Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allogeneic stem cell transplantation (allo SCT) is now frequently performed for the treatment of haematological malignancies and aplastic anaemia. However, graft-versus-host disease (GVHD) is still the major complication after allo SCT, producing immune deficiency, infection, organ damage and, occasionally, patient death. The antigen-specific signal mediated by the T-cell receptor (TCR) is essential for activation of T-cells; however, additional co-stimulatory signals are required for complete T-cell activation. Therefore, blocking strategies of co-stimulatory signals have been evaluated as targets of therapeutic intervention for GVHD after allo SCT. In a mouse bone-marrow transplantation (BMT) model, the administration of CTLA4-Ig, which blocks the interaction of CD28 on T-cells and B7 molecules on antigen-presenting cells (APCs), can prolong survival of allo BMT recipients, although this effect was not complete. In addition, the anti-CD40L (CD154) monoclonal antibody (mAb), which can interfere with the interaction of CD154 on T-cells and CD40 on APCs, can induce long-term graft survival in the murine model. Combined administration of CTLA4-Ig and anti-CD40L mAb can prevent allograft rejection in primates. Therefore, it seems the most powerful method to prevent the alloimmune response in vivo. The Fas/Fas ligand pathway is also involved in pathogenesis of GVHD. Anti-FasL mAb can reduce the mortality of GVHD and improve intestinal lesions. Recently, it was reported that donor bone marrow treated ex vivo using CTLA4-Ig reconstituted haematopoiesis in vivo with a relatively low risk of GVHD in human allo BMT. Therefore, selective blocking strategies for T-cell co-signalling might be useful for the prevention of GVHD in human allo SCT.
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PMID:T-cell co-signalling molecules in graft-versus-host disease. 1090 5

We have employed a new cytoreductive regimen to transplant two patients with Fanconi anaemia (FA), using T cell-depleted two HLA-allele disparate related peripheral blood stem cell transplants (PBSCTs). Patient 1, a 5-year-old male with FA and aplastic anaemia, initially received an HLA two-antigen mismatched unrelated cord blood transplant and failed to engraft. He received fludarabine (Flu) and cyclophosphamide (Cy), followed by a CD34(+) E-rosette(-) (CD34(+)E(-)), T cell-depleted, granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCT from his HLA B-DRB1 mismatched father. He received anti-thymocyte globulin (ATG), steroids, FK506 and G-CSF after transplant for rejection and graft-versus-host disease (GVHD) prophylaxis. The patient is now 23 months after SCT with no evidence of GVHD and with full haematopoietic and immune reconstitution. Patient 2, a 10-year-old boy with FA and myelodysplastic syndrome, received single-dose total body irradiation (SDTBI), Flu and Cy followed by a CD34(+)E(-), T-cell-depleted, G-CSF-mobilized PBSCT from his HLA B-DRB1 mismatched sister. He also received ATG, steroids, FK506 and G-CSF after transplant. The patient is now 12 months after SCT in complete remission with no evidence of GVHD. Absolute neutrophil counts (ANC) of > 1 x 10(9)/l were achieved on day 11 and day 10 post transplant respectively. Both patients are fully engrafted. In summary, we report two successful T-cell-depleted stem cell transplants from mismatched related donors for the treatment of Fanconi anaemia, using a fludarabine-based cytoreduction. Both patients experienced minimal toxicity, rapid engraftment and no GVHD.
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PMID:Stem cell transplantation for the treatment of Fanconi anaemia using a fludarabine-based cytoreductive regimen and T-cell-depleted related HLA-mismatched peripheral blood stem cell grafts. 1116 55

Because of progress in supportive therapies, the upper limit of age for conventional allogenic stem cell transplantation (allo-SCT) is rising. We retrospectively evaluated the impact of age on transplant outcomes in patients older than 50 years of age who underwent conventional allo-SCT in 8 institutions in Japan. The median age was 52-years old (range 50 to 65). The underlying diseases included severe aplastic anemia (n = 3), acute myelogenous leukemia (n = 20), acute lymphoblastic leukemia (n = 10), chronic myelogenous leukemia (n = 11), myelodysplastic syndrome (n = 18), and non-Hodgkin lymphoma (n = 3). Forty two patients (67%) with hematological malignancies received allo-SCT in an advanced disease stage at the time of transplant. The two-year overall survival and disease-free survival rate were 50.1% and 43.6%, respectively. In patients with hematological malignancies, the two-year probability rates of survival were 54.3% with standard risk patients, and 45.9% with poor risk patients. The severity of acute GVHD, the kind of grafts, and age (> or = 55) were related to poor prognosis. Our data suggest that prophylaxis of acute GVHD and selection of the graft is more important for older patients, and that patients less than 55-years old can be candidates for conventional allo-SCT.
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PMID:[Outcome of allogeneic stem cell transplantation in patients older than 50 years of age]. 1246 25

Allogeneic stem cell transplantation (allo-SCT) is a well-established treatment modality for children with severe aplastic anemia (SAA). Treatment failures are rare and mostly caused by graft rejection. Increasing mixed chimerism represents a stage at the very beginning of graft rejection, where immunological intervention might be an effective prophylactic approach. To substantiate this, we: (1) monitored peripheral blood cells from children with SAA after allo-SCT and performed pre-emptive immunotherapy in patients with increasing MC. In all, 23/34 courses of 32 children with SAA after allo-SCT showed a complete chimerism (CC) throughout and 10/34 developed different types of mixed chimerism (MC). Altogether, 4/10 with MC spontaneously developed decreasing MC, 2/10 courses persisted with low proportions of autologous cells below 30% (stable-MC), 4/10 developed increasing MC and one patient showed an autologous recovery. All patients with CC, decreasing MC or stable MC remained in continuous complete remission (CCR). In all, 2/4 patients with increasing MC developed graft rejection. Based on these observations, 2/4 new patients with increasing MC received low-dose DLIs prophylactically, and remained in CCR without any GVHD. These results substantiate that low-dose DLI in children with SAA and increasing MC can prevent graft rejection with a calculable risk to induce severe GVHD.
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PMID:Clinical relevance of serial quantitative analysis of hematopoietic chimerism after allogeneic stem cell transplantation in children for severe aplastic anemia. 1464 53

The first reported bone marrow transplant was published in 1939, although it was deemed unsuccessful. Between 1957 and 1965, numerous reports of bone marrow transplants, many of which were successful, were published for patients with irradiation injury, aplastic anemia, leukemia, lymphoma, and myeloma. Sources of marrow were autologous, isologous, and homologous (often unrelated, including cadaveric) donors. Bone marrow infusion was shown to be safe. It was also demonstrated that an aliquot of marrow, removed (harvested) from the ileum, had sufficient hematopoietic stem cells (SC) to repopulate the marrow and restore blood counts after myeloablation. For about 20 yr, bone marrow was the only source of hematopoietic stem cells (HSC) for transplantation. The first reported autologous peripheral blood HSC transplant was recorded in 1981 using chemotherapy 'mobilized' SC collected by leukapheresis. Mobilization is defined for these purposes to be any treatment that enhances the number of HSC in the blood such that the collection contains sufficient HSC to repopulate the marrow and restore blood counts after myeloablation. Since the early 1990s, SCT using blood-derived stem cells has become very popular and very common. The principal reason is that mobilized (whether by H growth factor or during recovery after chemotherapy) blood-derived stem cells engraft more rapidly than do marrow-derived stem cells. On the one hand, bone marrow was always harvested in the resting, unperturbed state (steady state). On the other hand, blood stem cells (BSC) were virtually always collected after mobilization, usually with granulocyte-colony stimulating factor (G-CSF). There is one report of collection of steady state BSC used for transplantation, and slow engraftment was documented. Bone marrow was never harvested after either chemotherapy or growth factor (priming). It is the mobilization (most often with G-CSF alone or after chemotherapy) of BSC that produces more rapid engraftment than for steady state marrow stem cells (MSC). This contribution shows the data that changes the old paradigm to a new paradigm which states bone MSC and BSC engraft identically if collected after the same pretreatment of the donor with growth factor.
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PMID:Granulocyte-colony stimulating factor primed bone marrow and granulocyte-colony stimulating factor mobilized peripheral blood stem cells are equivalent for engraftment: which to choose? 1630 16

Haematopoietic stem cell transplantation (HSCT) is now an established treatment fora number of non-malignant and malignant conditions. Bone marrow- or peripheral blood-derived allogeneic SCT from an HLA-identical sibling or matched unrelated donor cures more than half the patients with severe aplastic anaemia, thalassaemia major, congenital immunodeficiency diseases and genetic metabolic disorders. Among the malignant conditions, acute and chronic leukaemia, multiple myeloma, Hodgkin and non-Hodgkin lymphoma, and high risk neuroblastoma are important conditions that can be treated by HSCT. The major morbidities associated with HSCT are regimen-related toxicities, development of acute or chronic graft-versus-host disease (GVHD), failure of engraftment of the bone marrow and complications related to the immunodeficiency that occurs in the post-transplant period. Peripheral blood stem cells are now being used as an alternative to bone marrow stem cells for allogeneic HSCT and exclusively for autologous HSCT. Reduced intensity conditioning for allogeneic HSCT has resulted in a lower frequency and severity of GVHD and risk of infections. This has resulted in allogeneic HSCT being done in older patients and for those with co-morbid conditions. Patients with low grade Hodgkin and non-Hodgkin lymphoma, chronic lymphocytic leukaemia and multiple myeloma appear to benefit more with this approach. Prevention of acute GVHD while maintainingthe graft-versus-tumour effect and close monitoring of the kinetics of chimerism hold promise for improving the outcome of those receiving reduced intensity allogeneic HSCT. In recipients ofautologous HSCT, identification of patients at increased risk for relapse and use of agents (interferon, interleukin-2) post-transplant to augment the graft-versus-tumour effect are possible areas of further research.
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PMID:Haematopoietic stem cell transplantation: current status. 1786 17

Stem cell transplantation is curative in a number of otherwise fatal hematological diseases. In Pakistan, SCT was started in October 1995 at Dr Ziauddin Hospital by Dr Tahir Shamsi and his team. The first case was of a young man suffering from AML. In 1999, allogeneic BMT was started at Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre, Karachi. In 2001, the Armed Forces Bone Marrow Transplant Centre, started functioning. Since then, over 350 allogeneic stem cell transplants have been carried out in these latter two centers. Another 50 autologous procedures were carried out in all centers. In 2004, a third center started transplants at the Aga Khan Hospital. The main indications for transplant are aplastic anemia, beta-thalassemia major and hematological malignancies. HLA-identical sibling donors provide stem cells for the recipient. In 70% of cases, a matched donor is identified. In sharp contrast to the rest of the world, the majority of transplants are allogeneic, donor-recipient pairs are CMV positive and fungal infection, tuberculosis and malaria are particular problems. The early results are promising, with transplant-related mortality reported to be 10-20%, whereas long-term survival is reported to be 78, 72 and 49% in aplastic anemia, beta-thalassemia major and leukemia, respectively. Financial constraints, poor socioeconomic status, poor transfusion services, trained human resources and difficulty in keeping pace with technological advances are major hurdles in the growth of transplant medicine. Government support is badly needed to strengthen existing facilities and to develop more centers.
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PMID:The stem cell transplant program in Pakistan--the first decade. 1872 82

In Taiwan, hematopoietic SCT (HSCT) has been used to treat patients with hematological diseases since 1983. Since then, more than 2200 patients have undergone HSCT in 15 large hospitals. The disease entities included acute leukemia in 37% of cases, non-Hodgkin's lymphoma in 26%, CML in 10%, multiple myeloma in 7% and severe aplastic anemia in 6%. The conditioning regimens used were mainly myeloablative (84% of cases). Non-myeloablative regimens were fludarabine-based. The average age of allogeneic recipients was at least 10 years older than those in the era before their application. The grafts of all patients were derived from peripheral blood in 85% of cases, BM in 13% and cord blood (CB) in 2%. Forty percent of HSCT patients received autologous grafts, whereas more than 25% of allogeneic HSCT patients received grafts from unrelated donors, and overall, there were more than 200 Taiwan HSCT recipients. Currently, CB has been used successfully in pediatric patients with thalassemia major and also in adult patients with hematological malignancy. After transplantation, there was a relatively lower prevalence of acute GVHD. However, a relatively higher proportion of hepatitis B carriers in the recipients had led to a higher incidence of viral reactivation and clinical hepatitis, which was dramatically decreased following lamivudine prophylaxis. In conclusion, HSCT has been successfully adapted to routine clinical care in Taiwan. Several important findings contributing to the progress of HSCT in the past two decades have also been noticed on this island.
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PMID:Current status of hematopoietic stem cell transplantation in Taiwan. 1872 86

In 1998, the Tunisian team of the 'Centre National de Greffe de Moelle Osseuse' initiated allogeneic hematopoietic SCT (AHSCT) in Tunisia. As of June 2007, information was collected about 299 patients with a first AHSCT and 12 additional retransplants. The median age was 19 years (range 2-49 years). The main indications were aplastic anemia (n=106, 36%), leukemia and nonmalignant disorders (n=153, 51%), Fanconi anemia (n=26, 9%) and other nonmalignant disorders (n=14, 4%). Preparative regimens depended on indication. All donors were HLA geno-identical. The stem cell sources were BM (87%) and PBSCs (13%). At the time of analysis, 200 patients (67%) were alive after a median follow-up of 42 months (range 3-112 months). The overall TRM rate was 17%. Outcome depended on indication. According to our results, allogeneic HSCT is potentially curative for hematological diseases, but it is a toxic approach for malignant disorders.
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PMID:Allogeneic hematopoietic stem cell transplantation in Tunisia. 1872 88

Since the first successful allogeneic hematopoietic SCT (HSCT) was performed in Korea in 1983, there has been a noticeable progress in both the quantity and quality of HSCT over 24 years. There are 38 HSCT centers in Korea and the number of both allogeneic and autologous HSCTs has been increasing every year. As of December 2006, a total of 9561 HSCTs have been carried out in Korea, including 5617 allogeneic (59%) and 3944 autologous HSCTs (41%). The main indications were acute leukemia (3979, 78% allogeneic); lymphoma (1244, 90% autologous); myeloma (939, 92% autologous) and aplastic anemia (938). Characteristically, severe aplastic anemia accounts for a considerable proportion of transplants (10%), compared with western countries. Recently, there has been a marked increase in the number of unrelated transplants and the usage of PBSCs. The pattern of infectious diseases associated with HSCT is quite different. The rapid expansion of unrelated donor pools worldwide has changed the outlook of an unrelated donor search in Korea.
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PMID:The activity of hematopoietic stem cell transplantation in Korea. 1872 15


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