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 |
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Authors: | Wierzbowska Agnieszka Robak Tadeusz Pluta Agnieszka Wawrzyniak Ewa Cebula Barbara Ho?owiecki Jerzy Kyrcz-Krzemień S?awomira Grosicki Sebastian Giebel Sebastian Skotnicki Aleksander B Piatkowska-Jakubas Beata Kuliczkowski Kazimierz Kie?biński Marek Zawilska Krystyna K?oczko Janusz Wrzesień-Ku? Agata;Polish Adult Leukemia Group |
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Institution: | Department of Hematology, Medical University, Lodz, Poland;;Department of Hematology and Bone Marrow Transplantology, Medical University, Katowice, Poland;;Department of Hematology Medical University, Krakow, Poland;;Department of Hematology Medical University, Wroclaw, Poland;;Department of Hematology Medical University, Poznań, Poland;;Department of Hematology Medical University, Bia?ystok, Poland |
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Abstract: | 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/m2, Ara-C 2 g/m2, MIT 10 mg/m2, 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. |
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Keywords: | cladribine purine nucleoside analogs refractory acute myeloid leukemia relapsed acute myeloid leukemia salvage treatment |
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