A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group

Abstract

Purine nucleoside analogues, cladribine (2-chlorodeoxyadenosine, 2-CdA) and fludarabine (FAMP) are active agents in acute myeloid leukemias (AMLs). Synergistic interaction between FAMP or 2-CdA with cytarabine (cytosine arabinoside, Ara-C) has been demonstrated in preclinical and clinical studies. The current multicenter phase II study was initiated to evaluate the efficacy and toxicity of induction treatment consisting of 2-CdA (5 mg/m2), Ara-C (2 g/m2), mitoxantrone (MIT, 10 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (CLAG-M) in refractory AML. In case of partial remission, a second CLAG-M was administered. Patients in complete remission (CR) received consolidation courses based on high-dose Ara-C and MIT with or without 2-CdA. Forty-three patients from five centers were registered: 25 primary resistant and 18 relapsed. CR was achieved in 21 (49%) patients, 20 (47%) were refractory and 2 (5%) died early. Hematologic toxicity was the most prominent toxicity of this regimen. The overall survival (OS; 1 year) for the 42 patients as a whole and the 20 patients in CR were 43% and 73%, respectively. Disease-free survival (1 year) was 68.6%. None of the analyzed prognostic factors influenced the CR and OS probability significantly. We conclude that CLAG-M regimen has significant antileukemia activity in refractory AML, which seems to be better than the activity of many other regimens. The toxicity of the treatment is acceptable.

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo‐HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective, multicenter Polish Adult Leukemia Group study

“…As alternative reinduction chemotherapy, CLAG [14,15] and CLAG-M [16] were respectively used in Studies 1 and 2. In the former, patients with intermediate or high cytogenetic risk and those patients requiring two induction treatments to achieve CR were qualified for allo-HSCT.…”

Older and New Formulations of Cladribine. Pharmacology and Clinical Efficacy in Hematological Malignancies

“…Disease free survival after 1 year was 29%. Subsequently, we evaluated the efficacy and toxicity of induction treatment consisting of 2-CdA (5 mg/m 2 ), Ara-C (2g/m 2 ), mitoxantrone (10 mg/m 2 ) and G-CSF (CLAG-M) in 42 refractory AML patients (141). CR was achieved in 21 (49%) patients.…”

“…Larger Studies Evaluating the Efficacy of 2-CdA in AML Wrzesien-Kus et al2005[141] 2-CdA 5mg/m 2 dx5+Ara-C 2g/m 2 /d x5d+MIT 10mg/m 2 d1+G-CSF 300 µg/d sc x 6Abbreviations:AML-acute myleoid leukemia; 2-CdA-2-chlorodeoxyadenosine; Ara-C -cytarabine; IDA -idarubicin; DNR-daunorubicin; MIT -mitoxantrone; G-CSFgranulocyte-colony stimulating factor; CI -continuous infusion; d -day; wk-week; NR -not reported.…”

Approach to patients with primary refractory acute myeloid leukemia

“…There is no standard first-line salvage therapy for PRD because none has proven to be obviously superior with reported complete remission rates ranging from 10 to 50%, and second salvage regimen rates are even worse, below 10% (Table 2) [14,[31][32][33][34][35][36][37][38]. If HiDAC was not part of the initial induction therapy or extramedullary disease present, a HiDAC-containing salvage regimen is often favored.…”