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

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

Sixteen children with myelodysplastic syndrome as defined by the French-American-British co-operative group are presented. The mean age was 10.5 (2.5 to 16) years, with a male predominance. All patients belonged to the more aggressive subtypes of myelodysplastic syndromes. Seven patients presented with refractory anaemia with excess blasts, six had refractory anemia with excess blasts in transformation, and three had chronic myelomonocytic leukemia. Cytogenetic analysis done in 7 of the 16 patients, revealed karyotype abnormalities involving chromosomes 7, 8 and 17. One patient with Down's syndrome had karyotype of 47, XY, +21 (major clone) and 46, XY (minor clone). Five of these patients evolved to acute leukemia. The mean duration of survival was 5.5 months. Aggressive chemotherapy as a primary line of treatment induced remission in five out of six patients. Predominance of aggressive types of myelodysplastic syndromes in children and their good but short-lived response to aggressive chemotherapy suggests the need for early bone marrow transplantation following chemotherapy.
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PMID:Childhood myelodysplastic syndromes: clinical features, cytogenetics and prognosis. 145 62

Twenty patients with myelodysplastic syndromes were treated with daily subcutaneous injections of interferon alpha 2a, at the initial dose of 3 x 10(6) U/m2. Hemogram, chemistry profile, natural killer (NK) cell activity and lymphokine-activated killer (LAK) cell cytotoxicity were monitored serially. Bone marrow with cytogenetic analysis was done before therapy and every three months afterwards. Normalization to the complete blood count, and wherever applicable, decrease in blast count of 5% or less were defined as a complete response. Improvement in hemoglobin level to 12 g/dl, neutrophil count to 1000/mm3 and platelets to 100,000/mm3 was considered a partial response. The median age was 71 (range 59-83) years and 16 of the patients were males. Two patients withdrew from the treatment in the first week and were considered ineligible. Among the other 18, two had refractory anemia, two refractory anemia with ringed sideroblasts, four chronic myelomonocytic leukemia, eight refractory anemia with excess blasts, and two refractory anemia with excess blasts in transformation to acute leukemia. Twelve patients were treated for six months, the other six were taken off the treatment after six to eight weeks because of disease progression. Only one patient with chronic myelomonocytic leukemia had a partial response for two months. NK cell activity remained unchanged before (18.3 +/- 4.6 lytic units) and during interferon therapy (19.6 +/- 5.3 lytic units). LAK cytotoxicity was not detected in any patient before therapy and was seen in only one patient (not the responder) during therapy (5.7 lytic units). The toxicity of the interferon therapy was substantial. Seventeen patients required a dose reduction and fifteen lost greater than 10% of body weight. Eleven patients (61%) developed infections requiring antibiotic therapy, and eight (44%) required hospitalization. Seven patients developed neurologic toxicity. Interferon alpha 2a is an ineffective but toxic therapy in these elderly patients with myelodysplastic syndromes.
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PMID:Phase II trial of recombinant human interferon alpha in myelodysplastic syndromes. 156 60

Evidence suggests that prognosis in patients with myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML) depends more on karyotype than on formal classification as either MDS or AML according to the French-American-British (FAB) system. We provide further evidence of overlap between these two entities, reporting 4 patients who presented with either inv(16) (p13q22), del(16) (q22), or t(8;21) despite an FAB diagnosis of MDS rather than the diagnosis of AML with which these abnormalities are generally associated. In 3 patients, disease was relatively long-standing (3-10 months) prior to diagnosis, suggesting that the association between MDS and these cytogenetic abnormalities may not merely reflect a transient phenomenon. Two patients with inv(16) and the MDS subtype refractory anemia with excess blasts in transformation (RAEB-t) received AML-type chemotherapy as did a patient with t(8;21) and RAEB-t. All entered CR paralleling the high CR rate seen in patients with AML and these abnormalities. Our data support the concept that MDS and AML may be different manifestations of the same disease.
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PMID:AML-associated cytogenetic abnormalities (inv (16), del (16), t(8;21)) in patients with myelodysplastic syndromes. 160 22

Forty-three patients with myelodysplastic syndrome (MDS) were retrospectively analyzed for its prognostic factors. We evaluated the relationship of the clinical, biochemical, and hematological data, as well as colony-forming unit myeloid (CFU-C) culture, Bournemouth score, modified Bournemouth score, and modified Dutcher score to the prognosis. The median age was 65 years. Eighteen patients had refractory anemia (RA), 4 had refractory anemia with ringed sideroblasts (RARS), 15 had refractory anemia with excess blasts (RAEB), 2 had refractory anemia with excess blasts in transformation (RAEB-t), and 4 had chronic myelomonocytic leukemia (CMMoL). The median survival of all patients was 482 days. The median survival for each subtype was as follows: RA, 628 days; CMMoL, 350 days; RAEB, 240 days; RAEB-t, 90 days. For RARS, no data have yet been obtained, because only one out of 4 patients with RARS has died. We subdivided all patients into two groups: one group included patients with RA or RARS and the other group included patients with RAEB, RAEB-t or CMMoL. The former group had a median survival of 677 days and the latter group 240 days, p = 0.0035. In the former group, 3 out of 22 patients (13.6%) developed acute myeloid leukemia (AML), as compared to 8 out of 21 patients (38.1%) in the latter group, p = 0.0661. Twenty-five of the 43 patients died: 10 from AML and 15 from infection and/or bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myelodysplastic syndrome: a study of prognostic factors. 167 97

In vitro marrow hemopoietic cultures were utilized to determine the possible efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) for treating the refractory cytopenias present in the myelodysplastic syndromes (MDS). Our studies showed responsiveness of enriched hemopoietic precursors in vitro to the proliferative and granulocytic differentiative stimuli of G-CSF, generally without increased clonal self-generation. These in vitro parameters correlated with in vivo hematologic responses in our Phase I and II clinical trials. In this study 18 patients were treated for two months with s.c. administration (0.1-3 micrograms/kg/day) of G-CSF, escalating doses every two weeks. This study indicated normalization of neutrophil courses in 16 patients and reticulocyte responses with decreased red blood cell (RBC) transfusion requirements in three of 12 transfusion-dependent patients. Marrow myeloid maturation improved in the responding patients. Extended treatment for additional six- to 16-month periods has indicated persisting neutrophil responses. The relative risk of developing bacterial infections was significantly decreased in patients whose neutrophil level normalized (absolute neutrophil count greater than 1,500/mm3) during G-CSF therapy, compared to such episodes in their pretreatment neutropenic period. This therapy was well-tolerated, without serious toxicity being noted. In vitro neutrophil function (chemotaxis and phagocytosis) remained normal or improved in six of the eight tested patients. Transformation to acute myelogenous leukemia occurred in two patients with refractory anemia with excess blasts in transformation (RAEB-T) during or within a month of the treatment period. Marrow cytogenetic studies indicate persistence of the initial normal and/or abnormal clones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of prolonged treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. 169 Dec 48

Marrow cells from 36 patients with myelodysplastic syndromes (MDS) (13 refractory anemia [RA], 14 refractory anemia with excess of blasts [RAEB], 9 RAEB in transformation [RAEB-T]) were evaluated for their in vitro proliferative and differentiative responsiveness to recombinant human granulocyte colony-stimulating factor (G-CSF) or granulocyte-monocyte CSF (GM-CSF). GM-CSF exerted a stronger proliferative stimulus than G-CSF for marrow myeloid clonal growth (CFU-GM) in these patients (44 v 12 colonies per 10(5) nonadherent buoyant bone marrow cells [NAB], respectively, P less than .025). GM-CSF stimulated increased CFU-GM growth in the 16 patients with abnormal marrow cytogenetics in comparison with the 20 patients who had normal cytogenetics (52 and 30 colonies per 10(5) NAB, respectively, P less than .05), whereas no such difference could be demonstrated with G-CSF (11 and 16 colonies per 10(5) NAB, respectively). In contrast, granulocytic differentiation of marrow cells was induced in liquid culture by G-CSF in 15 of 32 (47% patients), while GM-CSF did so in only 4 of 18 (22%) patients (P less than .025) including, for RAEB/RAEB-T patients: 9 of 18 versus 0 of 9, respectively (P less than .025). For MDS patients with normal cytogenetics, G-CSF- and GM-CSF-induced marrow cell granulocytic differentiation in 12 of 18 (67%) versus 3 of 11 (27%), respectively (P less than .025), contrasted with granulocytic induction in only 3 of 14 (21%) and 1 of 7 (14%) patients with abnormal cytogenetics, respectively. We conclude that G-CSF has greater granulocytic differentiative and less proliferative activity for MDS marrow cells than GM-CSF in vitro, particularly for RAEB/RAEB-T patients and those with normal cytogenetics.
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PMID:Impact of marrow cytogenetics and morphology on in vitro hematopoiesis in the myelodysplastic syndromes: comparison between recombinant human granulocyte colony-stimulating factor (CSF) and granulocyte-monocyte CSF. 169 77

In a retrospective study, 45 (19.4%) out of 232 patients with MDS revealed myelosclerosis (MS) in bone marrow biopsy (BMB). Histological classification according to FAB criteria showed the following distribution: RA 21 (47%), RARS 1 (2%), RAEB 9 (20%), RAEB-T 3 (7%), and CMMol 11 (24%). Sclerosis occurred in all subtypes of MDS, but with a higher incidence in CMMol. Clinical data showed lower values of hemoglobin and lower platelet counts in MDS.MS. Life expectancy was reduced to 7.8 months, compared with 15.0 months in MDS without MS (p = 0.0026). In RA, the survival times were 9.7 months in MDS.MS, compared to 27.9 months in MDS without MS (p = 0.0035). 21 (47%) of the patients with MDS.MS experienced a transformation into ANLL. Myelosclerosis therefore seems to herald a bad prognosis.
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PMID:[Myelosclerosis in myelodysplastic syndromes (MDS). Retrospective analysis of 232 patients with MDS]. 170 73

Thirteen patients with myelodysplastic syndrome (MDS) were included in this study and consented to treatment with recombinant alpha-interferon (a-IFN). These patients were subclassified: six as RAEB, one as RAEB-T and six as CMML. T-cell subsets and natural killer cells were identified in the peripheral blood with the use of monoclonal antibodies and natural killer cell activity (NKa) was assayed before, during and after a-INF treatment. The treatment schedule consisted of 2.0 MU/m2 sc t.i.w. continuously for the three months. Prior to treatment, NKa was found decreased in 11 of 13 patients as compared to that of normal individuals. Following a-IFN administration, a rise of NKa was observed in eight of the eleven patients. In those who responded, a-IFN was continued for 1 to 21 months. Alpha-IFN treatment was myelosuppressive for most of the patients, but transient increase of the number of neutrophils and platelets was observed in 3 and of the reticulocytes in one patient. Disease progression was recorded in 9/13 patients (69%) at a median time of 17.3 months. The median overall survival was 30.5 months (range 7.5 to 65+ months). No evidence of a relationship was found between the rise in Nka and the limited clinical improvement observed. Two NKa responders under continuous a-IFN treatment are in stable clinical condition for 36+ and 65+ months. The study provides only limited evidence that a-IFN may improve the clinical course of patients with MDS.
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PMID:The effect of recombinant alpha-interferon on natural killer cell activity and clinical course in patients with myelodysplastic syndrome. 183 Feb 25

Interleukin-3 (IL-3) is a T-cell-derived colony-stimulating factor (CSF) whose primary targets include relatively early, multipotential, hematopoietic progenitor cells. In this trial, we treated 24 patients with recombinant human IL-3 given by a daily 4-hour intravenous infusion for 28 days. The dose levels were 30, 60, 125, 250, 500, 750, and 1,000 micrograms/m2/d. At least three patients were entered at every dose level. Each participant suffered from bone marrow failure, with the underlying diagnosis being myelodysplastic syndrome (13 patients), aplastic anemia (eight patients), or aplasia after prolonged high-dose chemotherapy (three patients) for multiple myeloma, breast cancer, or acute myelogenous leukemia. Most patients tolerated therapy well, with the most frequent side effects being low-grade fever and headaches. Hematopoietic changes included modest increases in neutrophil counts (eight patients), eosinophil counts (six patients), platelet counts (three patients), and reticulocyte counts (two patients). An increase in blasts occurred in one patient who had refractory anemia with excess blasts in transformation and was reversible once IL-3 was discontinued. In addition, one patient with chronic myelomonocytic leukemia showed an increase in monocytes (and granulocytes). Progression to acute leukemia did not occur. Pharmacokinetic analyses showed a rapid clearance with a mean half-life of 18.8 minutes at the 60 micrograms/m2/d dose, and 52.9 minutes at the 250 micrograms/m2/d dose. Serum concentrations of 10 to 20 ng/mL of IL-3 were achievable at the 250 micrograms/m2/d dose. Our observations indicate that recombinant human IL-3 can be given safely at doses of 1,000 micrograms/m2/d or less. In addition, on the basis of preclinical data and the biologic activity observed in this study, further trials of this molecule, alone and in combination with other growth factors, are warranted in patients with pancytopenia.
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PMID:Phase I study of recombinant human interleukin-3 in patients with bone marrow failure. 204 65


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