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)

A 71-year-old female was diagnosed as hypoplastic leukemia (ALL, L 2). Vitamin D3 (D3) therapy with alfacalcidol was successful and remission continued for approximately 4 months. However, the leukemia became refractory to D3, and low dose Ara-C combined with D3 was ineffective. Combined chemotherapy with vincristine, cyclophosphamide, L-asparaginase and prednisolone, low dose aclarubicin, OK-432 and etretinate ended in a failure. Treatment with mepitiostane was started and 1 month later obvious elevation of hemoglobin concentration, white cell and platelet count was observed. A bone marrow aspirate showed distinct recovery of normal hemopoiesis without residual leukemic cells. The patient has been staying in the complete remission for over 15 months with mepitiostane therapy (30 mg, daily). Androgen therapy, such as mepitiostane, appears to be effective in some patients with hypoplastic leukemia which does not indicate intensive chemotherapy.
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PMID:[Complete remission by mepitiostane in hypoplastic leukemia]. 268 84

We conducted a phase II trial of deoxycoformycin (pentostatin [DCF]) in chronic lymphocytic leukemia (CLL). Eligibility criteria included age greater than 18 years, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, lymphocyte count greater than or equal to 15,000 cells/microL, international stage B or C disease (multiple lymph nodes involved and/or hemoglobin [Hgb] less than 11 g and/or platelets less than 100,000/microL) and no more than one prior treatment regimen. DCF dose was 4 mg/m2 intravenously (IV) weekly for 3 weeks and then every 2 weeks. There were 39 eligible patients (35 men and four women; median age, 63 years; median time from diagnosis to study entry, 3 years). Of these 39 patients, 31% were stage B and 33% had no prior treatment. Median laboratory values at entry were Hgb 10.5 g, WBC 96,100/microL, and platelets 93,500/microL. Nodal involvement was present in 90%, splenomegaly in 81%, and hepatomegaly in 47%. Patients received a median of nine DCF injections, with a range of four to 26. Three patients were not evaluable for response. Overall, 3% achieved a complete response (CR), 23% a partial response (PR), 28% showed clinical improvement (CI), and 38% had stable disease (SD). Associated toxicities (grade 2 or worse) observed were infections (52%), worsening of thrombocytopenia (26%) or anemia (33%), nausea and vomiting (31%), rash or pruritus (20%), and stomatitis (8%). We conclude that DCF is an active agent in CLL with acceptable toxicity.
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PMID:Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia group B. 278 91

Limited-extent small-cell lung carcinoma (SCLC) remains a therapeutic problem with little improvement in complete response (CR) rates and long-term survival in the past 5 years. From June 1984 through January 1985, 56 patients with limited-extent SCLC were enrolled in a Cancer and Leukemia Group B (CALGB) phase II study using five cycles of cyclophosphamide (500 mg/m2 intravenously [IV] day 1), etoposide (80 mg/m2 IV days 1 to 3), and cisplatin (33 mg/m2 IV days 1 to 3) administered at 3-week intervals (CEP), with radiation therapy (50 Gy to chest and 30 Gy to brain) administered concomitant with cycles 4 and 5, followed by three cycles of cyclophosphamide (500 mg/m2 IV day 1), etoposide (80 mg/m2 IV days 1 to 3), and doxorubicin (50 mg/m2 IV day 1). Of 49 patients evaluable for response, the overall response rate was 88%, with 57% CRs. The median overall survival was 14 months; the median duration of CR was 10 months, and nine CRs remain disease free at a median follow-up of 23 months. Toxicity was significant: 56% patients experienced WBC less than 1,000 microL, 32% platelets less than 25,000 microL and 10% hemoglobin less than 7 g/dL. There was one treatment-related septic death. These results are as good as the best previous CALGB study of SCLC, despite a reduction in duration of treatment from 18 to 5 months. We are currently using a variant of this multimodality treatment approach as our standard management for patients with limited-extent SCLC.
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PMID:A phase II trial of cyclophosphamide, etoposide, and cisplatin with combined chest and brain radiotherapy in limited small-cell lung cancer: a Cancer and Leukemia Group B Study. 282 9

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.
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PMID:Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M. 289 97

In order to investigate the prognostic value of immunologic markers together with the most relevant clinical and hematological disease characteristics in acute myeloblastic leukemia (AML), the reactivity of blast cells from 102 patients with AML was analyzed with a panel of twenty monoclonal antibodies. The univariate analysis showed that five parameters had an adverse effect on both complete remission (CR) and survival: advanced age (greater than 60 years), anemia (hemoglobin concentration (Hb) less than 10g/dl), the expression of the antigens detected by the anti-megakaryocytic antibodies (CDw41/CDw42), the monocytic antibodies (CD14), and the CD9 (FMC56, FMC8) antigen. In addition, the failure to obtain CR had a significant adverse effect on survival (p less than 0.0001). Multivariate analysis showed that only age and Hb had a significant influence on CR while for predicting survival the most important independent prognostic factors were: CR, age, number of platelets and reactivity with the CD9 antibody. These results show that immunological markers could represent a valuable tool in the assignment of risk categories in AML patients.
Leukemia 1989 Feb
PMID:Prognostic value of immunological markers in acute myeloblastic leukemia. 291 Dec 3

A microassay for erythropoietin (Ep) activity in serum using [3H]thymidine uptake by K562 cells is presented. The method is similar to that of Krystal except that cells of the K562 human pluripotent leukemia cell line replace spleen cells from phenylhydrazine-treated anemic mice. Response to the hormone by K562 cells and spleen cells was colinear. Using the Krystal bioassay, 14 young hemoglobin S homozygotes had Ep activity levels of 17.9-113.8 mU/ml serum, whereas the new method with K562 cells gave a range of 19.2-115.3 mU/ml. The correlation coefficient between the two sets of data (r) was 0.999 (p less than 0.001). With the modified technique we have assayed 34 sickle cell patients, whose sera ranged from 19.2 to 1400 mU of Ep/ml with corresponding hemoglobin concentrations of 10.7 g % to 3.0 g %. Values for normal subjects were 22.1 +/- 2.1 mU/ml (n = 7). The stimulation of [3H]thymidine uptake is significantly inhibited by an anti-Ep antiserum. The assay permits quantification of stimulatory activities in a large number of samples with relative ease and is also suitable to explore the interactions of erythropoietic factors with their appropriate receptors on stem cells.
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PMID:Quantitation of erythropoietin stimulatory activity using [3H]thymidine uptake by K562 cells. 291 36

Cytogenetic analysis was successfully performed on 31 of 40 patients with chronic B cell leukemia. Clonal abnormalities were seen in 16 patients using various culture methods. Fourteen of these had unstimulated cultures established of which 13 had the clonal abnormality. Trisomy 12 was observed in seven patients while a 14q32 translocation was present in four. Race, age, hemoglobin, WBC, percentage of lymphocytes and prolymphocytes in BM and PB, platelets, Smig, lymph node, spleen, liver, pattern of bone marrow infiltration, therapy free interval, and overall survival were all compared. Significant correlations between the presence of clonal abnormalities and prior therapy (p less than 0.005) and an increase in prolymphocytes in bone marrow (p = 0.05) and/or peripheral blood (p = 0.0014) were observed.
Leukemia 1989 Mar
PMID:Chromosome abnormalities in B cell chronic lymphocytic leukemia and their clinical correlations. 291 55

Among 569 patients with newly diagnosed AML, 16% died in the 4 weeks following initiation of remission induction therapy. Eight pretreatment characteristics were found to be independently associated with 4-week survival: performance status, bilirubin, age, neutrophil count, fibrinogen, albumin, hemoglobin, and creatinine. A model incorporating these characteristics prospectively stratified a separate group of 198 patients into two comparably sized groups differing substantially in both 4-week survival rates (71% (95% confidence limits, 61-80%) vs. 91% (95% confidence limits, 83-96%] and in survival rates throughout remission induction. Characteristics associated with failure to survive 4 weeks were unassociated with resistance to therapy. This suggests that patients who fail to survive induction are qualitatively different than patients who survive induction but exhibit resistance to treatment. Different therapeutic strategies might be appropriate in the two groups. The model presented here can be used to identify patients at increased risk of death during remission induction.
Leukemia 1989 Apr
PMID:Prediction of survival during induction therapy in patients with newly diagnosed acute myeloblastic leukemia. 292 76

Abelson murine leukemia virus (A-MuLV) and Harvey murine sarcoma virus (Ha-MSV) are retroviruses carrying unrelated onc genes. However, both of these viruses are capable of stimulating the growth and differentiation of erythroid precursor cells; the target cells for both appear at the same time during fetal development and follow a similar pattern throughout ontogeny. In addition, the colonies induced by each virus are morphologically similar and synthesize the adult form of hemoglobin. However, A-MuLV-infected cells are Epo-independent, whereas Ha-MSV-infected cells are Epo-dependent. Superinfection of Ha-MSV-infected cells with A-MuLV overrides their Epo-dependency. Thus, the consequences of the infection are determined by the interaction of the different onc gene products with identical or similar erythroid cells.
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PMID:Abelson virus drives the differentiation of Harvey virus-infected erythroid cells. 300 34

The erythroleukemia induced by the Friend spleen focus-forming virus (SFFV) in mice exemplifies a multistep oncogenic process. Its sequential steps include a rapid polyclonal hyperplastic stage and a more slowly developing malignant stage characterized by autonomous erythroid cells. We report here that the helper virus normally present in mice infected by SFFV is not required for development of the second stage of transformation. In this study, mice were infected with a polycythemia-inducing variant of SFFV which was prepared as a helper-free stock (L. Wolff and S. Ruscetti, 1985, Science 228, 1549). Highly malignant cells could be detected in helper-free SFFV-infected mice by their transplantability into the omentum of sublethally irradiated mice, and erythroleukemia cell lines, typical of previously isolated Friend murine erythroleukemia cell lines, could be established from diseased spleens. Like their helper virus-containing counterparts, the lines established with helper-free SFFV are inducible for hemoglobin synthesis with a variety of chemicals, but not erythropoietin, and express p53, a marker of malignant transformation. Although the cells expressed SFFV encoded proteins, none expressed gene products of replication competent murine leukemia viruses.
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PMID:Induction of the autonomous stage of transformation in erythroid cells infected with SFFV: helper virus is not required. 301 73


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