Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four patients with refractory anaemia with excess blasts in transformation (RAEB-t) and seven patients with acute leukaemia (AL) transformed from myelodysplastic syndromes (MDS) were treated with etoposide (50 mg, 2 h infusion, two to seven times per week) for at least 4 weeks. Of 10 assessable patients, three RAEB-t patients achieved partial response and one AL patient achieved complete remission. Three of the four responders were resistant to prior repeated low-dose cytarabine therapy. The responders did not require transfusions for 2-9 months while continuing on etoposide therapy. The side-effects were mild and well tolerated. Three possible mechanisms, i.e. a cytotoxic effect, differentiation-induction of malignant cells, and prolongation of blood cell survival by destroying the reticuloendothelial system, may explain the effects of etoposide. We conclude that low-dose etoposide is a potential therapy for MDS and atypical leukaemia.
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PMID:Low-dose etoposide: a potential therapy for myelodysplastic syndromes. 141 18

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.
Leukemia 1992 Mar
PMID:Phase II trial of recombinant human interferon alpha in myelodysplastic syndromes. 156 60

To assess the effects of GM-CSF in patients with myelodysplasia, a total of 101 patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), and RA with an excess of blasts provided that the percentage of blasts in the bone marrow did not exceed 10% (RAEB) were enrolled in the EORTC Leukemia Cooperative Group study 06885. They were randomized to receive two daily subcutaneous injections of rhGM-CSF (mammalian, glycosylated, Sandoz/Schering-Plough) at a daily dose of either 108 micrograms glycoprotein (group I) or 216 micrograms glycoprotein (group II) for 8 weeks. Response was defined as an increase in Hb (greater than 2.5 g%), neutrophil count (more than 100%), or platelet count (more than 100%) without progression of the disease. After exclusion of 19 patients who did not meet the entry criteria, 82 were evaluated. Fifty-four patients (66%) responded (27 of 42 patients in group I and 27 of 40 in group II). Progressive disease was seen in two patients of group I and in four of group II. Two of the latter developed leukemia. All responses were reflected in the granulocytic series. In two patients platelet numbers also increased. Cytogenetic analysis, successfully performed in 43 cases, showed that 14 of 16 patients with normal karyotypes responded, compared with 14 of 27 patients with abnormal karyotypes (p = 0.008). In some cases GM-CSF was reduced in dose or discontinued prematurely due to side effects so that only 35% of all evaluable patients finished 8 weeks of treatment without a change of dose.
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PMID:A randomized phase-I/II multicenter study of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for patients with myelodysplastic syndromes and a relatively low risk of acute leukemia. EORTC Leukemia Cooperative Group. 158 5

Infants with acute leukemia have a poor chance of being cured by conventional chemotherapy. We therefore treated cases of infant leukemia with high dose chemotherapy followed by bone marrow transplantation (BMT). Six suffered from acute leukemia and one from refractory anemia with excess of blasts (RAEB-t). The conditioning regimen consisted of busulfan (BU) and cyclophosphamide (CY), and was intensified by adding etoposide (VP) in four cases. At the time of BMT the children were 4, 5, 12, 13, 13, 14, and 20 months old. Three children were autografted, three received HLA-identical marrow from a sibling donor, and one child received matched unrelated donor marrow. All five children who were grafted in complete (CR) or partial remission (PR) are alive and well in CR 7, 13, 24, 37, and 46 months after allogeneic (two patients) or autologous (three patients) BMT, and 13, 17, 29, 42, and 53 months after initial diagnosis. The child with RAEB-t and the one transplanted in second chemotherapy-resistant relapse of acute non-lymphoblastic leukemia relapsed at 7 and 17 months respectively. The chemotherapy regimen was well tolerated. BU-CY-VP is a promising alternative treatment to regimens including total body irradiation for very young children suffering from acute leukemia.
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PMID:Treatment of infant leukemia with busulfan, cyclophosphamide +/- etoposide and bone marrow transplantation. 161 14

Monoclonal antibody QBEND10 is reactive with the CD34 antigen in aldehyde-fixed, decalcified, paraffin-embedded bone marrow biopsies. In normal bone marrow it stained endothelial cells lining arterioles and capillaries, sinusoidal (littoral) cells and 0.89% of all haemopoietic cells. QBEND10+ mononuclear cells were seen as isolated, randomly distributed mononuclear cells in normal and regenerating bone marrows. Conversely, QBEND10+ cells were increased and present in aggregates of three or more cells in 6/8 cases of acute leukemia; in two cases of CD34-negative leukemia and in two patients after complete remission no aggregates were seen. QBEND10 immunohistochemistry may therefore be useful for diagnosis and follow-up of myeloid leukemias. In addition, increased numbers of CD34+ cells arranged in clusters were seen in 4/9 cases of refractory anemia with excess blasts (RAEB), 1 case of chronic myelomonocytic leukemia, 3/3 cases of RAEB in transformation, and in 3/7 cases of chronic myelogenous leukemia: in all these cases, CD34 staining of the bone biopsy may have prognostic value. QBEND10+ endothelial cells were significantly increased in all the pathological conditions examined (1.43% of all nucleated cells versus 0.80% in normal bone marrow; p = 0.0063), but especially in myeloid leukemias and in two fibrotic syndromes examined.
Leukemia 1991 Dec
PMID:Identification of CD34+ cells in normal and pathological bone marrow biopsies by QBEND10 monoclonal antibody. 172 30

We retrospectively evaluated the efficacy of androgen in the treatment of refractory anemia (RA) and compared patient characteristics and the probability of survival in androgen-responder and nonresponder groups. Forty patients with RA were treated in our hospital between 1975-1989, and 27 were treated with various derivatives of androgen. Eleven of the latter responded effectively to androgen therapy, representing an efficacy rate of 40.7%, higher than that of any other treatments thus far reported. The probability of 10-year survival estimated by the Kaplan-Meier method was 75.0% for the responder group and 41.3% for nonresponders, with a median follow-up of 1202 and 1272 days, respectively. In addition, the percent probability of transformation-free survival was higher among androgen-responders than among nonresponders, though the difference was not significant. Transformation from RA to RAEB or overt leukemia was seen in only one case among the former group, but in six among the latter. With respect to patient characteristics, only the percentage of marrow myeloblasts differed significantly between the groups.
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PMID:Androgen in the treatment of refractory anemia. 174 44

The results of a comprehensive study on 1,000 patients who had been cytogenetically diagnosed to have leukemia in our department since 1962 are reported, and the value of cytogenetic diagnosis for leukemia emphasized. In our series, we detected patients with FAB L1 and L2 showing an abnormality rate of 60 and 66%, respectively. They included 20% with Ph1 positive ALL. In FAB L3, we found t(8;14) in 5 of the 6 patients. The FAB M1 group showed the lowest abnormality rate (50%). Forty percent of the M2 patients exhibited t(8;21), 60% of which also showed loss of sex chromosome of either X or Y. Seventy-eight percent of the M3 patients presented t(15;17) (two patients with no detectable t(15;17) showed rearrangements of retinoic acid receptor alpha gene). Inversion of chromosome 16 was found in 10% of the patients with FAB M4. Patients with M6 exhibited relatively complex chromosomes aberrations. RAEB patients showed more frequent and complex type of chromosome aberrations than PARA patients. Cytogenetic and molecular-biological analyses provided valuable information on the pathophysiology of leukemia and suggested the possible localization of novel oncogene(s).
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PMID:[The significance of cytogenetic analysis in the diagnosis of leukemia]. 177 62

As anemia is frequently the main problem in myelodysplastic syndromes (MDS), we studied the efficacy of human erythropoietin (rhEpo) in stimulating the erythroid lineage in 14 patients, starting with 40 U/kg three times a week and doubling the dose every 6 weeks until a response was observed. The highest doses administered were 80 (n = 1), 160 (n = 4), 320 (n = 8) and 640 U/kg (n = 1). One patient (refractory anemia with an excess of blasts, RAEB) showed an increase of hemoglobin, white blood cells and platelets with 80 U/kg rhEpo. However, this patient developed acute leukemia while on therapy. Two other patients (RAEB and RAEB in transformation) also transformed to acute leukemia. In the other 11 patients no response was observed. There was no correlation between in vitro culture data and in vivo responsiveness. The treatment was well tolerated and no nonhematological side effects were observed. From this study we conclude that rhEpo, even when given at high doses, has a low response rate in patients with MDS. Further investigation is needed in order to clarify whether rhEpo increases the potential risk of transformation to acute leukemia.
Leukemia 1991 May
PMID:Recombinant human erythropoietin in patients with myelodysplastic syndromes. 203 64

To verify the clinical usefulness of extracellular cyclic nucleotide determinations as tumour markers in preneoplastic syndromes, plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were monitored in 47 patients with refractory anaemia with excess of blasts (35 RAEB and 12 RAEBt), 20 of whom progressed to acute leukaemia during the observation period. The control group consisted of 45 healthy subjects matched for age and sex. In all groups of patients plasma cAMP levels were within the normal range, whereas plasma cGMP levels were significantly higher than those of normal subjects in both RAEB and RAEBt patients, and increased further when progression to acute leukaemia occurred. These data suggest that serial determinations of plasma cGMP may be useful to monitor the progression of the disease, though there is no evidence that cGMP values at diagnosis may have a prognostic significance.
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PMID:Plasma cyclic nucleotide levels in patients with refractory anaemia with excess of blasts. 215 84

To study the therapeutic effect of low-dose aclarubicin (ACR), we carried out comparative treatment of 15 patients with myelodysplastic syndrome (MDS) and atypical leukemia using this drug. Complete remission (CR) was achieved in three patients with RAEB-t and one patient with AML, partial remission was obtained in one patient with RAEB and hematological improvement in one patient with refractory anemia (RA). Interestingly, prolonged CR for more than 26 months with persistent chromosomal abnormalities was observed in a case of AML, which progressed from RA. Myelosuppression caused by low-dose ACR was milder than that caused by low-dose Ara-C. Furthermore, in vitro studies indicated that ACR induced differentiation of bone marrow cells from one patient with MDS. From these observations, it is suggested that low-dose ACR may be an alternative to low-dose Ara-C for treatment of MDS, and that the in vivo effect of ACR may be mediated by the differentiation of abnormal hemopoietic clones.
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PMID:Treatment of myelodysplastic syndrome and atypical leukemia with low-dose aclarubicin. 217 36


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