and marrow reinfusion, were studied to determine the possible deleterious effects of the total-body irradiation and marrow transplant procedure. Pulmonary function studies showed some reduction in ventilation and perfusion to the upper lobe areas, which was probably related to technical factors but did demonstrate no severe adverse effects to the procedures. Autologous bone marrow reconstitution after total-body irradiation combined withallotransplantation of the lung has allowed long-term survival and function of lung transplants without the necessity for administration of immunosuppressive drugs after the transplantation procedure.

  17. Long-Term Engraftment of Primary Bone Marrow Stromal Cells Repairs Niche Damage and Improves Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Abbuehl, Jean-Paul; Tatarova, Zuzana; Held, Werner; Huelsken, Joerg

    2017-08-03

    Hematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and adaptive immunity often causes fatal complications. HSC maintenance and lineage differentiation are supported by stromal niches, and we now find that bone marrow stroma cells (BMSCs) are severely and permanently damaged by the pre-conditioning irradiation required for efficient HSC transplantation. Using mouse models, we show that stromal insufficiency limits the number of donor-derived HSCs and B lymphopoiesis. Intra-bone transplantation of primary, but not cultured, BMSCs quantitatively reconstitutes stroma function in vivo, which is mediated by a multipotent NT5E + (CD73) + ENG - (CD105) - LY6A + (SCA1) + BMSC subpopulation. BMSC co-transplantation doubles the number of functional, donor-derived HSCs and significantly reduces clinically relevant side effects associated with HSC transplantation including neutropenia and humoral immunodeficiency. These data demonstrate the potential of stroma recovery to improve HSC transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Pulmonary infections following bone marrow transplantation: High-resolution CT findings in 35 paediatric patients

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    Davaus Gasparetto, Taisa [Department of Diagnostic Radiology of the Federal Universitie Fluminense, Niteroi (Brazil); Federal University of Rio de Janeiro, Rio de Janeiro (Brazil)], E-mail: taisadavaus@gmail.com; Escuissato, Dante L. [Department of Diagnostic Radiology of the University of Parana, Curitiba (Brazil); Marchiori, Edson [Department of Diagnostic Radiology of the Federal Universitie Fluminense, Niteroi (Brazil); Federal University of Rio de Janeiro, Rio de Janeiro (Brazil)

    2008-04-15

    Purpose: The purpose of this study was to assess the high-resolution CT findings of paediatric patients who had pulmonary infections following bone marrow transplantation (BMT), and to evaluate the differential diagnosis through high-resolution CT of the various pathogens responsible for pulmonary infections after BMT. Patients and methods: The study included 35 consecutive patients who had documented pulmonary infection, high-resolution CT of the chest performed within 24 h of the beginning of symptoms, and proven diagnosis within 1 week of the onset of symptoms. The pulmonary infections were due to viruses (n = 16), bacteria (n = 9), fungi (n = 9), and protozoa (n = 1). Two radiologists analyzed the CT scans and reached final decisions regarding the findings by consensus. Results: Four patients with confirmed pneumonia had normal high-resolution CT scans. Regarding the viral infections, the most frequent features were areas of ground-glass attenuation (43.7%) and small centrilobular nodules (31.2%). Airspace consolidation (88.9%), small centrilobular nodules (22.2%) and ground-glass attenuation (22.2%) were the most frequent findings in patients with bacterial pneumonia following BMT. Large nodules were seen in 66.7% of the patients with fungal pneumonia, and in only one case of virus infection. The 'halo sign' (n = 5) was seen only in patients with fungal pneumonia. Conclusion: In conclusion, the main causes of pulmonary infection in paediatric patients following BMT share similar high-resolution CT findings. Large nodules and 'halo sign' are more common in patients with fungal infections.

  19. Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes.

    Science.gov (United States)

    Li, Qian; Luo, Changying; Luo, Chengjuan; Wang, Jianmin; Li, Benshang; Ding, Lixia; Chen, Jing

    2017-08-01

    Hematopoietic stem cell transplantation (HSCT) using an optimized conditioning regimen is essential for the long-term survival of patients with inherited bone marrow failure syndromes (IBMFS). We report HSCT in 24 children with Fanconi anemia (FA, n = 12), Diamond-Blackfan anemia (DBA, n = 7), and dyskeratosis congenita (DC, n = 5) from a single HSCT center. The graft source was peripheral blood stem cells (n = 19) or cord blood stem cells (n = 5). FA and DC patients received reduced-intensity conditioning, while DBA patients had myeloablative conditioning. The median numbers of infused mononuclear cells and CD34+ cells were 14.20 × 10 8 /kg and 4.3 × 10 6 /kg, respectively. The median time for neutrophil and platelet recovery was 12 and 18 days, respectively. Complete donor engraftment was achieved in 23 of 24 patients. There was one primary graft failure. During a median follow-up of 27.5 months (range, 2-130 months), the overall survival in all patients was 95.8%. The incidence of grade II-III acute graft versus host disease (GvHD) and chronic GvHD was 29.2% and 16.7%, respectively. We conclude that HSCT can be a curative option for patients with IBMFS. Modification of the conditioning regimen based on the type of disease may lead to encouraging long-term outcomes.

  20. High-resolution CT findings in cytomegalovirus pneumonitis after bone marrow transplantation

    International Nuclear Information System (INIS)

    Abe, Katsumi; Suzuki, Kenzo; Kamata, Noriko

    1998-01-01

    In order to explore the high-resolution CT (HRCT) findings of cytomegalovirus (CMV) pneumonitis after bone marrow transplantation, we retrospectively reviewed the HRCT findings in nine patients with CMV pneumonitis cytologically proven by bronchoalveolar lavege. In 67% of cases, HRCT showed ground-glass attenuation. Consolidation and bronchial wall thickening were demonstrated in 33%, pleural effusion in 22%, and micro centrilobular nodules, bronchiectasis, and reticulation in 11%, respectively. Lymphadenopathy and masses were not seen. The areas of ground-glass attenuation were distributed bilaterally in all cases, diffusely in 67%, centrilobularly in 50%, and panlobularly in 50%. Subpleural lung regions were spared in 83%. The areas of consolidation were bilateral in 67%, nonsegmental in 67%, and involved the lower lobe in all cases. A total of 25 follow-up HRCT were performed in six patients. Small centrilobular ground-glass opacities disappeared after treatment in one patient. Micro centrilobular nodules vanished after treatment in one patient. Small centrilobular ground-glass opacities developed into consolidation and resolved after treatment in one patient. In one patient, diffuse ground-glass opacities progressed to consolidation, and the patient died due to respiratory failure. No abnormal findings were observed in two patients. It may be considered that in the early phase of CMV pneumonitis HRCT shows small or micro centrilobular ground-glass opacities and nodules and that in the advanced phase these lesions progress to dense alveolar opacities as CMV infection advances, although a variety of HRCT appearances is observed in the course of CMV pneumonitis. (author)

  1. Living with the unknown: Posttraumatic stress disorder in pediatric bone marrow transplantation survivors and their mothers.

    Science.gov (United States)

    Taskıran, Gülseren; Sürer Adanır, Aslı; Özatalay, Esin

    2016-04-01

    Bone marrow transplantation (BMT) is used to treat children with various hematologic, oncologic, and metabolic diseases. Although the treatment can be lifesaving, it is also physically and psychologically demanding for both the child and caregivers. In previous studies, BMT is found to be related with anxiety, posttraumatic stress disorder (PTSD), depression, and psychosocial problems both in children and parents. The aim of this study was to investigate PTSD in pediatric BMT survivors and their mothers compared with the healthy controls. Twenty-seven BMT survivors and their mothers and 28 healthy peers and their mothers were recruited as the study group and as the comparison group, respectively. All children were interviewed using Child Posttraumatic Stress Disorder-Reaction Index (CPTSD-RI) for assessing posttraumatic stress responses. As for mothers, Clinician-Administered PTSD Scale (CAPS) was used. In healthy children and mothers, instead of BMT, the most important traumatic event reported by them was included. All data were analyzed by a neutral statistician from the Department of Biostatistics of the university. The BMT group, both children and mothers, obtained significantly higher PTSD rates than the control group (66.5% and 17.8%, respectively, in children; 57.6% and 7%, respectively, in mothers). However, there was a weak correlation between survivors' and mothers' posttraumatic stress responses. These findings suggest that BMT is a significant stressor for both children and mothers. Clinicians should be aware of psychiatric symptoms of children who underwent such a life-threatening condition. Combination of medical treatment with psychosocial support is imperative.

  2. Renal toxicity in children undergoing total body irradiation for bone marrow transplant

    International Nuclear Information System (INIS)

    Esiashvili, Natia; Chiang, K.-Y.; Hasselle, Michael D.; Bryant, Cynthia; Riffenburgh, Robert H.; Paulino, Arnold C.

    2009-01-01

    Purpose: Contribution of total body irradiation (TBI) to renal toxicity in children undergoing the bone marrow transplant (BMT) remains controversial. We report our institutional retrospective study that evaluates the frequency of acute and chronic renal dysfunction in children after using total body irradiation (TBI) conditioning regimens. Materials and methods: Between 1995 and 2003, 60 children with hematological malignancies underwent TBI as part of a conditioning regimen before allogeneic BMT. Patients received 4-14 Gy at 1.75-2 Gy/fraction in six-eight fractions. Lung shielding was used in all patients to limit lung dose to less than 10 Gy; renal shielding was not utilized. All patients had baseline renal function assessment and renal dysfunction post-BM was mainly evaluated on the basis of persistent serum creatinine elevation at acute (0-90 days) and chronic (>90 days) intervals after completion of BMT. Results: Acute renal dysfunction (ARD) was documented in 27 patients (45%); the majority had concurrent diagnosis of veno-occlusive disease (VOD) or graft-versus-host disease (GVHD) and other potential causes (sepsis, antibiotic). The risk for delayed renal dysfunction (DRD) at 1 year approached 25% for surviving patients. The ARD was strongly linked with the risk of the DRD. There was no statistically significant relationship between ARD, DRD and underlying diagnosis, GVHD, VOD or TBI doses with both univariate and multivariate analyses. The younger age (<5 years) had significantly increased risk for the development of ARD (p = 0.011). Conclusion: Our analysis validates high incidence of renal dysfunction in the pediatric BMT population. In contrast to other reports we did not find total body irradiation dose to be a risk factor for renal dysfunction. Future prospective studies are needed to assess risk factors and interventions for this serious toxicity in children following allogeneic BM

  3. Historical and current perspectives on bone marrow transplantation for prevention and treatment of immunodeficiencies and autoimmunities.

    Science.gov (United States)

    Good, R A; Verjee, T

    2001-01-01

    Primary immunodeficiency diseases often fully meet the definition of "experiments of nature." Much of the expanding understanding of the lymphoid systems and immunologic functions generated in recent years has been derived from studying patients with primary, generally genetically determined immunodeficiency diseases, as well as other relatively rare secondary immunodeficiency diseases. Increasing knowledge of immunologic defenses, their interacting cellular and molecular components, the evolving details of sequential stages of cellular differentiation, and the nature and control of the cellular and molecular interactions in immunity have now made it possible to define precisely many primary immunodeficiency diseases in full molecular genetic terms. With this wealth of scientific information based on experimental and clinical research, incredible advances have also been made in using bone marrow transplantation (BMT) often as a curative treatment for immunodeficiency, some 60 to 70 other diseases, leukemias, lymphomas, other cancers, and a rapidly expanding constellation of metabolic diseases or enzyme deficiencies. Also, progress in applying allogeneic BMT to prevent, treat, and cure complex autoimmune diseases, primary immunodeficiency diseases and certain forms of cancers, is considered. Further, mixed BMT (syngeneic plus allogeneic) that establishes a form of stable mixed chimerism has also been employed in animal experiments, which revealed that BMT can be used to treat not only immunodeficiency diseases, but also systemic and organ-specific autoimmune diseases, eg, diabetes and erythematous lupus-like diseases. Moreover, performing BMT in conjunction with organ allografts, eg, thymus or pancreatic transplants, has successfully prevented rejection of these allografts, sometimes without recourse to long-term irradiation or toxic chemical immunosuppressive agents. A crucial role for stromal cells in cellular engineering has now also been realized in animal

  4. Total body irradiation prior to bone marrow transplantation; some aspects of fifty year experience.

    Science.gov (United States)

    Gocheva, L

    2004-01-01

    There has been a remarkable growth in the use of bone marrow transplantation (BMT) in the past 30 years. The rapid expansion of BMT reflects its increasingly important role in the treatment of several life-threatening diseases of the hemopoietic system. The first BMT in human patients was performed after conditioning with total body irradiation (TBI). As an important part of BMT protocols, TBI has an established role in many preparative regimens used before BMT in the treatment of hematological diseases. Historically, TBI schedules varied during the last 30-year period with regard to different radiation source used, treatment technique, beam modifiers, actually delivered total dose, dose rate, and fractionation schedule. The aim of this review article is to discuss the 50- year experience in the field of TBI, as well as radiobiological, technical and dosimetric requirements and especially effects of total dose, dose rate and fractionation schedules on the prognosis of transplanted patients. The radiobiological and radio-oncological requirements demand special TBI treatment techniques quite different from usual radiotherapy. The technique needed depends extremely on the prescribed values of treatment parameters and on the local technical possibilities. TBI dosimetry has to account for the physical situation of treatment with very large field sizes at extended distances and should be performed under TBI conditions close to the real treatment situation. The effects of total dose, dose rate, fractionation schedule on the leukemia cell killing, immunosuppression, and sparing of normal tissues are considered in detail. Their effects on overall survival, leukemia recurrence, acute and chronic graft versus host disease (GvHD), late radiation-induced injuries to normal tissues or organs as well as incidence of interstitial pneumonitis, renal dysfunction and cataract development are analyzed. The definition of currently used TBI procedures is so different in different

  5. Intra coronary freshly isolated bone marrow cells transplantation improve cardiac function in patients with ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Bozdag-Turan Ilkay

    2012-04-01

    Full Text Available Abstract Background Autologous bone marrow cell transplantation (BMCs-Tx is a promising novel option for treatment of cardiovascular disease. In this study we analyzed whether intracoronary autologous freshly isolated BMCs-Tx have beneficial effects on cardiac function in patients with ischemic heart disease (IHD. Results In this prospective nonrandomized study we treated 12 patients with IHD by freshly isolated BMCs-Tx by use of point of care system and compared them with a representative 12 control group without cell therapy. Global ejection fraction (EF and infarct size area were determined by left ventriculography. Intracoronary transplantation of autologous freshly isolated BMCs led to a significant reduction of infarct size (p  Conclusions These results demonstrate that intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system is safe and may lead to improvement of cardiac function in patients with IHD. Trial registration Registration number: ISRCTN54510226

  6. Low-cost matched sibling bone marrow transplant for standard-risk thalassemia in a limited-resource setting

    Directory of Open Access Journals (Sweden)

    Stalin Ramprakash

    2017-12-01

    Full Text Available Thalassemias are the most common inherited genetic disorder in India and a major public health burden with bone marrow transplant (BMT considered the only established curative therapy. We describe outcomes for patients (n = 71 with standard-risk thalassemia (liver size 80 at the last follow up. 5 patients (7% died, mortality related to transplant. Enough data existed for 2 centers in India (36/71 transplants to analyze overall costs from admission up to one-year post-BMT which revealed a median cost of Rs 7,30,445 ($11519 [Range Rs 4,52,821–10,32,842 ($ 7079–16147]. In conclusion, children with thalassemia in resource limited settings can achieve good outcomes with BMT at a reasonable cost.

  7. Cell transplantation for the treatment of spinal cord injury - bone marrow stromal cells and choroid plexus epithelial cells.

    Science.gov (United States)

    Ide, Chizuka; Nakano, Norihiko; Kanekiyo, Kenji

    2016-09-01

    Transplantation of bone marrow stromal cells (BMSCs) enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury (SCI). BMSCs did not survive long-term, disappearing from the spinal cord within 2-3 weeks after transplantation. Astrocyte-devoid areas, in which no astrocytes or oligodendrocytes were found, formed at the epicenter of the lesion. It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas. Regenerating axons were associated with Schwann cells embedded in extracellular matrices. Transplantation of choroid plexus epithelial cells (CPECs) also enhanced axonal regeneration and locomotor improvements in rats with SCI. Although CPECs disappeared from the spinal cord shortly after transplantation, an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas, as in the case of BMSC transplantation. These findings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord, including axonal regeneration and reduced cavity formation. This means that transplantation of BMSCs and CPECs promotes "intrinsic" ability of the spinal cord to regenerate. The treatment to stimulate the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI. It should be emphasized that the generally anticipated long-term survival, proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety.

  8. Cell transplantation for the treatment of spinal cord injury - bone marrow stromal cells and choroid plexus epithelial cells

    Directory of Open Access Journals (Sweden)

    Chizuka Ide

    2016-01-01

    Full Text Available Transplantation of bone marrow stromal cells (BMSCs enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury (SCI. BMSCs did not survive long-term, disappearing from the spinal cord within 2-3 weeks after transplantation. Astrocyte-devoid areas, in which no astrocytes or oligodendrocytes were found, formed at the epicenter of the lesion. It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas. Regenerating axons were associated with Schwann cells embedded in extracellular matrices. Transplantation of choroid plexus epithelial cells (CPECs also enhanced axonal regeneration and locomotor improvements in rats with SCI. Although CPECs disappeared from the spinal cord shortly after transplantation, an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas, as in the case of BMSC transplantation. These findings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord, including axonal regeneration and reduced cavity formation. This means that transplantation of BMSCs and CPECs promotes "intrinsic" ability of the spinal cord to regenerate. The treatment to stimulate the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI. It should be emphasized that the generally anticipated long-term survival, proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety.

  9. High-resolution computed tomography findings in pulmonary complications after bone marrow transplantation: iconographic essay; Tomografia computadorizada de alta resolucao nas complicacoes pulmonares pos-transplante de medula ossea: ensaio iconografico

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    Gasparetto, Emerson L.; Ono, Sergio E.; Souza, Carolina A. [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Radiologia Medica e Diagnostico por Imagem]. E-mail: gasparetto@hotmail.com; Escuissato, Dante L. [Parana Univ., Curitiba, PR (Brazil). Faculdade de Medicina. Disciplina de Radiologia Medica; Rocha, Gabriela de Melo; Inoue, Cezar; Falavigna, Joao M. [Parana Univ., Curitiba, PR (Brazil). Faculdade de Medicina; Marchiori, Edson [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia; Universidade Federal, Rio de Janeiro (UFRJ), RJ (Brazil). Curso de Pos-graduacao em Radiologia

    2005-12-01

    Bone marrow transplantation has been the treatment of choice for many hematologic diseases. However, pulmonary complications, which may occur in up to 60% of the patients, are the main cause of treatment failure and may be divided in three phases according to the patient's immunity. In the first phase, up to 30 days after the procedure, there is a predominance of non-infectious complications and fungal pneumonia. Viral infections, mainly by cytomegalovirus, are common in the second phase (up to 100 days after bone marrow transplantation). Finally, in the late phase after bone marrow transplantation, non-infectious complications as bronchiolitis obliterans organizing pneumonia and graft-versus-host disease are most commonly seen. The authors present a pictorial essay of the high-resolution computed tomography findings in patients with pulmonary complications after bone marrow transplantation. (author)

  10. Animal experimental model of a graft-versus-host (GVH) reaction after allogenic transplantation of bone marrow in lethally irradiated mice

    International Nuclear Information System (INIS)

    Schwenke, H.; Muench, S.; Haubold, S.; Weber, B.

    1977-01-01

    The graft-versus-host (GVH) disease represents a serious still unsolved problem in the human allogenic transplantation of bone marrow. An experimental model of GVH reaction after an allogenic transplantation of bone marrow in the adult mouse has been worked out as a prerequisite for further studies on the therapeutic influence of this syndrome. 3 groups have been formed out of 82 lethally X-irradiated C57 Bl mice. The non-transplanted control group died to a hundred per cent within 12 days. While out of the 2nd group treated with syngenic bone marrow 55 per cent survived from the 22nd day, 30 per cent of the third animal group, allogenicly transplanted with histoincompatible AKR donor marrow developed a chronic GVH syndrome. The following symptoms were observed: retardation, alterations of the skin, diarrhea, edemas of the legs, failing increase of leukocytes in blood and proliferation of lymphocytes in bone marrow of about 60 per cent (18 per cent in syngenically transplanted animals), in lacking proliferation of hematopoiesis. The increase of liver and especially spleen index is not characteristic in comparison with the syngenically transplanted group, since in the latter there is also an increase of the values on account of a strong hematopoetic proliferation. The model is suitable and sufficiently well characterized for the performance of further experimental studies. (author)

  11. Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients

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    Christian Hendrich

    2009-12-01

    Full Text Available The clinical application of cellular based therapies with ex vivo cultivation for the treatment of diseases of the musculoskeletal system has until now been limited. In particular, the advanced laboratory and technical effort necessary, regulatory issues as well as high costs are major obstacles. On the other hand, newly developed cell therapy systems permit intra-operative enrichment and application of mesenchymal and progenitor stem cells from bone marrow aspirate concentrate (BMAC in one single operative session. The objective of the present clinical surveillance study was to evaluate new bone formation after the application of BMAC as well as to record any possible therapy-specific complications For this purpose, the clinical-radiological progress of a total of 101 patients with various bone healing disturbances was documented (surveillance study. The study included 37 necrosis of the head of the femur, 32 avascular necroses/bone marrow edema of other localization, 12 non-unions, 20 other defects. The application of BMAC was performed in the presence of osteonecrosis via a local injection as part of a core decompression (n=72 or by the local adsorption of intra-operative cellular bone substitution material (scaffold incubated with BMAC during osteosynthesis (n=17 or in further surgery (n=12. After an average of 14 months (2-24 months, the patients were re-examined clinically and radiologically and interviewed. Further surgery was necessary in 2 patients within the follow-up period. These were due to a progression of a collapsed head of the femur with initial necrosis in ARCO Stage III, as well as inadequate new bone formation with secondary loss of correction after periprosthetic femoral fracture. The latter healed after repeated osteosynthesis plus BMAC application without any consequences. Other than these 2 patients, no further complications were observed. In particular, no infections, no excessive new bone formation, no induction of

  12. Morphological study of the effect of cyclophosphamide, dimethylmyleran and whole-body irradiation for the conditioning of dogs to bone marrow transplantation

    International Nuclear Information System (INIS)

    Bayer, L.

    1980-01-01

    Dogs were treated with either cyclophosphamide (CY) or dimethylmyleran (DMM), both cytostatics or with total body irradiation (TBI) in order to find out which agents are most suitable for conditioning for bone marrow (BM) transplantation. The histomorphological changes in various organs (lung, bone marrow, lymphatic tissues, digestive tract, liver, kidney, bladder, heart and gonads) after treatment with different doses are described. (orig./MG) [de

  13. Haploidentical bone marrow transplants for haematological malignancies using non-myeloablative conditioning therapy and post-transplant immunosuppression with cyclophosphamide: results from a single Australian centre.

    Science.gov (United States)

    Bilmon, I A; Kwan, J; Gottlieb, D; Kerridge, I; McGurgan, M; Huang, G; George, B; Hertzberg, M; Bradstock, K F

    2013-02-01

    To demonstrate safety and efficacy of haploidentical bone marrow transplantation with non-myeloablative conditioning and high-dose post-transplant cyclophosphamide in adult patients with leukaemia or lymphoma. Human leukocyte antigen haploidentical bone marrow transplantation is a treatment option in patients with haematological malignancies who have no available human leukocyte antigen-matched donor but is limited by conditioning regimen toxicity, graft failure, relapse and graft-versus-host disease (GvHD). Twelve patients, median age of 51 years, underwent transplantation with T cell replete bone marrow from a haplotype-matched relative. The conditioning regimen consisted of cyclophosphamide, fludarabine and low-dose total body irradiation. Post-transplant immunosuppression consisted of a single dose of cyclophosphamide 50 mg/kg on day 3, followed by oral tacrolimus and mycophenolate mofetil. Outcomes reported are overall survival, engraftment and chimerism, toxicity, and clinical outcome. All patients had neutrophil recovery (median 14.5 days), and 11 of 12 had platelet engraftment (median 17 days). Two patients had autologous reconstitution. Seven of nine assessable patients had complete donor chimerism. Four patients had grades II-III GvHD, and none had grade IV GvHD. Four patients developed limited stage chronic GvHD. Five patients with acute myeloid leukaemia relapsed. Two patients died of nonrelapse causes, both from other malignancies, and five patients remain alive and relapse free. Median overall survival was 324 days (range 88-1163). This regimen is feasible and well tolerated in older patients with high-risk leukaemia or lymphoma, with minimal short-term toxicity and low rates of GvHD. The proportion of disease-free survivors indicates a graft-versus-malignancy effect is present in survivors. © 2012 The Authors; Internal Medicine Journal © 2012 Royal Australasian College of Physicians.

  14. Intravenous Autologous Bone Marrow Mononuclear Cell Transplantation for Stroke: Phase1/2a Clinical Trial in a Homogeneous Group of Stroke Patients.

    Science.gov (United States)

    Taguchi, Akihiko; Sakai, Chiaki; Soma, Toshihiro; Kasahara, Yukiko; Stern, David M; Kajimoto, Katsufumi; Ihara, Masafumi; Daimon, Takashi; Yamahara, Kenichi; Doi, Kaori; Kohara, Nobuo; Nishimura, Hiroyuki; Matsuyama, Tomohiro; Naritomi, Hiroaki; Sakai, Nobuyuki; Nagatsuka, Kazuyuki

    2015-10-01

    The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke. Major inclusion criteria included patients with cerebral embolism, age 20-75 years, National Institute of Health Stroke Scale (NIHSS) score displaying improvement of ≤ 5 points during the first 7 days after stroke, and NIHSS score of ≥ 10 on day 7 after stroke. Bone marrow aspiration (25 or 50 mL; N = 6 patients in each case) was performed 7-10 days poststroke, and bone marrow mononuclear cells were administrated intravenously. Mean total transplanted cell numbers were 2.5 × 10(8) and 3.4 × 10(8) cells in the lower and higher dose groups, respectively. No apparent adverse effects of administering bone marrow cells were observed. Compared with the lower dose, patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes. Compared with 1 month after treatment, patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment. In comparison with historical controls, patients receiving cell therapy had significantly better neurologic outcomes. Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible. Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale randomized controlled trials using this approach.

  15. Stop waiting and start creating: service learning with an outpatient bone marrow transplant unit art cart program.

    Science.gov (United States)

    Fletcher, Tina; Bayer, Christina; Beyer, Emily; Gonzales, Jessica; Ralston, Ashley; Yount, Phyllis

    2013-01-01

    This paper examines how master of occupational therapy students, their occupational therapy instructor, and a community-based licensed clinical social worker collaborated in a service learning art cart program on an outpatient bone marrow transplant unit. As they progressed through the phases of Kolb's model of service learning, occupational therapy students, their occupational therapy instructor, and the licensed clinical social worker were all able to meet mutual goals of serving a unique patient population, increasing knowledge of best practices, and building and fostering university/community relationships.

  16. Intact survival of refractory CMV limbic encephalitis in a patient with severe aplastic anemia after unrelated bone marrow transplantation.

    Science.gov (United States)

    Tam, Dorothy Yuen Shan; Cheng, Frankie Wai Tsoi; Chan, Paul Kay Sheung; Leung, Wing Kwan; Lee, Vincent; Shing, Ming Kong; Cheung, Jo Lai Ken; Li, Chi Kong

    2012-08-01

    We described a patient of refractory cytomegalovirus (CMV) limbic encephalitis who received matched unrelated bone marrow transplantation. Pyrosequencing study on serial cerebrospinal fluid samples revealed the emergence of resistant strains associated with exposure of antiviral agents. Combinations of antiviral agents had a role in partial suppression of CMV viral load but the clearance of virus mainly relied on the recovery of host's immunity and resulted in intact survival of host. Donor's CMV-seronegative status may contribute to the delay in controlling this serious infection. Prompt identification of drug-resistant mutant helps in selection of antiviral agents.

  17. HLA-DP and bone marrow transplantation: DP-incompatibility and severe acute graft versus host disease

    DEFF Research Database (Denmark)

    Ødum, Niels; Platz, P; Jakobsen, B K

    1987-01-01

    Thirteen recipients of HLA-haploidentical, DR compatible bone marrow (BM) and the corresponding BM donors were HLA-DP typed using primed lymphocyte typing (PLT). Severe acute GVHD (greater than or equal to grade 2) developed within 3 months after BM-transplantation in all of eight recipients of DP...... in 88 recipients of HLA-identical BM (p less than 0.0001). In contrast, there was no difference in acute GVHD between recipients of haploidentical, DR and DP compatible BM and recipients of HLA-identical BM. The data presented here provide strong evidence for the first time that HLA-DP antigens play...

  18. G-CSF-primed autologous and allogeneic bone marrow for transplantation in clinical oncology. Cell content and immunological characteristics

    Science.gov (United States)

    Grivtsova, L. Yu; Melkova, K. N.; Kupryshkina, N. A.; Vorotnikov, I. K.; Grigoryeva, T. A.; Selchuk, V. Yu; Grebennikova, O. P.; Titova, G. V.; Tupitsyn, N. N.

    2018-01-01

    60 samples of G-CSF-primed bone marrow (39 cancer patients and 21 healthy donors) to be used for transplantation to cancer patients were analyzed and compared by main characteristics with historical control and 13 bone marrow samples from control patient with mastopathy. Basing on morphological and multicolor flow cytometry findings certain characteristics of G-CSF-primed bone marrow were discovered, such as a significant increase in blast count in cancer patients as compared to donors and control patients (p<0.037), a higher neutrophil maturation index (p<0.001) and a lower percentage of mature lymphocytes (p<0.008) as compared to the control group. Among lymphocyte populations G-CSF-priming was associated with a significant increase in the total of mature CD3+ T-cells and CD8+ T-killers (p<0.0001) and a decrease in CD56+CD3- and/or CD16+CD3- NK-cells (p<0.006) both in cancer patients and healthy donors in comparison with the controls.

  19. Autologous bone marrow stem cell transplantation for the treatment of ulcerative colitis complicated with herpes zoster: a case report.

    Science.gov (United States)

    Xiang, Hang; Zhang, Xiaomei; Yang, Chao; Xu, Wenhuan; Ge, Xin; Zhang, Rong; Qiu, Ya; Sun, Wanjun; Li, Fan; Xiang, Tianyuan; Chen, Haixu; Wang, Zheng; Zeng, Qiang

    2016-12-01

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease with continuous or recurrent symptoms. A 42-year-old male patient with intermittent diarrhea accompanied by bloody mucopurulent stools was admitted to our hospital. The diagnosis of UC was confirmed by a combination of laboratory examination, colonoscopy, and histological assay. The patient developed herpes zoster in the hospital, which challenged traditional treatments. Therefore, we performed an autologous bone marrow cells to modulate the immune system with his permission. Autologous bone marrow mononuclear cells were collected and injected locally into the bowel mucosa, and subsequently injected systemically through a peripheral vein. After the patient underwent auto bone marrow mononuclear cells transplantations twice, the patient's symptoms were alleviated. Furthermore, he recovered from hematochezia, and his hypersensitive C reactive protein decreased. Colonoscopy results showed reduced lesions and decreased areas with bleeding and edema in the sigmoid colon and rectum. No recurrence occurred in the subsequent two years, but long-time monitoring is still necessary for the prophylaxis of colorectal cancer.

  20. Impaired CD8(+) T cell immunity after allogeneic bone marrow transplantation leads to persistent and severe respiratory viral infection.

    Science.gov (United States)

    Gowdy, Kymberly M; Martinu, Tereza; Nugent, Julia L; Manzo, Nicholas D; Zhang, Helen L; Kelly, Francine L; Holtzman, Michael J; Palmer, Scott M

    2015-01-01

    Bone marrow transplant (BMT) recipients experience frequent and severe respiratory viral infections (RVIs). However, the immunological mechanisms predisposing to RVIs are uncertain. Therefore, we hypothesized that antiviral T cell immunity is impaired as a consequence of allogeneic BMT, independent of pharmacologic immunosuppression, and is responsible for increased susceptibility to RVI. Bone marrow and splenocytes from C57BL/6(H2(b)) mice were transplanted into B10.BR(H2(k)) (Allo) or C57BL/6(H2(b)) (Syn) recipients. Five weeks after transplantation, recipient mice were inoculated intranasally with mouse parainfluenza virus type 1 (mPIV-1), commonly known as Sendai virus (SeV), and monitored for relevant immunological and disease endpoints. Severe and persistent airway inflammation, epithelial injury, and enhanced mortality are found after viral infection in Allo mice but not in control Syn and non-transplanted mice. In addition, viral clearance is delayed in Allo mice as evidenced by prolonged detection of viral transcripts at Day 15 post-inoculation (p.i.) but not in control mice. In concert with these events, we also detected decreased levels of total and virus-specific CD8(+) T cells, as well as increased T cellexpression of inhibitory receptor programmed death-1 (PD-1), in the lungs of Allo mice at Day 8 p.i. Adoptive transfer of CD8(+) T cells from non-transplanted mice recovered from SeV infection into Allo mice at Day 8 p.i. restored normal levels of viral clearance, epithelial repair, and lung inflammation. Taken together these results indicate that allogeneic BMT results in more severe RVI based on the failure to develop an appropriate pulmonary CD8(+) T cell response, providing an important potential mechanism to target in improving outcomes of RVI after BMT. Published by Elsevier B.V.

  1. Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

    International Nuclear Information System (INIS)

    Reske, S.N.; Buchmann, I.; Seitz, U.; Glatting, G.; Neumaier, B.; Kotzerke, J.; Buck, A.; Martin, H.; Bergmann, L.

    2001-01-01

    Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates ( 188 Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2±2.1 (range 6.9-15.8) GBq 188 Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4±5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188 Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia. (orig.)

  2. The Basel experience with total body irradiation for conditioning patients with acute leukemia for allogenic bone marrow transplantation

    International Nuclear Information System (INIS)

    Speck, B.; Cornu, P.; Nissen, C.; Gratwohl, A.; Sartorius, J.

    1979-01-01

    We are reporting our experience with 13 patients suffering from end stage acute leukemia that were prepared for allogeneic bone marrow transplantation by combined chemotherapy followed by high dose cyclophosphamide (Cy) and total body irradiation (TBI). Only one patient became a long term survivor. Of the evaluable 12 patients, 6 died of interstitial pneumonia, 4 of GvH and 1 of recurrent leukemia. We conclude that adding combined chemotherapy to the standard conditioning program with Cy and TBI probably increases the risk of developing fatal interstitial pneumonia without eliminating the risk of recurrent leukemia. We suggest that allogenic marrow grafts should be performed earlier in the course of refractory acute leukemias, because in patients with end stage disease its chances of being curative are small

  3. Hematopoietic stem cell transplantation in childhood: report from the bone marrow transplantation group of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

    Science.gov (United States)

    Pession, A; Rondelli, R; Paolucci, P; Pastore, G; Dini, G; Bonetti, F; Madon, E; Mandelli, F; Zanesco, L; Uderzo, C; Prete, A; Rabusin, M; Ugazio, A; Di Bartolomeo, P; Favre, C; Bojd-Faulkner, L; Poggi, V; Luksch, R; Donfrancesco, A; Argiolu, F; La Nasa, G; Amici, A; Locatelli, F

    2000-06-01

    Transplantation of hematopoietic stem cells from different sources is being increasingly used to treat a variety of diseases in children. Transplant procedures and indications have changed considerably during recent years. Monitoring of information about these changes is useful for interpretation of nationwide collected data. Since 1985, Centers belonging to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica), performing hematopoietic stem cell transplants (HSCT) in children, and members of the AIEOP-Bone Marrow Transplant (BMT) Group annually report data on their transplant activity to the AIEOP-BMT Registry employing specially prepared patient-oriented forms. From January 1985 to December 1998, a total of 2,474 bone marrow (BM), peripheral blood (PB) or umbilical cord blood (CB) transplants were reported: 1,296 (52%) were allogeneic (Allo) and 1,178 (48%) autologous (Auto) transplants. These transplants were performed in 19 Italian Centers on 2,249 patients aged less than 17 years. Among Allo-transplants, 1,198 (92%) were performed using BM progenitor cells, whereas 49 (4%) CB, 42 (3%) were PB, 4 BM plus PB, and 3 BM plus CB allografts; they were performed using HLA-identical sibling donors in 867 cases (67%) and alternative donors (i.e. partially-matched relatives or unrelated donors) in the remaining 429 (33%) cases. Allogeneic transplants were performed on 786 (67%) patients with malignancy and on 395 (33%) patients with non-malignant disorders. In the last 6 years, the number of Allo-transplants per year exceeded that of Auto-transplants. Of the Auto-transplants, 775 (66%) were performed using BM, and 403 (34%) using PB alone or combined with BM hematopoietic stem cells. Indications for Auto-BMT were myelo-lymphoproliferative disorders in 524 (49%) cases, solid tumor in 533 (50%) cases and non-malignant disease in 11 (1%) cases. In the last 5 years, the use of PB for autografts has increased from 7% to 70%. These data reflect the development and

  4. Toxicities of total-body irradiation for pediatric bone marrow transplantation

    International Nuclear Information System (INIS)

    Chou, Rachel H.; Wong, Garrett B.; Kramer, Joel H.; Wara, Diane W.; Matthay, Katherine K.; Crittenden, Mary R.; Swift, Patrick S.; Cowan, Morton J.; Wara, William M.

    1996-01-01

    Purpose: To determine the acute and late effects, including cognitive function, of total body irradiation (TBI) and chemotherapy for bone marrow transplant (BMT) in children with immunodeficiency or hematologic disorders. Methods and Materials: At UCSF, 15 children with immunodeficiency disorders and 58 children with leukemia received chemoradiotherapy between July 1982 and November 1993 and were evaluated for toxicity. Patients with severe combined immunodeficiency disorder (SCID) received 7 Gy TBI while leukemia patients received 12 Gy TBI. Results: Eight immunodeficient patients (53%) are alive at 4 months to 11 years posttransplant. Acute toxicity was limited and treatment well tolerated. Most patients developed mild nausea and vomiting, skin rash, or erythema. Transient fever/chills, oral mucositis, and alopecia were noted in approximately 50% of patients. Seventy-three percent of patients demonstrated acute liver dysfunction, but only four (27%) developed veno-occlusive disease. All children had decreased growth velocity but normal growth hormone levels. Other endocrinologic evaluations including adrenocorticotropic hormone (ACTH), cortisol, and thyroid hormones were normal. Only one evaluable girl had delayed puberty with late onset of secondary sexual characteristics. Neuropsychological testing demonstrated an intelligence quotient (IQ) reduction between the baseline and 1 year post-BMT, with some recovery at 3 years. Only one patient developed a clinically significant cataract. Thirteen percent of patients had chronic interstitial lung disease. Four children developed exostosis. Only 1 of the 15 children developed a second malignancy (acute myelogenous leukemia) at age 5, 51 months posttransplant for SCID. For patients with leukemia, similar toxicities were observed. Twenty-nine percent disease-free survival was noted with a mean follow-up of 4.7 years. Twenty-two percent had chronic interstitial lung disease and two patients were diagnosed with cataracts

  5. Assessment of renal function in patients with hematologic malignancies undergoing bone marrow transplantation

    International Nuclear Information System (INIS)

    Estorch, M.; Tembl, A.; Camacho, V.; Sancho, G.; Mena, E.; Flotats, A.; Carrio, I.; Keller, A.; Miralbell, R.

    2002-01-01

    Patients with hematologic malignancies undergoing bone marrow transplantation (BMT) may develop renal insufficiency. Isotopic determinations of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) are established methods to evaluate renal function. Aim: To asses renal function changes of patients with hematologic malignancies undergoing BMT by measurements of GFR and ERPF using 51Cr-EDTA and 131I-OIH respectively. Methods: Seventy-one patients (mean age 41 years) were studied prospectively. All patients underwent BMT for hematologic malignancies and had previous normal renal function. Their conditioning included chemotherapy and 12 Gy or 13.5 Gy fractionated total body irradiation (TBI). Kidney shielding blocks fabricated after renal opacification with non-ionic, hypo-osmolar contrast medium were used in 21 patients to limit kidney dose to 10 Gy. GFR and ERPF were measured before conditioning and at 4, 12, and 18 months, using 51Cr-EDTA and 131I-OIH respectively. A decrease of 30% in GFR or ERPF, compared with baseline values, was used to define renal insufficiency. The potential influence of patient- and treatment-related variables on renal dysfunction was assessed. Results: At 4 (early) and 12-18 (late) months, a 30% GFR decrease was observed in 54% and 49% of patients, and a 30% ERPF decrease in 44% and 34% of patients, respectively. GFR decrease at 4 months significantly correlated with age (greatest decrease if <40 years), TBI using kidney blocks (kidney shielding to 10 Gy was associated with a higher rate of renal dysfunction at 4 months compared with full TBI dose), and days of treatment with aminoglycosides/vancomycin. ERPF decrease at 4 months was independently related with amphotericin and prostaglandin E1 (PGE1) treatments. GFR and ERPF decrease at 12-18 months correlated with amphotericin and PGE1 treatments. Conclusion: Early post-BMT renal dysfunction is associated with the administration of potentially nephrotoxic drugs. Younger

  6. An informative constitutional cytogenetic marker found in a patient post bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Zaslav, A.L.; Graziano, J.; Ebert, R. [Albert Einstein College of Medicine, New Hyde Park, NY (United States)] [and others

    1994-09-01

    It is cytogenetically difficult to distinguish between host and donor cells in allogeneic bone marrow transplantation (BMT) individuals of the same sex. Here we describe a patient with a cytogenetic marker found after BMT. A 7-month-old male presented with leukemia which was CD7+, CD33+, HLADR+, and CD4-, CD8-, indicating a diagnosis of acute stem cell leukemia (ASCL). Cytogenetic analysis revealed an abnormal clone in all of the cells analyzed: 46,XY,t(2;8)(p11.2;q24),inv(9)(p13p24). This translocation is associated with B-cell acute lymphoblastic leukemia (ALL); thus, it was possible for this patient to develop B-cell ALL. The abnormal clone persisted along with normal 46,XY cells, and evolved in several of seven additional analyses. The patient was treated with two courses of chemotherapy and failed to attain cytogenetic remission. While in relapse, the patient received a BMT from his 3-year-old brother. Two weeks later, a different translocation was seen in all cells: 46,XY,t(3;12)(p21;q21). This result could be interpreted in two ways: (1) the structural abnormality was indicative of a newly evolved clone related to the patient`s disease; or (2) the donor was a balanced translocation carrier. Cytogenetic analysis of peripheral blood from the donor revealed the same translocation seen in the patient. Parental blood chromosomes were normal indicating that the donor carried a de novo balanced translocation. Subsequent chromosome analysis of both peripheral blood and BM from the patient revealed the presence of the translocation in all cells. De novo balanced translocations are rare and occur with a frequency of 1/2,000 live borns. The family received genetic counseling and was informed of the possible reproductive risks to translocation carriers. This unusual finding will serve as a useful cytogenetic marker to assist in monitoring the patient`s clinical course, i.e., chimerism and remission status.

  7. Hydrodynamic delivery of human IL-15 cDNA increases murine natural killer cell recovery after syngeneic bone marrow transplantation.

    Science.gov (United States)

    Barao, Isabel; Alvarez, Maite; Redelman, Doug; Weiss, Jonathan M; Ortaldo, John R; Wiltrout, Robert H; Murphy, William J

    2011-12-01

    Immune deficiency immediately following bone marrow transplantation (BMT) increases susceptibility to opportunistic infections as well as tumor relapse. Natural Killer (NK) cells play important roles in the resistance to virally infected and transformed cells. Interleukin (IL)-15 has been shown to be essential for NK cell development and survival. We administered human (h) IL-15 cDNA (pIL-15) via hydrodynamic delivery to murine recipients undergoing congenic BMT to determine its effects on NK cell reconstitution. Hydrodynamic pIL-15 delivery resulted in high levels of hIL-15 protein in the serum that lasted for several days and then quickly declined. The appearance of hIL-15 was followed by a significant increase of mature donor-derived NK cells within the bone marrow, spleens, and livers of the treated recipients. No accumulation of immature NK cell progenitors was observed. The NK cells from IL-15-treated recipients displayed an activated phenotype and were lytically active toward tumor targets in vitro to a similar degree as did those cells from recipients treated with control plasmid. This suggests that the predominant effect of IL-15 was a quantitative increase in total NK cell numbers and not qualitative changes in NK cell functions. No toxicities or adverse effects were observed. Studies performed in transplanted mice bearing renal carcinoma tumors demonstrated that this mode of hIL-15 gene delivery resulted in increased antitumor responses. These results support the use of cytokine gene transfer-based regimens as a platform to augment NK cell recovery after BMT. Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Biological significance of HLA locus matching in unrelated donor bone marrow transplantation

    Science.gov (United States)

    Kashiwase, Koichi; Matsuo, Keitaro; Azuma, Fumihiro; Morishima, Satoko; Onizuka, Makoto; Yabe, Toshio; Murata, Makoto; Doki, Noriko; Eto, Tetsuya; Mori, Takehiko; Miyamura, Koichi; Sao, Hiroshi; Ichinohe, Tatsuo; Saji, Hiroo; Kato, Shunichi; Atsuta, Yoshiko; Kawa, Keisei; Kodera, Yoshihisa; Sasazuki, Takehiko

    2015-01-01

    We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell–replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection. PMID:25519752

  9. High-dose therapy followed by autologous bone marrow transplantation (ABMT) in previously untreated non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Tura, S.; Mazza, P.; Gherlinzoni, F. and others

    1986-01-01

    13 previously untreated patients with poor prognosis non-Hodgkin's lymphoma (NHL) underwent high-dose therapy followed by autologous bone marrow transplantation (ABMT). All patients experienced a great cytoreductive effect and 9 of them reached a complete remission (mean duration 32 months). The best results were observed in patients with more limited disease and in those without symptoms. 7 patients still remain in complete unmaintained remission 15-46 months from the transplant. The probability of survival is 74% at 46 months. No therapy-related deaths were recorded. In differentiating our preliminary approach, we propose high dose therapy followed by ABMT as induction phase in patients with stage II and as consolidation after first line therapy in patients with stages III-IV. Further studies are warranted to determine which type of lymphoma may benefit more and which conditioning regimens may improve the remission rate.

  10. Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice

    DEFF Research Database (Denmark)

    Niemeyer, P; Vohrer, J; Schmal, H

    2008-01-01

    INTRODUCTION: Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose...... of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice. METHODS: Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were...... osteogenic-induced MSC (group B) could be detected in only three of 24 cases. Quantification of lymphocytes and macrophages revealed significantly higher cell numbers in group B compared with group A (Pcell...

  11. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

    Science.gov (United States)

    Jang, Dong-Kyu; Park, Sang-In; Han, Young-Min; Jang, Kyung-Sool; Park, Moon-Seo; Chung, Young-An; Kim, Min-Wook; Maeng, Lee-So; Huh, Pil-Woo; Yoo, Do-Sung; Jung, Seong-Whan

    2011-01-01

    This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (P < .05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway. PMID:21772790

  12. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

    Directory of Open Access Journals (Sweden)

    Dong-Kyu Jang

    2011-01-01

    Full Text Available This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (<.05. MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway.

  13. Treadmill exercise with bone marrow stromal cells transplantation potentiates recovery of locomotor function after spinal cord injury in rats.

    Science.gov (United States)

    Kim, You-Mi; Seo, Tae-Beom; Kim, Chang-Ju; Ji, Eun-Sang

    2017-06-01

    Transplantation of bone marrow stromal cells (BMSCs) is regarded as a promising candidate for the spinal cord injury (SCI). In the present study, we investigated whether treadmill exercise potentiate the effect of BM-SCs transplantation on the functional recovery in the SCI rats. The spinal cord contusion injury applied at the T9-T10 level using the impactor. Cultured BMSCs were transplanted into the lesion at 1 week after SCI induction. Treadmill exercise was conducted for 6 weeks. Basso-Beattie-Bresnahan (BBB) scale for locomotor function was determined. Sprouting axons in the lesion cavity were detected by immunofluorescence staining for neurofilament-200. Brain-derived neurotrophic factor (BDNF) and synapsin-I expressions were analyzed using western blotting. BMSCs transplantation improved BBB score and increased expressions of neurofilament-200, BDNF, and synapsin-I in the SCI rats. Treadmill exercise potentiated the improving effect of BMSCs transplantation on BBB score in the SCI rats. This potentiating effect of treadmill exercise could be ascribed to the enhancement of BDNF expression in the SCI rats.

  14. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury.

    Science.gov (United States)

    Dai, Guanghui; Liu, Xuebin; Zhang, Zan; Yang, Zhijun; Dai, Yiwu; Xu, Ruxiang

    2013-10-02

    Neuronal injuries have been a challenging problem for treatment, especially in the case of complete and chronic cervical spinal cord injury (SCI). Recently, particular attention is paid to the potential of stem cell in treating SCI, but there are only few clinical studies and insufficient data. This study explored the efficacy of autologous bone marrow mesenchymal stem cells (BMMSCs) transplantation in the treatment of SCI. Forty patients with complete and chronic cervical SCI were selected and randomly assigned to one of the two experimental groups, treatment group and control group. The treatment group received BMMSCs transplantation to the area surrounding injury, while the control group was not treated with any cell transplantation. Both the transplant recipients and the control group were followed up to 6 months, postoperatively. Preoperative and postoperative neurological functions were evaluated with AIS grading, ASIA score, residual urine volume and neurophysiological examination. Results showed that in the treatment group 10 patients had a significant clinical improvement in terms of motor, light touch, pin prick sensory and residual urine volume, while nine patients showed changes in AIS grade. Neurophysiological examination was consistent with clinical observations. No sign of tumor was evident until 6 months postoperatively. In the control group, no improvement was observed in any of the neurological functions specified above. BMMSCs transplantation improves neurological function in patients with complete and chronic cervical SCI, providing valuable information on applications of BMMSCs for the treatment of SCI. © 2013 Published by Elsevier B.V.

  15. No evidence of transfusion transmission of Adenovirus and Epstein-Barr virus infections in paediatric recipients post-bone marrow transplant.

    Science.gov (United States)

    Patel, P; Tuke, P; Tettmar, K; Cloutman-Green, E; Hartley, J; Klein, N; Veys, P; Tedder, R S

    2015-07-01

    Adenovirus and Epstein-Barr virus can cause significant morbidity and mortality in paediatric patients post-bone marrow transplant. The source of infection is thought to be either reactivation of latent viruses or primary infection. We have investigated whether transfusion of blood components from viraemic donors could provide a route of primary infection in these patients and sought the prevalence of viraemia in the blood donor population from England. In 32 linked donor/recipient samples and 300 unselected blood donors, we found no evidence to suggest that these infections in paediatric bone marrow transplant recipients had been acquired from transfused blood components. © 2015 International Society of Blood Transfusion.

  16. Intraventricular Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells via Ommaya Reservoir in Persistent Vegetative State Patients after Haemorrhagic Stroke: Report of Two Cases & Review of the Literature.

    Science.gov (United States)

    Fauzi, Asra Al; Suroto, Nur Setiawan; Bajamal, Abdul Hafid; Machfoed, Moh Hasan

    2016-01-01

    Background: One of the most devastating diseases, stroke, is a leading cause of death and disability worldwide with severe emotional and economic consequences. The purpose of this article is mainly to report the effect of intraventricular transplantation via an Ommaya reservoir using autologous bone marrow mesenchymal stem cells (BM-MSCs) in haemorrhagic stroke patients. Case Presentations: Two patients, aged 51 and 52, bearing sequels of haemorrhagic stroke were managed by intraventricular transplantation of BM-MSCs obtained from their own bone marrow. Before the procedure, both patients were bedridden, tracheostomised, on nasogastric (NG) tube feeding and in hemiparesis. The cells were transplanted intraventricularly (20 x 10 6 cells/2.5 ml) using an Ommaya reservoir, and then repeated transplantations were done after 1 and 2 months consecutively. The safety and efficacy of the procedures were evaluated 3, 6 and 12 months after treatment. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the patients' neurological status before and after treatment. No adverse events derived from the procedures or transplants were observed in the one-year follow-up period, and the neurological status of both patients improved after treatment. Conclusions: Our report demonstrates that the intraventricular transplantation of BM-MSCs via an Ommaya reservoir is safe and it improves the neurological status of post-haemorrhagic stroke patients. The repeated transplantation procedure is easier and safer to perform via a subcutaneously implanted Ommaya reservoir. Key Words: Haemorrhagic stroke, bone marrow mesenchymal stem cells (BM-MSCs), intraventricular transplantation.

  17. PCR-positivity in harvested bone marrow predicts relapse after transplantation with autologous purged bone marrow in children in second remission of precursor B-cell acute leukaemia

    NARCIS (Netherlands)

    Vervoordeldonk, S. F.; Merle, P. A.; Behrendt, H.; Steenbergen, E. J.; van den Berg, H.; van Wering, E. R.; von dem Borne, A. E.; van der Schoot, C. E.; van Leeuwen, E. F.; Slaper-Cortenbach, I. C.

    1997-01-01

    Purging of autologous bone marrow (BM) grafts of children in second remission after a relapse of precursor B acute lymphoblastic leukaemia (ALL) in the BM has been carried out in our laboratory since 1987, initially by complement mediated cell lysis. This protocol was extended by performing an

  18. Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

    OpenAIRE

    Babaei, Parvin; Soltani Tehrani, Bahram; Alizadeh, Arsalan

    2012-01-01

    The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs) grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months) were tested in Morris water maze (MWM) and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells ( 5 0 0 × 1 0 3 / ...

  19. [Our first experiences with autologous transplantation of bone marrow stem cells to treat pseudarthrosis, delayed fracture healing and long bone defects fracture].

    Science.gov (United States)

    Sír, M; Procházka, V; Gumulec, J; Pleva, L

    2009-03-01

    Traumatology and orthopaedics have undergone substantial progress in the use of new, sophisticated techniques, implants and navigation methods. Nevertheless, these new methods continue to fail in some instances. Regenerative medicine using the growth potential of stem cells that posses the ability to regenerate damaged tissues represent one of the possible ways forward. There is a potential for more comprehensive utilization of bone marrow stem cells that had for many years been used in transplant medicine. Traumatology and orthopaedics could utilise stem cells in the treatment of bone defects, i.e. in the treatment of pseudarthrosis, delayed fracture healing, defect fractures and aseptic bone necroses. Bone formation and growth is a complex, predominantly anabolic, process with a range of feedbacks. Nevertheless, it is the bone marrow where the necessary progenitors of bone growth are located. These are mesenchymal stem cells (MSCs), haematopoietic stem cells (HSCs) as well as thrombocytes containing a range of necessary growth factors. A number of studies showed positive results for stem cells treatment of pseudarthrosis, with only a fraction, however, being statistically significant in human medicine. This method was used in 11 patients of the Traumatology Centre of the Faculty Hospital in Ostrava, Czech Republic in 2008. The researched patients were treated for pseudarthrosis of long bones, delayed multifragmentary fracture haling and defect fractures of long bones. Autologous concentrate of bone marrow stem cells was applied in one session into the area of bone defect in a patient lightly anaesthetised with propofol. The results from this small sample of patients are not yet available. However, we are sharing our first experiences with this treatment option.

  20. Regenerative treatment in osteochondral lesions of the talus: autologous chondrocyte implantation versus one-step bone marrow derived cells transplantation.

    Science.gov (United States)

    Buda, Roberto; Vannini, Francesca; Castagnini, Francesco; Cavallo, Marco; Ruffilli, Alberto; Ramponi, Laura; Pagliazzi, Gherardo; Giannini, Sandro

    2015-05-01

    Osteochondral lesions of the talus (OLT) usually require surgical treatment. Regenerative techniques for hyaline cartilage restoration, like autologous chondrocytes implantation (ACI) or bone marrow derived cells transplantation (BMDCT), should be preferred. The aim of this work is comparing two clusters with OLT, treated with ACI or BMDCT. Eighty patients were treated with regenerative techniques, 40 with ACI and 40 with BMDCT. The two groups were homogenous regarding age, lesion size and depth, previous surgeries, etiology of the lesion, subchondral bone graft, final follow-up and pre-operative AOFAS score. The two procedures were performed arthroscopically. The scaffold was a hyaluronic acid membrane in all the cases, loaded with previously cultured chondrocytes (ACI) or with bone marrow concentrated cells, harvested in the same surgical session (BMDCT). All the patients were clinically and radiologically evaluated, using MRI Mocart score and T2 mapping sequence. Clinical results were similar in both groups at 48 months. No statistically significant influence was reported after evaluation of all the pre-operative parameters. The rate of return to sport activity showed slightly better results for BMDCT than ACI. MRI Mocart score was similar in both groups. MRI T2 mapping evaluation highlighted a higher presence of hyaline like values in the BMDCT group, and lower incidence of fibrocartilage as well. To date, ACI and BMDCT showed to be effective regenerative techniques for the treatment of OLT. BMDCT could be preferred over ACI for the single step procedure, patients' discomfort and lower costs.

  1. Hematologic recovery in patients who are treated with autologous stem cells transplantation taken from bone marrow after granulocyte-colony-stimulating factor stimulation.

    Science.gov (United States)

    Gawronski, K; Rzepecki, P; Oborska, S; Wasko-Grabowska, A

    2011-10-01

    We sought to compare hematologic recovery between patients who did or did not receive granulocyte-colony-stimulating factor (G-CSF)-stimulated bone marrow (rich bone marrow [RBM]). The study subjects were 20 patients whose bone marrow was taken without prior stimulation with G-CSF and 15 patients in whom bone marrow was taken after previous G-CSF mobilization. The bone marrow harvest took place on the fifth day after G-CSF initiation. The bone marrow aliquot was 20 mL/kg. The median value of nucleated cells obtained from patients without G-CSF preparation was 3.65×10(8)/kg. The median value of nucleated cells from RBM patients was 4.83×10(8)/kg. The median value of stem cells obtained from patients without G-CSF preparation was 0.96×10(6)/kg versus 1.9×10(6)/kg from RBM patients. The median time to recovery of the hematopoietic system based on an increase in PLT value>20 g/L was 12.6 days for RBM versus 18.8 days without G-CSF preparation. The median time to recovery of the hematopoietic system based on assessment of growth ANC>0.5 g/L was 13.0 days for RBM versus 17.8 days without G-CSF stimulation. Significantly higher values of nucleated cells and increased stem cells were observed among RBM patients compared with those whose bone marrow was harvested without any stimulation (P=.01). There was faster recovery of the hematopoietic system in cases where bone marrow was collected after G-CSF: PLT>20 g/L (P=.015) and ANC>0.5 g/L (P=.01). We also observed that the use of stimulated bone marrow shortened hospital stay after the administration of hematopoietic cells to 17.3 days compared with 23.1 days among patients receiving hematopoietic cells from nonstimulated bone marrow. The number of complications during transplantation was comparable in both cases, the most frequent ones being febrile neutropenia and grade III and IV mucositis. RBM is a better method to obtain stem cells from bone marrow. Stimulated bone marrow shows faster engraftment compared with

  2. B cell dysfunction after bone marrow transplantation is associated with decreased Ca2+ flux upon membrane Ig crosslinking.

    Science.gov (United States)

    Storek, J; Hultin, L E; Ferrara, S; Ku, N; Giorgi, J V; Champlin, R E; Saxon, A

    1994-08-01

    Patients undergoing bone marrow transplantation have a long-lasting defect of B cell-mediated immunity. Both quantitative (decreased blood B cell counts) and qualitative (decreased Ig production) abnormalities of B cells have been described. To better understand the mechanism of the qualitative defect and its potential relation to B cell immaturity, we studied the in vitro responsiveness of B cells to polyclonal stimuli in patients at 2-12 months post-transplant and in normal neonates. Several key steps of the B cell program were deficient in the patients while they were relatively normal in the neonates. These included (i) early activation as assessed by Ca2+ flux; (ii) late activation as assessed by the increase in cell size and upregulation of the activation antigens CD25 and CD71; and (iii) proliferation as assessed by the number of cycling cells after stimulation. We conclude that the functional B cell defect during the early (< 1 year) post-transplant period extends back to the level of early activation and cannot be simply attributed to the relative immaturity of post-transplant B cells.

  3. Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Parvin Babaei

    2012-01-01

    Full Text Available The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months were tested in Morris water maze (MWM and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500×103/ and PBS (phosphate buffer saline. In the second experiment, Ibotenic acid (Ibo was injected bilaterally into the nucleus basalis magnocellularis (NBM of young rats (3 months and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500×103/ and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

  4. Pulmonary complications of bone marrow transplantation: a comparison of total body irradiation and cyclophosphamide to busulfan and cyclophosphamide

    International Nuclear Information System (INIS)

    Hartsell, William F.; Czyzewski, E. Ann; Ghalie, Richard; Kaizer, Herbert

    1995-01-01

    Purpose: To retrospectively compare the acute and long-term pulmonary toxicities of total body irradiation and busulfan in bone marrow transplantation. Methods and Materials: From March 1984 through February 1991, 144 patients received high-dose therapy with cyclophosphamide plus either total body irradiation (TBI-CY) or busulfan (BU-CY) followed by bone marrow rescue. Treatment protocols were based on disease type. Cyclophosphamide dose was 120-200 mg/kg, given in 2-4 days. Total body irradiation was given as 12 Gy in four fractions over 4 days, or 14.4 Gy in eight fractions over 4 days. Busulfan dose was 16 mg/kg given over 4 days. Results: Seventy-nine patients were treated with TBI-CY and 65 patients with BU-CY. More patients in the TBI group had allogeneic transplants (40 vs. 18). Pulmonary events occurred in 48 patients, 19 in BU-CY and 29 in TBI-CY. Of the 58 patients with allogeneic transplants, 21 (36%) developed chronic graft-vs.-host disease (GVHD), and 10 of those patients developed pulmonary complications (including 2 with obliterative bronchitis and 1 with asthma). Interstitial pneumonitis (IP) occurred in 14 patients, 12 in the TBI-CY group and 2 in the BU-CY group. Cytomegalovirus and pneumocystis infections were associated with IP in 11 of those patients. Fatal idiopathic IP occurred in one patient in each of the TBI-CY and BU-CY groups. Multivariate analysis showed that only chronic GVHD and prior bleomycin use were significant predictors of interstitial pneumonitis; no difference was seen between TBI-CY and BU-CY. Conclusions: Pulmonary complications were most commonly associated with GVHD and prior bleomycin use. The incidence of cytomegalovirus or pneumocystis carinii pneumonitis was greater in the patients receiving the TBI regimen; fatal pulmonary complications were not significantly different between TBI and nonTBI regimens

  5. Bone marrow biopsy

    Science.gov (United States)

    ... test is used to diagnose leukemia, infections, some types of anemia, and other blood disorders. It may also be ... the bone marrow contains the proper number and types of blood-forming (hematopoietic) cells, fat cells, and connective tissues.

  6. Cost analysis and quality of life assessment comparing patients undergoing autologous peripheral blood stem cell transplantation or autologous bone marrow transplantation for refractory or relapsed non-Hodgkin's lymphoma or Hodgkin's disease : a prospective randomised trial

    NARCIS (Netherlands)

    van Agthoven, M; Vellenga, E; Fibbe, WE; Kingma, T; Uyl-de Groot, CA

    The cost-effectiveness of autologous peripheral blood stem cell transplantation (PBSCT) compared with autologous bone marrow transplantation (ABMT) for refractory or relapsed non-Hodgkin's lymphoma (NHL) or Morbus Hodgkin (MH) was assessed. Costs were determined from the induction chemotherapy

  7. Salvage bone marrow harvest in patients failing plerixafor-based stem cell mobilization attempt: feasibility and autologous transplantation outcomes.

    Science.gov (United States)

    Kanate, Abraham S; Watkins, Kathy; Cumpston, Aaron; Craig, Michael; Hamadani, Mehdi

    2013-07-01

    Inadequate mobilization of peripheral blood progenitor cells (PBPC) is sometimes a limiting factor to proceed with an autologous hematopoietic cell transplantation (auto-HCT), in an otherwise eligible patient. In such situations, a bone marrow harvest (BMH) procedure may be considered to achieve the CD34+ target dose for an autograft. Plerixafor-based mobilization has recently been shown to improve PBPC collection yields. However, the feasibility and outcomes of BMH in patients failing plerixafor-based mobilization is not known. We report here, 6 patients who underwent BMH after PBPC mobilization failure with plerixafor. The median CD34+ yield with plerixafor mobilization and BMH were 1.15 x 10^6/Kg (range, 0.2-1.7 × 10^6/Kg) and 0.32 (range, 0.12-0.38 × 10^6/Kg), respectively. Three patients proceeded to an auto-HCT, with only 1 patient receiving CD34+ cell dose of at least 2 × 10^6/Kg. While neutrophil recovery was seen, platelet recovery and red cell transfusion independence were delayed. All 3 autografted patients experienced disease progression by day +100. These data suggest, limited incremental benefit of a salvage BMH after plerixafor mobilization failure, cautioning against routine use of this strategy. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Platz, P

    1985-01-01

    Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+-enriched lymphocyte suspensions retain approximately 50...

  9. Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34(+) bone marrow cells, following gamma irradiation in cynomolgus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Derdouch, S.; Gay, W.; Prost, S.; Le Dantec, M.; Delache, B.; Auregan, G.; Andrieu, T.; Le Grand, R. [CEA, DSV, Serv Immunovirol, Inst Maladies Emergentes et Therapies Innovantes, Fontenay Aux Roses (France); Derdouch, S.; Gay, W.; Prost, S.; Le Dantec, M.; Delache, B.; Auregan, G.; Andrieu, T.; Le Grand, R. [Univ Paris 11, UMR E01, Orsay (France); Negre, D.; Cosset, F. [Univ Lyon, UCB Lyon 1, IFR 128, F-69007 Lyon (France); Negre, D.; Cosset, F. [INSERM, U758, F-69007 Lyon (France); Negre, D.; Cosset, F.L. [Ecole NormaleSuper Lyon, F-69007 Lyon (France); Leplat, J.J. [CEA, DSV, IRCM, SREIT, Lab Radiobiol, F-78352 Jouy En Josas (France); Leplat, J.J. [CEA, DSV, IRCM, SREIT, Etude Genome, F-78352 Jouy En Josas (France); Leplat, J.J. [INRA, DGA, Radiobiol Lab, F-78352 Jouy En Josas (France); Leplat, J.J. [INRA, DGA, Etude Genome, F-78352 Jouy En Josas (France)

    2008-07-01

    Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myelo-ablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34{sup +} bone marrow cells following gamma irradiation in cynomolgus macaques. The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% {+-} 4%. The vector used was derived from the simian immunodeficiency lentivirus SIVmac251, VSV-g pseudo-typed and encoded eGFP under the control of the phosphoglycerate kinase promoter. After myeloid differentiation, GFP was detected in colony-forming cells (37% {+-} 10%). A previous study showed that transduction rates did not differ significantly between colony-forming cells and immature cells capable of initiating long-term cultures, indicating that progenitor cells and highly immature hematopoietic cells were transduced with similar efficiency. Blood cells producing eGFP were detected as early as three days after transplantation,and eGFP-producing granulocyte and mononuclear cells persisted for more than one year in the periphery. Conclusion: The transplantation of CD34{sup +} bone marrow cells had beneficial effects for the ex vivo proliferation and differentiation of hematopoietic progenitors, favoring reconstitution of the T-and B-lymphocyte, thrombocyte and red blood cell compartments. (authors)

  10. THE EFFECT OF DONOR LYMPHOCYTES-T AND TOTAL-BODY IRRADIATION ON HEMATOPOIETIC ENGRAFTMENT AND PULMONARY TOXICITY FOLLOWING EXPERIMENTAL ALLOGENEIC BONE-MARROW TRANSPLANTATION

    NARCIS (Netherlands)

    DOWN, JD; MAUCH, P; WARHOL, M; NEBEN, S; FERRARA, JLM

    1992-01-01

    To study the effects of donor T lymphocytes on engraftment and graft-versus-host disease in relation to recipient total-body irradiation, we have returned small numbers of T cells to T-cell-depleted bone marrow transplanted across a minor histocompatibility barrier in mice (B10.BR --> CBA).

  11. Successful treatment with chemotherapy and subsequent allogeneic bone marrow transplantation for myeloid blastic crisis of chronic myelogenous leukemia following advanced Hodgkin's disease

    NARCIS (Netherlands)

    Punt, C. J.; Rozenberg-Arska, M.; Verdonck, L. F.

    1987-01-01

    A 33-year-old man was treated with intensive chemotherapy for myeloid blastic crisis of chronic myelogenous leukemia (CML), which developed after radiotherapy and chemotherapy for Hodgkin's disease. After achieving a second chronic phase, he underwent allogeneic bone marrow transplantation (BMT).

  12. Bone marrow stromal cells elicit tissue sparing after acute but not delayed transplantation into the contused adult rat thoracic spinal cord.

    NARCIS (Netherlands)

    Tewarie, R.D.; Hurtado, A.; Ritfeld, G.J.; Rahiem, S.T.; Wendell, D.F.; Barroso, M.M.; Grotenhuis, J.A.; Oudega, M.

    2009-01-01

    Bone marrow stromal cells (BMSC) transplanted into the contused spinal cord may support repair by improving tissue sparing. We injected allogeneic BMSC into the moderately contused adult rat thoracic spinal cord at 15 min (acute) and at 3, 7, and 21 days (delayed) post-injury and quantified tissue

  13. Early relapse of Burkitt lymphoma heralded by a bone marrow necrosis and numb chin syndrome successfully treated with allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Jan Cerny

    2014-01-01

    Full Text Available The optimal salvage therapy for patients with relapsed Burkitt lymphoma is unknown. Bone marrow necrosis is an underreported (2 years after the transplant. To our knowledge, this is the longest reported survival of the two syndromes in the setting of BL relapse.

  14. Monitoring of residual disease and guided donor leucocyte infusion after allogeneic bone marrow transplantation by chimaerism analysis with short tandem repeats

    NARCIS (Netherlands)

    de Weger, RA; Tilanus, MGJ; Scheidel, KC; van den Tweel, JG; Verdonck, LF

    In this study, we analysed the chimaeric status of peripheral blood leucocytes (PBLs) in recipients of allogeneic bone marrow transplantation (BMT) with the use of short tandem repeat (STR) microsatellite markers for monitoring the efficacy of BMT and donor leucocyte infusions (DLIs). A set of four

  15. Bone marrow transplantation has a significant effect on enzyme levels and storage of glycosaminoglycans in tissues and in isolated hepatocytes of mucopolysaccharidosis type VII mice

    NARCIS (Netherlands)

    Poorthuis, B. J.; Romme, A. E.; Willemsen, R.; Wagemaker, G.

    1994-01-01

    The effect of bone marrow transplantation (BMT) on enzyme and glycosaminoglycan levels of various tissues and isolated parenchymal cells of lethally irradiated gusmps/gusmps mice was studied. These mice have an inherited deficiency of the lysosomal enzyme beta-glucuronidase with less than 1% of

  16. Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation

    DEFF Research Database (Denmark)

    Vangsted, Annette; Gimsing, Peter; Klausen, Tobias W

    2007-01-01

    ) of polymorphism in the DNA repair genes ERCC1, ERCC2 and XRCC3, and in the apoptotic genes PPP1R13L and CD3EAP in 348 patients with multiple myeloma undergoing autologous bone marrow transplantation. Carriers of the variant C-allele of ERCC2 K751Q, the variant T-allele of XRCC3 T241M and the variant A...... the outcome for patients treated with autologous stem cell transplantation Udgivelsesdato: 2007-Mar-1...

  17. Intestinal amoebiasis in a patient with acute graft-versus-host disease after allogeneic bone marrow transplantation successfully treated by metronidazole.

    Science.gov (United States)

    Numata, A; Itabashi, M; Kishimoto, K; Motohashi, K; Hagihara, M; Kuwabara, H; Tanaka, M; Kato, H; Chiba, S; Kunisaki, R; Fujisawa, S

    2015-12-01

    Amoebiasis has rarely been reported in patients undergoing hematopoietic stem cell transplantation, although it is a world-wide infection and extremely common. We present a case of intestinal amoebiasis unexpectedly revealed by colonoscopy after allogeneic bone marrow transplantation from a human leukocyte antigen-mismatched unrelated donor for acute myeloid leukemia arising from chronic myelomonocytic leukemia and successfully treated by metronidazole. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Reduction and repopulation of recipient T4+ and T8+ T-lymphocytes in allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Gratama, J.W.; van den Bergh, R.L.; Naipal, A.; D'Amaro, J.; Zwaan, F.E.; Jansen, J.; de Gast, G.C.

    1986-01-01

    In eight recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repopulation of T4+ and T8+ T-lymphocytes of recipient origin were studied. The origin of the donor-recipient T4+ and T8+ T cells was studied using quinacrine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of five (range 1-8) days after BMT. T8+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells that appeared in the circulation at day 12 were predominantly T4+, and a large number of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection

  19. [Information and consent forms for hematopoietic stem cell transplantation donors and recipients: Guidelines from the Franchophone society of bone marrow transplantation and cellular therapy (SFGM-TC)].

    Science.gov (United States)

    Bruno, Bénédicte; Thibert, Jean-Baptiste; Bancillon, Nelly; Desbos, Anna; Fawaz, Abir; Fournier, Isabelle; Genty, Carole; Issarni, Dominique; Leveille, Sandrine; Premel, Christelle; Polomeni, Alice; Renault, Myriam; Tarillon, Sylvie; Wallart, Anne; Yakoub-Agha, Ibrahim; Bordessoule, Dominique

    2016-11-01

    Within the context of the SFGM-TC's 6th workshop series on the harmonization of clinical practices, our workshop proposes a standardization of the informed consent process for hematopoietic stem cell donors and recipients leading up to an autologous or allogenic transplantation. All informed consent was for bone marrow or peripheral stem cell donors, and mononuclear/lymphocyte donors according to usual procedures. The informed consent for autologous and allogenic related or unrelated adults and pediatric transplantation patients have been included. A first step has been conducted for collecting in advance the informed consent forms used routinely in all francophone transplantation centers. In a second step, a comprehensive version has been re-written by a multidisciplinary team. For the purposes of understanding the risks and advantages, language has been carefully considered and streamlined. In the third step, texts were sent to stem cell transplantation experts, experts at the French biomedical agency (agence de la biomédecine [ABM]), law specialists, members of the ethical committee of the French society of hematology and several transplant recipients to be edited and proofread. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  20. Cerebral Magnetic Resonance Spectroscopy Demonstrates Long-Term Effect of Bone Marrow Transplantation in α-Mannosidosis

    DEFF Research Database (Denmark)

    Danielsen, Else R; Lund, Allan M; Thomsen, Carsten

    2013-01-01

    α-Mannosidosis, OMIM #248500, is an autosomal recessive lysosomal storage disease caused by acidic α-mannosidase deficiency. Treatment options include bone marrow transplantation (BMT) and, possibly in the future, enzyme replacement therapy. Brain magnetic resonance spectroscopy (MRS) enables non......-invasive monitoring of cerebral treatment effect. Accumulated cerebral mannose-containing oligosaccharides were demonstrated by MRS in a patient who at age 2 years and 11 months received a BMT from a haploidentical non-carrier sibling. The cerebral mannose-containing oligosaccharides had disappeared as early as 9......½ months after BMT. MRS furthermore demonstrated the persistent treatment effect at regular intervals up to 5½ years after BMT. MRS is a non-invasive tool that can demonstrate the effect of BMT treatment. Likewise, MRS may be used to demonstrate the cerebral effect of other potential treatments...

  1. The relationship between hemolytic-uremic syndrome and radiotherapy in patients with neuroblastoma after bone marrow transplant

    Energy Technology Data Exchange (ETDEWEB)

    Mugishima, Hideo; Shimada, Toshiaki; Suzuki, Takashi (Nihon Univ., Tokyo (Japan). School of Medicine) (and others)

    1994-06-01

    Having identified hemolytic uremic syndrome (HUS) developed in patients with neuroblastoma (NB) after autologous bone marrow transplant (A-BMT), we discussed the relationship between HUS and radiotherapy in addition to the prophylaxis of HUS. Five of 30 (17%) patients developed HUS within 4.5 months post A-BMT. The prognosis of these patients have various course ranging from those patients recovered by conventional therapy to the ones died of renal failure. All patients developed HUS received CDDP and total body irradiation (TBI) for preconditioning regimen, however no patients whose kidney were shielded from TBI developed this syndrome. The difference between the two proves to be statistically significant (p=0.0008). It is postulated that TBI be the most important factor causing HUS. It would be crucial to shield the kidney from TBI to prevent development of HUS. (author).

  2. Screening for Y Chromosome Microdeletion in a Nonobstructive Azoospermic Male Patient with Allogeneic Bone Marrow Transplantation from His Sister

    Directory of Open Access Journals (Sweden)

    Hakan Gurkan

    2010-01-01

    Full Text Available Genomic DNA of a patient diagnosed with nonobstructive azoospermia and with the history of allogenic bone marrow transplantation from his sister due to chronic myeloid leukemia was isolated from peripheral blood in order to screen Y chromosome microdeletions. 13 short tagged sites belonging to AZF a, b, and c loci were detected with multiplex polymerase chain reaction technique. Bands were determined in ZFX/ZFY wells, whereas no bands were determined in wells of other STS regions. DNA isolation was done from buccal mucosa smear to obtain genomic DNA from patient's own cells and multiplex polymerase chain reaction technique was performed again. Bands were seen in all wells of 13 STS regions. Y chromosome microdeletion was not detected in the patient. In conclusion, genomic DNA isolation in patients undergoing BMT should be done from patients' own cells.

  3. Total body irradiation for allogeneic bone marrow transplantation in acute leukemia: A cooperative study from the TBI Subcommittee in Japan

    International Nuclear Information System (INIS)

    Inoue, T.; Masaoka, T.; Shibata, H.

    1986-01-01

    By means of national survey, records of 78 acute leukemia patients who underwent allogeneic bone marrow transplantation (BMT) from September 1975 through September 1983 were collected from 14 participating institutions in Total Body Irradiation (TBI) Subcommittee in Japan. Patients were classified into 37 of acute lymphocytic leukemia (ALL), and 41 of acute non-lymphocytic leukemia (ANLL). One-year survivals were 51% and 33% in ALL and ANLL patients, respectively. Uninfected patients in remission had significantly better survival than infected ones and/or in relapse. Overall incidence of interstitial pneumonia was 43%. Rejection and relapse were encountered in 26% of patients. Concerning cause of death, interstitial pneumonia was the most frequent cause (44%). Uni- and multivariate analyses strongly suggested that favorable prognostic factors were remission, uninfection, preparation of low-dose-rate fractionated TBI and cyclophosphamide, and mild graft-versus-host disease (GVHD) for acute leukemia patient treated with allogeneic BMT. (orig.) [de

  4. Anti-inflammatory Mechanism of Bone Marrow Mesenchymal Stem Cell Transplantation in Rat Model of Spinal Cord Injury.

    Science.gov (United States)

    Han, Dongji; Wu, Chenglong; Xiong, Qiuju; Zhou, Ling; Tian, Yuke

    2015-04-01

    To explore the effect of bone marrow mesenchymal stem cell (BMSC) transplantation on the levels of toll-like receptor 4 (TLR4), interleukin-1β (IL-1β), and tumor necrosis factor (TNF-α) in spinal cord tissue of rat model of spinal cord injury (SCI). BMSCs from 4-week-old male SD rats were isolated, cultured, and characterized after three generations using specific surface markers CD34 and CD44. Fifty four SD male rats were divided into sham group, model group, and cell transplantation group (18 rats each group). SCI model was generated using an improved Allen's method. Rats in cell transplantation group were treated with BMSCs in caudal vein. Rats were sacrificed at 24 h, 72 h, and 7 d post-injury, and spinal cord tissues were taken out for detection of IL-1β and TNF-α tissue content by enzyme-linked immunosorbent assay. IL-1β and TNF-α mRNA expression was evaluated by qPCR and TLR4 protein expression was analyzed by Western blotting. IL-1β and TNF-α protein levels, as well as IL-1β, TNF-α mRNA, and TLR4 expression were significantly increased in rats with established SCI, and reached its peak in spinal cord tissues at 72 h after the initial injury (p spinal cord inflammation by weakening TLR4-mediated signaling pathways and reducing tissue content of IL-1β and TNF-α.

  5. Bone marrow stromal cells transplantation combined with ultrashortwave therapy promotes functional recovery on spinal cord injury in rats.

    Science.gov (United States)

    Yin, Yan-Mei; Lu, Yu; Zhang, Li-Xin; Zhang, Guang-Ping; Zhang, Zhi-Qiang

    2015-03-01

    This study investigated the effects of bone marrow stromal cells (BMSCs) transplantation combined with low dose ultrashortwave (USW) radiation on functional recovery from spinal cord injury (SCI) in rats. Female Sprague-Dawley rats (n = 64) were randomly divided into five groups: sham-operated, as well as control, USW, BMSCs, and BMSCs + USW that were subjected to spinal cord contusion. BMSCs were transplanted into rats in the BMSCs and BMSCs+USW groups, while those in the USW and BMSCs + USW were exposed to radiation; Basso-Beattie-Bresnahan (BBB) tests were performed before the operation and at 1-week intervals after SCI for 7 weeks. 7 weeks later, animals were assessed footprint pattern, motor evoked potential (MEP), histological features, and expression of the ED1 and glial fibrillary acidic protein (GFAP), markers of activated macrophages and astrocytes, respectively, in the lesion area. BBB scores were higher in the BMSCs + USW than in the BMSCs and control groups. The USW and BMSCs + USW groups had improved coordination compared to the BMSCs and control groups (P spinal cord area than the other injured rats, and also had expression of GFAP in transplanted BMSCs. All treatment groups had lower ED1 expression and MEP latency than the controls (P spinal cord repair. © 2015 Wiley Periodicals, Inc.

  6. Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation.

    Science.gov (United States)

    Busca, A; Saroglia, E M; Lanino, E; Manfredini, L; Uderzo, C; Nicolini, B; Messina, C; Rabusin, M; Miniero, R

    2000-05-01

    Mycophenolate mofetil (MMF) is an alternative immunosuppressant which inhibits the proliferation of T and B lymphocytes. The purpose of the present study was to evaluate the safety and efficacy of MMF as salvage therapy for chronic GVHD (cGVHD) in children receiving allogeneic bone marrow transplantation. Fifteen children, 3-16 years of age, who had received grafts from HLA-compatible siblings (n = 8), partially matched related donors (n= 2) or matched unrelated donors (n = 5), developed extensive cGVHD which had proved unresponsive to standard immunosuppressive therapy. Patients were treated with MMF at the dose of 15-40 mg/kg/day in combination with other immunosuppressive therapy for a median of 4 months (range 1-15 months). The overall response rate (complete or partial response) was 60%. Thirteen percent had only minor responses, whereas 27% of patients had progressive disease. Best responses were seen in patients with GI tract (60% of complete responses) or mouth (33% of complete responses) cGVHD and skin involvement (43% of complete responses) that did not include sclerodermatous manifestations. Once MMF was started, improvements in the clinical manifestations of cGVHD allowed a significant reduction of steroids in 45% of patients and discontinuation in 27% of cases. Six patients (40%) experienced adverse events, with gastrointestinal symptoms predominating. Five patients experienced opportunistic infections. MMF was discontinued after 35-180 days in six patients for the following reasons: parents choice (n = 2), liver toxicity (n = 1), poor compliance (n = 2), and no response (n = 1). In conclusion, these preliminary results suggest that MMF in combination with other immunosuppressive agents may have a role to play in patients with cGVHD. Prospective clinical trials are needed to establish exact indications for therapy and dosage scheduling. Bone Marrow Transplantation (2000).

  7. Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Sydney X Lu

    Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

  8. Total body irradiation in the bone marrow transplantation in leukemia:an experience

    International Nuclear Information System (INIS)

    Zapatero, A.; Martin de Vidales, C.; Pinar, B.; Marin, A.; Cerezo, L.; Dominguez, P.; Perez, A.

    1996-01-01

    The purpose of this report was to evaluate long-term survival and morbidity of fractioned total body irradiation (TBI) prior to allogeneicbone marrow transplantation (BMT) for leukemia. From June 1985 to May 1992, 94 patients with acute leukemia and chronic myelogenous leukemia (CML), were treated with high dose cyclophosphamide(CY) and fractionated TBI to a total dose of 12 Gy in six fractions prior to allogeneic BMT. The Kaplan-Meier 5-year overall survival and disease-free survival were 53% +-6 and 48%+- respectively for patients with standard risk disease (first remission of acute leukemia and first chronic phase of CML), and 24%+-7 and 21%+-6 for patients with more advanced disease (p=3D0.01). The incidence of interstitial pneumonitis (IP), venoocclusive disease of the liver (VOD) and grade=3D>II acute graft-versus-host disease (GVHD) were respectively 15%, 29% and 51%. Fractionated TBI combined with high dose CY before allogeneic BMT for leukemia is an effective treatment in prolonging relapse-free survival witha low incidence of lung toxicity. (Author) 13 refs

  9. Propofol injection combined with bone marrow mesenchymal stem cell transplantation better improves electrophysiological function in the hindlimb of rats with spinal cord injury than monotherapy.

    Science.gov (United States)

    Wang, Yue-Xin; Sun, Jing-Jing; Zhang, Mei; Hou, Xiao-Hua; Hong, Jun; Zhou, Ya-Jing; Zhang, Zhi-Yong

    2015-04-01

    The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantation via tail vein injection and/or propofol injection via tail vein using an infusion pump. Four weeks after cell transplantation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve fibers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electrophysiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

  10. Propofol combined with bone marrow mesenchymal stem cell transplantation improves electrophysiological function in the hindlimb of rats with spinal cord injury better than monotherapy

    Directory of Open Access Journals (Sweden)

    Yue-xin Wang

    2015-01-01

    Full Text Available The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantation via tail vein injection and/or propofol injection via tail vein using an infusion pump. Four weeks after cell transplantation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve fibers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electrophysiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

  11. Third party cord blood transplant boosts autologous hematopoiesis in a case of persistent bone marrow aplasia after double transplant failure for β-thalassemia major

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    Giuseppe Visani

    2013-04-01

    Full Text Available A 9-year-old female received a double allogeneic stem cell transplant (SCT from an ABO-incompatible HLA-matched sibling for β-thalassemia major, without achieving a complete donor chimerism. Subsequently, the patient received autologous SCT and five donor lymphocyte infusion, without increasing donor chimerism. After the double transplant failure, we performed an unrelated transplant from a full-matched umbilical cord blood (UCBT. Due to the severe immunosuppression of the patient, we did not administer any conditioning regimen nor GVHD prophylaxis. On day +40 after UCBT, trilinear engraftment was documented. Surprisingly, the hematopoietic reconstitution was related to the re-expansion of the autologous (β-thalassemic hematopoietic stem cell, as documented by chimerism studies on both peripheral blood and bone marrow. At present, 30 months after UCBT, there is stable hematopoietic autologous reconstitution. This is the first description of the restoration of autologous hematopoiesis obtained with cord blood infusion in a thalassemia-major patient after a double transplant failure.

  12. Extraskeletal and intraskeletal new bone formation induced by demineralized bone matrix combined with bone marrow cells

    International Nuclear Information System (INIS)

    Lindholm, T.S.; Nilsson, O.S.; Lindholm, T.C.

    1982-01-01

    Dilutions of fresh autogenous bone marrow cells in combination with allogeneic demineralized cortical bone matrix were tested extraskeletally in rats using roentgenographic, histologic, and 45 Ca techniques. Suspensions of bone marrow cells (especially diluted 1:2 with culture media) combined with demineralized cortical bone seemed to induce significantly more new bone than did demineralized bone, bone marrow, or composite grafts with whole bone marrow, respectively. In a short-term spinal fusion experiment, demineralized cortical bone combined with fresh bone marrow produced new bone and bridged the interspace between the spinous processes faster than other transplantation procedures. The induction of undifferentiated host cells by demineralized bone matrix is further complemented by addition of autogenous, especially slightly diluted, bone marrow cells

  13. Bone marrow aspiration

    Science.gov (United States)

    Bain, B

    2001-01-01

    Bone marrow aspiration biopsies are carried out principally to permit cytological assessment but also for immunophenotypic, cytogenetic, molecular genetic, and other specialised investigations. Often, a trephine biopsy is carried out as part of the same procedure. Bone marrow aspirations should be carried out by trained individuals who are aware of the indications, contraindications, and hazards of the procedure. They should follow a standard operating procedure. The operator should have made an adequate assessment of clinical and haematological features to ensure both that appropriate indications exist and that all relevant tests are performed. For the patient's comfort and safety, the posterior iliac crest is generally the preferred site of aspiration. Films of aspirated marrow and, when appropriate, films of crushed particles should be made and labelled. Once thoroughly dry, films should be fixed and stained. As a minimum, a Romanowsky stain and a Perls' stain are required. A cover slip should be applied. The bone marrow films should be assessed and reported in a systematic manner so that nothing of importance is overlooked, using a low power, then intermediate, then high power objective. A differential count should be performed. An interpretation of the findings, in the light of the clinical and haematological features, should be given. The report should be signed or computer authorised, using a secure password, and issued in a timely manner. Key Words: bone marrow aspirate • haematological diagnosis PMID:11533068

  14. Effect of transplantation of olfactory ensheathing cell conditioned medium induced bone marrow stromal cells on rats with spinal cord injury.

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    Feng, Linjie; Gan, Hongquan; Zhao, Wenguo; Liu, Yingjie

    2017-08-01

    Spinal cord injury is a serious threat to human health and various techniques have been deployed to ameliorate or cure its effects. Stem cells transplantation is one of the promising methods. The primary aim of the present study was to investigate the effect of the transplantation of olfactory ensheathing cell (OEC) conditioned medium‑induced bone marrow stromal cells (BMSCs) on spinal cord injury. Rat spinal cord compression injury animal models were generated, and the rats divided into the following three groups: Group A, (control) Dulbecco's modified Eagle's medium‑treated group; group B, normal BMSC‑treated group; group C, OEC conditioned medium‑induced BMSC‑treated group. The animals were sacrificed at 2, 4 and 8 weeks following transplantation for hematoxylin and eosin staining, and fluorescence staining of neurofilament protein, growth associated protein‑43 and neuron‑specific nuclear protein. The cavity area of the spinal cord injury was significantly reduced at 2 and 4 weeks following transplantation in group C, and a significant difference between the Basso, Beattie and Bresnahan score in group C and groups A and B was observed. Regenerated nerve fibers were observed in groups B and C; however, a greater number of regenerated nerve fibers were observed in group C. BMSCs induced by OEC conditioned medium survived in vivo, significantly reduced the cavity area of spinal cord injury, promoted nerve fiber regeneration following spinal cord injury and facilitated recovery of motor function. The present study demonstrated a novel method to repair spinal cord injury by using induced BMSCs, with satisfactory results.

  15. 1. modification of the proliferative capacity of transplanted bone marrow colony forming units by changes in the host environment

    International Nuclear Information System (INIS)

    Beran, M.; Tribukait, B.

    1974-01-01

    Regulation of the proliferation of transplanted colony forming units (CFUs) was investigated in lethally irradiated mice, pretreated by methods known to accelerate hemopoietic recovery after sublethal irradiation. Prospective recipients were exposed to either hypoxia, vinblastine or priming irradiation and at different intervals thereafter lethally irradiated and transplanted with bone marrow. Repopulation of CFUs was determined by counting the number of splenic colonies in primary recipients or by retransplantation. Regeneration of grafted CFUs was greatly accelerated and their self-renewal capacity increased in mice grafted within 2 days after hypoxia. Also the number of splenic colonies formed by grafted syngeneic CFUs as well as by C57B1 parent CFUs growing in BC3F1 hosts was significantly increased. The effect was not dependent on the seeding efficiency of CFUs and apparently resulted from hypoxia induced changes in the hosts' physiological environment. Proliferative capacity of grafted CFUs increased remarkably in hosts receiving vinblastine 2 or 4 days prior to irradiation. Priming irradiation given 6 days before main irradiation accelerated, given 2 days before impaired regeneration of CFUs. The increased rate of regeneration was not related to the cellularity of hemopoietic organs at the time of transplantation. The growth of CFUs in diffusion chambers implanted into posthypoxic mice was only slightly improved which does indicate that the accelerated regeneration of CFUs in posthypoxic mice is mainly due to the changes in the hemopoietic microenvironment. A short conditioning of transplanted CFUs by host factor(s) was sufficient to improve regeneration. The results might suggest that the speed of hemopoietic regeneration depends on the number of CFUs being induced to proliferate shortly after irradiation, rather than on the absolute numbers of CFUs available to the organism. (author)

  16. Effect of transplantation of olfactory ensheathing cell conditioned medium induced bone marrow stromal cells on rats with spinal cord injury

    Science.gov (United States)

    Feng, Linjie; Gan, Hongquan; Zhao, Wenguo; Liu, Yingjie

    2017-01-01

    Spinal cord injury is a serious threat to human health and various techniques have been deployed to ameliorate or cure its effects. Stem cells transplantation is one of the promising methods. The primary aim of the present study was to investigate the effect of the transplantation of olfactory ensheathing cell (OEC) conditioned medium-induced bone marrow stromal cells (BMSCs) on spinal cord injury. Rat spinal cord compression injury animal models were generated, and the rats divided into the following three groups: Group A, (control) Dulbecco's modified Eagle's medium-treated group; group B, normal BMSC-treated group; group C, OEC conditioned medium-induced BMSC-treated group. The animals were sacrificed at 2, 4 and 8 weeks following transplantation for hematoxylin and eosin staining, and fluorescence staining of neurofilament protein, growth associated protein-43 and neuron-specific nuclear protein. The cavity area of the spinal cord injury was significantly reduced at 2 and 4 weeks following transplantation in group C, and a significant difference between the Basso, Beattie and Bresnahan score in group C and groups A and B was observed. Regenerated nerve fibers were observed in groups B and C; however, a greater number of regenerated nerve fibers were observed in group C. BMSCs induced by OEC conditioned medium survived in vivo, significantly reduced the cavity area of spinal cord injury, promoted nerve fiber regeneration following spinal cord injury and facilitated recovery of motor function. The present study demonstrated a novel method to repair spinal cord injury by using induced BMSCs, with satisfactory results. PMID:28656221

  17. Impact of Human Leukocyte Antigen Allele Mismatch in Unrelated Bone Marrow Transplantation with Reduced-Intensity Conditioning Regimen.

    Science.gov (United States)

    Yokoyama, Hisayuki; Kanda, Junya; Fuji, Shigeo; Kim, Sung-Won; Fukuda, Takahiro; Najima, Yuho; Ohno, Hitoshi; Uchida, Naoyuki; Ueda, Yasunori; Eto, Tetsuya; Iwato, Koji; Kobayashi, Hikaru; Ozawa, Yukiyasu; Kondo, Tadakazu; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

    2017-02-01

    The impact of HLA mismatch in hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) has not been fully examined. We analyzed a total of 1130 cases to examine the effects of HLA allele mismatch in unrelated bone marrow transplantation (BMT) with RIC in the Japan Marrow Donor Program registry cohort. Compared with HLA 8/8-allele match (n = 720, 8/8 match), both 1 (n = 295, 7/8 match) and 2 allele mismatches (n = 115, 6/8 match) were associated with significant reduction of overall survival (OS) (hazard ratio [HR],  1.34; P = .0024 and HR, 1.33; P = .035 for 7/8 and 6/8 match, respectively). The incidence of grades 2 to 4 acute graft-versus-host disease (aGVHD) increased with increasing number of mismatched alleles (HR, 1.36 and HR, 2.08 for 7/8 and 6/8 match, respectively). Nonrelapse mortality showed a similar tendency to aGVHD (HR, 1.35 for 7/8 and HR, 1.63 for 6/8). One-allele mismatches at the HLA-A or -B and HLA-C loci were significantly associated with inferior OS compared with 8/8 match (HR, 1.64 for A or B mismatch and HR, 1.41 for C mismatch), whereas HLA-DRB1 allele mismatch was not (HR, 1.16; P = .30). However, the effect of HLA-A or -B and -C mismatch on OS was not observed in those who received RIC BMT since 2010, in contrast to recipients before 2010. These results suggested that in unrelated RIC BMT, 1-allele mismatch is associated with poorer outcome, and the impact of HLA mismatch may differ depending on the HLA locus, although these HLA mismatch effects may be different in recent cases. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Effect of cotransplantation of hematopoietic stem cells and embryonic AGM stromal cells on hematopoietic reconstitution in mice after bone marrow transplantation

    International Nuclear Information System (INIS)

    Tao Si; Sun Hanying; Liu Wenli

    2007-01-01

    Objective: To explore the effects of cotransplantation of hematopoietic stem cells and stromal cells derived from aorta-gonad-mesonephros (AGM) region on hematopoietic reconstitution in mice after bone marrow transplantation (BMT). Methods: The typical mice model of syngeneic BMT was established and the mice were randomly divided into 4 groups: the control group, the BMT group, the group of cotransplantation of HSC with AGM stromal cells (the cotransplantation group) and the ligustrazine group (the LT group). On days 3, 7, 10, 14, 21 and 28 after BMT, the peripheral blood cells and bone marrow mononuclear cells (BMMNC) were counted, and histology changes of bone marrow were detected. Results: The levels of peripheral WBC, RBC, platelet, and BMMNC in the contransplantation group were significantly higher than those in the single BMT group and the LT group (P<0.05). Conclusions: Cotransplantation with AGM stromal cells could significantly promote hematopoietic reconstruction in mice after BMT. (authors)

  19. The onset of hemoglobin synthesis in spleens of irradiated mice after bone marrow transplantation

    International Nuclear Information System (INIS)

    Ponka, P.; Fuchs, O.; Borova, J.; Necas, E.

    1977-01-01

    Messenger RNA (mRNA) for globin was isolated from spleens of irradiated mice in which erythroid differentiation was induced by a bone marrow graft. The globin mRNA was isolated either by means of sucrose gradients of reticulocyte polysomal RNA or by affinity chromatography of total spleen RNA on poly (U)-sepharose. The globin mRNA was tested in a wheat embryo cell-free system. The appearance of mRNA in the spleen erythroid colonies was correlated with other parameters of erythroid differentiation such as globin synthesis, activity of delta-aminolevulinic acid synthetase and iron uptake. Poly(A) containing mRNA did appear already on the 3rd day after grafting. However, significant translational activity of globin mRNA could be demonstrated only one day later together with increase in globin synthesis and delta-aminolevulinic acid synthetase and enhanced iron uptake. In the second part of this study mouse spleen cells rich in erythroid elements were incubated with a specific heme synthesis inhibitor (isonicotinic acid hydrazide, INH) and the synthesis of 9 S RNA was estimated. It was found that a 40-minute incubation with INH reduced uridine incorporation into 9 S RNA fraction by about 40%. (author)

  20. Feasibility and Efficacy of Autologous Bone Marrow Aspirate Transplantation Combined with Human Parathyroid Hormone 1-34 Administration to Treat Osteonecrosis in a Rabbit Model.

    Science.gov (United States)

    Makihara, Takeshi; Yoshioka, Tomokazu; Sugaya, Hisashi; Aoto, Katsuya; Wada, Hiroshi; Uemura, Kenta; Tanaka, Kenta; Akaogi, Hiroshi; Yamazaki, Masashi; Mishima, Hajime

    2017-01-01

    No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30  μ g/kg) or saline administration three times per week ( n = 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy.

  1. Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: comparison with bone marrow transplantation.

    Science.gov (United States)

    Paquette, R L; Tebyani, N; Frane, M; Ireland, P; Ho, W G; Champlin, R E; Nimer, S D

    1995-01-01

    The outcome of 155 adult aplastic anemia (AA) patients treated with antithymocyte globulin (ATG, Upjohn, Kalamazoo, MI) at University of California, Los Angeles from 1977 to 1988 was evaluated. The median survival of the 146 patients who did not undergo bone marrow transplantation was 5.6 years, with 49% +/- 4% surviving more than 6 years. The most important predictor of survival was positive response to ATG (P < 0.001), which was observed in 48% of patients. Among pretreatment variables, disease severity was the best predictor of survival. Patients with moderate AA (MAA) had significantly better survival than those with severe (SAA) or very severe (VSAA) disease (P = 0.04). The 6-year actuarial survival rates of the three groups were 71% +/- 9%, 48% +/- 7% and 38% +/- 7%, respectively. Cox regression analysis found disease severity to be the only pretreatment variable significantly associated with survival (P = .02). Patient age, sex, disease etiology, concurrent treatment with androgens, or duration of ATG therapy were not associated with differences in survival or response to ATG. Late clonal hematologic complications (ie, myelodysplasia, acute myelogenous leukemia) were observed in 5 of the 77 patients followed for more than 2 years after ATG treatment. In addition, one case of non-Hodgkin's lymphoma and three solid tumors occurred in the ATG-treated patients. The survival of 56 ATG-treated patients with SAA or VSAA between the ages of 16 and 43 did not differ significantly from that of 55 adult AA patients who underwent bone marrow transplant (BMT) during the same time period (P = 0.6). However, 6-year survival rates improved from 43% for patients transplanted before 1984, to 72% for those who underwent BMT between 1984 and 1989. In contrast, there was no difference in the survival rates of patients treated with ATG during these two time periods (46% v 45%, respectively). The results suggest a superior long-term outcome for adult patients with SAA treated with

  2. δ-ALA-D activity is a reliable marker for oxidative stress in bone marrow transplant patients

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    Bonfanti Gabriela

    2009-05-01

    Full Text Available Abstract Background Bone marrow transplantation (BMT is often used in the treatment of various diseases. Before BMT, patients are submitted to a conditioning regimen (CR, which consists of the administration of high doses of chemotherapy. The action of many cytostatic drugs involves the overproduction of reactive oxygen species, which together with inadequate antioxidant protection can lead to oxidative stress and this has been implicated in the etiology of various diseases. The objectives of this study were to look for evidence of oxidative stress and also to analyze δ-Aminolevulinato dehydratase (δ-ALA-D activity as a possible marker of oxidative stress in autologous and allogeneic BMT patients. Methods Lipid peroxidation, vitamin C and thiol group levels as well as catalase, superoxide dismutase and δ-ALA-D activity were determined in 37 healthy controls, 13 patients undergoing autologous peripheral blood stem cell transplantation and 24 patients undergoing allogeneic BMT. Results We found that patients presented signs of oxidative stress before they were submitted to BMT, during CR and up to 20 days after BMT. There was a decrease in enzymatic and non enzymatic antioxidant defenses, in δ-ALA-D activity, and an increase in lipoperoxidation in the blood of both patient groups. Conclusion This study has indicated that autologous and allogeneic BMT are associated with oxidative stress. Moreover, blood δ-ALA-D activity seems to be an additional biomarker of oxidative stress in BMT patients.

  3. Modulation of microglial activation enhances neuroprotection and functional recovery derived from bone marrow mononuclear cell transplantation after cortical ischemia.

    Science.gov (United States)

    Franco, Edna C S; Cardoso, Marcelo M; Gouvêia, Amauri; Pereira, Antonio; Gomes-Leal, Walace

    2012-06-01

    Activated microglia may exacerbate damage in neural disorders; however, it is unknown how they affect stem cells transplanted after stroke. Focal ischemia was induced by microinjections of 40 pmol of endothelin-1 into the motor cortex of adult rats. Ischemic animals were treated with sterile saline (n = 5), bone marrow mononuclear cells (BMMCs, n = 8), minocycline (n = 5) or concomitantly with minocycline and BMMCs (n = 5). BMMC-treated animals received 5 × 10(6)BMMCs through the caudal vein 24h post-ischemia. Behavioral tests were performed to evaluate functional recovery. Morphometric and histological analyses were performed to assess infarct area, neuronal loss and microglia/macrophage activation up to 21 days post-ischemia. Treatments with minocycline, BMMCs or minocycline-BMMCs reduced infarct area, increased neuronal survival and decreased the number of caspase-3+ and ED-1+ cells, but these effects were more prominent in the minocycline-BMMC group. Behavioral analyses using the modified sticky-tape and open-field tests showed that ischemic rats concomitantly treated with BMMCs and minocycline showed better motor performance than rats treated with BMMCs or minocycline only. The results suggest that proper modulation of the inflammatory response through the blockage of microglia activation enhances neuroprotection and functional recovery induced by intravenous transplantation of BMMCs after motor cortex ischemia. Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  4. Intraventricular Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells via Ommaya Reservoir in Persistent Vegetative State Patients after Haemorrhagic Stroke: Report of Two Cases & Review of the Literature

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    Fauzi AA

    2016-11-01

    Full Text Available Background: One of the most devastating diseases, stroke, is a leading cause of death and disability worldwide with severe emotional and economic consequences. The purpose of this article is mainly to report the effect of intraventricular transplantation via an Ommaya reservoir using autologous bone marrow mesenchymal stem cells (BM-MSCs in haemorrhagic stroke patients. Case Presentations: Two patients, aged 51 and 52, bearing sequels of haemorrhagic stroke were managed by intraventricular transplantation of BM-MSCs obtained from their own bone marrow. Before the procedure, both patients were bedridden, tracheostomised, on nasogastric (NG tube feeding and in hemiparesis. The cells were transplanted intraventricularly (20 x 106 cells/2.5 ml using an Ommaya reservoir, and then repeated transplantations were done after 1 and 2 months consecutively. The safety and efficacy of the procedures were evaluated 3, 6 and 12 months after treatment. The National Institute of Health Stroke Scale (NIHSS was used to evaluate the patients' neurological status before and after treatment. No adverse events derived from the procedures or transplants were observed in the one-year follow-up period, and the neurological status of both patients improved after treatment. Conclusions: Our report demonstrates that the intraventricular transplantation of BM-MSCs via an Ommaya reservoir is safe and it improves the neurological status of post-haemorrhagic stroke patients. The repeated transplantation procedure is easier and safer to perform via a subcutaneously implanted Ommaya reservoir.

  5. Chronic spinal cord injury treated with transplanted autologous bone marrow-derived mesenchymal stem cells tracked by magnetic resonance imaging: a case report.

    Science.gov (United States)

    Chotivichit, Areesak; Ruangchainikom, Monchai; Chiewvit, Pipat; Wongkajornsilp, Adisak; Sujirattanawimol, Kittipong

    2015-04-09

    Intrathecal transplantation is a minimally invasive method for the delivery of stem cells, however, whether the cells migrate from the lumbar to the injured cervical spinal cord has not been proved in humans. We describe an attempt to track bone marrow-derived mesenchymal stem cells in a patient with a chronic cervical spinal cord injury. A 33-year-old Thai man who sustained an incomplete spinal cord injury from the atlanto-axial subluxation was enrolled into a pilot study aiming to track bone marrow-derived mesenchymal stem cells, labeled with superparamagnetic iron oxide nanoparticles, from intrathecal transplantation in chronic cervical spinal cord injury. He had been dependent on respiratory support since 2005. There had been no improvement in his neurological function for the past 54 months. Bone marrow-derived mesenchymal stem cells were retrieved from his iliac crest and repopulated to the target number. One half of the total cells were labeled with superparamagnetic iron oxide nanoparticles before transplantation to the intrathecal space between L4 and L5. Magnetic resonance imaging studies were performed immediately after the transplantation and at 48 hours, two weeks, one month and seven months after the transplantation. His magnetic resonance imaging scan performed immediately after the transplantation showed hyposignal intensity of paramagnetic substance tagged stem cells in the subarachnoid space at the lumbar spine area. This phenomenon was observed at the surface around his cervical spinal cord at 48 hours. A focal hyposignal intensity of tagged bone marrow-derived stem cells was detected at his cervical spinal cord with magnetic resonance imaging at 48 hours, which faded after two weeks, and then disappeared after one month. No clinical improvement of the neurological function had occurred at the end of this study. However, at 48 hours after the transplantation, he presented with a fever, headache, myalgia and worsening of his motor function (by one

  6. Cataract-free interval and severity of cataract after total body irradiation and bone marrow transplantation: influence of treatment parameters

    International Nuclear Information System (INIS)

    Kempen-Harteveld, M. Loes van; Struikmans, Henk; Kal, Henk B.; Tweel, Ingeborg van der; Mourits, Maarten; Verdonck, Leo F.; Schipper, Jan; Battermann, Jan J.

    2000-01-01

    Purpose: To determine prospectively the cataract-free interval (latency time) after total body irradiation (TBI) and bone marrow transplantation (BMT) and to assess accurately the final severity of the cataract. Methods and Materials: Ninety-three of the patients who received TBI as a part of their conditioning regimen for BMT between 1982 and 1995 were followed with respect to cataract formation. Included were only patients who had a follow-up period of at least 23 months. TBI was applied in one fraction of 8 Gy or two fractions of 5 or 6 Gy. Cataract-free period was assessed and in 56 patients, who could be followed until stabilization of the cataract had occurred, final severity of the cataract was determined using a classification system. With respect to final severity, two groups were analyzed: subclinical low-grade cataract and high-grade cataract. Cataract-free period and final severity were determined with respect to type of transplantation, TBI dose, and posttransplant variables such as graft versus host disease (GVHD) and steroid treatment. Results: Cataract incidence of the analyzed patients was 89%. Median time to develop a cataract was 58 months for autologous transplanted patients. For allogeneic transplanted patients treated or not treated with steroids, median times were 33 and 46 months, respectively. Final severity was not significantly different for autologous or allogeneic patients. In allogeneic patients, however, final severity was significantly different for patients who had or had not been treated with steroids for GVHD: 93% versus 35% high-grade cataract, respectively. Final severity was also different for patients receiving 1 x 8 or 2 x 5 Gy TBI, from patients receiving 2 x 6 Gy as conditioning therapy: 33% versus 79% high-grade cataract, respectively. The group of patients receiving 2 x 6 Gy comprised, however, more patients with steroid treatment for GVHD. So the high percentage of high-grade cataract in the 2 x 6 Gy group might also

  7. Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Laurent Spahr

    Full Text Available OBJECTIVE: Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD. We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT improved liver function in decompensated ALD. DESIGN: 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy were randomized early after hospital admission to standard medical therapy (SMT alone (n = 30, including steroids in patients with a Maddrey's score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28. Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC compartment. RESULTS: Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64% from the BMMCT group and 18 patients (53% from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49-5.4 in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001, and proliferating HPC tended to decrease in both groups (-35 and -33%, respectively. CONCLUSION: Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. TRIAL REGISTRATION

  8. Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of SATB2 prevents alveolar bone loss in ovariectomized rats.

    Science.gov (United States)

    Xu, Rongyao; Fu, Zongyun; Liu, Xue; Xiao, Tao; Zhang, Ping; Du, Yifei; Yuan, Hua; Cheng, Jie; Jiang, Hongbing

    2016-11-01

    Estrogen-deficient osteoporosis is an aging-related disease with high morbidity that not only significantly increases a woman's risk of fragility fracture but is also associated with tooth and bone loss in the supporting alveolar bone of the jaw. Emerging evidence suggests that the aging of bone marrow stromal cells (BMSCs) contributes to the development of osteoporosis. In this study, we aimed to investigate the role of the special AT-rich sequence-binding protein 2 (SATB2), a stemness and senescence regulator of craniofacial BMSCs, in rat ovariectomy-induced alveolar osteoporosis. We also sought to determine whether transplantation of SATB2-modified BMSCs could ameliorate estrogen deficient alveolar bone loss. Our data revealed that BMSCs from ovariectomy-induced alveolar bone exhibited typical senescence phenotypes such as diminished stemness and osteogenic capacity, increased expression of senescence or osteoclastic markers and enhanced adipogenic potential. These phenotypic changes are a result of SATB2-mediated senescence dysregulation as evidenced by nuclear γH2AX foci formation. Moreover, overexpression of SATB2 significantly alleviated the senescence of osteoporotic BMSCs in vitro. Importantly, transplantation of SATB2-modified BMSCs significantly attenuated ovariectomy-induced alveolar bone loss in vivo. Together, our results revealed that SATB2 is a critical regulator of alveolar BMSC senescence, and its overexpression decreases these senescent changes both in vitro and in vivo. SATB2-modified BMSC delivery could be a viable and promising therapeutic strategy for alveolar bone loss induced by estrogen-deficient osteoporosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. I. Orthoptic liver allographs

    International Nuclear Information System (INIS)

    Myburgh, J.A.; Smit, J.A.; Browde, S.; Hill, R.R.H.

    1980-01-01

    Fractionated total lymphoid irradiation (TLI) and allogeneic bone marrow (BM) injection have been reported to produce stable chimerism without graft-versus-host disease (GVHD) in inbred mice and rats and mongrel dogs, and transplantation tolerance for skin and heart grafts in rodents. This concept has been studied in outbred chacma baboons receiving orthotopic liver allografts with the use of five different irradiation protocols. Eight fractions of 200 rad to the whole torso, followed immediately by allogeneic BM injections, and liver grafts from the BM donors 3 to 4 weeks later resulted in markedly prolonged survivals of 63 to 106 days in four baboons (median survival of untreated controls 19 days). Only one of the four animals died directly from the effects of rejection. BM chimerism was demonstrated in two baboons. There were no clinical or histological signs of GVHD in any of the animals. Two fractions of TLI, totaling 800 rad, 23 hr apart and followed immediately by BM injection and liver grafting resulted in profound thrombocytopenia and death form intraperitoneal hemorrhage in four of five baboons. In one animal BM injection and liver transplantation were delayed for 75 days. The baboon is still alive more than 6 months later. Three groups received single doses of 300, 400, and 500 rad to the whole torso, followed by allogeneic BM injections 1 and 2 weeks later, and liver transplants from their BM donors after an additional 3 to 4 weeks. The four baboons receiving 300 rad survived for 42, 86, 123, and >180 days. Two of the four baboons receiving 400 rad died of septic intraabdominal complications with minimal or no evidence of rejection. Fourh of the five baboons receiving 500 rad died from rejection

  10. Intrathecal transplantation of bone marrow stromal cells attenuates blood-spinal cord barrier disruption induced by spinal cord ischemia-reperfusion injury in rabbits.

    Science.gov (United States)

    Fang, Bo; Wang, He; Sun, Xue-Jun; Li, Xiao-Qian; Ai, Chun-Yu; Tan, Wen-Fei; White, Paul F; Ma, Hong

    2013-10-01

    Intrathecal administration of bone marrow stromal cells has been found to produce beneficial effects on ischemia-reperfusion injury to the spinal cord. The blood-spinal cord barrier is critical to maintain spinal cord homeostasis and neurologic function. However, the effects of bone marrow stromal cells on the blood-spinal cord barrier after spinal cord ischemia-reperfusion injury are not well understood. This study investigated the effects and possible mechanisms of bone marrow stromal cells on blood-spinal cord barrier disruption induced by spinal cord ischemia-reperfusion injury. This was a prospective animal study conducted at the Central Laboratory of the First Affiliated Hospital, China Medical University. The study used 81 Japanese white rabbits (weight, 1.8-2.6 kg). Spinal cord ischemia-reperfusion injury was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Two days before the injury was induced, bone marrow stromal cells (1 × 10(8) in 0.2-mL phosphate-buffered saline) were transplanted by intrathecal injection. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histologic examination. The permeability of the blood-spinal cord barrier was examined using Evans blue (EB) and lanthanum nitrate as vascular tracers. The expression and localization of tight junction protein occludin were assessed by Western blot, real-time polymerase chain reaction, and immunofluorescence analysis. Matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) expression were also measured. Intrathecal transplantation of bone marrow stromal cells minimized the neuromotor dysfunction and histopathologic deficits (P spinal cord ischemia-reperfusion injury. In addition, bone marrow stromal cells treatment suppressed spinal cord ischemia-reperfusion injury-induced decreases in occludin (P bone marrow stromal cells reduced the excessive expression of MMP-9 and TNF-α (P bone marrow

  11. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Ringden, O. [Huddinge Hospital, Stockholm (Sweden). Dept. of Clinical Immunology; Labopin, M.; Gorin, N.C. [Hopital Saint-Antoine, Paris (France). Centre International Greffes de Moelle; Tura, S. [Orsola University Hospital, Bologna (Italy); Arcese, W. [University `La Sapienza`, Rome (Italy). Haematology; Iriondo, A. [Hospital National, Santander (Spain); Zittoun, R. [Hotel-Dieu, Paris (France). Service d`Hematologie; Sierra, J. [Hospital Clinic, Barcelona (Spain)

    1996-06-01

    We retrospectively compared the outcome in patients in the EBMT database transplanted for acute leukaemia from January 1987 to January 1994 who received busulphan and cyclophosphamide (BU/CY) as a pretransplant regimen versus those who received cyclophosphamide and total-body irradiation (CY-TBI). The patients were matched for type of transplant (autologous bone marrow transplantation (ABMT) versus allogenic (BMT)), diagnosis (acute lymphoblast leukaemia (ALL) ora cute myeloid leukaemia (AML)), status (early first complete remission, CR-1) versus intermediate (second or later remission, first relapse), age, FAB classification for AML, prevention of graft-versus-host disease and year of transplantation. BU/CY and CY/TBI as pretransplant regimens gave similar results in all situations, except ABMT for ALL intermediate stages with more than 2 years from diagnosis to transplantation, where a lower RI and a higher LFS were associated with CY/TBI. (author).

  12. The Comparative Study Of Saprophytic Fungi In Air Canal, Air, Hospital Instruments And Clinical Samples From Patients With Bone Marrow Transplantation

    Directory of Open Access Journals (Sweden)

    Hashemi S J

    2004-08-01

    Full Text Available Background: Bone Marrow Transplantation is one of the most important therapeutic methods in much malignant and nonmalignant disease. Patients with Bone Marrow Transplantation (BMT following radiotherapy and chemotherapy will suffer from immuno-suppression. Therefore they are susceptible to get saprophytic fungi infection that sometimes are killer. Materials and Methods: The purpose of this cross-sectional survey is isolation of saprophytic fungi from patients with BMT and wards space and instruments. Therefore sampling from ventilator system (HEPA filter and common filter, air canal, air, hospital instruments and clinical samples (nasal discharge, sputum, urine were done and cultured in sabouro dextrose agar with choloramphenicol (SC. In assessing total frequency from 4838 plates of wards space and instruments, 985 fungi colonies includes 21 genus were isolated. Results and Conclusion: Most fungi colonies present were Penicillium , Aspergillus and Cladosporium and low present were Trichoderma ,Stereptomyses, Chrysosporium, Rhizopus.

  13. [EFFECTS OF BONE MARROW MESENCHYMAL STEM CELLS TRANSPLANTATION FOR TREATING RAT SPINAL CORD INJURY AND CYTOKINE EXPRESSION AT INJURY SITES].

    Science.gov (United States)

    Mo, Cuiping; Ren, Lijie; Zhao Zhenfu; Zhou, Guangqian; Yao, Xiaolu; Gong, Feipeng; Chen, Gang

    2016-03-01

    To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) transplantation for treating spinal cord injury (SCI) in rat and the cytokine expression changes in the local injury tissues. BMSCs were separated from Sprague Dawley (SD) rat and cultured with the whole bone marrow culture method. rAd-EGFP was used to transfect the 5th generation BMSCs for green fluorescent protein (GFP) label. Twelve SD rats were randomly divided into experimental group (n = 6) and control group (n = 6). After the T10 SCI model was established with Allen's impact device in 2 groups, 1 x 1096) GFP-labeled BMSCs and PBS were administered by subarachnoid injection in situ in experimental group and control group, respectively. Basso-Beattie-Bresnahan (BBB) score was used to detect the motor function at immediat, 1, 2, 3, 4, and 5 weeks after SCI. At 5 weeks, the spinal cord tissues were harvested for the histological and immunofluorescent staining examinations to measure the expressions of neural marker molecules, including Nestin, glial fibrillary acidic protein (GFAP), and neuron-specific nuclear protein (NeuN). Cytokine was analyzed with antibody array. At 5 weeks, 2 rats died of urinary tract infection in 2 groups respectively, the other rats survived to the end of experiment. BBB score of experimental group was significantly higher than that of control group at 1, 2, 3, 4, and 5 weeks (P < 0.05). At 5 weeks, histological results showed that there were many cells with regular arrangement in the experimental group; there were less cells with irregular arrangement in the control group. Compared with the control group, Nestin and NeuN expressions significantly increased (P < 0.05), and GFAP expression significantly decreased (P < 0.05) in the experimental group. Leptin and ciliary neurotrophic factor levels were higher in the experimental group than the control group, but granulocyte-macrophage colony-stimulating factor, tumor necrosis factor β, interleukin 1 β, and tissue

  14. Dose escalation of consolidation radiation therapy (involved field) following autologous bone marrow transplant for recurrent Hodgkin's disease and lymphoma

    International Nuclear Information System (INIS)

    Brasacchio, R.; Constine, L; Rapoport, A; Rowe, J.; Liesveld, J.; Muhs, A.; Rubin, P.

    1996-01-01

    Purpose: Patients with recurrent or refractory non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) are frequently treated with intensive chemotherapy and autologous stem-cell rescue. Subsequent relapse is usually in sites of previous disease. We questioned whether radiotherapy (RT) to such sites after autologous bone marrow transplant (ABMT) might diminish such failures while not interrupting pre-ABMT chemotherapy or increasing peri-transplant morbidity. Methods: Since 11/88, 225 patients with recurrent or refractory NHL or or HD have undergone ABMT. Since 9/90, involved field (IF) RT was administered between 4-12 weeks post-ABMT to 70 of these patients who entered pre-transplant salvage chemotherapy with clinical or radiographic evidence of disease. The dose of IFRT was dependent on the disease response to induction chemotherapy and the BMT conditioning regimen. Patients demonstrating a complete response (CR) to reinduction chemo received 20 Gy IFRT. Patients with residual disease at the time of BMT but demonstrating a CR to the BMT conditioning regimen received 30 Gy. Patients with identifiable disease post BMT who showed diminution of disease after 30 Gy were boosted to 36 - 40 Gy. Patients were not irradiated if they had received TBI, previous RT to sites of concern, refused RT, relapsed too quickly to receive RT, or were in complete remission by ABMT. Patients were also analyzed according to their disease burden at ABMT defined as 2 cm disease. Field placement and design to include tumor volume was tailored to response but initially included the preBMT tumor volume with cone-down as dose was escalated in order to exclude dose limiting normal tissue. Results: The results are promising, and similar to our previously reported 3 years survival. For all patients, the 3-year actuarial event-free survival (EFS) rate (Kaplan-Meier log rank test) for 150 NHL and 75 HD patients is 45% and 50%, respectively. The 2 year EFS for NHL patients treated with or without

  15. Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission

    DEFF Research Database (Denmark)

    Nagler, Arnon; Labopin, Myriam; Shimoni, Avichai

    2012-01-01

    -IV) and chronic GVHD did not differ between the groups. leukemia-free survival (LFS), relapse, and non-relapsed mortality (NRM) were 51 ± 2%, 32 ± 1%, and 17 ± 1% vs. 50 ± 6%, 38 ± 6%, and 12 ± 3% for the PBSC and BM groups, respectively. Our results indicate faster engraftment, but no difference in GVHD, LFS......Reduced-intensity conditioning (RIC)-alloSCT is increasingly used for acute myelogenous leukemia. Limited data are available for the comparison of peripheral blood stem cells with bone marrow for RIC-alloSCT. We used the European Group for Blood and Marrow Transplantation (EBMT) ALWP data...... to compare the outcome of mobilized peripheral blood stem cells (PBSC) (n = 1430) vs. bone marrow (BM) (n = 107) for acute myelogenous leukemia (AML) patients with complete remission that underwent RIC-alloSCT from compatible sibling donors. The leukemia features, the disease status, and the time from...

  16. Transplantation of autologous bone marrow stem cells via hepatic artery for the treatment of acute hepatic injury: an experimental study in rabbits

    International Nuclear Information System (INIS)

    Zhu Yinghe; Han Jinling; Liu Yanping; Gao Jue; Xu Ke; Zhang Xitong; Ding Guomin

    2009-01-01

    Objective: To evaluate the transplantation of autologous bone marrow stem cells via hepatic artery in treating acute hepatic injury in experimental rabbit models and to clarify the synergistic effect of hepatocyte growth-promoting factor (pHGF) in stem cell transplantation therapy for liver injury. Methods Acute hepatic injury models were established in 15 experimental rabbits by daily subcutaneous injection of CCl 4 olive oil solution with the dose of 0.8 ml/kg for 4 days in succession. The experimental rabbits were randomly and equally divided into three groups: study group A (stem cell transplant, n = 5), study group B (stem cell transplant + pFHG, n = 5), and control group (n = 5). Bone marrow of 5 ml was drawn from the tibia in all rabbits of both study groups, from which bone marrow stem cells were isolated by using density gradient centrifugation, and 5 ml cellular suspension was prepared. Under fluoroscopic guidance, catheterization through the femoral artery was performed and the cellular suspension was infused into the liver via the hepatic artery. Only injection of saline was carried out in the rabbits of control group. For the rabbits in group B, pFHG (2.0 mg/kg) was administered intravenously every other day for 20 days. At 2, 4 and 8 weeks after stem cell transplantation, hepatic function was determined. Eight weeks after the transplantation all the rabbits were sacrificed and the liver specimens were collected and sent for pathological examination. Results After stem cell transplantation, the hepatic function was gradually improved.Eight weeks after the transplantation, the activity of AST, ALT and the content of ALB, TBIL were significantly lower than that before the procedure, while the content of GOLB was markedly increased in all rabbits. In addition, the difference in the above parameters between three groups was statistically significant (P < 0.05). Pathologically, the hepatocyte degeneration and the fiberous hyperplasia in the study groups

  17. Clinical and epidemiological analysis of bone marrow transplantation in a pediatric oncology unit

    OpenAIRE

    Castro Junior, Cláudio Galvão de; Gregianin, Lauro José; Brunetto, Algemir Lunardi

    2003-01-01

    OBJETIVOS: Descrever o perfil e as complicações agudas mais importantes das crianças que receberam transplante de medula óssea no serviço de oncologia pediátrica do Hospital de Clínicas de Porto Alegre. CASUÍSTICA E MÉTODOS: Análise retrospectiva de 41 pacientes, menores de 21 anos, transplantados entre agosto de 1997 até junho de 2002. Deste total, 20 pacientes receberam transplante alogênico, e 21 transplante autogênico. RESULTADOS: No transplante de medula óssea alogênico, a média de idade...

  18. Utility of the inspiratory phase in high-resolution computed tomography evaluations of pediatric patients with bronchiolitis obliterans after allogeneic bone marrow transplant: reducing patient radiation exposure

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Togni Filho

    Full Text Available Abstract Objective: To evaluate the utility of the inspiratory phase in high-resolution computed tomography (HRCT of the chest for the diagnosis of post-bone marrow transplantation bronchiolitis obliterans. Materials and Methods: This was a retrospective, observational, cross-sectional study. We selected patients of either gender who underwent bone marrow transplantation and chest HRCT between March 1, 2002 and December 12, 2014. Ages ranged from 3 months to 20.7 years. We included all examinations in which the HRCT was performed appropriately. The examinations were read by two radiologists, one with extensive experience in pediatric radiology and another in the third year of residency, who determined the presence or absence of the following imaging features: air trapping, bronchiectasis, alveolar opacities, nodules, and atelectasis. Results: A total of 222 examinations were evaluated (mean, 5.4 ± 4.5 examinations per patient. The expiratory phase findings were comparable to those obtained in the inspiratory phase, except in one patient, in whom a small uncharacteristic nodule was identified only in the inspiratory phase. Air trapping was identified in a larger number of scans in the expiratory phase than in the inspiratory phase, as was atelectasis, although the difference was statistically significant only for air trapping. Conclusion: In children being evaluated for post-bone marrow transplantation bronchiolitis obliterans, the inspiratory phase can be excluded from the chest HRCT protocol, thus reducing by half the radiation exposure in this population.

  19. Treated of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue

    International Nuclear Information System (INIS)

    Yasumizu, R.; Sugiura, K.; Iwai, H.

    1987-01-01

    Non-obese diabetic (NOD) mice provide a model for type 1 diabetes mellitus. We previously showed that allogeneic bone marrow transplantation (ABMT) can prevent and treat insulitis and overt diabetes in NOD mice. However, ABMT alone could not be used to treat overt diabetes in NOD mice whose islets had been completely destroyed. To provide insulin-producing cells, pancreatic tissue from newborn mice was grafted under the renal capsules in combination with ABMT. The aims of concomitant ABMT are as follows. (i) It induces immunological tolerance to the donor-type major histocompatibility complex determinants and permits the host to accept subsequent pancreatic allografts from the bone marrow donor. (ii) ABMT replaces abnormal stem cells with normal stem cells. After transplantation of bone marrow plus newborn pancreas, NOD mice showed reduction of the glycosuria and a normal response in the glucose-tolerance test. Immunohistological study revealed the presence of clustered insulin-containing beta cells in the grafted pancreatic transplants. ABMT may become a viable treatment of established type 1 diabetes mellitus in humans

  20. Long-term clinical results of autologous bone marrow CD 133+ cell transplantation in patients with ST-elevation myocardial infarction

    Science.gov (United States)

    Kirgizova, M. A.; Suslova, T. E.; Markov, V. A.; Karpov, R. S.; Ryabov, V. V.

    2015-11-01

    The aim of the study was investigate the long-term results of autologous bone marrow CD 133+ cell transplantation in patients with primary ST-Elevation Myocardial Infarction (STEMI). Methods and results: From 2006 to 2007, 26 patients with primary STEMI were included in an open randomized study. Patients were randomized to two groups: 1st - included patients underwent PCI and transplantation of autologous bone marrow CD 133+ cell (n = 10); 2nd - patients with only PCI (n = 16). Follow-up study was performed 7.70±0.42 years after STEMI and consisted in physical examination, 6-min walking test, Echo exam. Total and cardiovascular mortality in group 1 was lower (20% (n = 2) vs. 44% (n = 7), p = 0.1 and 22% (n = 2) vs. 25% (n = 4), (p=0.53), respectively). Analysis of cardiac volumetric parameters shows significant differences between groups: EDV of 100.7 ± 50.2 mL vs. 144.40±42.7 mL, ESV of 56.3 ± 37.8 mL vs. 89.7 ± 38.7 mL in 1st and 2nd groups, respectively. Data of the study showed positive effects of autologous bone marrow CD 133+ cell transplantation on the long-term survival of patients and structural status of the heart.

  1. Utility of the inspiratory phase in high-resolution computed tomography evaluations of pediatric patients with bronchiolitis obliterans after allogeneic bone marrow transplant: reducing patient radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Togni Filho, Paulo Henrique; Casagrande, Joao Luiz Marin; Lederman, Henrique Manoel, E-mail: paulotognifilho@gmail.com [Universidade Federal de Sao Paulo (EPM/UNIFESP), Sao Paulo, SP (Brazil). Escola Paulista de Medicina. Dept. of Diagnostico por Imagem; Universidade de Sao Paulo (InRad/HC/FMUSP), Sao Paulo, SP (Brazil). Hospital das Clinicas. Instituto de Radiologia

    2017-03-15

    Objective: To evaluate the utility of the inspiratory phase in high-resolution computed tomography (HRCT) of the chest for the diagnosis of post-bone marrow transplantation bronchiolitis obliterans. Materials and Methods: This was a retrospective, observational, cross-sectional study. We selected patients of either gender who underwent bone marrow transplantation and chest HRCT between March 1, 2002 and December 12, 2014. Ages ranged from 3 months to 20.7 years. We included all examinations in which the HRCT was performed appropriately. The examinations were read by two radiologists, one with extensive experience in pediatric radiology and another in the third year of residency, who determined the presence or absence of the following imaging features: air trapping, bronchiectasis, alveolar opacities, nodules, and atelectasis. Results: A total of 222 examinations were evaluated (mean, 5.4 ± 4.5 examinations per patient). The expiratory phase findings were comparable to those obtained in the inspiratory phase, except in one patient, in whom a small uncharacteristic nodule was identified only in the inspiratory phase. Air trapping was identified in a larger number of scans in the expiratory phase than in the inspiratory phase, as was atelectasis, although the difference was statistically significant only for air trapping. Conclusion: In children being evaluated for post-bone marrow transplantation bronchiolitis obliterans, the inspiratory phase can be excluded from the chest HRCT protocol, thus reducing by half the radiation exposure in this population. (author)

  2. Nosocomial coagulase-negative staphylococcal infections in bone marrow transplantation recipients with central vein catheter. A 5-year prospective study.

    Science.gov (United States)

    Engelhard, D; Elishoov, H; Strauss, N; Naparstek, E; Nagler, A; Simhon, A; Raveh, D; Slavin, S; Or, R

    1996-02-15

    The purpose of this study was to examine coagulase-negative staphylococcal infections in bone marrow transplantation (BMT) patients with central vein catheters by investigating incidence, clinical relevance, risk factors, methicillin resistance, clinical impact of initial empiric antimicrobial therapy without vancomycin, and management of documented catheter-related infections. A 5-year prospective study was conducted with daily evaluation of 242 BMT patients during hospitalization, including clinical assessment and blood culture via the Hickman/Broviac catheter. If fever or infected appearance occurred, peripheral blood cultures or exit site cultures, respectively, were done. Results showed a septicemia incidence of 7.0%, including in 6 patients following colonization, in 1 patient with tunnel infection, in 1 patient with thrombophlebitis, in 1 patient with exit site infection, and in 8 patients with septicemia of unknown origin. Total colonization incidence was 7%, with colonization only in 11 patients who had 16 episodes; incidence of exit site infection was 3.7%. Age > or = 18 years was the only identified risk factor for developing staphylococcal infection (P = 0.03). Despite a methicillin resistance rate of 45% and omission of vancomycin from the routine initial empiric antimicrobial regimen, the clinical course of coagulase-negative staphylococcal infections was relatively benign. A single patient, who experienced marrow rejection, died on day +31 with septicemia and only one patient experienced microbiological failure with recurrent colonization. Bacteria grown in both aerobic and anaerobic bottles were more likely true bacteremia than contaminant (P = 0.03). We conclude that the hazard of coagulase-negative staphylococcal infection does not mandate inclusion of a glycopeptide in the initial empiric antimicrobial regimen in BMT patients, even during febrile neutropenia. Hickman/Broviac-related staphylococcal infections, except for tunnel infection or

  3. Immunological effects of donor lymphocyte infusion in patients with chronic myelogenous leukemia relapsing after bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Castro F.A.

    2004-01-01

    Full Text Available Allogeneic bone marrow transplantation (alloBMT is the only curative therapy for chronic myelogenous leukemia (CML. This success is explained by the delivery of high doses of antineoplastic agents followed by the rescue of marrow function and the induction of graft-versus-leukemia reaction mediated by allogeneic lymphocytes against host tumor cells. This reaction can also be induced by donor lymphocyte infusion (DLI producing remission in most patients with CML who relapse after alloBMT. The immunological mechanisms involved in DLI therapy are poorly understood. We studied five CML patients in the chronic phase, who received DLI after relapsing from an HLA-identical BMT. Using flow cytometry we evaluated cellular activation and apoptosis, NK cytotoxicity, lymphocytes producing cytokines (IL-2, IL-4 and IFN-gamma, and unstimulated (in vivo lymphocyte proliferation. In three CML patients who achieved hematological and/or cytogenetic remission after DLI we observed an increase of the percent of activation markers on T and NK cells (CD3/DR, CD3/CD25 and CD56/DR, of lymphocytes producing IL-2 and IFN-gamma, of NK activity, and of in vivo lymphocyte proliferation. These changes were not observed consistently in two of the five patients who did not achieve complete remission with DLI. The percent of apoptotic markers (Fas, FasL and Bcl-2 on lymphocytes and CD34-positive cells did not change after DLI throughout the different study periods. Taken together, these preliminary results suggest that the therapeutic effect of DLI in the chronic phase of CML is mediated by classic cytotoxic and proliferative events involving T and NK cells but not by the Fas pathway of apoptosis.

  4. Electrical Stimulation Enhances Migratory Ability of Transplanted Bone Marrow Stromal Cells in a Rodent Ischemic Stroke Model.

    Science.gov (United States)

    Morimoto, Jun; Yasuhara, Takao; Kameda, Masahiro; Umakoshi, Michiari; Kin, Ittetsu; Kuwahara, Ken; Kin, Kyohei; Okazaki, Mihoko; Takeuchi, Hayato; Sasaki, Tatsuya; Toyoshima, Atsuhiko; Tajiri, Naoki; Agari, Takashi; Borlongan, Cesario V; Date, Isao

    2018-03-20

    Bone marrow stromal cells (BMSCs) transplantation is an important strategy for the treatment of ischemic stroke. Currently, there are no effective methods to guide BMSCs toward the targeted site. In this study, we investigated the effect of electrical stimulation on BMSCs migration in an ischemic model of rats. Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. BMSCs (2.5×105 cells/ 4 µl PBS) were stereotaxically injected into the left corpus callosum at 1 day after MCAO. After BMSCs injection, a plate electrode with a diameter of 3 mm connected to an implantable electrical stimulator was placed on the right frontal epidural space and a counter electrode was placed in the extra-cranial space. Electrical stimulation at preset current (100 µA) and frequency (100 Hz) was performed for two weeks. Behavioral tests were performed at 1, 4, 8, and 15 days after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at 15 days after MCAO for evaluation of infarction area and the migration distance and area of BMSCs found in the brain tissue. After evaluating cell migration, we proceeded to explore the mechanisms guiding these observations. MCAO rats without BMSCs transplantation were stimulated with same current and frequency. At 1 and 2 weeks after MCAO, rats were euthanized to evaluate stromal cell-derived factor 1 alpha (SDF-1α) level of brain tissues in the bilateral cortex and striatum. Behavioral tests at 4, 8, and 15 days after MCAO revealed that stimulation group displayed significant amelioration in mNSS and cylinder test compared to control group (pstimulation group were significantly decreased compared to control group (pstimulation group. An increased concentration gradient of SDF-1α in stimulation group accompanied this enhanced migration of transplanted cells. These results suggest that electrical stimulation enhances migratory ability of

  5. Effects of blood transfusion and cyclophosphamide before total lymphoid irradiation on survival of rats with bone marrow transplantation

    International Nuclear Information System (INIS)

    Ran Xinze; Yan Yongtang

    1994-01-01

    The effects of blood transfusion at various intervals before and after bone marrow transplantation (BMT) and with different donors on the survival of rats with BMT were investigated. Cyclophosphamide was administered before total lymphoid irradiation (TLI) with 10 Gy γ-rays from a 60 Co source. All the rats in control groups and in the group with blood transfusion alone died within 4-12 days after TLI. The 60-day survival rate after TLI in the group of donor-specific blood transfusion given one day after BMT was not significantly different from that in the group with BMT alone (the 60-day survival rate was 10%). The survival rates in the groups with transfusion of both donor specific and non-specific blood one day before BMT were 20% and 40% (P<0.05) respectively. All the rats given blood transfusion three days before BMT died within 4-10 days after TLI. The survival rate in the group with both donor-specific blood transfusion and cyclophosphamide given in divided dose one day before BMT increased to 80% (P<0.01). The results show that the therapeutic effect of blood transfusion on rats with BMT is related to the time of blood transfusion

  6. POLYCLONAL OUTBREAK OF BLOODSTREAM INFECTIONS CAUSED BY Burkholderia cepacia COMPLEX IN HEMATOLOGY AND BONE MARROW TRANSPLANT OUTPATIENT UNITS

    Science.gov (United States)

    Boszczowski, Icaro; do Prado, Gladys Villas Boas; Dalben, Mirian F.; Telles, Roberto C. P.; Freire, Maristela Pinheiro; Guimarães, Thaís; Oliveira, Maura S.; Rosa, Juliana F.; Soares, Robson E.; Llacer, Pedro Enrique Dorlhiac; Dulley, Frederico Luiz; Costa, Silvia F.; Levin, Anna S.

    2014-01-01

    Aim: The objective was to describe an outbreak of bloodstream infections by Burkholderia cepacia complex (Bcc) in bone marrow transplant and hematology outpatients. Methods: On February 15, 2008 a Bcc outbreak was suspected. 24 cases were identified. Demographic and clinical data were evaluated. Environment and healthcare workers' (HCW) hands were cultured. Species were determined and typed. Reinforcement of hand hygiene, central venous catheter (CVC) care, infusion therapy, and maintenance of laminar flow cabinet were undertaken. 16 different HCWs had cared for the CVCs. Multi-dose heparin and saline were prepared on counter common to both units. Findings: 14 patients had B. multivorans (one patient had also B. cenopacia), six non-multivorans Bcc and one did not belong to Bcc. Clone A B. multivorans occurred in 12 patients (from Hematology); in 10 their CVC had been used on February 11/12. Environmental and HCW cultures were negative. All patients were treated with meropenem, and ceftazidime lock-therapy. Eight patients (30%) were hospitalized. No deaths occurred. After control measures (multidose vial for single patient; CVC lock with ceftazidime; cleaning of laminar flow cabinet; hand hygiene improvement; use of cabinet to store prepared medication), no new cases occurred. Conclusions: This polyclonal outbreak may be explained by a common source containing multiple species of Bcc, maybe the laminar flow cabinet common to both units. There may have been contamination by B. multivorans (clone A) of multi-dose vials. PMID:24553612

  7. Manhattan transfer: lethal radiation, bone marrow transplantation, and the birth of stem cell biology, ca. 1942-1961.

    Science.gov (United States)

    Kraft, Alison

    2009-01-01

    This study investigates how, in the late 1940s and 1950s, fears of nuclear accidents and nuclear warfare shaped postwar radiobiology. The new and intense forms of radiation generated by nuclear reactor technology, and which would be released in the event of a nuclear war, created concerns about a public-health hazard unprecedented in form and scale. Fears of inadvertent exposure to acute and potentially lethal radiation launched a search for anti-radiation therapies, out of which emerged the new technique of bone marrow transplantation (BMT). This study analyzes the use of BMT first as a research tool to explore the biological effects of ionizing radiation, and then as an adjunct to radiotherapy for the treatment of cancer. In highlighting how BMT became the province of different research and clinical constituencies, this study develops an understanding of the forces and contingencies that shaped its development. Exploring the emergence of BMT and the uses to which it was put, it reveals that BMT remained a technique in the making -- unstable and far from standardized, even as it became both a widely used research tool and rapidly made its way into the clinic. More broadly, it casts new light on one route through which the Manhattan Project influenced postwar radiobiology; it also affords new insights into one means by which radiobiology came to serve the interests of the Cold War state. In its focus on BMT this paper provides a new perspective on the evolving relationship between radiobiology and biomedicine in the postwar period.

  8. Kinetics and biodistribution of In-111 platelets in patients with bone marrow transplants, refractory to platelet transfusions

    International Nuclear Information System (INIS)

    Civelek, C.; Braine, H.; Scheffel, U.; Drew, H.; Koester, A.; LaFrance, N.; Kasecamp, W.; Wagner, H. Jr.

    1984-01-01

    The kinetics and biodistribution of HLA identical In-111 labeled platelets was studied in 10 leukemic patients with bone marrow transplants refractory to HLA matched platelet transfusions. Platelet survival time was short (x-bar +- SEM =1.64 +- 0.83 days). The mean recovery (extrapolated to zero time) was 29.9%, ranging from 14.2 to 63.0%. The deposition of the In-111 platelets in the liver and spleen was quantified by the geometric mean method using anterior and posterior imaging. In 3 patients liver uptake was significantly increased. The highest hepatic accumulation of In-111 occurred 2 hrs after injection (x-bar=76 +- 6% dose (SEM); at 48 hrs 62% of the dose remained in the liver. In 7 patients the spleen was the organ with the highest labeled platelet deposition. The splenic uptake of In-111 platelets in this group correlated with the spleen size (r=+0.95). At 30 min after injection 75+-6% of the dose was found in the spleen. Splenic activity decreased to 62% after 48 hrs. At the same time, In-111 liver accumulation increased from 14 to 31%. This finding suggests that In-111 may be released from the spleen and subsequently sequestered by the liver. Two patients with high splenic uptake underwent splenectomy after the In-111 platelet study. Both benefited from splenectomy in terms of platelet survival after transfusion

  9. B-cell dysfunction following human bone marrow transplantation: functional-phenotypic dissociation in the early posttransplant period.

    Science.gov (United States)

    Kagan, J M; Champlin, R E; Saxon, A

    1989-08-01

    We investigated the defect in humoral immunity that occurs following bone marrow transplantation (BMT). B cells from BMT recipients were tested for their ability to undergo the sequential steps of activation (RNA synthesis on stimulation with anti-mu or PMA), proliferation (DNA synthesis on stimulation with anti-mu plus B cell growth factor [BCGF], phorbol myristate acetate [PMA], or Staphylococcus aureus Cowan I [SAC] strain bacteria) and differentiation (Ig synthesis stimulated by T cell replacing factor [TRF]). B-cell maturation-associated cell surface markers were simultaneously investigated. "Early" (less than 10 months) posttransplant patients demonstrated defective B-cell activation and also failed to undergo normal proliferation and differentiation. Despite their functional impairment, the early patients' B cells displayed an "activated" phenotype with increased proportions of B cells displaying CD23 (a BCGF receptor) and decreased proportions of Leu 8+ B cells. Furthermore, these patients were uniquely distinguished by the fact that their B cells only weakly (if at all) expressed the CD19 antigen. In contrast, B cells from "late" patients (greater than or equal to 10 months post-BMT) activated and proliferated normally and displayed a normal cell surface phenotype, yet were unable to differentiate to high rate Ig secretion with TRF. Our results suggest a phenotype/function dissociation in early posttransplant period. With time, B cells in BMT patients acquire a normal surface phenotype and can activate and proliferate normally, yet still demonstrate a block in terminal differentiation.

  10. The effect of total body irradiation and bone marrow transplantation during childhood and adolescence on growth and endocrine function

    International Nuclear Information System (INIS)

    Leiper, A.D.; Stanhope, R.; Lau, T.; Grant, D.B.; Blacklock, H.; Chessells, J.M.; Plowman, P.N.

    1987-01-01

    Seventeen children with acute leukaemia and myeloproliferative disorders were investigated for growth and endocrine dysfunction. All had undergone bone marrow transplantation prepared with cyclophosphamide and single fraction total body irradiation (900-1000 cGy) between 1.5 and 3.8 (mean 2.2) years previously. The majority exhibited growth failure, of multiple aetiology. Ten patients, of whom eight had had previous prophylactic cranial irradiation, had evidence of growth hormone deficiency based on reduced growth hormone reponse to insulin induced hypoglycaemia. Three had evidence of hypothalamic damage. Gonadal failure was common. All four girls of adolescent age (10.6-14.1 years) had ovarian failure requiring sex steroid replacement. Of eight boys of adolescent age (12.3-18.3 years), two had testicular failure requiring sex steroid supplements. Both had had previous testicular irradiation. Five others had compensated gonadal failure; one had normal Leydig cell function. Abnormalities of the TSH response to TRH occurred in 10 patients but only three had overt hypothyroidism. Unlike growth hormone deficiency, gonadal and thyroid dysfunction showed no correlation with previous cranial radiotherapy. (author)

  11. Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia

    NARCIS (Netherlands)

    Kekre, Natasha; Zhang, Ying; Zhang, Mei Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem M.; Joachim Deeg, H.; Kapoor, Neena; Lee, Jong Wook; Nakamura, Ryotaro; Pulsipher, Michael A.; Eapen, Mary; Antin, Joseph H

    2017-01-01

    For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin

  12. In vivo expansion of the endogenous B-cell compartment stimulated by radiation and serial bone marrow transplantation induces B-cell leukaemia in mice.

    Science.gov (United States)

    Holyoake, T L; Freshney, M G; Samuel, K; Ansell, J; Watson, G E; Wright, E G; Graham, G J; Pragnell, I B

    2001-07-01

    Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5(+) B cells. This B-cell lineage is established during ontogeny and replenished by the process of self-renewal. Spontaneous and induced leukaemias that frequently affect this lineage are thought to arise as a result of the frequent cell division required to maintain the population throughout adulthood and in response to repeated exposure to environmental antigens. In a series of bone marrow transplant (BMT) experiments performed in B6D2F1 mice, B-cell leukaemia occurred in recipients of serially transplanted syngeneic bone marrow. This study was therefore designed to determine the frequency and phenotype of the observed leukaemia. Male donor cells were initially transplanted into lethally irradiated female hosts and secondary (2 degrees ) BMT was performed at 3 months. At 1, 2, 3 and 16 months following primary (1 degrees ) BMT, and when 2 degrees BMT recipients developed leukaemia, animals were sacrificed and their tissues extensively examined. These analyses confirmed a host-derived CD5(+) transplantable B-cell leukaemia that was initiated in 50% of 1 degrees BMT recipients. With serial passage, the leukaemia became more aggressive and lost CD5 expression, suggesting transformation to a high-grade leukaemia/lymphoma. This previously unreported observation suggests that the combination of radiation and subsequent serial transplantation induces a proliferative stress to the host B-cell compartment that is causative in leukaemic transformation.

  13. Resident Arterial Cells and Circulating Bone Marrow-Derived Cells both Contribute to Intimal Hyperplasia in a Rat Allograft Carotid Transplantation Model

    Directory of Open Access Journals (Sweden)

    Yi He

    2017-07-01

    Full Text Available Background/Aims: Neointimal formation following vascular injury remains a major mechanism of restenosis, whereas the precise sources of neointimal cells are still uncertain. We tested the hypothesis that both injured arterial cells and non-arterial cells contribute to intimal hyperplasia. Methods: Following allograft transplantation of the balloon-injured carotid common artery (n = 3-6, the cellular composition of the transplant grafts and the origins of neointimal cells were measured by immunohistochemistry and immunofluorescence staining. Results: Smooth muscle actin (SMA-positive and CD68-positive cells were clearly observed 14 days later in the neointima after allograft transplantation of the balloon-injured carotid common artery, where re-endothelialization was not yet complete. Green fluorescent protein (GFP and wild-type (WT allograft transplantation revealed that the majority of the neointima cells were apparently from the recipient (≈85% versus the donor (≈15%. Both monocyte chemotactic protein-1 (MCP-1/CCR2 and stromal cell-derived factor-1 (SDF-1/CXCR4 signaling were involved in intimal hyperplasia, with bone marrow-derived cells also playing a role. Conclusion: These data support the hypothesis that intimal hyperplasia could develop in our novel rat allograft transplantation model of arterial injury, where neointima is attributable not only to local arterial cells but also non-arterial cells including the bone marrow.

  14. Second allogeneic hematopoietic cell transplantation for Patients with Fanconi anemia and Bone Marrow Failure

    Science.gov (United States)

    Ayas, Mouhab; Eapen, Mary; Le-Rademacher, Jennifer; Carreras, Jeanette; Abdel-Azim, Hisham; Alter, Blanche P.; Anderlini, Paolo; Battiwalla, Minoo; Bierings, Marc; Buchbinder, David K.; Bonfim, Carmem; Camitta, Bruce M.; Fasth, Anders L.; Gale, Robert Peter; Lee, Michelle A.; Lund, Troy C.; Myers, Kasiani C.; Olsson, Richard F.; Page, Kristin M.; Prestidge, Tim D.; Radhi, Mohamed; Shah, Ami J.; Schultz, Kirk R.; Wirk, Baldeep; Wagner, John E.; Deeg, H. Joachim

    2015-01-01

    Second allogeneic hematopoietic cell transplantation (HCT) is the only salvage option for those for develop graft failure after their first HCT. Data on outcomes after second HCT in Fanconi anemia (FA) are scarce. We report outcomes after second allogeneic HCT for FA (n=81). The indication for second HCT was graft failure after the first HCT. Transplants occurred between 1990 and 2012. The timing of second transplantation predicted subsequent graft failure and survival. Graft failure was high when the second transplant occurred less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between first and second transplant was less than 3 months compared to 23% when the interval was longer (pfirst and second transplant was less than 3 months, 23% at 1-year compared to 58%, when the interval was longer (p=0.001). The corresponding 5-year probabilities of survival were 16% and 45%, respectively (p=0.006). Taken together, these data suggest that fewer than half of FA patients undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to lower graft failure after first HCT. PMID:26116087

  15. Total lymphoid irradiation and cyclophosphamide conditioning prior to bone marrow transplantation for patients with severe aplastic anemia

    International Nuclear Information System (INIS)

    Ramsay, N.K.; Kim, T.H.; McGlave, P.; Goldman, A.; Nesbit, M.E. Jr.; Krivit, W.; Woods, W.G.; Kersey, J.H.

    1983-01-01

    A preparative regimen, consisting of total lymphoid irradiation and cyclophosphamide, was utilized in 40 patients with severe aplastic anemia undergoing allogeneic marrow transplantation. This regimen was successful in decreasing rejection in these previously transfused patients, as only one patient rejected the marrow graft. Twenty-nine of the 40 transplanted patients are surviving from 1.5 to 59 mo, with a median follow-up of 24 mo. The actuarial survival rate for these heavily transfused patients with aplastic anemia is 72% at 2 yr. This preparative regimen is extremely effective in decreasing rejection following transplantation for severe aplastic anemia. Future efforts in this area must be aimed at the elimination of graft-versus-host disease and control of fatal infections

  16. Epiretinal transplantation of human bone marrow mesenchymal stem cells rescues retinal and vision function in a rat model of retinal degeneration.

    Science.gov (United States)

    Tzameret, Adi; Sher, Ifat; Belkin, Michael; Treves, Avraham J; Meir, Amilia; Nagler, Arnon; Levkovitch-Verbin, Hani; Rotenstreich, Ygal; Solomon, Arieh S

    2015-09-01

    Vision incapacitation and blindness associated with incurable retinal degeneration affect millions of people worldwide. In this study, 0.25×10(6) human bone marrow stem cells (hBM-MSCs) were transplanted epiretinally in the right eye of Royal College Surgeons (RCS) rats at the age of 28 days. Epiretinally transplanted cells were identified as a thin layer of cells along vitreous cavity, in close proximity to the retina or attached to the lens capsule, up to 6 weeks following transplantation. Epiretinal transplantation delayed photoreceptor degeneration and rescued retinal function up to 20 weeks following cell transplantation. Visual functions remained close to normal levels in epiretinal transplantation rats. No inflammation or any other adverse effects were observed in transplanted eyes. Our findings suggest that transplantation of hBM-MSCs as a thin epiretinal layer is effective for treatment of retinal degeneration in RCS rats, and that transplanting the cells in close proximity to the retina enhances hBM-MSC therapeutic effect compared with intravitreal injection. Copyright © 2015. Published by Elsevier B.V.

  17. [General and ethical considerations for the informed consent process: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

    Science.gov (United States)

    Thibert, Jean-Baptiste; Polomeni, Alice; Yakoub-Agha, Ibrahim; Bordessoule, Dominique

    2016-11-01

    Informed consent is not restricted to clinical research and must be applied to high-risk care such as hematopoietic stem cell transplantation. If standardized informed consent might improve inequalities in medical practices between different transplantation centers, it is strongly recommended that it be adapted with an honest dialogue between physicians and patients and physicians and donors. In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country. The purpose of this paper is to highlight the French law concerning patients' rights and ethical practices for an informed consent process to be applied to care or research. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  18. Rescuing Self: Transient Isolation and Autologous Transplantation of Bone Marrow Mitigates Radiation-Induced Hematopoietic Syndrome and Mortality in Mice.

    Science.gov (United States)

    Ghosh, Subhajit; Indracanti, Namita; Joshi, Jayadev; Indraganti, Prem Kumar

    2017-01-01

    The inflamed bone marrow niche shortly after total body irradiation (TBI) is known to contribute to loss of hematopoietic stem cells in terms of their number and function. In this study, autologous bone marrow transfer (AL-BMT) was evaluated as a strategy for mitigating hematopoietic form of the acute radiation syndrome by timing the collection phase (2 h after irradiation) and reinfusion (24 h after irradiation) using mice as a model system. Collection of bone marrow (BM) cells (0.5 × 10 6 total marrow cells) 2 h after lethal TBI rescued different subclasses of hematopoietic stem and progenitor cells (HSPCs) from the detrimental inflammatory and damaging milieu in vivo . Cryopreservation of collected graft and its reinfusion 24 h after TBI significantly rescued mice from lethal effects of irradiation (65% survival against 0% in TBI group on day 30th) and hematopoietic depression. Transient hypometabolic state (HMS) induced 2 h after TBI effectively preserved the functional status of HSPCs and improved hematopoietic recovery even when BM was collected 8 h after TBI. Homing studies suggested that AL-BMT yielded similar percentages for different subsets of HSPCs when compared to syngeneic bone marrow transfer. The results suggest that the timing of collection, and reinfusion of graft is crucial for the success of AL-BMT.

  19. Bone marrow transplantation for girls with aplastic anemia utilizing modified field of total lymphoid irradiation and cyclophosphamide; With emphasis on the field of pelvic cavity

    Energy Technology Data Exchange (ETDEWEB)

    Hanada, Ryoji; Kawakami, Tetsuo; Akuta, Naoko; Moriwaki, Kohichi; Kato, Shizue; Inaba, Toshiya; Hayashi, Yasuhide; Yamamoto, Keiko (Saitama Children' s Medical Center, Saitama (Japan))

    1990-12-01

    A preparative regimen for allogeneic bone marrow transplantation, consisting of total lymphoid irradiation (TLI) with 750 cGy and cyclophosphamide (CY), was used in five girls with aplastic anemia. All patients received bone marrow from HLA matched/mixed lymphocyte culture negative siblings. In our regimen the 'inverted Y' field to irradiate the pelvic nodes was modified, which did not include the whole pelvic cavity in an attempt to protect the ovaries from irradiation. Although some of the pelvic nodes was supported not to be irradiated in order to protect the ovaries, engraftment occurred in all five patients including four who had been transfused prior to transplantation. All five are alive from 47 days to 1378 days (median 285 days) after transplantation without tranplantation-associated complications. The calculated dose to the ovaries was sixteen percent of the entire dose of the regimen. Both of the two evaluable patients that had received tranplantation just before or during the puberty are developing normal sex maturity including menstruation. This study suggests that our preparative regimen is effective not only for engraftment of the donor marrow but also for protecting the ovaries from irradiation. (author).

  20. [A FOLLOW-UP STUDY ON AUTOLOGOUS BONE MARROW MONONUCLEAR CELLS TRANSPLANTATION FOR CRITICAL LOWER ARTERIOSCLEROSIS OBLITERANS IN DIABETIC PATIENTS].

    Science.gov (United States)

    Dou, Yanhua; Zhao, Jin; Zhang, Li; Wang, Xueying; Yuan, Hong; Yuan, Chunhui

    2015-07-01

    To assess the long-term effectiveness and safety of autologous bone marrow mononuclear cells (BM-MNC) transplantation in the treatment of critical diabetic lower arteriosclerosis obliterans (ASO). Between January 2007 and January 2010, 61 patients with critical diabetic lower ASO were treated with standard medical therapies in 29 cases (control group) or with standard medical therapies and autologous BM-MNC transplantation in 32 cases (treatment group). There was no significant difference in gender, age, disease duration, Fontatine stage, glucose (GLU), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein-cholesterol (LDL-C), hemoglobin Alc (HbA1c), systolic blood pressure (SBP), and diastolic blood pressure (DBP) between 2 groups (P > 0.05). The endpoints were overall survival (OS) and amputation-free survival (AFS). The risk indexes for ASO were observed and compared between 2 groups before and after treatments. The patients were followed up 2-36 months, and no malignant tumor occurred. The OS rate, OS time, AFS rate, and AFS time were 82.76% (24/29), (32.31 ± 9.08) months, 37.50% (9/24), and (21.28 ± 13.35) months in the control group and were 78.13% (25/32), (32.47 ± 6.96) months, 68.00% (17/25), and (28.38 ± 9.48) months in the treatment group; all indexes showed no significant differences (P > 0.05). OS rate, OS time, AFS rate, and AFS time showed no significant differences between 2 groups at the other time (P > 0.05) except AFS time at 1 year, which was significantly short in the control group than the treatment group (t = 2.806, P = 0.007). At the endpoint of follow-up, the indexes of GLU, TG, CHOL, LDL-C, HbAlc, SBP, and DBP showed no significant differences between before and after treatments and between 2 groups (P > 0.05) in 49 survival patients (24 in control group and 25 in treatment group). Autologous BM-MNC transplantation is safe and effective in the treatment of critical diabetic lower ASO, which can significantly improve AFS

  1. Thoracic radiation therapy before autologous bone marrow transplantation in relapsed or refractory Hodgkin's disease

    Energy Technology Data Exchange (ETDEWEB)

    Tsang, R.W.; Gospodarowicz, M.K. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, 610 University Avenue, Toronto (Canada); Sutcliffe, S.B. [B.C. Cancer Agency, Vancouver Cancer Centre, 600 West 10th Avenue, Vancouver (Canada); Crump, M.; Keating, A. [University of Toronto Autologous Blood and Marrow Transplant Program, The Toronto Hospital, General Division, MLW2-036, 200 Elizabeth St., Toronto (Canada)

    1999-01-01

    The aim of this study was to assess the relationship between radiation therapy (RT) and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT) for recurrent/refractory Hodgkin's disease (HD). Between December 1986 and December 1992, 59 patients previously treated at the Princess Margaret Hospital underwent HDCT (etoposide 60 mg/kg, melphalan 160 mg/m{sup 2}) and ABMT, performed for refractory (13 patients) or relapsed (46 patients) HD. RT was incorporated in the salvage treatment with the intent to achieve complete control of disease prior to ABMT. RT was given before ABMT in 33 patients, and after ABMT in 4 patients. Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. With a median follow-up of 4.6 years (range 1.2-7.4 years), the actuarial overall survival was 41%{+-}14% at 5 years. We observed 37 deaths, and 10 of these were TR deaths. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, 3 of these solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure with complicating sepsis as a major medical problem. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 survivors (mean 105 days; range 0-263 days) (P=0.026). Among 9 patients with ABMT within 50 days of thoracic RT, 6 had TR death. In contrast, among the 35 patients without thoracic RT (26 no RT, 9 non-thoracic RT), there were only 2 TR deaths. The 4 patients treated with mantle RT post-ABMT had no serious pulmonary complications. The use of thoracic RT before HDCT and ABMT was associated with a high post-transplant mortality rate. It was most evident in patients who received thoracic RT within 50 days prior to ABMT, or when the target volume included large volume of lung. We recommend that

  2. Expression of antigens coded in murine leukemia viruses on thymocytes of allogeneic donor origin in AKR mice following syngeneic or allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Wustrow, T.P.; Good, R.A.

    1985-01-01

    Removal of T-lymphocytes from marrow inoculum with monoclonal antibody plus complement permitted establishment of long-lived allogeneic chimeras between C57BL/6 and AKR/J mice. Development of leukemia was prevented for 15 mo. Protection from leukemia occurred with both young (4 wk) and older (4 mo) recipients. AKR mice reconstituted with syngeneic marrow or control AKR mice all developed leukemia-lymphoma before 1 yr of age. During spontaneous lymphomagenesis in AKR mice, amplified expression of gag or env gene-coded virus antigens on the surface of thymocytes preceded leukemia development and evidence for amplification of other virus genes. These changes generally appeared before 6 mo. Similar viral gene expression and viral gene amplification occurred in the thymus and spleen cells of leukemia-resistant chimeric mice. Using monoclonal antibodies to Mr 70,000 glycoprotein epitopes characteristic of ecotropic, xenotropic, or dualtropic viruses, antigens marking each virus form were found on thymocytes of allogeneic 4-wk and 4-mo chimeras as well as on the cells of AKR mice and of AKR mice reconstituted with syngeneic marrow. Flow cytometric analysis showed amplification of the virus genes in mice protected from leukemia-lymphoma by allogeneic bone marrow transplantation from leukemia-resistant mice. Allogeneic chimeras and syngeneically transplanted mice both showed evidence of accelerated viremia and of recombinant virus formation. The findings suggest that an event essential to leukemogenesis which occurs within the AKR lymphoid cells or their environment is lacking in the allogeneic chimeras. The nature of this influence of a resistance gene or genes introduced into AKR mice by allogeneic bone marrow transplantation deserves further study

  3. Autologous transplantation of bone marrow/blood-derived cells for chronic ischemic heart disease: a systematic review and meta-analysis.

    Science.gov (United States)

    Xu, Rende; Ding, Song; Zhao, Yichao; Pu, Jun; He, Ben

    2014-11-01

    Studies focused on cell therapy for chronic ischemic heart disease (CIHD) have been published with conflicting results. In this meta-analysis, we aimed to assess the effectiveness and safety of autologous bone marrow/blood-derived cell transplantation in patients with CIHD. Randomized controlled trials (RCTs) were identified in PubMed, OVID, EMBASE, and Cochrane Library reviews and reference lists of relevant articles. Weighted mean difference was calculated for changes in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) using a random-effects model. Nineteen trials with a total of 886 patients were included. Compared with controls, patients who received transplantation of bone marrow/blood-derived cells had significantly improved LVEF (3.54%; 95% confidence interval [CI], 1.92%-5.17%; P bone marrow mononuclear cell number was ≤ 1 × 10(8). Furthermore, cell therapy was associated with a significant decrease in all-cause death (relative risk: 0.49; 95% CI, 0.29-0.84; P = 0.01). Current evidence showed that cell therapy moderately improved left ventricle function and significantly decreased all-cause death in patients with CIHD and supports further RCTs with larger sample size and longer follow-up. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. [Polymorphism in HLA and KIR genes and the impact on hematopoietic stem cell transplantation outcomes and unrelated donor selection: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

    Science.gov (United States)

    Dubois, Valérie; Brignier, Anne; Elsermans, Vincent; Gagne, Katia; Kennel, Anne; Pedron, Béatrice; Picard, Christophe; Ravinet, Aurélie; Varlet, Pauline; Cesbron, Anne; Delbos, Florent; Yakoub-Agha, Ibrahim; Loiseau, Pascale

    2016-11-01

    In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country with the purpose of offering careful analysis of published studies on clinical practice issues that remain to be disputed. This article addresses the impact of HLA and KIR gene polymorphism on the outcome of the transplantation in order to optimize unrelated donor selection. Copyright © 2016. Published by Elsevier Masson SAS.

  5. [Indications and follow-up for autologous hematopoietic stem cell transplantation in autoimmune and autoinflammatory diseases: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

    Science.gov (United States)

    Pugnet, Grégory; Castilla-Llorente, Christina; Puyade, Mathieu; Terriou, Louis; Badoglio, Manuela; Deligny, Christophe; Guillaume-Jugnot, Perrine; Labeyrie, Céline; Benzidia, Ilham; Faivre, Hélène; Lansiaux, Pauline; Marjanovic, Zora; Bourhis, Jean-Henri; Faucher, Catherine; Furst, Sabine; Huynh, Anne; Martin, Thierry; Vermersch, Patrick; Yakoub-Agha, Ibrahim; Farge, Dominique

    2017-12-01

    The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2017 in Lille, France and updated recommendations for indications and follow-up in autologous hematopoietic stem cell transplantation in autoimmune and autoinflammatory diseases, previously published under the auspices of SFGM-TC. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  6. Comparison of the Treatment Efficiency of Bone Marrow-Derived Mesenchymal Stem Cell Transplantation via Tail and Portal Veins in CCl4-Induced Mouse Liver Fibrosis

    Directory of Open Access Journals (Sweden)

    Nhung Hai Truong

    2016-01-01

    Full Text Available Because of self-renewal, strong proliferation in vitro, abundant sources for isolation, and a high differentiation capacity, mesenchymal stem cells are suggested to be potentially therapeutic for liver fibrosis/cirrhosis. In this study, we evaluated the treatment effects of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs on mouse liver cirrhosis induced by carbon tetrachloride. Portal and tail vein transplantations were examined to evaluate the effects of different injection routes on the liver cirrhosis model at 21 days after transplantation. BM-MSCs transplantation reduced aspartate aminotransferase/alanine aminotransferase levels at 21 days after injection. Furthermore, BM-MSCs induced positive changes in serum bilirubin and albumin and downregulated expression of integrins (600- to 7000-fold, transforming growth factor, and procollagen-α1 compared with the control group. Interestingly, both injection routes ameliorated inflammation and liver cirrhosis scores. All mice in treatment groups had reduced inflammation scores and no cirrhosis. In conclusion, transplantation of BM-MSCs via tail or portal veins ameliorates liver cirrhosis in mice. Notably, there were no differences in treatment effects between tail and portal vein administrations. In consideration of safety, we suggest transfusion of bone marrow-derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment.

  7. Translation and validation of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) version 4 quality of life instrument into Arabic language.

    Science.gov (United States)

    Soudy, Hussein; Maghfoor, Irfan; Elhassan, Tusneem Ahmed M; Abdullah, Eman; Rauf, Shahzad M; Al Zahrani, Ahmed; Akhtar, Saad

    2018-03-12

    Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) has been translated from English into several languages. Currently, there is no validated translation of FACT-BMT in Arabic. Here, we are reporting the first Arabic translation and validation of the FACT-BMT. The study was approved by the Institutional Research Advisory Council. The Arabic translation followed the standard Functional Assessment of Chronic Illness Therapy (FACIT.org) translation methodology (with permission). Arabic FACT-BMT (50- items) was statistically validated. Cronbach's alpha for internal consistency, Spearman's rank correlation coefficients method for Inter-scale correlations and Principal Component Analysis for factorial construct validity was used. One hundred and eight consecutive relapsed /refractory lymphoma patients who underwent high dose chemotherapy and autologous stem cell transplant were enrolled. There were 68 males (63%) and 40 females (37%) with a median age of 29 years (range 14-62). After Arabic questionnaire pre-testing (Cronbach's alpha 0.744), the study included 108 patients. Cronbach's alpha for the entire FACT-BMT indicated an excellent internal consistency (0.90); range (0.67 to 0.91). Cronbach's alpha for sub-groups of social (0.78), emotional (0.67) and functional wellbeing was (0.88). Cronbach's alpha for bone marrow transplant (0.81), FACT-General (0.89), and FACT- Trial Outcome Index (TOI); (0.91) also revealed excellent internal consistency. Patients had high scores in all domains of quality of life, indicating that most patients were leading a normal life. This translation of FACT-BMT in Arabic was reviewed and approved for submission by the FACIT.org. Our data reports the first translated, validated and approved Arabic version of FACT-BMT. This will help large numbers of Arabic speaking patients undergoing stem cell/bone marrow transplantation, across the globe.

  8. Bone marrow transplantation in the rat. III. Structure of the liver inflammatory lesion in acute graft-versus-host disease

    International Nuclear Information System (INIS)

    Leszczynski, D.; Renkonen, R.; Haeyry, P.

    1985-01-01

    The liver is a major parenchymal target organ of acute graft-versus-host disease (aGVHD) after bone marrow transplantation in the rat. The authors have analyzed the nature of cellular infiltrates in the liver using monoclonal antibodies against white cell subsets and investigated the anatomic distribution of the inflammatory cell subsets inside the liver parenchyma. Several types of white cells are present in a normal control liver: In the portal area the T-helper (Th) cells predominate, (surface) immunoglobulin-expressing B cells are present in ample numbers, and most of the phagocytes are Ia-positive. In the central vein area the T-suppressor/killer cells (Tsk) dominate, no B cells are present, and most of the phagocytes are Ia-negative. During aGVHD the number of T cells increases rapidly in the portal area; and after an initial strong increase, the Th/Tsk ratio decreases but remains still above 1. In the central vein area there is also an increase in the number of T cells, compared with that in the syngeneic recipient, but the Th/Tsk ratio rapidly decreases and remains uniformly below 1. During aGVHD the B cells entirely disappear from the portal area, whereas a small but distinct number of mature plasma cells with intracellular immunoglobulin appear in the central vein area. Following irradiation the Ia-positive phagocytic cells entirely disappear from the portal area and decrease distinctly in number in the central vein area. During aGVHD the number of Ia-positive phagocytes increases again in both locations. In the central vein area the positive phagocytes are seen over the background level, and, concomitantly, the Ia-negative phagocytes disappear

  9. Primary amenorrhea after bone marrow transplantation and adjuvant chemotherapy misdiagnosed as disorder of sex development: A case report.

    Science.gov (United States)

    Huang, He; Tian, Qinjie

    2016-11-01

    Disorders of sex development (DSD) is a congenital condition in which the development of chromosomal, gonadal or genital sex is atypical. Majority of patients present clinical characteristics of primary amenorrhea, absent secondary sex characters, and abnormal hormone level. A female appearance patient with primary amenorrhea and 46 XY karyotype seems to be solid evidences to diagnose Y-chromosome-related DSD diseases, while it is not necessarily the accurate diagnosis. We report the case of an 18-year-old girl with primary amenorrhea and 46 XY karyotype misdiagnosed as Y-chromosome-related DSD. The patient has normal female reproductive organs and a disrupted pubertal development after the treatment for acute myeloid leukemia (AML). We consider that her gonads were probably functional and later impaired after AML. The clinical manifestations were not consistent with DSD. With doubts, we found that she received bone marrow transplantation (BMT) from her brother and adjuvant chemotherapy 6 years ago. Her karyotype changed from normal female to a karyotype of donor (her brother) origin after BMT.Adjuvant chemotherapy for AML may impair her ovarian function and finally bring about disrupted puberty or primary ovarian insufficiency (POI). We provided close follow-up. During the second visit, the patient had her menarche lasting 4 days without any medication. The present case serves as a reminder that a correct diagnosis depends on the comprehensive collection of present and past medical history, complete physical examination, and careful evaluation of related adjuvant tests. Do not presumptively judge a test and mislead reasoning. In addition, ovarian function protection should be considered for young girls having chemotherapy.

  10. Prostaglandin E2 Production and T Cell Function in Mouse Adenovirus Type 1 Infection following Allogeneic Bone Marrow Transplantation.

    Science.gov (United States)

    McCarthy, Mary K; Procario, Megan C; Wilke, Carol A; Moore, Bethany B; Weinberg, Jason B

    2015-01-01

    Adenovirus infections are important complications of bone marrow transplantation (BMT). We demonstrate delayed clearance of mouse adenovirus type 1 (MAV-1) from lungs of mice following allogeneic BMT. Virus-induced prostaglandin E2 (PGE2) production was greater in BMT mice than in untransplanted controls, but BMT using PGE2-deficient donors or recipients failed to improve viral clearance, and treatment of untransplanted mice with the PGE2 analog misoprostol did not affect virus clearance. Lymphocyte recruitment to the lungs was not significantly affected by BMT. Intracellular cytokine staining of lung lymphocytes demonstrated impaired production of INF-γ and granzyme B by cells from BMT mice, and production of IFN-γ, IL-2, IL-4, and IL-17 following ex vivo stimulation was impaired in lymphocytes obtained from lungs of BMT mice. Viral clearance was not delayed in untransplanted INF-γ-deficient mice, suggesting that delayed viral clearance in BMT mice was not a direct consequence of impaired IFN-γ production. However, lung viral loads were higher in untransplanted CD8-deficient mice than in controls, suggesting that delayed MAV-1 clearance in BMT mice is due to defective CD8 T cell function. We did not detect significant induction of IFN-β expression in lungs of BMT mice or untransplanted controls, and viral clearance was not delayed in untransplanted type I IFN-unresponsive mice. We conclude that PGE2 overproduction in BMT mice is not directly responsible for delayed viral clearance. PGE2-independent effects on CD8 T cell function likely contribute to the inability of BMT mice to clear MAV-1 from the lungs.

  11. Bone marrow transplantation from genetically HLA-nonidentical donors in children with fatal inherited disorders excluding severe combined immunodeficiencies: use of two monoclonal antibodies to prevent graft rejection.

    Science.gov (United States)

    Jabado, N; Le Deist, F; Cant, A; De Graeff-Meeders, E R; Fasth, A; Morgan, G; Vellodi, A; Hale, G; Bujan, W; Thomas, C; Cavazzana-Calvo, M; Wijdenes, J; Fischer, A

    1996-09-01

    For children with life-threatening inborn errors of metabolism without a matched related bone marrow donor, transplantation from an HLA genetically nonidentical donor is the only therapeutic option. To reduce the high risk of graft rejection in this setting without increasing the conditioning regimen, a protocol based on the infusion of an antiadhesion antibody directed against the CD11a (leukocyte function-associated antigen 1 [LFA-1]) molecule was performed by the European Bone Marrow Transplantation-European Society for Immunodeficiency group with promising results. To optimize engraftment, and thereby survival, further, the additional blockade of a second important leukocyte adhesion and signalization pathway mediated by the CD2 and LFA-3 interaction was attempted in a multicenter protocol conducted by the European Bone Marrow Transplantation-European Society for Immunodeficiency group. Results of this study (ie, engraftment and survival) were compared with a historical control group that received the anti-LFA-1 antibody alone. Factors that may have affected engraftment and survival were also considered in this study. Forty-four children with inborn errors, including inherited immunodeficiencies (excluding severe combined immunodeficiencies), Chédiak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis, and malignant osteopetrosis, received bone marrow from HLA-nonidentical related donors or from HLA-identical unrelated donors at 13 European centers between August 1990 and June 1993. Bone marrow was depleted of T cells by use of either erythrocyte (E) rosetting or monoclonal antibodies (MoAbs) to prevent graft-versus-host disease. The conditioning regimen consisted of busulfan and cyclophosphamide for all patients plus etoposide for patients with osteopetrosis, familial hemophagocytic lymphohistiocytosis, and Chédiak-Higashi syndrome. Infusions of MoAbs specific for the CD11a and the CD2 molecules were started 4 and 3 days, respectively, before and

  12. Importance of B cells to development of regulatory T cells and prolongation of tissue allograft survival in recipients receiving autologous bone marrow transplantation.

    Science.gov (United States)

    Gorczynski, Reginald M; Farrokhi, Kaveh; Gorczynski, Christopher; Sadozai, Hassan; Zhu, Fang; Khatri, Ismat

    2018-01-16

    We previously showed that congenic bone marrow transplantation (BMTx) post myeloablation augmented tissue allograft survival in association with increased regulatory T (Treg) cells of both host and bone marrow donor origin. Regulatory B (Breg) cells can also modulate T-cell immunity and B cells may be implicated in the development of Treg cells. Accordingly, we explored the effect of B-cell depletion in vivo on augmented graft survival post BMTx. C57BL/6 mice received BALB/c skin allografts followed 7 days later by myeloablation using cyclophosphamide and busulphan. Mice then received T-cell-depleted bone marrow from CD45.1 congenic donors, and ongoing immunosuppression with rapamycin (to day 28 after BMTx). Control mice received cyclophosphamide and busulphan followed by rapamycin, but not congenic bone marrow. At different times post BMTx, mice received B-cell-depleting antibody treatment, and the effect on both skin graft survival, and induction of Treg cells was assessed. BMTx resulted in significantly prolonged skin graft survival versus control mice, in association with attenuated donor-specific alloreactivity relative to controls, increased splenic Treg cells and significantly diminished anti-donor IgG. In mice receiving infusion of B-depleting antibodies for 12 days from day 15 post BMTx, both graft survival and Treg cell activity were diminished, particularly for functional Treg cells of donor origin. Adoptive transfer of Breg cells from mice harvested at 15 days post BMTx prolonged survival in naive transplanted mice and increased Treg cell levels. Thus, autologous BMTx augmentation of graft survival is dependent in part upon a population of Breg cells that can modulate the function of donor-derived Treg cells. © 2018 John Wiley & Sons Ltd.

  13. Allogeneic Bone Marrow Transplant from MRL/MpJ Super-Healer Mice Does Not Improve Articular Cartilage Repair in the C57Bl/6 Strain.

    Directory of Open Access Journals (Sweden)

    Catherine A Leonard

    Full Text Available Articular cartilage has been the focus of multiple strategies to improve its regenerative/ repair capacity. The Murphy Roths Large (MRL/MpJ "super-healer" mouse demonstrates an unusual enhanced regenerative capacity in many tissues and provides an opportunity to further study endogenous cartilage repair. The objective of this study was to test whether the super-healer phenotype could be transferred from MRL/MpJ to non-healer C57Bl/6 mice by allogeneic bone marrow transplant.The healing of 2mm ear punches and full thickness cartilage defects was measured 4 and 8 weeks after injury in control C57Bl/6 and MRL/MpJ "super-healer" mice, and in radiation chimeras reconstituted with bone marrow from the other mouse strain. Healing was assessed using ear hole diameter measurement, a 14 point histological scoring scale for the cartilage defect and an adapted version of the Osteoarthritis Research Society International scale for assessment of osteoarthritis in mouse knee joints.Normal and chimeric MRL mice showed significantly better healing of articular cartilage and ear wounds along with less severe signs of osteoarthritis after cartilage injury than the control strain. Contrary to our hypothesis, however, bone marrow transplant from MRL mice did not confer improved healing on the C57Bl/6 chimeras, either in regards to ear wound healing or cartilage repair.The elusive cellular basis for the MRL regenerative phenotype still requires additional study and may possibly be dependent on additional cell types external to the bone marrow.

  14. A Depleting Anti-CD45 Monoclonal Antibody as Isolated Conditioning for Bone Marrow Transplantation in the Rat.

    Directory of Open Access Journals (Sweden)

    Mark D Jäger

    Full Text Available A monoclonal antibody (mAb against the leukocyte common antigen CD45 (RT7 in rats could facilitate bone marrow transplantation (BMT. This study in rats evaluates a depletive rat anti-RT7a mAb as isolated tool for BMT conditioning without using irradiation or any chemotherapeutic / immunosuppressive agent.The model used a CD45 di-allelic polymorphism (RT7a/RT7b. The anti-RT7a mAb was intravenously administered to LEW.1W rats (RT1uRT7a at 5, 10 and 15 mg/kg. 1x108 BM cells of MHC syngeneic (RT1u, MHC disparate (RT1l or MHC haploidentical (RT1u/l donors were transplanted. All BM donor strains carried the RT7b allele so that their CD45+ cells were not affected by the anti-RT7a mAb. Recipients were monitored for reconstitution and donor-chimerism in blood leukocytes.mAb dosages of 5 or 10 mg/kg were myelosuppressive, whereas 15 mg/kg was myeloablative. Multi-lineage donor-chimerism at day 100 indicated engraftment of MHC syngeneic BM after any used mAb dosage (5 mg/kg: 46+/-7%; 10 mg/kg: 62+/-5%; 15 mg/kg: 80+/-4%. MHC disparate BM resulted in autologous reconstitution after conditioning by 10 mg/kg of the mAb and caused transient chimerism ending up in death associated with aplasia after conditioning by 15 mg/kg of the mAb. MHC haploidentical BM (F1 to parental engrafted only after conditioning by 15 mg/kg (chimerism at day 100: 78+/-7%. Abandonment of α/β TCR+ cell depletion from BM grafts impaired the engraftment process after conditioning using 15 mg/kg of the mAb in the MHC syngeneic setting (2 of 6 recipients failed to engraft and the MHC haploidentical setting (3 of 6 recipients failed.This depletive anti-RT7a mAb is myelosuppressive and conditions for engraftment of MHC syngeneic BM. The mAb also facilitates engraftment of MHC haploidentical BM, if a myeloablative dose is used. RT7b expressing, BM-seeded α/β TCR+ cells seem to impair the engraftment process after myeloablative mAb conditioning.

  15. An open-label proof-of-concept study of intrathecal autologous bone marrow mononuclear cell transplantation in intellectual disability.

    Science.gov (United States)

    Sharma, Alok; Sane, Hemangi; Gokulchandran, Nandini; Pai, Suhasini; Kulkarni, Pooja; Ganwir, Vaishali; Maheshwari, Maitree; Sharma, Ridhima; Raichur, Meenakshi; Nivins, Samson; Badhe, Prerna

    2018-01-31

    The underlying pathophysiology in intellectual disability (ID) involves abnormalities in dendritic branching and connectivity of the neuronal network. This limits the ability of the brain to process information. Conceptually, cellular therapy through its neurorestorative and neuroregenerative properties can counteract these pathogenetic mechanisms and improve neuronal connectivity. This improved networking should exhibit as clinical efficacy in patients with ID. To assess the safety and efficacy of cellular therapy in patients with ID, we conducted an open-label proof-of-concept study from October 2011 to December 2015. Patients were divided into two groups: intervention group (n = 29) and rehabilitation group (n = 29). The intervention group underwent cellular transplantation consisting of intrathecal administration of autologous bone marrow mononuclear cells and standard neurorehabilitation. The rehabilitation group underwent only standard neurorehabilitation. The results of the symptomatic outcomes were compared between the two groups. In the intervention group analysis, the outcome measures used were the intelligence quotient (IQ) and the Wee Functional Independence Measure (Wee-FIM). To compare the pre-intervention and post-intervention results, statistical analysis was done using Wilcoxon's matched-pairs test for Wee-FIM scores and McNemar's test for symptomatic improvements and IQ. The effect of age and severity of the disorder were assessed for their impact on the outcome of intervention. Positron emission tomography-computed tomography (PET-CT) brain scan was used as a monitoring tool to study effects of the intervention. Adverse events were monitored for the safety of cellular therapy. On symptomatic analysis, greater improvements were seen in the intervention group as compared to the rehabilitation group. In the intervention group, the symptomatic improvements, IQ and Wee-FIM were statistically significant. A significantly better outcome of the

  16. Differentiation of human bone marrow precursor cells into neuronal-like cells after transplantation into canine spinal cord organotypic slice cultures.

    Science.gov (United States)

    Fei, Zhi-qiang; Xiong, Jian-yi; Chen, Lei; Shen, Hui-yong; Stephanie, Ngo; Jeffrey, Wang; Wang, Da-ping

    2012-11-01

    Treatments to regenerate different tissue involving the transplantation of bone marrow derived mesenchymal precursor cells are anticipated. Using an alternative methods, in vitro organotypic slice culture method, would be useful to transplant cells and assessing the effects. This study was to determine the possibility of differentiating human bone marrow precursor cells into cells of the neuronal lineage by transplanting into canine spinal cord organotypic slice cultures. Bone marrow aspirates were obtained from posterior superior iliac spine (PSIS) of patients that had undergone spinal fusion due to a degenerative spinal disorder. For cell imaging, mesenchymal precursor cells (MPCs) were pre-stained with PKH-26 just before transplantation to canine spinal cord slices. Canine spinal cord tissues were obtained from three adult beagle dogs. Spinal cords were cut into transverse slices of 1 mm using tissue chopper. Two slices were transferred into 6-well plate containing 3 ml DMEM with antibiotics. Prepared MPCs (1×10(4)) were transplanted into spinal cord slices. On days 0, 3, 7, 14, MPCs were observed for morphological changes and expression of neuronal markers through immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). The morphological study showed: spherical cells in the control and experiment groups on day 0; and on day 3, cells in the control group had one or two thick, short processes and ones in the experiment group had three or four thin, long processes. On day 7, these variously-sized processes contacted each other in the experiment group, but showed typical spindle-shaped cells in the control group. Immunofluorescence showed that PKH-26(+) MPCs stained positive for NeuN(+) and GFAP(+) in experimental group only. Also RT-PCR showed weak expression of β-tubulin III and GFAP. Human bone marrow mesenchymal precursor cells (hMPCs) have the potential to differentiate into the neuronal like cells in this canine spinal cord

  17. Bone marrow edema syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Korompilias, Anastasios V.; Lykissas, Marios G.; Beris, Alexandros E. [University of Ioannina, Department of Orthopaedic Surgery, School of Medicine, Ioannina (Greece); Karantanas, Apostolos H. [University of Crete School of Medicine, Department of Radiology, Heraklion (Greece)

    2009-05-15

    Bone marrow edema syndrome (BMES) refers to transient clinical conditions with unknown pathogenic mechanism, such as transient osteoporosis of the hip (TOH), regional migratory osteoporosis (RMO), and reflex sympathetic dystrophy (RSD). BMES is primarily characterized by bone marrow edema (BME) pattern. The disease mainly affects the hip, the knee, and the ankle of middle-aged males. Many hypotheses have been proposed to explain the pathogenesis of the disease. Unfortunately, the etiology of BMES remains obscure. The hallmark that separates BMES from other conditions presented with BME pattern is its self-limited nature. Laboratory tests usually do not contribute to the diagnosis. Histological examination of the lesion is unnecessary. Plain radiographs may reveal regional osseous demineralization. Magnetic resonance imaging is mainly used for the early diagnosis and monitoring the progression of the disease. Early differentiation from other aggressive conditions with long-term sequelae is essential in order to avoid unnecessary treatment. Clinical entities, such as TOH, RMO, and RSD are spontaneously resolving, and surgical treatment is not needed. On the other hand, early differential diagnosis and surgical treatment in case of osteonecrosis is of crucial importance. (orig.)

  18. [Allogenic bone marrow transplantation versus autograft in acute lymphoblastic leukemia, in second remission in 113 children. Results of the Grupo Español de Transplante de Medula Niños (GETMON)].

    Science.gov (United States)

    Badell, I; Ortega, J J; Muñoz, A; Bureo, E; Madero, L; Olivé, T; Cubells, J; Maldonado, M S; Baro, J; Díaz, M A

    1996-04-01

    Using the data from the GETMON ("Grupo Español de Trasplante de Medula Osea en Niños") we carried out a retrospective analysis of the results of allogeneic bone marrow transplantation (alloBMT) compared to autologous bone marrow transplantation (ABMT) in 113 paediatric patients with acute lymphoblastic leukaemia (ALL) in second remission. Transplants were performed by the following centers, from April 1983 to December 1991: H. Vall d'Hebrón and H. Sant Pau from Barcelona, H. Ramón y Cajal and H. Niño Jesús from Madrid and H. Marqués de Valdecilla from Santander. The study included 113 patients between the ages of two and 16 years with ALL in second remission at marrow transplant. Fifty-six underwent alloBMT and 57 ABMT. Both groups were homogeneous with respect to age, sex, immunophenotype, duration of first remission, risk at diagnosis, percentage of early and late relapses, percentage with marrow or extramedullary relapse prior to transplant, time interval from attainment of second remission to transplant, and conditioning regimens applied for marrow transplant, with predominance of chemoradiotherapy in both. Haematologic recovery was observed to be faster in alloBMT than in ABMT. A granulocyte count > 0.5 x 10(9)/l was reached in alloBMT patients in a median of 19 days and in ABMT patients in a median of 25 days (p 30 months) 61.1 +/- 13.8%, than those who had presented an early relapse (< 30 months) 18.3 +/- 6.5% (p < 0.005). Probability of relapse was significantly greater in ABMT (70%) compared to alloBMT (46%) (p < 0.025). Transplant offers a better DFS in extramedullary relapses compared to isolated or combined bone marrow relapses: 71.4 +/- 17.1% with alloBMT and 38.1 +/- 14.7% with ABMT (p = NS). In our experience we observed a better DFS with alloBMT compared with ABMT, overcoat in early relapses, but without significant difference. A higher relapse rate in ABMT group is partially compensated by more early deaths in alloBMT offers a few survival

  19. Avaliação da Barreira Hemato-Encefálica no transplante de medula óssea Blood-Brain Barrier evaluation in bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    1997-01-01

    Full Text Available A barreira hemato-encefálica (BHE contribui para o isolamento imunológico do sistema nervoso central (SNC. Sua avaliação nunca foi realizada em pacientes submetidos a transplante de medula óssea (TMO. Neste estudo a integridade da BHE foi avaliada através das proteínas do LCR, de forma quantitativa, a fim de observar a incidência e entender a fisiopatologia da doença do enxerto contra o hospedeiro crônica (DECH-C no SNC. Foram estudadas amostras pareadas de LCR e soro de 33 pacientes com leucemia mielóide crônica submetidos a TMO alogênico, de doador aparentado, HLA idêntico. As amostras foram coletadas nos períodos pré TMO, pós TMO e concomitante à DECH-C. Não foi evidenciada quebra de BHE durante a DECH-C em nenhum dos casos estudados.The blood-brain barrier (BBB contributes to the central nervous system (CNS immunological isolation. BBB has never been studied in patients who developed chronic graft-versus-host disease (GVHD after allogeneic bone marrow transplants (BMT, from HLA identical related donors. BBB disruption was investigated through the cerebrospinal fluid (CSF proteins, quantitative and graphically, in order to detect the incidence and possible pathophysiology of the CNS involvement in chronic GVHD. Thirty three CSF and matched serum samples from chronic myeloid leukemia patients were collected pre BMT, pos BMT and during chronic GVHD. There was no evidence of BBB disruption in any patient studied.

  20. Bone marrow laminins influence hematopoietic stem and progenitor cell cycling and homing to the bone marrow.

    Science.gov (United States)

    Susek, Katharina Helene; Korpos, Eva; Huppert, Jula; Wu, Chuan; Savelyeva, Irina; Rosenbauer, Frank; Müller-Tidow, Carsten; Koschmieder, Steffen; Sorokin, Lydia

    2018-01-31

    Hematopoietic stem and progenitor cell (HSPC) functions are regulated by a specialized microenvironment in the bone marrow - the hematopoietic stem cell niche - of which the extracellular matrix (ECM) is an integral component. We describe here the localization of ECM molecules, in particular the laminin α4, α3 and α5 containing isoforms in the bone marrow. Laminin 421 (composed of laminin α4, β2, γ1 chains) is identified as a major component of the bone marrow ECM, occurring abundantly surrounding venous sinuses and in a specialized reticular fiber network of the intersinusoidal spaces of murine bone marrow (BM) in close association with HSPC. Bone marrow from Lama4 -/- mice is significantly less efficient in reconstituting the hematopoietic system of irradiated wildtype (WT) recipients in competitive bone marrow transplantation assays and shows reduced colony formation in vitro. This is partially due to retention of Lin - c-kit + Sca-1 + CD48 - long-term and short-term hematopoietic stem cells (LT-HSC/ST-HSC) in the G0 phase of the cell cycle in Lama4 -/- bone marrow and hence a more quiescent phenotype. In addition, the extravasation of WT BM cells into Lama4 -/- bone marrow is impaired, influencing the recirculation of HSPC. Our data suggest that these effects are mediated by a compensatory expression of laminin α5 containing isoforms (laminin 521/522) in Lama4 -/- bone marrow. Collectively, these intrinsic and extrinsic effects lead to reduced HSPC numbers in Lama4 -/- bone marrow and reduced hematopoietic potential. Copyright © 2018 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  1. Heterogenic transplantation of bone marrow-derived rhesus macaque mesenchymal stem cells ameliorates liver fibrosis induced by carbon tetrachloride in mouse

    Directory of Open Access Journals (Sweden)

    Xufeng Fu

    2018-02-01

    Full Text Available Liver fibrosis is a disease that causes high morbidity and has become a major health problem. Liver fibrosis can lead to the end stage of liver diseases (livercirrhosisand hepatocellularcarcinoma. Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, the shortage of organ donors, high cost of medical surgery, immunological rejection and transplantation complications severely hamper liver transplantation therapy. Mesenchymal stem cells (MSCs have been regarded as promising cells for clinical applications in stem cell therapy in the treatment of liver diseases due to their unique multipotent differentiation capacity, immunoregulation and paracrine effects. Although liver fibrosis improvements by MSC transplantation in preclinical experiments as well as clinical trials have been reported, the in vivo fate of MSCs after transportation and their therapeutic mechanisms remain unclear. In this present study, we isolated MSCs from the bone marrow of rhesus macaques. The cells exhibited typical MSC markers and could differentiate into chondrocytes, osteocytes, and adipocytes, which were not affected by labeling with enhanced green fluorescent protein (EGFP. The harvested MSCs respond to interferon-γ stimulation and have the ability to inhibit lymphocyte proliferation in vitro. EGFP-labeled MSCs (1 × 106 cells were transplanted into mice with carbon tetrachloride-induced liver fibrosis via tail vein injection. The ability of the heterogenic MSC infusion to ameliorate liver fibrosis in mice was evaluated by a blood plasma chemistry index, pathological examination and liver fibrosis-associated gene expression. Additionally, a small number of MSCs that homed and engrafted in the mouse liver tissues were evaluated by immunofluorescence analysis. Our results showed that the transplantation of heterogenic MSCs derived from monkey bone marrow can be used to treat liver fibrosis in the mouse model and that the

  2. Bone marrow stromal cell : mediated neuroprotection for spinal cord repair

    NARCIS (Netherlands)

    Ritfeld, Gaby Jane

    2014-01-01

    Currently, there is no treatment available that restores anatomy and function after spinal cord injury. This thesis explores transplantation of bone marrow-derived mesenchymal stem cells (bone marrow stromal cells; BMSCs) as a therapeutic approach for spinal cord repair. BMSCs secrete neurotrophic

  3. The effect of donor T lymphocytes and total-body irradiation on hemopoietic engraftment and pulmonary toxicity following experimental allogeneic bone marrow transplantation.

    Science.gov (United States)

    Down, J D; Mauch, P; Warhol, M; Neben, S; Ferrara, J L

    1992-11-01

    To study the effects of donor T lymphocytes on engraftment and graft-versus-host disease in relation to recipient total-body irradiation, we have returned small numbers of T cells to T-cell-depleted bone marrow transplanted across a minor histocompatibility barrier in mice (B10.BR-->CBA). T-cell-depleted B10.BR marrow (10(7) cells) was transplanted into CBA recipients prepared with TBI doses ranging from 4 to 14 Gy. Selected animals also received 10(4) (0.1%) and 10(5) (1.0%) measured B10.BR T lymphocytes. The extent of donor marrow engraftment was determined from hemoglobin and carbonic anhydrase phenotyping of peripheral blood at 3 months posttransplant. Toxicity was assessed from breathing-rate measurements, histopathology, and animal survival. Addition of T cells had a profound effect on survival related to radiation dose. The TBI doses resulting in an LD50 at 12 weeks were 6.9 Gy, 9.3 Gy, and 13.0 Gy for animals receiving 10(5), 10(4), and no T cells, respectively. Mortality was associated with pulmonary dysfunction as measured by an elevation of breathing rates. Autopsy and histological analysis revealed extensive damage to the lung parenchyma. In contrast to the toxicity data, addition of T cells to the donor marrow had no effect on the TBI dose required for equivalent erythroid engraftment. These results demonstrate that in combination with TBI small numbers of T cells in the transplanted marrow do not aid engraftment but do significantly increase the risk of pulmonary toxicity.

  4. MRI in bone marrow lesions

    International Nuclear Information System (INIS)

    Linden, A.; Theissen, P.; Schauerte, G.; Schicha, H.; Diehl, V.

    1989-01-01

    MRI has the potential to demonstrate bone marrow pathology due to its good soft tissue contrast. Inflammation and necrosis can be detected very early before there is evidence of radiological changes. In bone tumors intramedullary infiltration can be visualized in addition to soft tissue changes. Metastases of bone and bone marrow, especially in spinal and pelvic regions, are well depicted, often before bone scintigraphy yields pathological findings. In haematological disorders MRI permits follow-up studies due to its good reproducibility. Infiltration by malignant lymphoma and multiple myeloma and its extension in bone marrow can be visualized by MRI, too. However, the most common pathological MRI findings in bone marrow are not very specific, and final diagnosis requires further clinical or histological information. (orig.) [de

  5. Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome.

    Science.gov (United States)

    Witt, C; Sayer, D; Trimboli, F; Saw, M; Herrmann, R; Cannell, P; Baker, D; Christiansen, F

    2000-02-01

    Previous retrospective studies have demonstrated improved outcome in patients whose donors were matched for non-HLA markers in the MHC as well as for HLA genes. Forty patients receiving transplants from unrelated donors were typed prospectively for HLA and non-HLA markers. Non-HLA markers near HLA-B (beta-block markers) and in the DRB1 introns (delta-block markers) were used to assess MHC match between donors and recipient. Patients whose donors were matched at the beta- and delta-blocks had improved event free survival (63%) compared to patients whose donors were mismatched at one or both blocks (25%) (p matched at the beta-block had significantly less severe acute graft versus host disease (p block matching was correlated with HLA matching as determined by DNA sequencing. Beta-block matching was highly correlated with matching for exons 2 and 3 of HLA-B but less so for HLA-C. Delta-block matching was highly correlated with matching for exon 2 of HLA DRB1. It is concluded that matching for non-HLA markers in the MHC improves matching for HLA genes. Further studies are required to determine whether matching for non-HLA markers improves outcome to a greater extent than matching for the HLA genes alone.

  6. Merleau-Ponty and me: some phenomenological reflections upon my recent bone marrow transplant.

    Science.gov (United States)

    Morstyn, Ron

    2009-06-01

    During my illness and transplant I experienced an overwhelming existential crisis involving a complex intertwining of meaning and body which was often ignored, rejected, or misunderstood by others and at times by myself, which led to painful feelings of alienation. My treatment and my own conceptualizations seemed founded on assumptions of a separation of body and mind that were not true to what I was experiencing. I searched for a more accurate understanding, which I eventually found in the writings of the French existential philosopher Merleau-Ponty. Merleau-Ponty's extensive elaboration of the deep ambiguity of our existence as body-subjects provides an alternative model to those of the mind/body dichotomy currently in vogue in medicine and psychiatry. I found his writings a useful framework within which to comprehend my experiences. I wanted to write about these experiences and how they relate to Merleau-Ponty's insights because I found that those individuals who were able to relate to me at this level of existential ambiguity were invaluable to my recovery.

  7. Bone marrow mesenchymal stromal cells and olfactory ensheathing cells transplantation after spinal cord injury--a morphological and functional comparison in rats.

    Science.gov (United States)

    Torres-Espín, Abel; Redondo-Castro, Elena; Hernández, Joaquim; Navarro, Xavier

    2014-05-01

    Cell therapy for spinal cord injury (SCI) is a promising strategy for clinical application. Both bone marrow mesenchymal stromal cells (MSCs; also known as bone marrow-derived 'mesenchymal stem cells') and olfactory ensheathing cells (OECs) have demonstrated beneficial effects following transplantation in animal models of SCI. However, due to the large number of affecting parameters that determine the therapy success and the lack of methodological consensus, the comparison of different works is difficult. Therefore, we compared the effects of MSC and OEC transplants at early or delayed time after a spinal cord contusion injury in the rat. Functional outcomes for locomotion, sensory perception and electrophysiological responses were assessed. Moreover, the grafted cells survival and the amount of cavity and spared tissue were studied. The findings indicate that grafted cells survived until 7 days post-injection, but markedly disappeared in the following 2 weeks. Despite the low survival of the cells, MSC and OEC grafts provided tissue protection after early and delayed transplantation. Nevertheless, only acute MSC grafts improved locomotion recovery in treadmill condition and electrophysiological outcomes with respect to the other injured groups. These results, together with previous works, indicate that the MSC seem a better option than OEC for treatment of contusion injuries. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. Evaluation of the survival of bone marrow-derived mononuclear cells and the growth factors produced upon intramedullary transplantation in rat models of acute spinal cord injury.

    Science.gov (United States)

    Arai, Kiyotaka; Harada, Yasuji; Tomiyama, Hiroyuki; Michishita, Masaki; Kanno, Nobuo; Yogo, Takuya; Suzuki, Yoshihisa; Hara, Yasushi

    2016-08-01

    Intramedullary bone marrow-derived mononuclear cell (BM-MNC) transplantation has demonstrated neuroprotective effects in the chronic stage of spinal cord injury (SCI). However, no previous study has evaluated its effects in the acute stage, even though cell death occurs mainly within 1week after injury in all neuronal cells. Moreover, the mechanism underlying these effects remains unclear. We aimed to investigate the survival of intramedullary transplanted allogeneic BM-MNCs and the production of growth factors after transplantation to clarify the therapeutic potential of intramedullary transplanted BM-MNCs and their protective effects in acute SCI. Sprague-Dawley rats were subjected to traumatic SCI and received intramedullary transplantation of EGFP(+)BM-MNCs (n=6), BM-MNCs (n=10), or solvent (n=10) immediately after injury. To evaluate the transplanted BM-MNCs and their therapeutic effects, immunohistochemical evaluations were performed at 3 and 7days post-injury (DPI). BM-MNCs were observed at the injected site at both 3 (683±83 cells/mm(2)) and 7 DPI (395±64 cells/mm(2)). The expression of hepatocyte growth factor was observed in approximately 20% transplanted BM-MNCs. Some BM-MNCs also expressed monocyte chemotactic protein-1 or vascular endothelial growth factor. The demyelinated area and number of cleaved caspase-3-positive cells were significantly smaller in the BM-MNC-transplanted group at 3 DPI. Hindlimb locomotor function was significantly improved in the BM-MNC-transplanted group at 7 DPI. These results suggest that intramedullary transplantation of BM-MNCs is an efficient method for introducing a large number of growth factor-producing cells that can induce neuroprotective effects in the acute stage of SCI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. An In Vivo Characterization of Trophic Factor Production Following Neural Precursor Cell or Bone Marrow Stromal Cell Transplantation for Spinal Cord Injury

    Science.gov (United States)

    Hawryluk, Gregory W.J.; Mothe, Andrea; Wang, Jian; Wang, Shelly; Tator, Charles

    2012-01-01

    Cellular transplantation strategies for repairing the injured spinal cord have shown consistent benefit in preclinical models, and human clinical trials have begun. Interactions between transplanted cells and host tissue remain poorly understood. Trophic factor secretion is postulated a primary or supplementary mechanism of action for many transplanted cells, however, there is little direct evidence to support trophin production by transplanted cells in situ. In the present study, trophic factor expression was characterized in uninjured, injured-untreated, injured-treated with transplanted cells, and corresponding control tissue from the adult rat spinal cord. Candidate trophic factors were identified in a literature search, and primers were designed for these genes. We examined in vivo trophin expression in 3 paradigms involving transplantation of either brain or spinal cord-derived neural precursor cells (NPCs) or bone marrow stromal cells (BMSCs). Injury without further treatment led to a significant elevation of nerve growth factor (NGF), leukemia inhibitory factor (LIF), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β1 (TGF-β1), and lower expression of vascular endothelial growth factor isoform A (VEGF-A) and platelet-derived growth factor-A (PDGF-A). Transplantation of NPCs led to modest changes in trophin expression, and the co-administration of intrathecal trophins resulted in significant elevation of the neurotrophins, glial-derived neurotrophic factor (GDNF), LIF, and basic fibroblast growth factor (bFGF). BMSCs transplantation upregulated NGF, LIF, and IGF-1. NPCs isolated after transplantation into the injured spinal cord expressed the neurotrophins, ciliary neurotrophic factor (CNTF), epidermal growth factor (EGF), and bFGF at higher levels than host cord. These data show that trophin expression in the spinal cord is influenced by injury and cell transplantation, particularly when combined with intrathecal trophin infusion

  10. Cell fusion of bone marrow cells and somatic cell reprogramming by embryonic stem cells

    OpenAIRE

    Bonde, Sabrina; Pedram, Mehrdad; Stultz, Ryan; Zavazava, Nicholas

    2010-01-01

    Bone marrow transplantation is a curative treatment for many diseases, including leukemia, autoimmune diseases, and a number of immunodeficiencies. Recently, it was claimed that bone marrow cells transdifferentiate, a much desired property as bone marrow cells are abundant and therefore could be used in regenerative medicine to treat incurable chronic diseases. Using a Cre/loxP system, we studied cell fusion after bone marrow transplantation. Fused cells were chiefly Gr-1+, a myeloid cell mar...

  11. Graft Transit Time Has No Effect on Outcome of Unrelated Donor Hematopoietic Cell Transplants Performed in Australia and New Zealand: A Study from the Australasian Bone Marrow Transplant Recipient Registry.

    Science.gov (United States)

    Patton, William Nigel; Nivison-Smith, Ian; Bardy, Peter; Dodds, Anthony; Ma, David; Shaw, Peter John; Kwan, John; Wilcox, Leonie; Butler, Andrew; Carter, John M; Blacklock, Hilary; Szer, Jeffrey

    2017-01-01

    A previous study found that platelet recovery and mortality were worse in recipients of myeloablative bone marrow transplants where graft transit times were longer than 20 hours. This retrospective study of unrelated myeloablative allogeneic transplantation performed within Australia and New Zealand analyzed transplant outcomes according to graft transit times. Of 233 assessable cases, 76 grafts (33%) were sourced from bone marrow (BM) and 157 (67%) from peripheral blood. Grafts sourced from Australia and New Zealand (47% of total) were associated with a median transit time of 6 hours versus 32 hours for overseas sourced grafts (53% of total). Graft transit temperature was refrigerated in 85%, ambient in 6%, and unknown in 9% of cases, respectively. Graft transit times had no significant effect on neutrophil or platelet engraftment, treatment-related mortality, overall survival, and incidence of acute or chronic graft-versus-host disease. Separate analysis of BM grafts, although of reduced power, also showed no significant difference in either neutrophil or platelet engraftment or survival between short and longer transport times. This study gives reassurance that both peripheral blood stem cell and especially BM grafts subjected to long transit times and transported at refrigerated temperatures may not be associated with adverse recipient outcomes. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Membrane complement regulatory protein reduces the damage of transplanting autologous bone marrow mesenchymal stem cells by suppressing the activation of complement.

    Science.gov (United States)

    Xiao, Kai; Fang, Zhenhua; Gao, Xinfeng; Zhao, Jingjing; Huang, Ruokun; Xie, Ming

    2017-10-01

    There are few studies on the interaction of transplanting autologous bone marrow mesenchymal stem cells (BMSCs) and complement. In order to further explore the effect of complement on BMSCs, BMSCs were obtained from bone marrow of 20 cases clinical patients, and then experimented in vitro. The cytotoxicity of complement on the mesenchymal stem cells in autologous human serum (AHS) was measured by Europium cytotoxicity assay. The complement membrane attack complex (MAC) deposited on the membrane surface was detected by flow cytometry. Finally, the cytotoxicity on BMSCs was measured after mCRPs overexpression or knockdown. We found that more than 90% of cells derived from bone marrow were identified to be mesenchymal stem cells through detection of cell membrane surface markers by flow cytometry. BMSCs harvested from the 20 patients all had cytotoxicity after incubated with AHS, and the cytotoxicity was significant higher than that incubated with complement inactivated autologous human serum (iAHS). Complement attack complex (MAC) could be detected on the BMSCs incubated with AHS, which implied the complement activation. We also found that mCRPs CD55 and CD59 overexpressions can resist the cytotoxicity induced by complement activation, while mCRPs CD55 and CD59 knockdown can enhance the cytotoxicity. Thus, the results indicated that mCRPs could effectively protect BMSCs from attacking by complement by suppressing the activation of complement. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Transplantation of bone marrow stromal cell-derived neural precursor cells ameliorates deficits in a rat model of complete spinal cord transection.

    Science.gov (United States)

    Aizawa-Kohama, Misaki; Endo, Toshiki; Kitada, Masaaki; Wakao, Shohei; Sumiyoshi, Akira; Matsuse, Dai; Kuroda, Yasumasa; Morita, Takahiro; Riera, Jorge J; Kawashima, Ryuta; Tominaga, Teiji; Dezawa, Mari

    2013-01-01

    After severe spinal cord injury, spontaneous functional recovery is limited. Numerous studies have demonstrated cell transplantation as a reliable therapeutic approach. However, it remains unknown whether grafted neuronal cells could replace lost neurons and reconstruct neuronal networks in the injured spinal cord. To address this issue, we transplanted bone marrow stromal cell-derived neural progenitor cells (BM-NPCs) in a rat model of complete spinal cord transection 9 days after the injury. BM-NPCs were induced from bone marrow stromal cells (BMSCs) by gene transfer of the Notch-1 intracellular domain followed by culturing in the neurosphere method. As reported previously, BM-NPCs differentiated into neuronal cells in a highly selective manner in vitro. We assessed hind limb movements of the animals weekly for 7 weeks to monitor functional recovery after local injection of BM-NPCs to the transected site. To test the sensory recovery, we performed functional magnetic resonance imaging (fMRI) using electrical stimulation of the hind limbs. In the injured spinal cord, transplanted BM-NPCs were confirmed to express neuronal markers 7 weeks following the transplantation. Grafted cells successfully extended neurites beyond the transected portion of the spinal cord. Adjacent localization of synaptophysin and PSD-95 in the transplanted cells suggested synaptic formations. These results indicated survival and successful differentiation of BM-NPCs in the severely injured spinal cord. Importantly, rats that received BM-NPCs demonstrated significant motor recovery when compared to the vehicle injection group. Volumes of the fMRI signals in somatosensory cortex were larger in the BM-NPC-grafted animals. However, neuronal activity was diverse and not confined to the original hind limb territory in the somatosensory cortex. Therefore, reconstruction of neuronal networks was not clearly confirmed. Our results indicated BM-NPCs as an effective method to deliver neuronal lineage

  14. Synergistic Effects of Aerobic Exercise after Bone Marrow Stem Cell Transplantation on Recovery of Dopaminergic Neurons and Angiogenesis Markers of Parkinsonian Rats

    Directory of Open Access Journals (Sweden)

    Seyed Abdollah Hashemvarzi

    2016-03-01

    Full Text Available Abstract: Parkinson is a progressive neurodegenerative disease in central nervous system. Non-pharmacologic treatment methods such as stem cell transplantation and exercise have been considered as a treatment. The purpose of this study was to evaluate the synergistic effects of aerobic exercise after bone marrow stem cells transplantation on recovery of dopaminergic neurons and promotion of angiogenesis markers in the striatum of parkinsonian rats. 42 rats were divided into six groups: Normal (N, Sham (S, Parkinson’s (P, Stem cells transplanted Parkinson’s (SP, Exercised Parkinson’s (EP and Stem cells transplanted+Exercised Parkinson’s (SEP. To create a model of Parkinson's, the striatum was destroyed by injection of 6-hydroxy-dopamine into the striatum through stereotaxic apparatus. Stem cells were derived from the bone marrow of femur and tibia of male rats aged 6-8 weeks. After cultivation, approximately 5×105 cells were injected into the striatum of rats through the channel. Aerobic exercise was included 8 weeks of running on treadmill with a speed of 15 meters per minute. At the end of the study, all subjects were decapitated and striatum tissues were separately isolated for measurement of vascular endothelial growth factor (VEGF, dopamine (DA and tyrosine hydroxylase (TH levels. VEGF, DA and TH levels in the striatum of parkinsonian rats significantly increased in treatment groups (SP, EP and SEP, especially in SEP group compared to P group after treatment (P<0.05. The BMSCs transplantation in combination with exercise would have synergistic effects leading to functional recovery, dopaminergic neurons recovery and promotion of angiogenesis marker in the striatum of parkinsonian rats. Keywords: Stem cells, Aerobic exercise, Neurotrophic factors, Parkinson

  15. Effects of radiations on bone marrow

    International Nuclear Information System (INIS)

    Tubiana, M.; Frindel, E.; Croizat, H.; Parmentier, C.

    1979-01-01

    After total body irradiation for kidney transplant, the initial decrease of circulating blood cells is more rapid, the nadir is reached sooner and the regeneration occurs earlier when the doses are higher than a few hundred rads. The LD 50 in man seems to be higher than 450 rads. The in vivo and in vitro assays of hemopoietic stem cells have greatly increasedd the understanding of acute and late effects. Multipotential stem cells are very radiosensitive, furthermore the differentiation of the surviving stem cells is accelerated after irradiation. This results in a severe depletion of the stem cell compartment. When this stem cell number falls below a critical value, the stem cell no longer differentiates till the completion of the regeneration of the stem cell compartment. Stem cell proliferation is regulated by inhibitors and stimulators. Release of stimulators by irradiated bone marrow has been demonstrated. Severe sequellae are observed after irradiation of animal and human bone marrow. They seem to be due either to the damage of the stromal cell or to the stem cell population. In patients, four compensating mechanisms are observed after a regional bone marrow irradiation: stimulation of non irradiated bone marrow, extension of hemopoietic areas, regeneration of irradiated bone marrow when the irradiated volume is large and increase in the amplification factor resulting in an increase in the output of mature cells for one stem cell input. Assay of progenitor cells provides useful information and a reduction in their number is still observed many years after a large regional irradiation

  16. An observational study of autologous bone marrow-derived stem cells transplantation in seven patients with nervous system diseases: a 2-year follow-up.

    Science.gov (United States)

    Ren, Chao; Geng, Run-lu; Ge, Wei; Liu, Xiao-Yun; Chen, Hao; Wan, Mei-Rong; Geng, De-Qin

    2014-05-01

    Currently, autologous bone marrow-derived stem cell is one of the most innovative areas of stem cells research. Previous studies on animal models of nervous system diseases have shown that these cells have a good effect on nervous system disorders. The alternative treatment with stem cells for the nervous system diseases has also gradually reached to clinical application stage. The prospect is captivating, but the safety and efficacy of this procedure need further research. To observe the clinical efficacy and side effects of the treatment for autologous mesenchymal stem cells and neural stem/progenitor cells which are in differentiated form by inducing with cerebrospinal fluid in the patients with nervous system diseases, thirty patients were selected from our hospital (2009-10 to 2012-07) and were followed at 1 month, 3 months, 6 months, 1 year and 2 years after the treatment with autologous mesenchymal stem cells and neural stem/progenitor cells in differentiated form was introduced. In this paper, we will introduce the process to make cells accessible for the clinical application by the description of the changes observed in 7 cases were followed for 2 years. The time for bone marrow mesenchymal stem cells could be available for clinical needs is as early as 5 days, not later than 10 days, and the median time is 8 days, while neural stem/progenitor cells in differentiated form can be available for clinical needs in as early as 12 days, not later than 15 days, and the median time is 13.5 days (statistical explanation: Case 5 only uses autologous mesenchymal stem cells, and Case 7 has two times bone marrow punctures). The neurological function of the patients was improved in 1-month follow-up, and the patients have a better discontinuous trend (statistical explanation: sometimes the neurological function of the patients between two adjacent follow-ups does not change significantly). After transplantation, four patients appeared to have transient fever, but it was

  17. Transplantation of human bone marrow stromal cell-derived Schwann cells reduces cystic cavity and promotes functional recovery after contusion injury of adult rat spinal cord.

    Science.gov (United States)

    Kamada, Takahito; Koda, Masao; Dezawa, Mari; Anahara, Reiko; Toyama, Yoshiro; Yoshinaga, Katsunori; Hashimoto, Masayuki; Koshizuka, Shuhei; Nishio, Yutaka; Mannoji, Chikato; Okawa, Akihiko; Yamazaki, Masashi

    2011-02-01

    The aim of this study was to evaluate whether transplantation of human bone marrow stromal cell-derived Schwann cells (hBMSC-SC) promotes functional recovery after contusive spinal cord injury of adult rats. Human bone marrow stromal cells (hBMSC) were cultured from bone marrow of adult human patients and induced into Schwann cells (hBMSC-SC) in vitro. Schwann cell phenotype was confirmed by immunocytochemistry. Growth factors secreted from hBMSC-SC were detected using cytokine antibody array. Immunosuppressed rats were laminectomized and their spinal cords were contused using NYU impactor (10 g, 25 mm). Nine days after injury, a mixture of Matrigel and hBMSC-SC (hBMSC-SC group) was injected into the lesioned site. Five weeks after transplantation, cresyl-violet staining revealed that the area of cystic cavity was smaller in the hBMSC-SC group than that in the control group. Immunohistochemistry revealed that the number of anti-growth-associated protein-43-positive nerve fibers was significantly larger in the hBMSC-SC group than that in the control group. At the same time, the number of tyrosine hydroxylase- or serotonin-positive fibers was significantly larger at the lesion epicenter and caudal level in the hBMSC-SC group than that in the control group. In electron microscopy, formation of peripheral-type myelin was recognized near the lesion epicenter in the hBMSC-SC group. Hind limb function recovered significantly in the hBMSC-SC group compared with the control group. In conclusion, the functions of hBMSC-SC are comparable to original Schwann cells in rat spinal cord injury models, and are thus potentially useful treatments for patients with spinal cord injury. © 2010 Japanese Society of Neuropathology.

  18. Bone marrow transplantation across major histocompatibility barriers in mice. II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    International Nuclear Information System (INIS)

    Vallera, D.A.; Soderling, C.C.; Carlson, G.J.; Kersey, J.H.

    1982-01-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatibility barriers. Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then give to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 200-rad TLI. In TLI plus CY-conditional recipients, we have also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. Furthermore, graft failure in mice receiving normal dosages of anti-Thy-1.2 plus C-treated donor cells was not a strain-restricted phenomenon. Moreover, removal of bone marrow T cells with monoclonal anti-Lyt-1 plus complement also resulted in graft failure in TLI-conditioned recipients. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for there findings are discussed

  19. Bone marrow transplantation across major histocompatibility barriers in mice. II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    Energy Technology Data Exchange (ETDEWEB)

    Vallera, D.A.; Soderling, C.C.; Carlson, G.J.; Kersey, J.H.

    1982-03-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatibility barriers. Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then give to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 200-rad TLI. In TLI plus CY-conditional recipients, we have also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. Furthermore, graft failure in mice receiving normal dosages of anti-Thy-1.2 plus C-treated donor cells was not a strain-restricted phenomenon. Moreover, removal of bone marrow T cells with monoclonal anti-Lyt-1 plus complement also resulted in graft failure in TLI-conditioned recipients. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for there findings are discussed.

  20. The effect of a polyurethane-based reverse thermal gel on bone marrow stromal cell transplant survival and spinal cord repair.

    Science.gov (United States)

    Ritfeld, Gaby J; Rauck, Britta M; Novosat, Tabitha L; Park, Daewon; Patel, Pavan; Roos, Raymund A C; Wang, Yadong; Oudega, Martin

    2014-02-01

    Cell therapy for nervous tissue repair is limited by low transplant survival. We investigated the effects of a polyurethane-based reverse thermal gel, poly(ethylene glycol)-poly(serinol hexamethylene urethane) (ESHU) on bone marrow stromal cell (BMSC) transplant survival and repair using a rat model of spinal cord contusion. Transplantation of BMSCs in ESHU at three days post-contusion resulted in a 3.5-fold increase in BMSC survival at one week post-injury and a 66% increase in spared nervous tissue volume at four weeks post-injury. These improvements were accompanied by enhanced hindlimb motor and sensorimotor recovery. In vitro, we found that ESHU protected BMSCs from hydrogen peroxide-mediated death, resulting in a four-fold increase in BMSC survival with two-fold fewer BMSCs expressing the apoptosis marker, caspase 3 and the DNA oxidation marker, 8-oxo-deoxyguanosine. We argue that ESHU protected BMSCs transplanted is a spinal cord contusion from death thereby augmenting their effects on neuroprotection leading to improved behavioral restoration. The data show that the repair effects of intraneural BMSC transplants depend on the degree of their survival and may have a widespread impact on cell-based regenerative medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Antigen-Encoding Bone Marrow Terminates Islet-Directed Memory CD8+ T-Cell Responses to Alleviate Islet Transplant Rejection

    DEFF Research Database (Denmark)

    Coleman, Miranda; Jessup, Claire F.; Bridge, Jennifer A.

    2016-01-01

    Islet-specific memory T cells arise early in type 1 diabetes (T1D), persist for long periods, perpetuate disease, and are rapidly reactivated by islet transplantation. As memory T cells are poorly controlled by “conventional” therapies, memory T cell–mediated attack is a substantial challenge in ...... responses, and this can alleviate destruction of antigen-expressing islets. This addresses a key challenge facing islet transplantation and, importantly, the clinical application of personalized β-cell replacement therapies using patient-derived stem cells.......Islet-specific memory T cells arise early in type 1 diabetes (T1D), persist for long periods, perpetuate disease, and are rapidly reactivated by islet transplantation. As memory T cells are poorly controlled by “conventional” therapies, memory T cell–mediated attack is a substantial challenge...... in islet transplantation, and this will extend to application of personalized approaches using stem cell–derived replacement β-cells. New approaches are required to limit memory autoimmune attack of transplanted islets or replacement β-cells. Here, we show that transfer of bone marrow encoding cognate...

  2. Bone marrow transplantation across major histocompatibility barriers in mice: II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    Energy Technology Data Exchange (ETDEWEB)

    Vallera, D.A.; Soderling, C.C.B.; Carlson, G.J.; Kersey, J.H.

    1982-03-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatability barriers.Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then given to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 100-rad TLI. In TLI plus CY-conditioned recipients, it was also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for these findings are discussed. (JMT)

  3. Bone marrow transplantation across major histocompatibility barriers in mice: II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    International Nuclear Information System (INIS)

    Vallera, D.A.; Soderling, C.C.B.; Carlson, G.J.; Kersey, J.H.

    1982-01-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatability barriers.Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then given to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 100-rad TLI. In TLI plus CY-conditioned recipients, it was also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for these findings are discussed

  4. Immunodeficiency after allogeneic bone marrow transplantation in man. Effect of phorbol ester (phorbol myristate acetate) and calcium ionophore (A23187) in vitro

    DEFF Research Database (Denmark)

    Møller, J; Hofmann, B; Langhoff, E

    1989-01-01

    This study was undertaken to clarify the mechanism behind the severely decreased lymphocyte proliferative response upon stimulation with mitogens and antigens seen after allogeneic bone marrow transplantation (BMT) in man. We investigated eight BMT patients and eight controls and found that the p......This study was undertaken to clarify the mechanism behind the severely decreased lymphocyte proliferative response upon stimulation with mitogens and antigens seen after allogeneic bone marrow transplantation (BMT) in man. We investigated eight BMT patients and eight controls and found...... that the proliferative response of patient cells was reduced both when the cells were stimulated with phytohaemagglutinin (PHA) and when they were stimulated with a combination of phorbol myristate acetate (PMA), which is an activator of protein kinase C (PKC), and the calcium ionophore A23187, which irreversibly opens......) receptors (CD25) was only slightly decreased. However, the production of IL-2 was severely decreased in patient cells after stimulation with A23187/PMA (median 3541 units), although it was higher than in PHA-stimulated control cells (median 354 units). These results show that a direct activation of PKC...

  5. Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation Leucoencefalopatia posterior reversível associada a transplante de medula óssea

    Directory of Open Access Journals (Sweden)

    Hélio A.G. Teive

    2001-09-01

    Full Text Available Reversible posterior leucoencephalopathy syndrome (RPLS has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity.A síndrome de leucoencefalopatia posterior reversível (SLPR tem sido descrita em pacientes com insuficiência renal, eclâmpsia, encefalopatia hipertensiva e em pacientes que recebem terapia imunossupressora. O mecanismo pelo qual os agentes imunossupressores podem causar a síndrome ainda não são conhecidos, porém estão provavelmente relacionados aos efeitos citotóxicos destes agentes no endotélio vascular. Relatamos oito pacientes que receberam ciclosporina A (CSA após transplante de medula óssea alogênico ou para tratamento de anemia aplástica severa e que desenvolveram a SLPR. Os sinais e sintomas mais comuns foram convulsões e cefaléia. A disfunção neurológica ocorreu simultaneamente ou precedida por elevação da pressão arterial sistêmica e disfunção renal aguda em seis pacientes. O exame de

  6. Suppressed retinal degeneration in aged wild type and APPswe/PS1ΔE9 mice by bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Yue Yang

    Full Text Available Alzheimer's disease (AD is an age-related condition characterized by accumulation of neurotoxic amyloid β peptides (Aβ in brain and retina. Because bone marrow transplantation (BMT results in decreased cerebral Aβ in experimental AD, we hypothesized that BMT would mitigate retinal neurotoxicity through decreased retinal Aβ. To test this, we performed BMT in APPswe/PS1ΔE9 double transgenic mice using green fluorescent protein expressing wild type (wt mice as marrow donors. We first examined retinas from control, non-transplanted, aged AD mice and found a two-fold increase in microglia compared with wt mice, prominent inner retinal Aβ and paired helical filament-tau, and decreased retinal ganglion cell layer neurons. BMT resulted in near complete replacement of host retinal microglia with BMT-derived cells and normalized total AD retinal microglia to non-transplanted wt levels. Aβ and paired helical filament-tau were reduced (61.0% and 44.1% respectively in BMT-recipient AD mice, which had 20.8% more retinal ganglion cell layer neurons than non-transplanted AD controls. Interestingly, aged wt BMT recipients also had significantly more neurons (25.4% compared with non-transplanted aged wt controls. Quantitation of retinal ganglion cell layer neurons in young mice confirmed age-related retinal degeneration was mitigated by BMT. We found increased MHC class II expression in BMT-derived microglia and decreased oxidative damage in retinal ganglion cell layer neurons. Thus, BMT is neuroprotective in age-related as well as AD-related retinal degeneration, and may be a result of alterations in innate immune function and oxidative stress in BMT recipient mice.

  7. A pilot study of autologous CD34-depleted bone marrow mononuclear cell transplantation via the hepatic artery in five patients with liver failure.

    Science.gov (United States)

    Park, Chung-Hwa; Bae, Si Hyun; Kim, Hee Yeon; Kim, Ja Kyung; Jung, Eun Sun; Chun, Ho Jong; Song, Myeong Jun; Lee, Sung-Eun; Cho, Seok Goo; Lee, Jong Wook; Choi, Jong Young; Yoon, Seung Kew; Han, Nam Ik; Lee, Young Sok

    2013-12-01

    Many rodent experiments and human studies on stem cell therapy have shown promising therapeutic approaches to liver diseases. We investigated the clinical outcomes of five patients with liver failure of various causes who received autologous CD34-depleted bone marrow-derived mononuclear cell (BM-MNC) transplantation, including mesenchymal stromal cells, through the hepatic artery. CD34-depleted BM-MNCs were obtained from five patients waiting for liver transplantation by bone marrow aspiration and using the CliniMACS CD34 Reagent System (Miltenyi Biotech, Bergisch Gladbach, Germany), and autologous hepatic artery infusion was performed. The causes of hepatic decompensation were hepatitis B virus (HBV), hepatitis C virus (HCV), propylthiouracil-induced toxic hepatitis and Wilson disease. Serum albumin levels improved 1 week after transplantation from 2.8 g/dL, 2.4 g/dL, 2.7 g/dL and 1.9 g/dL to 3.3 g/dL, 3.1 g/dL, 2.8 g/dL and 2.6 g/dL. Transient liver elastography data showed some change from 65 kPa, 33 kPa, 34.8 kPa and undetectable to 46.4 kPa, 19.8 kPa, 29.1 kPa and 67.8 kPa at 4 weeks after transplantation in a patient with Wilson disease, a patient with HCV, and two patients with HBV. Ascites decreased in two patients. One of the patients with HBV underwent liver transplantation 4 months after the infusion, and the hepatic progenitor markers (cytokeratin [CD]-7, CD-8, CD-9, CD-18, CD-19, c-Kit and epithelial cell adhesion molecule [EpCAM]) were highly expressed in the explanted liver. Serum albumin levels, liver stiffness, liver volume, subjective healthiness and quality of life improved in the study patients. Although these findings were observed in a small population, the results may suggest a promising future for autologous CD34-depleted BM-MNC transplantation as a bridge to liver transplantation in patients with liver failure. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  8. Autologous bone marrow stem cell transplantation attenuates hepatocyte apoptosis in a rat model of ex vivo liver resection and liver autotransplantation.

    Science.gov (United States)

    Xu, Tubing; Wang, Xiaojun; Chen, Geng; He, Yu; Bie, Ping

    2013-10-01

    To investigate the efficacy of autologous bone marrow stem cell (BMSC) transplantation in the treatment of hepatic injury in ex vivo liver resection and liver autotransplantation (ELRLA). Rat hepatic fibrosis was induced by intraperitoneal injection of 50% CCl4-olive oil solution at a dose of 2 mL/kg twice weekly for 4 wk. ELRLA was performed 3 d post the last injection of CCl4. Six rats in each group were killed 12, 24, 48, 72, and 168 h after the operation. Hepatocyte apoptosis was determined by TUNEL assay. The expression of Bcl-2, Bax, transforming growth factor (TGF) β1, TGFβ1 receptor1/2, and phosphorylated p38 MAPK were determined by Western blot. Autologous BMSC transplantation significantly inhibited the increase of alanine aminotransferease and aspartate aminotransferase at 12, 24, and 48 h post operation and attenuated ELRLA-induced hepatocyte apoptosis. In BMSC-treated rats, the expression of Bcl-2 was significantly upregulated, whereas there were no obvious changes in Bax level. The expression of TGFβ1 was significantly upregulated in the rat liver after the surgery. Autologous BMSC transplantation significantly downregulated the TGFβ1 levels at 48, 72, and 168 h post surgery. However, autologous BMSC transplantation showed little effect on the levels of TGFβ receptor 1/2 at all the time points observed. Furthermore, autologous BMSC transplantation significantly inhibited the activation of p38 MAPK. Autologous BMSC transplantation may reduce ELRLA-induced liver injury and improve survival rates in hepatic fibrosis rats. Autologous BMSC transplantation may be useful to improve the outcome of patients who undergo ELRLA. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Recovery of Unrelated Donors of Peripheral Blood Stem Cells versus Recovery of Unrelated Donors of Bone Marrow: A Prespecified Analysis from the Phase III Blood and Marrow Transplant Clinical Trials Network Protocol 0201.

    Science.gov (United States)

    Burns, Linda J; Logan, Brent R; Chitphakdithai, Pintip; Miller, John P; Drexler, Rebecca; Spellman, Stephen; Switzer, Galen E; Wingard, John R; Anasetti, Claudio; Confer, Dennis L

    2016-06-01

    We report a comparison of time to recovery, side effects, and change in blood counts from baseline to after donation from unrelated donors who participated in the Blood and Marrow Transplant Clinical Trials Network phase III randomized, multicenter trial (0201) in which donor-recipient pairs were randomized to either peripheral blood stem cell (PBSC) or bone marrow (BM) donation. Of the entire cohort, 262 donated PBSC and 264 donated BM; 372 (71%) donors were from domestic and 154 (29%) were from international centers (145 German and 9 Canadian). PBSC donors recovered in less time, with a median time to recovery of 1 week compared with 2.3 weeks for BM donors. The number of donors reporting full recovery was significantly greater for donors of PBSC than of BM at 1, 2, and 3 weeks and 3 months after donation. Multivariate analysis showed that PBSC donors were more likely to recover at any time after donation compared with BM donors (hazard ratio, 2.08; 95% confidence interval [CI], 1.73 to 2.50; P hemoglobin. This analysis provided an enhanced understanding of donor events as product donated was independent of physician bias or donor preference. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    Directory of Open Access Journals (Sweden)

    Guihong Li

    2016-01-01

    Full Text Available Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  11. The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection

    Directory of Open Access Journals (Sweden)

    Vinnitsa Buzoianu-Anguiano

    2015-01-01

    Full Text Available Functional recovery following spinal cord injury (SCI is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN and the transplantation of bone marrow stromal cells (BMSCs have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI without treatment, TSCI + Fibrin Glue (FG, TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model.

  12. Ultrasound imaging as the basis of a clinical diagnosis of systemic bartonellosis in a patient after bone marrow transplantation. A case report

    Directory of Open Access Journals (Sweden)

    Aleksandra Krasowska-Kwiecień

    2016-06-01

    Full Text Available Infections in immunocompromised patients after hematopoietic stem cell transplantation can have a severe and atypical course. Some opportunistic pathogens are difficult to detect in microbiological tests, and that is why treatment success depends on an accurate clinical diagnosis. This article presents a case of a 7-year-old girl with severe aplastic anemia treated with bone marrow transplantation with post-transplantation period complicated by persistent, hectic fever, with peak episodes of 39–40°C, lasting several weeks. Repeated microbiological tests failed to reveal the etiological agent, and empirical anti-infective treatment was ineffective. In the fourth week of fever, imaging showed multiple foci resembling abscesses in the patient’s internal organs and, subsequently, in soft tissues. The characteristics of these changes and data concerning environmental exposure led to the clinical diagnosis of cat scratch disease (bartonellosis with multi-organ involvement and enabled the targeted treatment to be implemented. Fever subsided and organ lesions regressed. In this case, repeated ultrasound imaging was the basic diagnostic tool that helped arrive at a correct diagnosis and implement effective treatment of this life-threatening complication after hematopoietic stem cell transplantation.

  13. Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

    Energy Technology Data Exchange (ETDEWEB)

    Tait, R.C.; Burnett, A.K.; Robertson, A.G.; McNee, S.; Riyami, B.M.; Carter, R.; Stevenson, R.D. (Department of Haematology, Royal Infirmary, Glasgow (Scotland))

    1991-06-01

    Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients.

  14. Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: Evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery

    International Nuclear Information System (INIS)

    Tiberghien, P.; Longo, D.L.; Wine, J.W.; Alvord, W.G.; Reynolds, C.W.

    1990-01-01

    Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery

  15. Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: Evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery

    Energy Technology Data Exchange (ETDEWEB)

    Tiberghien, P.; Longo, D.L.; Wine, J.W.; Alvord, W.G.; Reynolds, C.W. (Program Resources, Inc., Frederick, MD (USA))

    1990-10-01

    Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery.

  16. Transplante de célula-tronco hematopoética para síndrome mielodisplásica Bone marrow transplantation in myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Daniel G. Tabak

    2010-05-01

    Full Text Available As síndromes mielodisplásicas (SMD constituem um grupo de doenças hematológicas caracterizadas por citopenias crônicas, associadas a uma maturação celular anormal. A melhor forma de classificação atual destas patologias é o International Prognostic Scoring System (IPSS, que se baseia no grau de citopenia, número de mieloblastos na medula óssea e alterações citogenéticas. Há quatro estágios: baixo risco, riscos intermediário-1 e 2 e alto risco. Um grupo destes pacientes pode ser curado com o transplante de células-tronco hematopoéticas (TCTH. Esta forma de tratamento pode ser considerada para pacientes com idade inferior a 60 anos, que possuam um doador familiar HLA-idêntico. A opção por esta modalidade terapêutica depende de alguns critérios, que incluem o IPSS, o risco de progressão de doença, o risco de infecção e o estado geral do paciente. O TCTH autólogo pode ser considerado em pacientes que alcancem uma remissão completa citogenética e que não disponham de doador HLAidêntico. Em pacientes não candidatos ao TCTH mieloablativo, uma possibilidade é o transplante com regimes de intensidade reduzida. Estudos recentes têm demonstrado resultados favoráveis com esta opção terapêutica, pois, apesar do alto rico de recaída, as taxas de mortalidade associada ao procedimento são menores. Os pacientes com SMD devem ser dispostos em ensaios clínicos que considerem as comorbidades, DECH e riscos de recaída.The myelodysplastic syndrome (MDS encompasses a series of hematological conditions characterized by chronic cytopenias with abnormal cellular maturation. Based on the cytopenias, number of blast cells in bone marrow and cytogenetic abnormalities, MDS may be best classified by the International Prognostic Scoring System (IPSS in four groups: low risk, intermediate 1, intermediate 2 risks and high risk. A subset of patients can be cured following allogeneic hematopoietic stem cell transplantation (SCT. This

  17. Co- transplantation of Bone Marrow Stromal Cells with Schwann Cells Evokes Mechanical Allodynia in the Contusion Model of Spinal Cord Injury in Rats

    Science.gov (United States)

    Pourheydar, Bagher; Joghataei, Mohammad Taghi; Bakhtiari, Mehrdad; Mehdizadeh, Mehdi; Yekta, Zahra; Najafzadeh, Norooz

    2012-01-01

    Objective: Several studies have shown that, although transplantation of neural stem cells into the contusion model of spinal cord injury (SCI) promotes locomotor function and improves functional recovery, it induces a painful response, Allodynia. Different studies indicate that bone marrow stromal cells (BMSCs) and Schwann cells (SCs) can improve locomotor recovery when transplanted into the injured rat spinal cord. Since these cells are commonly used in cell therapy, we investigated whether co-transplantation of these cells leads to the development of Allodynia. Materials and Methods: In this experimental research, the contusion model of SCI was induced by laminectomy at the T8-T9 level of the spinal cord in adult female wistar rats (n=40) weighting (250-300g) using the New York University Device. BMSCs and SCs were cultured and prelabeled with 5-bromo-2-deoxyuridine (BrdU) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) respectively. The rats were divided into five groups of 8 including: a control group (laminectomy only), three experimental groups (BMSC, SC and Co-transplant) and a sham group. The experimental groups received BMSCs, SCs, and BMSCs and SCs respectively by intraspinal injection 7 days after injury and the sham group received serum only. Locomotion was assessed using Basso, Beattie and Bresnahan (BBB) test and Allodynia by the withdrawal threshold test using Von Frey Filaments at 1, 7, 14, 21, 28, 35, 42, 49 and 56 days after SCI. The statistical comparisons between groups were carried out by using repeated measures analysis of variances (ANOVA). Results: Significant differences were observed in BBB scores in the Co- transplant group compared to the BMSC and SC groups (pspinal cord can improve functional recovery, it leads to the development of mechanical Allodynia. This finding indicates that strategies to reduce Allodynia in cell transplantation studies are required. PMID:23508042

  18. Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

    International Nuclear Information System (INIS)

    Yoshihara, Takao; Fujii, Noriko; Naya, Mayumi

    1999-01-01

    We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m 2 x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin's lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

  19. Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Yoshihara, Takao; Fujii, Noriko [Matsushita Memorial Hospital, Moriguchi, Osaka (Japan); Naya, Mayumi [and others

    1999-02-01

    We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m{sup 2} x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin`s lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

  20. Factors Associated With Post-Traumatic Growth, Quality of Life, and Spiritual Well-Being in Outpatients Undergoing Bone Marrow Transplantation: A Pilot Study.

    Science.gov (United States)

    Sinclair, Shane; Booker, Reanne; Fung, Tak; Raffin-Bouchal, Shelley; Enns, Bert; Beamer, Kate; Ager, Naree

    2016-11-01

    To examine the relationships between spiritual, religious, and sociodemographic factors and post-traumatic growth, quality of life, and spiritual well-being in outpatients undergoing bone marrow and/or stem cell transplantation (BMSCT).
. Cross-sectional, descriptive, exploratory.
. Outpatient bone marrow transplantation clinic at the Tom Baker Cancer Centre in Calgary, Alberta, Canada.
. 100 patients (21 pre-BMSCT and 79 post-BMSCT) accrued consecutively via non-probability sampling.
. Study participants completed the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT), the Post-Traumatic Growth Inventory (PTGI), the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp), and a demographic questionnaire. Data analysis included descriptive statistics, t tests, and correlational analyses.
. Demographic variables, FACT-BMT scores, PTGI scores, FACIT-Sp scores. 
. The majority of participants identified themselves as being at least somewhat spiritual. Significant differences were noted between those who identified as being not religious at all versus having at least some religiosity in several subscales of the PTGI, as well as on the FACIT-Sp. Similarly, significant differences were observed between participants who identified as being not spiritual at all versus having at least some spirituality for several subscales on the PTGI. Most participants indicated they would be at least somewhat likely to recommend spiritual care to a new patient. 
. Most patients in this study within a publicly funded healthcare system self-identified with spirituality, used spiritual resources, and would recommend that other patients undergoing BMSCT seek the support of a spiritual care professional or chaplain. Spirituality, along with practical and relational factors, had a positive impact on certain aspects of post-traumatic growth, quality of life, and spiritual and physical well-being.
. Oncology nurses are

  1. Extracellular high mobility group box 1 plays a role in the effect of bone marrow mononuclear cell transplantation for heart failure.

    Directory of Open Access Journals (Sweden)

    Masahiro Kaneko

    Full Text Available Transplantation of unfractionated bone marrow mononuclear cells (BMCs repairs and/or regenerates the damaged myocardium allegedly due to secretion from surviving BMCs (paracrine effect. However, donor cell survival after transplantation is known to be markedly poor. This discrepancy led us to hypothesize that dead donor BMCs might also contribute to the therapeutic benefits from BMC transplantation. High mobility group box 1 (HMGB1 is a nuclear protein that stabilizes nucleosomes, and also acts as a multi-functional cytokine when released from damaged cells. We thus studied the role of extracellular HMGB1 in the effect of BMC transplantation for heart failure. Four weeks after coronary artery ligation in female rats, syngeneic male BMCs (or PBS only as control were intramyocardially injected with/without anti-HMGB1 antibody or control IgG. One hour after injection, ELISA showed that circulating extracellular HMGB1 levels were elevated after BMC transplantation compared to the PBS injection. Quantitative donor cell survival assessed by PCR for male-specific sry gene at days 3 and 28 was similarly poor. Echocardiography and catheterization showed enhanced cardiac function after BMC transplantation compared to PBS injection at day 28, while this effect was abolished by antibody-neutralization of HMGB1. BMC transplantation reduced post-infarction fibrosis, improved neovascularization, and increased proliferation, while all these effects in repairing the failing myocardium were eliminated by HMGB1-inhibition. Furthermore, BMC transplantation drove the macrophage polarization towards alternatively-activated, anti-inflammatory M2 macrophages in the heart at day 3, while this was abolished by HMGB1-inhibition. Quantitative RT-PCR showed that BMC transplantation upregulated expression of an anti-inflammatory cytokine IL-10 in the heart at day 3 compared to PBS injection. In contrast, neutralizing HMGB1 by antibody-treatment suppressed this anti

  2. Interleukin-7 improves T-cell recovery after experimental T-cell-depleted bone marrow transplantation in T-cell-deficient mice by strong expansion of recent thymic emigrants

    NARCIS (Netherlands)

    A.E. Broers (Anna Elisabeth Clasine); S.J. Posthumus-van Sluijs (Sandra); H. Spits (Hergen); B. van der Holt (Bronno); B. Löwenberg (Bob); E. Braakman (Eric