Addition of Purine Analogues to Induction/Consolidation Regimen Does Not Impair Peripheral Blood Stem Cell Mobilization and Bone Marrow Harvest for Autotransplantation in Acute Myeloid Leukemia.

Abstract

In the previous study by the Polish Adult Leukemia Group (PALG 1999 Study) we demonstrated that addition of cladribine to standard daunorubicine + cytarabine (DA-7) induction potentiates antileukemic activity of the regimen in acute myeloid leukemia (AML). However, there is a concern that the treatment with purine analogues may affect a successful collection of hematopoietic cells for transplantation (autoHCT).The goal of this study was to compare the efficacy of peripheral blood and bone marrow hematopoietic CD34+ cell harvest in patients who both in induction and consolidation were treated with or without purine analogues and who were intended for autoHCT.Sixty-seven AML patients, aged 41 (17–58) years, were included in this study; 33 patients received cladribine-containing regimen (DAC-7), one patient - fludarabine-containing regimen (DAF-7), 33 patients received standard treatment (DA-7, HAM, HD cytarabine). In the DAC-7 treated patients cladribine was also given as a adjunct to second HD cytarabine consolidation. AutoHCT using bone marrow (autoBMT) or peripheral blood (autoBCT) as a source of hematopoietic cells was performed in first complete remission after completion of consolidation therapy. An additional course of AraC 2x2g/m2 on days 1, 3, 5 + G-CSF 10 mg/kg since day 7 was used as mobilization in case of autoBCT.The number of collected CD34+cells/kg was similar for patients pre-traeted with purine analogues and those not receiving purine analogues: 2.55 (0,79-9,25) x106/kg vs 2.5 (1,41–23,5) x106/kg (p=NS) for peripheral blood and 1.62 (0,32–3,01) x106/kg vs 1.55 (0,5–2,45) x106/kg (p=NS) for bone marrow, respectively. In 90% and 95% of patients for both subgroups sufficient number of hematopoietic cells for transplantation could not be collected (p=NS). The proportion of unsuccessful bone marrow harvest was significantly lower for patients pre-treated purine analogues with purine analogues compared to those not receiving purine analogues (90% vs 56%, p=0,04), wheras not difference was found with respect to peripheral blood cell collection (95% vs 62%, p=NS). All patients who received autoHCT engrafted. The time to neutrophil and platelet recovery was similar for both study subgroups.We conclude that treatment with purine analogues in course of induction/consolidation therapy does not impair the hematopoietic cell harvest and does not decrease a chance to perform autoBCT or autoBMT in AML patients.