The Treatment of Acute Myelogenous Leukemia in Children and Adults: VAPA Update

Weinstein, Howard J.; Mayer, Robert J.; Rosenthal, D. S.; Coral, F; Camitta, Bruce; Gelber, RD; Nathan, David G.; Frei, Emil

doi:10.1007/978-3-642-68761-7_8

Cited by 25 publications

(26 citation statements)

References 18 publications

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“…8 However, the 65% remission rate was lower when compared with the concurrent BFM studies (79 and 76% for AML-BFM-78 and -83, respectively), 12 and slightly inferior to the 70% CR rate as reported for the VAPA protocol. 13 Apart from induction failures, a large number of patients included in the AML-82 study relapsed, either during or early after the maintenance treatment phase, and results were inferior to the original VAPA-10 regimen. 13 One reason for the high number of relapses could be the long time interval between induction and intensification, which might have allowed leukemic regrowth.…”

Section: Discussionmentioning

confidence: 99%

“…13 Apart from induction failures, a large number of patients included in the AML-82 study relapsed, either during or early after the maintenance treatment phase, and results were inferior to the original VAPA-10 regimen. 13 One reason for the high number of relapses could be the long time interval between induction and intensification, which might have allowed leukemic regrowth.…”

Section: Discussionmentioning

confidence: 99%

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Treatment strategy and results in children treated on three Dutch Childhood Oncology Group acute myeloid leukemia trials

et al. 2005

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This report describes the long-term follow-up data of three consecutive Dutch Childhood Oncology Group acute myeloid leukemia (AML) protocols. A total of 303 children were diagnosed with AML, of whom 209 were eligible for this report. The first study was the AML-82 protocol. Results were inferior (5-year probability of overall survival (pOS) 31%) to other available regimes. Study AML-87 was based on the BFM-87 protocol, with prophylactic cranial irradiation in high-risk patients only, and without maintenance therapy. This led to a higher cumulative incidence of relapse than that reported by the Berlin-Frankfurt-Mü nster (BFM), but survival was similar (5-year pOS 47%), suggesting successful retrieval at relapse. The subsequent study AML-92/94 consisted of a modified BFM-93 protocol, that is, without maintenance therapy and prophylactic cranial irradiation. However, all patients were to be transplanted (auto-or allogeneic), although compliance was poor. Antileukemic efficacy was offset by an increase in the cumulative incidence of nonrelapse mortality, especially in remission patients, and survival did not improve (5-year pOS 44%). Our results demonstrate that outcome in childhood AML is still unsatisfactory, and that further intensification of therapy carries the risk of enhanced toxicity. Our patients are currently included in the MRC AML studies, based on the results of their AML 10 trial.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Treatment strategy and results in children treated on three Dutch Childhood Oncology Group acute myeloid leukemia trials

et al. 2005

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“…The VAPA protocol, developed at the DFCI, was the first to use the principle of intensive postremission chemotherapy, based on the use of sequential, noncrossresistant, combinations of active agents, administered in short monthly courses at myelosuppressive doses. 4 With this approach, approximately 40% of children achieving CR were predicted to survive, leukaemia-free, at 5 years.…”

Section: Before 1982mentioning

confidence: 99%

Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols

et al. 2005

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Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3 þ 7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better (Po0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P ¼ 0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy.

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“…There was no CNS leukemia. Weinstein et al 1983). We considered such intermittent treatment programmed 5 or more times per year too complicated for patients in remission who had returned to social life.…”

Section: Resultsmentioning

confidence: 99%

An eight year experience with gradually longer interval postremission therapy for adults with acute leukemia.

Kawamura

Mikami

Sawada

et al. 1989

Tohoku J. Exp. Med.

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a study was conducted into the effects of postremission therapy on 20 patients with acute leukemia who had achieved complete remission through induction therapy. Postremission therapy consisted of cyclic administration of six combination therapies given at gradually longer intervals. Postremission therapy used RCMP (D, daunorubicin ; C, cytosine arabinoside ; M, 6-mercaptopurine ; P, prednisolone), DCyMP (Cy, cyclocytidine), DCVP (V, vincristine), BHAC-DMP (BHAC, behenoyl-ara-c), BHAC-AMP (A, aclarubicin) and ACM-MP (ACM, aclacinomycin). Six combinations were given sequentially starting at one month interval, and then at 2, 3, 4, 5 and eventually 6 month intervals until 5 year survival was reached. The median remission duration was 38 months for acute myelogenous leukemia (AML), and 17 months for acute lymphoblastic leukemia (ALL). The median survival was 66 months for AML, and 33 months for ALL. The survival rate at 5 years was 60% for AML., 40% for ALL, and 50% in all 20 patients. Methotrexate and prednisolone were administrered intrathecally for prophylaxis of CNS leukemia on Day 4 of each stage of postremission therapy. There was no CNS leukemia. This postremission therapy was shown to be effective in improving the prognosis of adults with acute leukemia. postremission therapy ; adult actute leukemia; acute myelogenous leukemia ; acute lymphoblastic leukemia RCMP therapy by Kamei et al. (1970) and the two step DCMP therapy by Uzuka et al. (1976) have increased remission rates in adults with acute leukemia from 60% to 85%. While a satisfactory remission rate had been achieved in adults, how to prolong survival time has become an important problem to be solved.Our previous study on prognostic factors (Kawamura et al. 1977) revealed that therapeutic factors, especially postremission therapy, affected long term survival.

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The Treatment of Acute Myelogenous Leukemia in Children and Adults: VAPA Update

Cited by 25 publications

References 18 publications

Treatment strategy and results in children treated on three Dutch Childhood Oncology Group acute myeloid leukemia trials

Treatment strategy and results in children treated on three Dutch Childhood Oncology Group acute myeloid leukemia trials

Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols

An eight year experience with gradually longer interval postremission therapy for adults with acute leukemia.

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