Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-nine adults with acute leukaemia who had relapsed when receiving extensive chemotherapy were treated with a combination of methotrexate and colaspase (L-asparaginase) given sequentially. Patients initially received 50-80 mg/m(2) methotrexate, followed three hours later by intravenous colaspase, 40 000 IU/m(2). Seven days later intravenous methotrexate, 120 mg/m(2) was given. Each dose of methotrexate was followed 24 hours later by colaspase, and the two-day course of treatment was repeated every 7-14 days. The methotrexate dose was increased to tolerance by increments of 40 mg/m(2) with each course, while the colaspase dose remained constant unless abnormal liver function developed, when it was reduced by half.Overall, 18 out of 39 patients achieved complete remission (46%). Of these, 13 out of 21 (62%) had acute lymphoblastic leukaemia, three out of seven (43%) acute undifferentiated leukaemia, and two out of 11 (18%) acute myeloblastic leukaemia. The median duration of complete remission was 20 weeks and the median duration of survival in complete responders was 45 weeks. The median number of courses needed to achieve complete remission was three. The maximum tolerated dose of methotrexate was 400 mg/m(2) (median 200 mg/m(2)). Major side effects were due to colaspase. Methotrexate in doses of up to 400 mg/m(2) caused minimal myelosuppression and stomatitis, which suggested that colaspase given sequentially provides relative protection from methotrexate toxicity without the need for folinic acid (citrovorum factor) rescue.The combination of sequential colaspase and methotrexate is highly effective in reinducing remission in patients with acute lymphoblastic leukaemia or acute undifferentiated leukaemia. The regimen is easy to administer and relatively non-toxic, so it is suitable for use in outpatients, either alone or combined with other agents.
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PMID:Refractory acute leukaemia in adults treated with sequential colaspase and high-dose methotrexate. 27 87

An 18-year-old primagravida received combination chemotherapy with vincristine, prednisone, L-asparaginase, cyclophosphamide, daunomycin, 6-mercaptopurine and central nervous system (CNS) prophylaxis with intrathecal methotrexate and whole-brain irradiation for acute lymphoblastic leukemia (ALL) beginning in the 12th week of pregnancy. Therapy resulted in sustained complete remission of the leukemia and delivery of a normally developed female infant whose immediate neonatal course was complicated by transient severe bone marrow hypoplasia. Our experience confirms the reports of others that intensive chemotherapy can be administered in the last two trimesters of pregnancy without serious teratogenic complications. However, we conclude that such therapy may cause significant myelosuppression in the newborn.
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PMID:Acute leukemia in pregnancy: transient neonatal myelosuppression after combination chemotherapy in the mother. 29 85

The combination of sequential L-asparaginase and methotrexate (MTX) was evaluated in 33 patients with advanced refractory breast cancer. There were nine partial responses and one complete response, giving an overall response rate of 30% and a median duration of response of 8 months. Five of 17 patients (28%) who had received prior MTX at doses of less than 50 mg/m2 responded. Toxicity was acceptable. Moderate-to-severe stomatitis occurred in most patients and was the dose-limiting factor. Myelosuppression was minimal until the dose of MTX was escalated to greater than or equal to 180 mg/m2. The maximum tolerated dose of MTX was 280 mg/m2 and the median toxic dose was 220 mg/m2. These data indicate a selective "rescue" from MTX damage to normal target tissue by L-asparaginase. The antitumor effect observed even in patients who had been previously exposed to conventional doses of MTX suggests a possible improved therapeutic index of MTX given sequentially with L-asparaginase in this combination.
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PMID:Phase II study with sequential L-asparaginase and methotrexate in advanced refractory breast cancer. 36 95

An escalating-dose trial of idarubicin, used weekly for 3 doses in combination with vincristine, prednisone, and L-asparaginase (VPLI), to reinduce remission of childhood ALL at first bone marrow relapse was conducted by the Childrens Cancer Study Group (CCSG). The maximum tolerated dose (MTD) of idarubicin, used in the manner, was determined to be 12.5 mg/m2/dose. Twelve of 16 (75%) evaluable patients in first marrow relapse of ALL treated at a dose of 10 or 12.5 mg/m2 entered a second complete remission, compared to 41 of 69 evaluable patients (59%) treated in a comparable way with daunorubicin (30 mg/m2) (VPLD). Prolonged myelosuppression was observed in both groups, but the frequency of documented bacterial sepsis and the duration of required hospitalization were greater among patients treated with idarubicin. No additional toxicity, specifically attributable to idarubicin, was observed at these doses.
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PMID:Determination of the maximum tolerated dose of idarubicin when used in a combination chemotherapy program of reinduction of childhood ALL at first marrow relapse and a preliminary assessment of toxicity compared to that of daunorubicin: a report from the Childrens Cancer Study Group. 173 17

A new salvage treatment protocol consisting of VP-16, cytosine arabinoside (Ara-C), methotrexate (MTX) and L-asparaginase, known as VAMA, was administered to twelve patients with relapsed or resistant non-Hodgkin's lymphoma. All twelve patients were in advanced stage with aggressive histologic type. Four of eight patients whose tumor cells had been immunologically determined, had T-cell phenotype. Three complete and five partial responses were obtained, for an overall response rate of 67%. It is of particular interest that all four patients with T-cell phenotype responded(CR; 3 cases, PR; 1 case), and a CR duration over 31 months has been achieved in a case of T-lymphoblastic lymphoma. Severe myelosuppression was the major toxic effect, but it was generally well-tolerated with supportive therapy. These results indicate that VAMA salvage regimen can play an important role in the treatment of relapsed or resistant non-Hodgkin's lymphoma.
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PMID:[VAMA salvage regimen (VP-16, ARA-C, MTX and L-asparaginase) in relapsed or resistant non-Hodgkin's lymphoma]. 341 72

4 patients with refractory AML or AML in relapse were treated with high dose Ara-C and L-asparaginase. Although only one patient was resistant against this type of treatment, a durable complete remission could be achieved in only one case. Severe myelosuppression was observed in all 4 cases; non-hematologic toxicity, however, was minimal.
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PMID:[High-dose cytarabine treatment with asparaginase (Capizzi schedule) in recurrent or refractory AML in the adult]. 388 23

Analysis of the remission induction phase in three Medical Research Council trials of treatment of acute lymphoblastic leukaemia has provided evidence of the adverse effect of the combination of colaspase (L-asparaginase) with vincristine and prednisolone. Significant myelosuppression, particularly of the granulocytic series, resulted in an increase in Gram-negative sepsis and death during the neutropenic phase induced by colaspase. The rate of blast-cell regression was increased by colaspase. It is suggested that the introduction of colaspase should be delayed until there is evidence of bone marrow regeneration in order to procure this benefit without the attendant toxicity.
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PMID:Myelosuppressive effect of colaspase (L-asparaginase) in initial treatment of acute lymphoblastic leukaemia. 460 4

One hundred twenty-five hematologic relapses of acute lymphoblastic leukemia (ALL) were treated with a four-drug reinduction regimen consisting of L-asparaginase, vincristine, daunomycin, and prednisone (Asp-VDP). Complete remission was achieved in 114 of 125 (91%) treatment courses. The regimen also proved to be highly effective in the management of multiple subsequent relapses which occurred in patients who had previously attained complete remissions with this regimen. The rates of remission induction for second and third reinduction attempts were 89% and 90%, respectively. Ten patients received this regimen for the treatment of four or more consecutive relapses and achieved complete remissions on each occasion. Toxicities related to therapy were not excessive. Although myelosuppression was the most frequently encountered toxicity, documented infection complicated only 14% of the treatment courses. These results constitute a considerable improvement in the management of recurrent ALL.
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PMID:Improved treatment results in the management of single and multiple relapses of acute lymphoblastic leukemia. 693 Mar 18

Seventy-six patients with advanced acute leukemia refractory to conventional chemotherapy were treated with a sequential combination of methotrexate (MTX) and L-asparaginase (L-ASP), based on the reported schedule-dependent synergism between the two drugs in human leukemic cells in vitro. On Day 1, patients received 60 mg/m2 of MTX iv, followed 24 hours later by L-ASP at a dose of 10,000 IU/m2 iv. This sequence was repeated weekly with 50% escalations in the dose of MTX with each course. Overall, 31 of 76 patients (40.7%) achieved complete remission after a median of three courses; the response rate was 35.5% in patients with acute nonlymphocytic leukemia (21 of 59 patients) and 58.8% in patients with acute lymphocytic leukemia (ten of 17). Increasing the starting dose of MTX to 200 mg/m2 did not improve the response rate. Maintenance therapy with the same combination given every 2 weeks produced a median complete remission of 10 weeks. Toxicity was manifested by: acute hypersensitivity reactions to L-ASP (five patients), stomatitis (36 patients), and mild liver abnormalities (five patients). MTX in doses up to 200 mg/m2 caused minimal myelosuppression. We conclude that the MTX-L-ASP combination is a well-tolerated, highly effective induction regimen for refractory acute leukemia.
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PMID:Sequential combination of methotrexate and L-asparaginase in the treatment of refractory acute leukemia. 693 51

We have treated 37 adults with acute lymphoblastic leukemia (ALL), who have relapsed on previous intensive chemotherapy, with a combination of L-asparaginase and methotrexate (MTX) +/- ifosfamide. The initial study included 26 patients who received the two-drug combination of L-asparaginase and MTX given sequentially. Of the 26 patients, 15 (58%) achieved complete remission (CR), while 3 patients had a partial remission (PR), resulting in an overall response rate of 69%. The median duration of CR was 17.5 weeks. The median survival of complete responders was 39 weeks compared with 10 weeks for failures (P=0.001). The regimen was generally well tolerated and it was possible to give MTX doses of up to 400 mg/m2 with minimal myelosuppression, and severe stomatitis was infrequent. A further study involved the use of this regimen combined with ifosfamide in 11 patients. In this continuing study, there were six CR's (55%) and two PR's, with an overall response rate of 73%. The median duration of CR was 14+ weeks, and the median survival was 40+ weeks. Combination chemotherapy with asparaginase and MTX is effective in inducing remission in adults with ALL in relapse. It should now be considered for inclusion as part of induction therapy of previously untreated adults with ALL.
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PMID:Asparaginase and methotrexate combination chemotherapy in relapsed acute lymphoblastic leukemia in adults. 694 10


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