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)

It has been shown that human umbilical cord blood contains stem/progenitor cells comparable in number to that of adult bone marrow. We report here the first successful cases of transplantation of umbilical cord blood cells. The patients were suffering from Fanconi's anemia, complicated by severe aplastic anemia. During pregnancy, it was shown that the mother was carrying a sibling unaffected by the disease and with HLA identical to the patient. Cord blood was collected and frozen in liquid nitrogen at birth. After conditioning with low-dose cyclophosphamide (20 mg/kg) and thoraco-abdominal irradiation (5 grays), the patients received a cord blood transplant of thawed cells. Three patients have been transplanted without any immediate side-effect. One has not enough follow-up, but two patients are alive and well with complete donor hematologic reconstitution and no chronic graft versus host disease. Potential developments of this technique are an extension of applicability with regard to other diseases that might be transplanted and whether such transplants can be performed in adults. The relative immaturity of the lymphoid system at birth may be advantageous in decreasing the graft versus host reaction if these cells are used in a mismatched transplantation. Cord blood cell banks may be useful for transplants in patients lacking an HLA-identical donor.
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PMID:Transplantation of umbilical cord blood in Fanconi's anemia. 198 24

From April 1976 through August 1989, 66 patients with aplastic anemia were treated on either of two immunosuppressive regimens in preparation for allogeneic bone marrow transplantation (BMT) from matched donor. Seventeen patients were treated with cyclophosphamide (50 mg/kg for 3 days) followed by thoracoabdominal irradiation (TAI), 6 Gy/1 fr and 2 patients, receiving marrow graft from partially matched family donors, were treated with cyclophosphamide (50 mg/kg for 3 days), TAI (6 Gy/1 fr) and Ara-C (4 g/mq for 2 days). Forty-seven more patients were treated with cyclophosphamide alone (50 mg/kg for 4 days). All patients received prophylactic treatment with methotrexate (15) or cyclosporine A (51) to avoid graft-versus-host disease. Mean time to engraftment was 12 days after chemotherapy and TAI and 15 days after cyclophosphamide (Cy) alone. No marrow rejections were observed in the TAI group: the two infants that received partially matched marrow allografted and are alive and well. Two patients treated with cyclophosphamide alone rejected allogeneic marrow. Long-term overall survivals are similar: 64% for TAI + Cy group and 56% for Cy alone group. In spite of the immunosuppressive regimen employed, young patients (under 20 years) do better than older ones (survival: 65% vs 45%, respectively). Thus, patient's age seems to be the main factor determining overall survival after allogeneic BMT. We conclude that the use of irradiation does not add significantly to the survival of aplastic patients; given the possible toxic long-term effects of irradiation, it would probably be wise to restrict the combined use of cyclophosphamide and irradiation to the patients sensitized to their donors, to those receiving partially matched marrow from family donors or in programs involving T-cell depletion.
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PMID:[Immunosuppressive role of radiotherapy in bone marrow transplant in patients with aplastic anemia]. 200 22

From May 1978 to September 1989 45 patients underwent 25 allogeneic and 21 autologous bone marrow transplantations (BMT) and 1 peripheral stem cell transplantation for the following indications: severe aplastic anemia (n = 4), hematological malignancies (n = 28), malignant solid tumours (n = 12) and sideroblastic anemia (n = 1). The first group of 20 patients was isolated in a conventional hospital room, while management of the aplastic phase in the second group of 25 patients was performed in a laminar air flow (LAF) unit. All patients received total decontamination. In a retrospective analysis the number of positive blood cultures during the neutropenic period was 85% in the first group, as compared with 40% in the second group, and the number of febrile episodes was 85% versus 64%, respectively. Despite the fact that the septic morbidity was lower in the LAF group, mortality during the neutropenic period (15% in group I versus 16% in group II) was unaffected and survival rate (45% in group I versus 36% in group II) did not improve. We conclude that LAF protection will only have a positive impact on survival rate if the incidence of non-infectious complications of BMT, such as organ toxicity or graft-versus-host disease, is likewise reduced.
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PMID:[Infections in the neutropenic phase following bone marrow transplantation: comparison of laminar airflow isolation with conventional isolation]. 202 17

We have performed bone marrow transplants on four children with severe aplastic anemia who lacked an human leukocyte antigen (HLA)-identical sibling donor. Patients were prepared with cyclophosphamide and 600 cGy fractionated total body irradiation, and then received marrow from a parent donor mismatched for one (two patients), two (one patient), or three (one patient) HLA antigens. All four patients engrafted. One died early of acute graft-versus-host disease. The three others showed sustained complete hematopoietic reconstitution. Two are alive and hematologically normal 43-87 months after transplant. Both have had acute and chronic graft-versus-host disease (CGVHD), and one of the two remains on immunosuppressive drugs. The fourth died at 48 months after transplant of CGVHD. The previous experience with HLA-incompatible marrow transplants is reviewed, and the rationale for this preparative regimen is discussed. Cyclophosphamide and 600 cGy fractionated total body irradiation is an effective preparative regimen for children with severe aplastic anemia receiving transplants from HLA-nonidentical parental donors, allowing engraftment and full hematologic reconstitution.
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PMID:Successful treatment of severe aplastic anemia by bone marrow transplantation from HLA nonidentical family members: preliminary results utilizing cyclophosphamide and 600 cGY fractionated total body irradiation. 202 71

Thirty-five patients underwent allogeneic bone marrow transplantation (BMT) from unrelated donors (UD), in a pilot study of the Canadian Bone Marrow Transplant Group with techniques routinely used in BMT from HLA-identical related donors. Thirty-two of the patients had hematologic malignancies and 3 had aplastic anemia. Donors and patients were matched at all HLA loci tested serologically in 29 cases; 19 of these patients had mutually non-reactive mixed leukocyte cultures (MLC's). Six patients had some degree of serologic mismatch. Stable engraftment occurred in all but 3 evaluable patients. Acute graft-versus-host disease (GVHD) developed in greater than 80% and fatal BMT-related deaths occurred in a total of 55% of all patients. Conversely, only two relapses have occurred, and the 1-year actuarial event-free survival for all patients is 40% (95% confidence intervals [CI], 24-55%) with a follow-up of 0.8 to 2.7 years. All survivors are out of the hospital and all save 1 have a normal performance status. Our study has confirmed the utility of unrelated donors for allogeneic BMT. Although more complications are seen than with HLA-matched sibling donors, these patients did not have such donors available and virtually all were incurable without transplants. Further studies, especially those using new methods to prevent transplant-related complications, are needed.
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PMID:The use of unrelated donors (UD) for allogeneic bone marrow transplantation (BMT): a pilot study of the Canadian BMT Group. 204 87

Bone marrow transplantation (BMT) in patient affected by severe aplastic anemia (SAA), is successful in 70-80% of cases, when performed with HLA identical brother or syngeneic twin as donors, and in 11-45% of cases when performed from aploidentical-identical related or HLA identical unrelated donor. The different conditioning regimens (Cy alone or in combination with TBI) have shown similar results in the long term outcomes. Cyclosporin-A is very effective in avoiding rejection and controlling GVHD.
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PMID:[Bone marrow transplantation in the treatment of severe aplastic anemia]. 205 53

The in vivo efficacy of 25.3 monoclonal antibody (mAb) directed against human LFA1 molecule was assessed in ten patients with steroid-resistant grade III-IV acute graft-versus-host disease (AGVHD). These patients received non-T-cell-depleted allogeneic bone marrow transplantation for aplastic anemia in two cases and hematologic malignancies in eight cases. Five grafts were fully matched, three were one antigen-mismatched, and two were two antigen-mismatched. Despite GVHD prophylaxis with cyclosporin A and short-term methotrexate, AGVHD occurred after a median of 24 days and clearly progressed under prednisone (median 2 mg/kg), given for a median of 12 days. 25.3 mAb was given at a dosage of 0.1 mg/kg in a 4-h perfusion for five daily doses without any clinical or biological side effects. Thirty percent of the patients experienced a reduction in the overall grading with two complete responses. Partial response in at least one involved organ (mostly skin) occurred in 80% of the patients. However, seven out of the eight responding patients experienced a new episode of AGVHD. This observation, which confirms that inhibiting a functional molecule is as efficient as a cytolytic therapy, offers an alternative strategy to antithymocyte globulin (ATG) and cytotoxic mAb in controlling steroid-resistant GVHD.
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PMID:Anti-LFA1 monoclonal antibody (25.3) for treatment of steroid-resistant grade III-IV acute graft-versus-host disease. 205 97

Intensive chemoradiotherapy conditioning regimens and acute graft-versus-host disease (GVHD) are both associated with significant morbidity and mortality after bone marrow transplantation. In this study, we investigated whether the conditioning regimen affected the development of acute GVHD. Thirty-four patients, four with severe aplastic anemia and 30 with a lymphohemopoietic malignancy, were prepared for transplantation either with cyclophosphamide (CY) alone, with CY combined with total body irradiation (TBI) or CY combined with etoposide and either TBI or busulfan. GVHD prophylaxis included methotrexate (MTX 10 mg/m2) given on days 1, 3 and 6, and daily cyclosporine (CSP) on days--1 through 180. The overall incidence of acute GVHD was 36% (15% for HLA identical, 87% for HLA non-identical recipients). However, when assessed by the severity of conditioning regimen-related toxicity, the incidence of GVHD grades II-IV (HLA identical; HLA non-identical) was 0% (0%; 0%), 37% (20%; 67%) and 50% (22%; 100%) for patients with mild, moderate and severe toxicity, respectively. Compliance with GVHD prophylaxis declined with increasing intensity and toxicity of the conditioning regimen. These data suggest that a regimen of three doses of MTX and daily CSP is as effective as four doses of MTX/CSP for GVHD prophylaxis in patients given HLA identical marrow grafts. However, GVHD regimen compliance and efficacy of GVHD prevention are inversely related to the intensity of the conditioning regimen.
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PMID:Conditioning-related toxicity and acute graft-versus-host disease in patients given methotrexate/cyclosporine prophylaxis. 205 56

At Huddinge Hospital 275 patients underwent allogeneic bone marrow transplantation. Among children in first remission of acute leukemia or chronic phase CML (early leukemia), with HLA-identical marrow the 8-year leukemia-free survival was 77%. This was better than 38% in children undergoing transplantation in second to fourth remission (p less than 0.0009). In adults with early leukemia, the 8-year leukemia-free survival was 47% compared to 21% for intermediate-risk adults (p = 0.007). Among 25 patients with severe aplastic anemia receiving marrow from HLA-identical siblings, the actuarial 10-year survival was 78%. In 14 patients with various metabolic disorders, of whom half received marrow from HLA-mismatched donors, the actuarial 7-year survival was 71%. Forty-three patients were given marrow from HLA-mismatched donors and had an increased incidence of acute graft-versus-host disease (GvHD) and death due to GvHD compared to recipients of HLA-identical bone marrow. The major causes of death among our patients were relapse of leukemia, death due to GvHD, cytomegalovirus (CMV) pneumonitis, bacterial infection and invasive fungal infections. By preventing GvHD with T-cell depletion or methotrexate (MTX) combined with cyclosporine (CsA) acute GvHD decreased, but the incidence of relapse increased compared to patients treated with MTX or CsA alone. This resulted in improved survival in patients older than 30 years, but a nonsignificant decrease in leukemia-free survival in younger patients. There was an association between herpes virus immunity in the recipient and GvHD. CMV pneumonitis increased following GvHD and decreased in patients treated with MTX combined with CsA. Invasive fungal infections may be treated or prevented using amphotericin B encapsulated in liposomes with few side effects.
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PMID:Allogeneic bone marrow transplantations at Huddinge Hospital and strategies to improve survival. 210 43

Thirty-four patients received bone marrow transplants from unrelated donors. Donors and recipients were phenotypically matched for 6 of 6 HLA-A, B, and DR antigens in 27 cases and at 5 of 6 antigens in 7 cases. Twenty-three patients had leukemia, six had myelodysplasia, and five had aplastic anemia. Twenty-four patients had durable engraftment. Five died of sepsis prior to engraftment. Five patients failed to engraft; 2 of these patients had autologous bone marrow recovery. Seventeen patients developed grade greater than or equal to II acute graft-versus-host disease for an actuarial probability of 67 +/- 20%. The severity of acute graft-versus-host disease and its mortality appeared increased for recipients matched for 5 of 6 HLA-A, B, and DR antigens. Of the 34 patients, 13 (38%) are alive; actuarial survival beyond 6 months is 44 +/- 17%. None of the 25 leukemia and myelodysplasia patients achieving engraftment have relapsed. For leukemia and myelodysplasia recipients of 6 of 6 HLA-matched grafts, actuarial survival at 6 months was 55 +/- 21% compared with 14 +/- 26% for recipients matched for 5 of 6 HLA loci (P = 0.19). Infection and acute graft-versus-host disease were the primary causes of death in the engrafted patients. Survival for aplastic anemia patients was 20%. Late deaths due to pneumonia and bronchiolitis obliterans occurred after one year in 2 patients. Closely matched unrelated donor bone marrow transplants are associated with a higher incidence of graft failure and graft-versus-host disease than typically reported for transplants from HLA-identical siblings, but these preliminary data suggest a lower rate of relapse.
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PMID:Bone marrow transplantation using unrelated donors for patients with advanced leukemia or bone marrow failure. 214 25


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