Long‐term results in the treatment of acute nonlymphocytic leukemia: A pediatric oncology group study
Jeffrey P. KrischerC. Philip SteuberTeresa J. ViettiSteven J. CulbertAbdelsalam H. RagabSamuel K. MorganD. H. BerryEva HvizdalaPaul J. ThomasVita J. LandRobert P. Castleberry
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Abstract Complete remission (CR), 5‐year remission duration (RD), and overall 5‐year survival rates are 74%, 28%, and 25%, respectively, for previously untreated children with acute nonlymphocytic leukemia diagnosed between 1977 and 1981, following induction therapy with vincristine, doxorubicin and prednisone (VAP), consolidation therapy with 6‐thioguanine, cytosine arabinoside (TA) and cyclophosphamide/vincristine/cytosine arabinoside/prednisone (COAP), and maintenance therapy of alternating TA and COAP with or without VAP pulses. Approximately 20% are free of their disease for more than 5 years. High white blood cell counts (WBC) at diagnosis and M3 and M6 morphology were associated with lower CR rates, while M5 morphology was associated with higher CR rates. Patients with M1 morphology had shorter remission duration as compared to those with M4 or M5 morphology. Low WBC and age between 2 and 10 years at diagnosis were associated with longer remission durations and survival. Patients with M4 morphology also survived longer. The observed CR rates are comparable to other studies initiated at the same time as this study but survival is less than those reported more recently. Low WBC at diagnosis and M4/M5 morphology may identify relatively favorable prognostic groups.Spontaneous remission
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A total of 180 children with acute leukemia was randomized to one of two induction regimens: vincristine plus prednisone, or 6-mercaptopurine plus prednisone. Of 170 patients evaluable for induction therapy, a hematologic remission was achieved in 83% (72/87) on vincristine plus prednisone, and in 93% (77/83) on 6-mercaptopurine plus prednisone. When hematologic remission was achieved, patients were randomized to one of three maintenance schedules: 6-mercaptopurine alone, 6-mercaptopurine plus prednisone for 4 weeks every 3 months, or 6-mercaptopurine plus prednisone plus vincristine for 4 weeks every 3 months. The durations of hematologic remission were compared from the achievement of hematologic remission to bone marrow relapse. The survival data were presented as an overview of the effect of this initial therapy on duration of survival. There was no statistical difference between the two induction regimens. The most important finding in the comparison of the three maintenance schedules was that reinforcement of 6-mercaptopurine maintenance therapy with either prednisone or prednisone plus vincristine resulted in significantly longer durations of remission. Vincristine added to prednisone for reinforcement after induction of remission by vincristine plus prednisone did not increase the duration of hematologic remission or survival over prednisone reinforcement alone.
Mercaptopurine
Maintenance therapy
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Abstract At the present time, it is possible to achieve up to a 95% complete remission in childhood acute lymphoblastic leukemia, using the combination of vincristine and prednisone. Nevertheless, it has not been possible to reproduce these results in the adult. For this reason, a third drug, in this case adriamycin in a low dose, was added to the vincristineprednisone combination in the treatment of adult acute lymphoblastic leukemia (ALL). Complete remission was achieved in 45 of the 50 patients (90%). The median duration of remission was 23 months and the median survival time in this group was 31 months. The complications were minimal and the tolerance was good. From the point of view of our results and others reported in the literature, we consider that the combination of vincristine, prednisone, and adriamycin is a useful method for induction of remission of adult ALL.
Acute lymphocytic leukemia
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Fifty-six children with refractory acute lymphocytic leukemia (ALL) were assessed for remission-induction responses to VM-26 (250 mg/m2 per week) in combination with prednisone (40 mg/m2 per day) and vincristine (1.5 mg/m2 per week). Each child had been treated intensively with steroids, vincristine, daunorubicin and L-asparaginase. In fact, all patients had failed to respond to previous reinduction therapy with prednisone-vincristine or had relapsed while receiving vincristine. Our intent in this study was to test whether or not addition of VM-26 to prednisone-vincristine would overcome clinical resistance to these established agents. Complete remissions were induced in 17 patients (0.30) over 4 to 6 weeks. Five of these children, all clinically unresponsive to prednisone-vincristine alone, had complete remissions that lasted longer than 1 year; two remain in remission for 2 1/2 years and both are now off therapy. Myelosuppression, the most serious treatment complication, was documented in 20 of 26 evaluable patients. The median time to recovery of normal marrow function was 15 days. These results demonstrate further the potential of VM-26 in combined-drug treatment of refractory ALL. Whether the effectiveness of this combination represents potentiation of prednisone and vincristine activity by VM-26 or some other, as yet unidentified interaction, remains to be determined.
Refractory (planetary science)
Acute lymphocytic leukemia
Daunorubicin
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Abstract Objective —To evaluate the effect of prednisone alone, compared with a combination of prednisone and vincristine, on platelet counts in bleeding dogs with severe primary immune-mediated thrombocytopenia (IMT). Design —Prospective case study. Animals —24 dogs with severe primary IMT. Procedure —All dogs received immunosuppressive doses of prednisone (1.5 to 2 mg/kg [0.7 to 0.9 mg/lb] of body weight, PO, q 12 h). In addition, 12 dogs received a single dose of vincristine (0.02 mg/kg [0.01 mg/lb], IV). Platelet count, transfusion requirement, and outcome were monitored. A response was defined as an increase in platelet count to ≥ 40,000/µl. Dogs in the prednisone group that failed to respond received 1 dose of vincristine on day 7. Results —Dogs that received prednisone and vincristine had a significantly faster increase in platelet count to ≥ 40,000/µl than dogs that received prednisone alone (mean ± SD, 4.9 ± 1.1 vs 6.8 ± 4.5 days, respectively). A similarly rapid response was observed in dogs that received vincristine on day 7 after treatment with prednisone alone failed. Furthermore, duration of hospitalization was reduced in the vincristine group, compared with the prednisone group (5.4 ± 0.3 vs 7.3 ± 0.5 days, respectively). No adverse effects attributable to vincristine were observed in any dog. Conclusions and Clinical Relevance —Administration of combined vincristine and prednisone is associated with more rapid increase in platelet numbers and shortened duration of hospitalization in dogs with IMT, compared with use of prednisone alone. Early use of vincristine seems warranted in dogs with severe primary IMT. ( J Am Vet Med Assoc 2002; 220:477–481)
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Abstract Second remission induction rates for vincristine and prednisone alone (VP) and vincristine, L‐asparaginase, and prednisone (VLP) are compared for children with acute lymphocytic leukemia. No evidence of a significant difference between the second induction complete remission rate for VP (78.6%) and VLP (73.7%) was found. Duration of first remission and prognostic group at initial diagnosis (defined on the basis of age and white blood count at initial diagnosis) are shown to be significant prognostic factors for second remission induction; and three second remission induction risk groups are defined on the basis of these two factors. Periodic reinforcement with prednisone in first remission does not appear to lower second induction complete response (CR) rates for VP. There was no evidence of a significant difference in the frequency of occurrence of severe toxicity between the VP and VLP regimens.
Acute lymphocytic leukemia
Induction chemotherapy
Spontaneous remission
White blood cell
Asparaginase
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T w o different regimens utilizing daunomycin, vincristine sulfate, and prednisone were administered in combination to treat 64 children with acute leukemia in relapse.All patients had received previous therapy with vincristine, prednisone, and/or daunomycin but none had received the 3 drugs in combination.Seven were known to be resistant to both vincristine and prednisone.The triple combination was effective in inducing remission in 44 of the children, but myelosuppression was severe and t h e results obtained were not significantly better than the much less toxic combination of vincristine and prednisone. HE ANTILEUKEhllC ACTIVITY OF DAUNOMY-T cin when used in combination with vincristine sulfate and prednisone has been studied by the Southwest Cancer Chemotherapy Study Group (SWCCSG).Daunomycin, an antibiotic isolated from cultures of Streptomyces peucetius, is capable of inhibiting growth of mammalian cells throughout the proliferative cycle.3Daunomycin complexes
Childhood leukemia
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Summary After complete remission had been induced by prednisone and vincristine in children with acute leukemia, hydroxyurea was used in an effort to maintain remission. No significant prolongation of remission occurred despite the appearance of toxicity in over 50% of the high dosage group. An equally significant observation was that the duration of remission produced by prednisone and vincristine was longer in those who had not received vincristine during a prior induced remission.
Spontaneous remission
Acute lymphocytic leukemia
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L-Asparaginase was added to vincristine and prednisone for induction of first remission in 815 children with acute lymphocytic or acute undifferentiated leukemia. This combination resulted in an overall remission rate of 93%. The addition of L-asparaginse to the standard induction regimen using prednisone and vincristine did not significantly increase the morbidity or mortality rate during the induction period. The most common side effect was transient L-asparaginase-induced hyperglycemia. The safe administration of L-asparaginase i.m. and the dose efficacy of 6000 I.U./sq m were confirmed. For these reasons, L-asparaginase should be combined with vincristine and prednisone for the initial induction of children with acute lymphocytic or acute undifferentiated leukemia.
Acute lymphocytic leukemia
Asparaginase
Regimen
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Abstract Forty‐five children with acute nonlymphoblastic leukemia in relapse received a total of 56 courses of L‐asparaginase combined with vincristine and prednisone. The complete remission rate of 40% (12 of 30 trials) in patients resistant to vincristine and prednisone was almost identical to that in children still sensitive to vincristine and prednisone (42%, 11 of 26 trials). The complete remission rate of 38% (14 of 37 exposures) in those children who had not received L‐asparaginase previously compared favorably with the complete remission rate in those children who had received prior L‐asparaginase (47%, 9 of 19 exposures). Forty‐seven of the 56 induction trials were in children with 1 or more remissions and 14 of these were in children with 3 or more prior remissions. Toxicity was minimal.
Asparaginase
Induction chemotherapy
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