Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixty-seven patients with hematological malignancies and 4 with cancers were evaluated in this study. Standard administration of MCNU was instituted intravenously using 50-100 mg/m2 every 2 or 4 weeks, whereas some cases were treated with a higher dose therapy. Of 10 patients with chronic myelogenous leukemia, 7 achieved complete remission (CR), and 1 achieved partial remission (PR). A good response was also obtained in 9 of 10 patients with polycythemia vera and in all 4 patients with essential thrombocythemia. MCNU was less effective in malignant lymphoma (ML) and multiple myeloma (MM) than in myeloproliferative disorders. Two of 15 patients with ML and one of 21 patients with MM achieved CR, and two with ML and three MM achieved PR. Three patients with lung cancer and 1 with gastric cancer showed no response to MCNU. Delayed anemia, leukocytopenia and thrombocytopenia were observed in 38.7% of patients, and these were regarded as major side effects of MCNU. Nausea, vomiting, anorexia and elevated transaminase were also found in about 24% of patients, but only transiently. Our study indicates that MCNU is useful for chemotherapy of hematological malignancies, especially of myeloproliferative disorders. Therefore, further studies on combination chemotherapy with MCNU should be developed.
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PMID:[Phase II study of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU)]. 385 48

The toxic effects of high-dose busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) with autologous or syngeneic bone marrow rescue were evaluated in 19 patients (11 with acute myelocytic leukemia, one with acute lymphocytic leukemia, one with acute myelofibrosis, two with chronic myelocytic leukemia, one with Hodgkin's disease, and three with non-Hodgkin's lymphoma). Their mean age was 26 years (range, 6-50); nine patients had syngeneic and ten had autologous bone marrow rescue (six of whom had in vitro bone marrow incubation with 4-hydroperoxycyclophosphamide). Severe myelosuppression was expected and was seen in all patients; leukocyte and platelet count recovery occurred at a median of 19 days (range, 11-59) and 30 days (range, 20-89), respectively. Nausea, vomiting, and diarrhea were frequent but readily managed with vigorous medical therapy. Stomatitis was severe in 14 patients. Skin, renal, cardiac, pulmonary, and CNS complications directly attributable to drug-related toxic effects were transient and non-life-threatening. Hepatic function abnormalities were common but tended to be transient. Most patients tolerated high-dose busulfan and cyclophosphamide with manageable side effects. Hepatic veno-occlusive disease was fatal in two patients, while diffuse interstitial pneumonitis with disseminated herpes virus infection was fatal in three patients with lymphoma. All patients treated in relapse or without previous therapy had a complete tumor response. Further studies with this regimen should be pursued.
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PMID:Preliminary results of high-dose busulfan and cyclophosphamide with syngeneic or autologous bone marrow rescue. 637 4

m-AMSA is a synthetic aminoacridine DNA intercalator found to have experimental murine antitumor activity. A phase I investigation was undertaken in 71 patients with solid tumors and acute leukemia. Using an intermittent every 3-week schedule in solid tumors, toxicity encountered was primarily hematologic, predominantly leukopenia with relative platelet sparing. The recommended dose for phase II evaluation in patients with solid tumors is 90 mg/m2 every 3 weeks; patients with minimal prior therapy could be treated at 120 mg/m2 and patients with hepatic dysfunction or marginal bone marrow reserve should have an initial dose reduction to 70 mg/m2. Therapeutic activity was seen in Hodgkin's disease, hepatoma, and epidermoid carcinoma of the esophagus. Various dose schedules were studied in leukemia. The recommended dose for phase II evaluation is 120 mg/m2 daily for 5 days as a daily 30-minute infusion. At this dose, nausea, vomiting, mucositis, alopecia, and hepatic toxicity were noted. Therapeutic activity was seen in AML, blastic CML, and CLL. Further clinical trials with this agent are warranted.
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PMID:Phase I study of m-AMSA in patients with solid tumors and leukemias. 689 83

AMSA, an acridine derivative with significant antitumor activity in experimental tumors, was administered to 17 patients with advanced tumors refractory to standard chemotherapies. A phase I study was undertaken in 10 patients with solid tumors and lymphomas. Dose-limiting toxicity was myelosuppression. With a median dose of 90 mg/m2 (75-148 mg/m2), median lowest WBC count was 1,000/mm3 (100-3,200) on day 11 and its recovery up to 4,000/mm3 was seen on day 21, while lowest platelet count was 42 X 10(3)/mm3 (7-300 X 10(3) on day 12 and its recovery up to 100 X 10(3)/mm3 was on day 20. Non-hematological toxicities were nausea (39%), vomiting (11%) and phlebitis (17%) in 18 courses of therapy. The result indicated that the recommended dose schedule for a phase II evaluation was 90 mg/m2, every three weeks. Therapeutic activity was observed in patients with non-Hodgkin's lymphoma (one partial response and two minor responses out of four). Two out of five breast, one ovarian, and one melanoma patients showed stable diseases. Five leukemic patients (three AMLs, one MoL, and one blastic CML) were treated with AMSA, and in these cases cytoreduction of peripheral and bone marrow blasts was seen, but it was not adequate to induce remission. Further clinical trials with this agent are warranted, especially in patients with acute leukemia, lymphoma and breast cancer.
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PMID:[Phase I-II studies of a new antineoplastic agent, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA)]. 689 58

In an effort to determine if cell cycle active agents are augmented when given after non-cell cycle active agents, 104 patients with either multiply relapsed or refractory acute nonlymphocytic leukemia or blast crisis of chronic myelogenous leukemia were treated with mitoxantrone. Patients whose bone marrow did not show significant cytoreduction received 5-azacytidine. Twenty-seven of the 93 evaluable patients (23%) with ANLL achieved a complete remission. A total of 28% of patients receiving mitoxantrone alone achieved remission compared to 15% for those receiving mitoxantrone and 5-azacytidine. Relapsed patients had a higher CR rate (36%) than refractory patients (15%). Nausea, vomiting, and stomatitis were common but rarely severe. The median duration of remission was 3.7 months and patients with abnormal karyotypes had longer remission durations than those with normal karyotypes. In this patient population, there was no evidence that 5-azacytidine given after mitoxantrone increased the complete remission rate.
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PMID:Mitoxantrone and 5-azacytidine for refractory/relapsed ANLL or CML in blast crisis: a leukemia intergroup study. 769 May 19

The safety, tolerance, and clinical effects of combined therapy with recombinant interferon-alpha (IFN-alpha) and interleukin-2 (rIL-2) administered subcutaneously for 2 courses of 4 weeks each, with 4 weeks interval between courses, given as outpatient therapy have been assessed in 10 patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML). All patients were previously treated with conventional chemotherapy and 3 failed to respond to IFN-alpha administered prior to our study. Median duration of disease from diagnosis was 36 months. Seven patients were in first chronic phase and the other 3 were in blast crisis, second chronic phase, and relapse post-bone marrow transplantation (BMT), respectively. Hematological response (median follow-up 16 months) was observed in 9 patients, with a decline in number of white blood cells and platelets. Elimination of Ph1 was observed in the patient who relapsed post-BMT with complete elimination bcr/abl RNA by polymerase chain reaction. Rebound lymphocytosis and eosinophilia were observed in most of the patients. Toxicity was acceptable. The main adverse effects were fever, chills, fatigue, anorexia, nausea, and vomiting. The side effects were reversible and no interruption of treatment was required. There was no treatment-related hospitalization or deaths. These data suggest that simultaneous subcutaneous IFN-alpha and rIL-2 home therapy is feasible, reasonably well tolerated, and potentially beneficial in CML patients. These observations may have important implications for the treatment of minimal residual disease following allogeneic and autologous marrow transplantation.
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PMID:Treatment of chronic myelogenous leukemia with recombinant human interleukin-2 and interferon-alpha 2a. 792 12

An early phase II study of CPT-11 (irinotecan hydrochloride) was conducted in patients with hematological malignancies by 4 administration regimens in a cooperative study involving 13 institutes in Japan. The overall response rate was 23% (7/30) for non-Hodgkin's lymphoma, 33% (1/3) for Hodgkin's disease, 18% (2/11) for acute lymphoblastic leukemia and 7% (1/15) for acute myelogenous leukemia. One PR was also obtained in a patient with chronic myelogenous leukemia. Among responders, 6 relapsed and refractory malignant lymphomas (ML) and 2 relapsed and refractory acute leukemias (AL) were involved. The response rates in ML with the regimens B (40 mg/m2 for 5 days every 3-4 weeks) and C (40 mg/m2 for 3 days every weeks) were 31% (5/16) and 33% (3/9), respectively. The other regimens (regimen A, 200 mg/m2 once a day every 3-4 weeks and regimen D) resulted in no response. Responses in AL were only observed in regimen D (20 mg/m2 twice a day for 7 days every 3-4 weeks). Major toxicities were leukopenia (91%), nausea/vomiting (74%), diarrhea (73%) and anorexia (64%). The incidence of severe gastrointestinal symptoms was higher in regimen B than regimen C. Further studies are warranted to confirm the effectiveness and safety of CPT-11 against ML and AL. The recommended administration schedule was regimen C for ML and regimen D for AL.
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PMID:[An early phase II study of CPT-11 (irinotecan hydrochloride) in patients with hematological malignancies]. 829 18

The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 3.5 mg/m2 to 18 mg/m2 per course. Twenty-seven patients were treated, including 17 patients with acute myelogenous or undifferentiated leukemia, 7 with acute lymphocytic leukemia, and 3 with chronic myelogenous leukemia in blastic phase. Severe mucositis was the dose-limiting toxicity occurring in two of five patients treated with Topotecan 11.8 mg/m2 per course; a third patient had prolonged myelosuppression. At the MTD of 10 mg/m2 per course, 1 of 12 patients had severe mucositis and 5 had mild-to-moderate mucositis. Nausea, vomiting, diarrhea, and prolonged myelosuppression were uncommon. Three patients (11%) achieved a complete response, two (7%) had a partial response, and one (4%) had a hematologic improvement. The overall complete plus partial response rate was 19%, and 24% in acute myelogenous or undifferentiated leukemia. A novel in vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes in patient samples was used, which demonstrated heterogeneity in the ability of Topotecan to interact with topo I, the intracellular target of Topotecan. This phase I study defined the MTD of Topotecan to be 10 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Severe mucositis was the dose-limiting toxicity. Future studies will define the precise activity of Topotecan in different leukemia subsets, its efficacy in combination with other antileukemic drugs, and correlations between Topotecan-induced topo I-DNA complex formation and individual patient response to Topotecan.
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PMID:Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia. 838 70

Six patients with either acceleration or blast crisis of transformed chronic myeloid leukemia (CML) were treated with high-dose interferon alpha in combination with hydroxyurea. All patients responded to the treatment by reversal to stable chronic phase. Two of these patients responded repeatedly during their course of disease. Median time for return to chronic phase was 4 weeks. Adverse side-effects such as nausea, vomiting, hairloss, fever, prolonged cytopenia were not observed.
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PMID:Successful treatment of accelerated and blastic phase of chronic myeloid leukemia with high-dose interferon alpha and hydroxyurea: a novel approach. 857 62

Five patients with Ph+ chronic myeloid leukemia and no detectable diploid cells in the marrow received 6 g hydroxyurea twice daily for 7 days followed by G-CSF to harvest Ph-cells 1-84 months after diagnosis. Three were in first chronic phase, and two in accelerated phase. One stopped hydroxyurea after 4 doses due to intractable vomiting and was not apheresed, while two stopped hydroxyurea after 9 and 11 doses because of mucositis and skin rash. Two tolerated all doses; one with no significant side effects, and one with mucositis and painful plantar rash. The nadir leukocyte, neutrophil, and platelet counts were 0.4-0.8, 0-0.1, and 2-19 x 10(9)/L respectively. Apheresis was commenced when the leukocytes were 1.2-3.8 x 10(9)/L 9-10 days after starting G-CSF, and 6 aphereses were performed. Four collections were 100% Ph+, and two 22% and 90% Ph-. The total nucleated cell, CD34+/CD34-subset, CD34+/CD33+ subset, and CFU-GM yields per kg per collection were 0.48-2.38 (median 1.18) x 10(8), 0-0.48 (median 0.012) x 10(6), 0.028-10.19 (median 0.92) x 10(6), and 0.29-41.81 (median 21.78) x 10(4) respectively. We conclude that hydroxyurea in the dose we used is poorly tolerated, and is associated with significant adverse effects including severe myelosuppression. It is possible to harvest diploid cells during recovery, but achievement of Ph-negativity appears to be erratic and cell yields are poor.
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PMID:High-dose hydroxyurea and G-CSF to collect Philadelphia-negative cells in chronic myeloid leukemia: preliminary results. 902 92


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