Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-one patients (median age = 34, range = 10-49; F:M = 7:14) received a preparative regimen consisting of busulfan 4 mg/kg/day x 4, cytosine arabinoside 2 g/m2/12 h x 4 and cyclophosphamide 60 mg/kg/day x 2 ('BAC' regimen) for allogeneic bone marrow transplantation. Out of 12 patients with acute myeloid leukemia (AML), two were in first remission, six were in second remission and four had resistant, relapsed disease or prolonged marrow aplasia after induction chemotherapy. Five of the 12 patients with AML had secondary AML. Four patients had transfusion-dependent myelodysplastic syndrome. Three patients with chronic myeloid leukemia were in the accelerated phase and two were in the blastic phase. Organ toxicities related to the preparative regimen were graded. Liver toxicity occurred in 11 patients, two of these were fatal veno-occlusive disease (VOD) (10%). Nineteen of the 21 patients had grade 2 or less diarrhea, and 13 also had mucositis. One patient developed grade 3 cardiac toxicity, and one other patient had grade 1 skin toxicity. Four patients had gross hematuria related to treatment (19%). No renal, pulmonary or CNS toxicities were encountered. Ten patients have died, two from regimen-related hepatic VOD. Of the remaining eight deaths, four were from respiratory failure in four patients (one case each of Pneumocystis pneumonia, CMV pneumonia, bronchiolitis obliterans associated with chronic graft-versus-host disease, and interstitial pneumonitis complicated pulmonary emboli), and one patient each from GI bleeding, cardiac arrhythmia, sepsis and CNS bleeding. Thus far, only one patient transplanted for secondary AML in second remission relapsed at day 230.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allogeneic bone marrow transplantation in high-risk myeloid disorders using busulfan, cytosine arabinoside and cyclophosphamide (BAC). 154 49

Eight patients with myelodysplastic syndromes (MDS) were treated with bone marrow transplantation (BMT). Median age was 34.5 years and ranged between 3 and 45. FAB diagnosis was refractory anaemia (RA) in three, RA with excess of blasts (RAEB) in four and RAEB in transformation (RAEB-t) in one case. Four patients were prepared with cyclophosphamide and total body irradiation whilst the other four received busulphan and cyclophosphamide. Engraftment was documented in seven of eight patients. Two patients died from complications related to the procedure. One had early veno-occlusive disease of the liver whilst the other died 46 months after BMT from pulmonary fibrosis. One patient died from recurrent disease 11 months after BMT. Five patients are alive and in complete remission 9-35 months post-transplantation. Four of these patients have a Karnofsky score greater than or equal to 90%. These results suggest that BMT can induce prolonged disease-free survival in patients under 50 years of age. If a compatible donor is available, marrow transplantation should be seriously considered in the treatment of MDS.
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PMID:Bone marrow transplantation for myelodysplastic syndromes. 328 4

Allogeneic bone marrow transplantations were carried out between March 1983 and July 1985 in 31 patients aged 7 to 45 years (median 18 years). Acute lymphoblastic leukaemia in 1st to 5th remission was present in 8 patients, acute myeloblastic leukaemia in 1st and 2nd remission in 4 patients, chronic myeloid leukaemia, with various remission status, in 6 patients, 3 patients had severe aplastic anaemia and there were single cases of myelodysplasia and immature cell megakaryocytic myelosis. Transplantation was carried out during relapse in 8 patients with either acute myeloid or lymphoblastic leukaemia. Phenotypic HLA-identical mothers (n = 2) as well as genotypic HLA-identical siblings (n = 27), and in two cases HLA-non-identical mothers, served as bone marrow donors. In leukaemia patients the conditioning treatment consisted of fractionated total body irradiation and high dose cyclophosphamide or etoposide. Patients with severe aplastic anaemia received cyclophosphamide (4 X 50 mg/kg) and fractionated total nodal irradiation (total dose 8 Gy). 19 patients (61%) survived 14 to 605 days after bone marrow transplantation. 15 patients (48%) continue to remain in complete remission with Karnofsky indices of greater than or equal to 90%. Causes for death were infection (n = 3), interstitial pneumonia (n = 3), relapse (n = 3) as well as single cases involving acute graft-versus-host-disease, non-engraftment of donor marrow and veno-occlusive disease of the liver.
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PMID:[Allogeneic bone marrow transplantation after fractionated whole body irradiation. Results at the Kiel transplantation center]. 389 27

Eight-five consecutive patients with relapsed or refractory Hodgkin's disease (HD) underwent high-dose chemotherapy or chemo/radiotherapy followed by autologous bone marrow (ABMT) and/or peripheral blood stem cell (PBSC) transplantation. Two preparative regimens were used. Twenty-two patients (26%) without prior radiation received fractionated total body irradiation (FTBI) 1,200 Gy in combination with high-dose etoposide (VP-16) 60 mg/kg and cyclophosphamide (CTX) 100 mg/kg. Sixty-three patients (74%) with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. The median age was 32 years (range, 16 to 56). The median number of prior chemotherapy regimens was three (range, 1 to 7). Forty-three patients (51%) received transplants in first relapse or second complete remission (CR), whereas 33 (39%) received transplants after second or subsequent relapse. All relapsed patients, except one, received conventional salvage chemotherapy and/or radiotherapy in an attempt to reduce tumor bulk before transplant. At the time of analysis in April 1994, fifty-seven patients (67%) are alive, including 44 (52%) in continuous CR, with a median follow-up for the surviving patients of 28 months (range, 7 to 66). Thirty patients (35%) relapsed at a median of 9 months (range, 1 to 43). Eleven patients (13%) died of transplant-related complications including veno-occlusive disease of the liver (VOD) in five, acute and late interstitial pneumonitis in three, graft failure in one, cerebral hemorrhage in one, and therapy-induced myelodysplasia (MDS)/acute leukemia in one patient. At a median follow-up of 25 months (range, 0.6 to 66), the cumulative probability of 2-year overall and disease-free survival (DFS) of all 85 patients is 75% (95% confidence interval [CI] 64% to 84%) and 58% (95% CI 47% to 69%), respectively. Three independent prognostic variables were identified by univariate analysis: number of prior chemotherapy regimens, prior radiotherapy, and extranodal disease at ABMT. Multivariate stepwise Cox regression identified the number of prior chemotherapy regimens as the only significant prognostic factor predicting for both relapse and DFS. There were no significant differences in the outcome of the treatment between the two preparative regimens. Our results confirm that high-dose therapy and ABMT is an effective therapy for patients with relapsed or refractory HD. Earlier transplantation is recommended before the development of drug resistance and end organ damage that results from repeated attempts of salvage therapy.
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PMID:High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors. 785 68

The outcomes of 39 patients with hematological disorders who had undergone allogeneic bone marrow transplantation (BMT) from September 1986 to March 1992 were reported. The length of follow-up was six to 50 months. Twenty patients with acute leukemia, eight patients with aplastic anemia, seven patients with chronic myelogenous leukemia, two patients with non-Hodgkin's lymphoma, and two patients with myelodysplastic syndrome were included. Major complications were acute graft-versus-host disease (GVHD) (17 cases out of 36 evaluable cases; 47 percent), chronic GVHD (13/25; 52 percent), sepsis (20/41; 49 percent), interstitial pneumonitis (IP) (10/30; 33 percent), and veno-occlusive disease (VOD) of the liver (5/41; 12 percent). Acute and chronic GVHD were well managed with cyclosporin, methotrexate, and steroids. VOD of the liver seemed to be associated with the pretransplant regimen including busulfan and cyclophosphamide. The overall probability of disease free survival of 39 patients who had undergone allogeneic BMT was 0.56. This includes nine high risk cases such as HLA antigen mismatch between the donor and the recipient, and as in the second or subsequent remission or in relapsed cases. The probability of disease free survival in patients with acute leukemia, chronic myelogenous leukemia, and aplastic anemia including high risk cases was 0.55 (n = 20), 0.71 (n = 7), and 0.50 (n = 8) respectively. These results indicate that allogeneic BMT is the major therapeutic strategy for patients whose survival could not be expected by conventional chemotherapy and that drug intensification for conditioning regimen is also important.
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PMID:Allogeneic bone marrow transplantation as a therapeutic modality for hematological disorders: a report based on 39 cases. 786 58

Four consecutive children with myelodysplastic syndromes (MDS) underwent matched allogeneic bone marrow transplantation (BMT). Ages ranged from 3.2 to 6.3 years. Diagnosis was assessed according to FAB classification: refractory anemia-RA (n = 1), RA with excess of blasts (RAEB) (n = 1), and juvenile chronic myelogenous leukemia (JCML) (n = 2). Initial treatment included transfusions for all of them, splenectomy (n = 2) and chemotherapy (n = 1). Patients were all prepared with busulfan 21 mg/kg (480 mg/m2), cytosine arabinoside 24,000 mg/m2, melphalan 140 mg/m2. Graft-versus-host disease (GVHD) prophylaxis associated cyclosporine-methotrexate. Engraftment was prompt and complete in all children. Toxicity included severe mucositis (n = 3), moderate veno-occlusive disease (n = 2), acute GVHD (n = 3), chronic GVHD (n = 1). Sequelae have not yet been seen. All patients are alive and disease-free with a follow-up ranging from 7 to 35 months, with a Karnofsky score of 90-100%. Combined busulphan conditioning can offer an alternative to total body irradiation-based regimens in order to avoid late side-effects in children.
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PMID:Intensified conditioning regimen with busulfan followed by allogeneic BMT in children with myelodysplastic syndromes. 792 Mar 11

Case 1: A 26-year-old female was admitted because of leukocytosis with 43.6% myeloblasts and 33.6% monocytes, and trilineage myelodysplasia (T-MDS) was detected on bone marrow (BM) smear. She was diagnosed as having acute myeloid leukemia (AML) (M4) with T-MDS and was treated with the Japan Adult Leukemia Study Group (JALSG) AML87 protocol. After completion of chemotherapy, leukemic myeloblasts remained minimally and myelodysplastic changes were still detected on BM smear. She underwent allo-BMT from an HLA-identical sibling. The conditioning regimen consisted of busulfan and cyclophosphamide. Cyclosporine A and short term methotrexate were administered prophylactically for graft-versus-host disease (GVHD). She developed slight veno-occlusive disease and pancytopenia, which improved soon. She is surviving free of disease for 37 months from BMT. Case 2: A 41-year-old male was diagnosed as having T-MDS AML (M2) and achieved complete remission with the AML89 protocol, but relapsed soon. He underwent allo-BMT from an HLA-identical sibling. The conditioning regimen and prophylaxis against GVHD were the same as in case 1. He developed mild acute GVHD, pleural effusion and later mild chronic GVHD. These improved soon. He is surviving free of disease for 21 months from BMT. Some reports suggest that intensive chemotherapy can induce CR in 40%-70% of patients with T-MDS AML, but most of them tend to relapse and rarely survive long. We consider that the best strategy for treatment of T-MDS AML is allo-BMT at present, if suitable donors are available.
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PMID:[Allogeneic bone marrow transplantation for two patients with acute myeloid leukemia with trilineage myelodysplasia (T-MDS)]. 813 16

Patients with Fanconi anemia (FA) commonly develop bone marrow failure, which may evolve to myelodysplasia or acute myeloid leukemia (AML). Treatment of these patients is complicated by their marked hypersensitivity to DNA cross-linking agents. In this report we describe the results of allogeneic unrelated donor bone marrow transplantation in seven FA patients, using a low-dose cyclophosphamide (40 mg/kg) and TBI (400-450 cGy) conditioning regimen. Two patients had bone marrow failure with normal chromosomes and no dysplasia prior to transplant. The remaining five had clonal chromosomal abnormalities. One patient had refractory anemia with excess blasts in transformation and two had early AML with 20 and 25% blasts, respectively. Two patients died early (before day 28) without hematological evidence of engraftment, one of veno-occlusive disease and one of infection (fungal). Four of the remaining five patients achieved sustained engraftment after the first marrow infusion; one patient had secondary graft failure requiring repeat marrow infusion but subsequently achieved engraftment. Of five evaluable patients, three had mild (grades I-II) acute GVHD and two had grade IV GVHD, which was fatal in both cases. Two of three evaluable surviving patients have chronic GVHD controlled with immunosuppression. Three patients survive 9 months to 3 years post-unrelated donor BMT: two who had early leukemia and one with severe aplasia at the time of transplant. These data indicate that unrelated donor BMT can be performed successfully in FA patients using cyclophosphamide 40 mg/kg and TBI 400 to 450 cGy, even after evolution to early leukemia. However, significant problems with both GVHD and engraftment remain. Future studies will evaluate the role of T cell depletion in improving the results of unrelated donor marrow transplantation in FA patients.
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PMID:Unrelated donor bone marrow transplantation for Fanconi anemia. 867 53

Eleven patients with advanced multiple myeloma (MM) received syngeneic marrow (n = 10) or peripheral blood stem cell (n = 1) transplants following cyclophosphamide (CY) and total body irradiation (TBI) (n = 8), busulfan (Bu) and CY (n = 1), Bu, CY and TBI (n = 1) or Bu, melphalan and thiotepa (n = 1). At the time of transplant one patient had stage II and 10 patients had stage III disease. Four patients had refractory disease, two had chemotherapy sensitive disease and five had progressed after an initial response to chemotherapy. The median time from diagnosis to transplant was 353 days (range 176-6118). After transplant, the median time to achieve granulocytes of 0.5 x 10(9)/l and platelets of 20 x 10(9)/l was 12 days (range 9-20) and 12 days (9-27), respectively. One patient died of interstitial pneumonia syndrome on day 32 and one died of veno-occlusive disease of the liver on day 44 post-transplant, and these were unevaluable for response. Five of nine evaluable patients achieved a complete response (CR), three a partial response, and one patient had no response. Three patients who did not achieve CR died of progressive disease 106, 142 and 321 days post-transplant. Of five patients who achieved a CR, three relapsed on days 539, 737 and 1706 and died on days 1759, 1596 and 1736, respectively; one patient died of myelodysplastic syndrome on day 1407 without evidence of MM and one patient is alive and disease-free 3297 days after transplant. One of the two long-term survivors has a persistent monoclonal protein in the blood 15 years post-transplant. These data show that high-dose therapy and infusion of normal syngeneic marrow cells can cure a small fraction of patients with MM. However, the majority of patients did not achieve durable CR, demonstrating the need for improved transplant conditioning regimens, earlier transplant or additional post-transplant treatment strategies when syngeneic transplants are performed.
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PMID:Syngeneic marrow transplantation in patients with multiple myeloma. 887 13

Between October 1991 and May 1994, 42 patients were treated with cyclophosphamide, thiotepa, and total body irradiation followed by an allogeneic transplantation of marrow depleted of T cells with soybean agglutinin and E-rosetting. Patients included in this study had acute myelogenous leukemia (13), chronic myelogenous leukemia (12), acute lymphocytic leukemia (nine), Hodgkin's disease or non-Hodgkin's lymphoma (four), multiple myeloma (three), or myelodysplastic syndrome (one). The mean age was 34 (range 8 to 51 years). Nineteen patients had a matched sibling donor and 18 received marrow from 6/6 matched unrelated donors while five received transplants from unrelated donors disparate at one DR locus (5/6 match). Time to granulocyte engraftment (AGC > or = 500/mm3) occurred at a mean of 16.5 days for related and 11.4 days for unrelated transplant recipients, and was related to the increased use of G-CSF in the unrelated population. There was no correlation with number of mononuclear cells, T cells, or CD34-positive cells infused, the rate of engraftment or the incidence of transplant complications. Multivariate analysis determined that G-CSF administration and a diagnosis other than ALL were the only factors associated with a faster rate of engraftment. Patients receiving unrelated donor transplants, those with ALL, or those who had a low T cell number infused (< or = 8.0 x 10(3) cells/kg) experienced delayed hospital discharge. The regimen resulted in excellent rates of engraftment (95.2%) with only one failure to engraft and one graft rejection. The incidence of grade III-IV acute graft-versus-host disease was 0% with sibling and 26.1% with unrelated donors. There were no cases of veno-occlusive disease. Fifty percent of patients are alive with a mean follow-up of 26.4 months. We conclude that this regimen is well tolerated and results in excellent engraftment with a low incidence of severe graft-versus-host disease and few therapy-related toxicities.
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PMID:Minimizing graft rejection in allogeneic T cell-depleted bone marrow transplantation. 893 45


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