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Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G‐CSF (CLAG‐M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group
Author(s) -
Wierzbowska Agnieszka,
Robak Tadeusz,
Pluta Agnieszka,
Wawrzyniak Ewa,
Cebula Barbara,
Hołowiecki Jerzy,
KyrczKrzemień Sławomira,
Grosicki Sebastian,
Giebel Sebastian,
Skotnicki Aleksander B.,
PiątkowskaJakubas Beata,
Kuliczkowski Kazimierz,
Kiełbiński Marek,
Zawilska Krystyna,
Kłoczko Janusz,
WrzesieńKuś Agata
Publication year - 2008
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2007.00988.x
Subject(s) - cladribine , mitoxantrone , medicine , fludarabine , regimen , cytarabine , neutropenia , refractory (planetary science) , toxicity , gastroenterology , chemotherapy , salvage therapy , oncology , surgery , cyclophosphamide , biology , astrobiology
Objectives: Patients with primary refractory AML and with early relapses have unfavorable prognoses and require innovative therapeutic approaches. Purine analogs fludarabine (FA) and cladribine (2‐CdA) increase cytotoxic effect of Ara‐C in leukemic blasts and inhibit DNA repair mechanisms; therefore its association with Ara‐C and mitoxantrone (MIT) results in a synergistic effect. In the current report, we present the final results of multi‐center phase II study evaluating the efficacy and toxicity of CLAG‐M salvage regimen in poor risk refractory/relapsed AML patients. Methods: The induction chemotherapy consisted of 2‐CdA 5 mg/m 2 , Ara‐C 2 g/m 2 , MIT 10 mg/m 2 , and granulocyte‐colony stimulating factor. In the case of PR, a second CLAG‐M was administered. Patients in CR received consolidation courses based on high doses of Ara‐C and MIT with or without 2‐CdA. Results: One hundred and eighteen patients from 11 centers were registered; 78 primary resistant and 40 relapsed. Sixty‐six patients (58%) achieved CR after one or two courses of CLAG‐M, 49 (35%) were refractory, and 8 (7%) died early. WBC >10 g/L and age >34 yr were factors associated with increased risk of treatment failure. Hematological toxicity was the most prominent toxicity of this regimen. The probability of OS at 4 yr was 14% (95% CI 4–23%). OS was influenced by age, WBC >10 g/L and poor karyotype in both univariate and multivariate analyses. The probability of 4 yr DFS was 30% for all 66 patients in CR (95% CI 11–49%). Poor karyotype was the only factor associated with decreased probability of DFS. Conclusions: We conclude that CLAG‐M is a well‐tolerated and highly effective salvage regimen in poor risk refractory/relapsed AML.