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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An in vitro hematopoietic microenvironment was established from explained fragments of bone marrow from adult noninbred NIH Swiss mice with the use of corticosteroid-reconstituted horse serum. Infection with Kirsten murine sarcoma virus (Ki-MuSV) with either a Rauscher murine leukemia virus (R-MuLV) or Balb:virus-1 helper virus coat reduced proliferation of granulocytic and pluripotent hematopoietic stem cells and produced neoplastic transformation of both macrophages and preadipocytes in the adherent cell population within a 4-week period. Ki-MuSV-transformed, virus-releasing macrophages formed clusters of 4-49 cells in 0.8% methylcellulose-containing medium in the absence of added colony-stimulating factor (CSF), synthesized lysozyme, ASD-chloroacetate substrate-specific esterase-M, and CSF, and produced tumors following inoculation iv into adult NIH Swiss mice or ip into newborn NIH Swiss mice. In cultures infected with helper leukemia viruses R-MuLV or Balb:virus-1, gradual transformation of a distinct cell phenotype was observed over a 9-week period with generation of increasing numbers of atypical myeloblasts and promyelocytes which showed dyssynchronous nuclear-cytoplasmic maturation, basophilic granulation, cytoplasmic vacuolation, and formation of incompletely maturing CSF-dependent granulocyte-macrophage colonies in vitro and small spleen colonies in vivo. These data demonstrated that rapid biologic expression of the murine sarcoma virus genome in specific adherent "stromal" marrow cells prevents detection of a more subtle helper-virus-induced dysmyelopoiesis in a distinct nonadherent cell population.
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PMID:Phenotypically distinct target cells for murine sarcoma virus and murine leukemia virus marrow transformation in vitro. 21 35

One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4-33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS.
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PMID:The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study. 142 May 4

A total of 56 patients were diagnosed as primary myelodysplastic syndrome (MDS) at Chang Gung Memorial Hospital, Kaohsiung from April 1986 to December 1991. The median age was 65 years with an equal sex ratio. All patients presented with anemia and 52% with pancytopenia. The overall median survival for the entire group was 7 months, in which the chronic myelomonocytic leukemia (CMMoL) was 7 months, and 4 months for each of the refractory anemia with excess of blasts (RAEB) or the refractory anemia with excess of blasts in transformation (RAEB-T), however, the median survival had not been reached at 27 months for refractory anemia (RA) and at 33 months for refractory anemia with ring sideroblasts (RARS). Low-does arabinosyl cytosine (Ara-C) was administered in 9 patients with RAEB and RAEB-T, but no survival benefit was noted. Infection, especially pneumonia, was the most common cause of death. In 61 febrile episodes with clinically suspected sepsis, 10 (17%) were documented to associate with bacteremia. Twelve patients (7 RAEB, 4 RAEB-T, and 1 CMMoL) evolved to acute myelogenous leukemia (AML), the median interval from diagnosis to evolution was 4.8 months. This series indicates that only two groups of FAB subtypes could be clearly separated in terms of morphological findings and clinical outcome; RA and RARS constitute a good prognostic group, whereas RAEB, CMMoL, and RAEB-T constitute a poor prognostic group.
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PMID:Primary myelodysplastic syndrome: an analysis of 56 patients. 146 34

Symptomatic patients with myelodysplastic syndromes (MDS) and 10-30% blasts in the bone marrow were treated with low-dose AraC (2 x 10 mg/m2 subcutaneously (sc) days 1-14) and GM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day sc) given either subsequently (days 15-21) or simultaneously (days 8-14 and one week rest). Evaluations were carried out after three courses (nine weeks); responding patients could be continued for two further cycles. Eighty-two patients with refractory anaemia and excess of blasts (RAEB), with (RAEBt) or without transformation, were evaluable: 45 RAEB and 37 RAEBt, mean age 64 years (range 17-80 years). A complete remission was achieved in 14 cases (17%), 11 had a good response (13%), and 12 a partial response (15%). Stable disease was found in 21 cases (26%). There were 12 cases of toxic death (15%), progression was noted in eight patients (10%), and death due to disease in three (4%). No difference existed between the two treatment arms with respect to response. Major adverse events during treatment were haemorrhage (25%), infections (23%), and fever with GM-CSF (21%). GM-CSF did not induce leukaemia nor contribute to haemorrhage induced by AraC, but gave rise to an overall response rate of 46% which is high and relatively durable as compared to other treatments in this disease.
Infection 1992
PMID:Treatment of myelodysplastic syndromes (MDS) and high leukaemic risk with low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rh GM-CSF). The EORTC Leukaemia Group. 149 35

Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic molecule which displays a broad range of haematopoietic activities, has become available for clinical evaluation in various patient groups. It has been shown to be effective in preventing or reversing neutropenia. Adverse effects of GM-CSF, however, are dose related. Appropriate dose, route and schedules for GM-CSF in various clinical settings have recently been defined, the usual range being 5-10 micrograms/kg/day either by 4-6 h intravenous infusion or by subcutaneous injection. At such doses, adverse effects are predominantly mild-to-moderate in nature, occur in 20-30% of patients and usually comprise fever, myalgia, malaise, rash and injection site reaction. Early trials using very high doses of GM-CSF were often associated with marked adverse effects, which in rare cases proved severe (pericarditis and thrombosis). Similarly, a so-called "first-dose reaction", defined as a syndrome of hypoxia and hypotension after the initial but not subsequent doses of GM-CSF, was observed in certain predisposed patients following doses above 10 micrograms/kg/day. Subsequent trials have established that intravenous bolus or short infusions of GM-CSF are more likely to promote adverse effects. Certain patient groups, for example those with myelodysplastic syndrome, acute myeloid leukaemia, inflammatory disease, autoimmune thrombocytopenia or malfunctional immunological responsiveness, require careful clinical monitoring in order to avoid potential complications following the administration of GM-CSF. With the current appropriate administration and doses of GM-CSF, the benefit:risk ratio has been greatly improved.
Infection 1992
PMID:The side-effect profile of GM-CSF. 149 36

Infection due to the human immunodeficiency virus (HIV) has been complicated by the development of acute nonlymphocytic leukemia in five patients whose cases have previously been reported; other manifestations, including preleukemia, myelofibrosis, and myeloid hyperplasia, have also been reported in patients infected with HIV. We report the sixth case of an HIV-infected patient who developed acute myelomonocytic leukemia; HIV infection was documented by tests for serum antibodies (enzyme-linked immunosorbent assay and western blotting), by a markedly elevated p24 antigen level in plasma, and by cultures of CSF and peripheral blood that were positive for HIV. Furthermore, myelomonoblasts that were cultured without the addition of growth factors displayed evidence of HIV replication through the presence of p24 antigen and reverse transcriptase activity, both of which lasted for 4 weeks in the supernatant fluid of the cell cultures. This case report provides the first data indicating that HIV may infect myelomonoblasts in vivo and represents the sixth reported case of an association between HIV infection and pure acute nonlymphocytic leukemia.
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PMID:Relationship between acute myelomonoblastic leukemia and infection due to human immunodeficiency virus. 190 61

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

Myelodysplasia, characterized by varied reductions of peripheral blood elements with normal or hypercellular bone marrow, is relatively frequent among older patients and may evolve to acute leukemia. We reviewed findings in 35 patients whom, according to the FAB classification were distributed as follows: simple refractory anemia (RA) 34%, sideroblastic refractory anemia (SRA) 14%, refractory anemia with excess blast forms (RAEB) 31%, chromic myelomonocytic leukemia (CMML) 12% and refractory anemia with excess blast forms in transformation (RAEBT) 9%. Cytogenetic studies performed in 16 patients were abnormal in 5 (31%), all among patients with poor prognosis forms of the disorder. All patients had anemia; thrombopenia and neutropenia were more frequent in subtypes RAEB, CMML and RAEBT). Mean survival rate was 30 months, significantly greater in RA and SRA compared to the other groups. Infections and development of acute leukemia were the causes of death.
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PMID:[Myelodysplasias: clinical experience with 35 patients]. 215 45

On cytological bone marrow examination we distinguished between pure sideroblastic anaemia (PSA), which is confined to dyserythropoiesis, and refractory anaemia with ring sideroblasts (RARS), which is characterized by additional dysplastic features of granulopoiesis and/or megakaryopoiesis. In a follow-up study of 94 patients with AISA diagnosed according to FAB criteria for myelodysplastic syndromes we found a striking difference in the risk of leukaemic transformation between PSA and RARS (5 year cumulative rate 1.9% v. 48%). Overall survival was much better in PSA than in RARS (5 year cumulative chance 69% v. 19%). Infections and haemorrhages were frequent causes of death in RARS but not in PSA. Bone marrow culture studies (CFU-GM) were performed on 10 consecutive patients with PSA and RARS, respectively. RARS patients showed grossly impaired colony growth, typical of the myelodysplastic syndromes. Patients with PSA had persisting colony formation, even if moderately decreased in frequency, with numbers of CFU-GM being inversely correlated with the degree of erythroid hyperplasia in the bone marrow. We conclude that on cytomorphological grounds AISA can be divided into pure (dyserythropoietic) sideroblastic anaemia (PSA) and a true myelodysplastic form (RARS), with both types differing considerably in terms of survival, risk of leukaemic transformation and findings on bone marrow culture (CFU-GM).
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PMID:Two types of acquired idiopathic sideroblastic anaemia (AISA) 227 59

We undertook a phase I-II trial in elderly (age greater than or equal to 60 years) untreated acute myelogenous leukemia (AML) patients using brief, intensive therapy to improve induction rates and overall survival in older AML patients. Twenty-one patients ranging in age from 60 to 81 years (median, 66 years) were treated using either a 4- or 5-day course of high-dose cytosine arabinoside, 3 g/m2 intravenously (IV) every 12 hours; followed by daunorubicin, 45 mg/m2/d IV bolus for 3 consecutive days. Thirteen patients were entered at the first dose level (a 4-day course or eight doses of cytosine arabinoside), whereas eight patients underwent therapy at the second dose level (a 5-day course or ten doses). Patients who achieved a complete remission received a repeat course of high-dose cytosine arabinoside and daunorubicin within 4 weeks of attaining remission. Seven patients had an antecedant history of a myelodysplastic syndrome. Infection was the major complication experienced by this elderly patient group, and included ten episodes of bacteremia or fungemia (four of which were fatal) and five cases of pneumonia (one fatality). Nine of the 21 patients (three of 13 at the first dose level and six of eight at the second dose level) achieved a complete remission. Median remission duration was 9 months (range, 4-19+ months). Although high-dose cytosine arabinoside plus daunorubicin was an effective antileukemic therapy, it is too toxic to recommend for most elderly leukemic patients.
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PMID:High-dose cytosine arabinoside and daunorubicin as primary therapy in elderly patients with acute myelogenous leukemia. A phase I-II study of the Southeastern Cancer Study Group. 291 7


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