The Use of Purine Analogues During Induction and Consolidation Therapy of Acute Myeloid Leukemia Does Not Increase the Need for More Frequent Transfusions of Red Blood Cell Concentrates, Platelet Concentrates and Fresh Frozen Plasma
Authors: Seweryn Marek , Kata Dariusz , Kyrcz-Krzemien Slawomira 
Published: October 2019

Abstract
Abstract 4358

Background
Addition of purine analogues to standard induction therapy of acute myeloid leukemia (AML) had previously been demonstrated to increase complete remission rate and does not aggravate infectious complications. The aim of this study was to analyze whether the use of cladribine or fludarabine during induction and consolidation treatment increase the need for more frequent transfusions of red blood cell concentrates, platelet concentrates and fresh frozen plasma.

Material and methods
118 AML patients, included in two consecutive randomized trials between 1999–2006 in a single centre were analyzed. Induction therapy consisted of daunorubicin + cytarabine (DA-7, n=53) alone or in combination with cladribine or fludarabine (DAC-7 + DAF-7, n=65). Consolidation included one course of high-dose AraC + mitoxantrone and one course of high-dose AraC +/− purine analogues. A median age was 45(17-58) years and 48(20-60) years for patients treated with and without purine analogues, respectively.

Results
During induction treatment 7 (1-19) units of red blood cell concentrates (median and range) was transfused in the group with purine analogues compared to 6 (1-23) in the group without purine analogues, p=0,24. Number of transfused platelet concentrates bags was 6 (1-30) in the group of purine analogues and 7 (0-19) in the group without purine analogues, p = 0.49. In the group with purine analogues 0 (0-31) units of fresh frozen plasma was transfused compared to 0 (0-26) in the group without purine analogues, p = 0.91.
During HAM consolidation therapy 3 (0-11) units of red blood cell concentrates was transfused in the group with purine analogues compared to 2 (0-9) in the group without purine analogues, p = 0.15. Number of transfused platelet concentrates bags in the group with purine analogues was 2 (0-8) vs. 2 (0-12) in the group without purine analogues, p = 0.25. In the course of HAM consolidation treatment - 0 (0-56) units of fresh frozen plasma was transfused in the group with purine analogues compared to 0 (0-0) in the group without purine analogues, p = 0.027.
During HD Ara-C consolidation therapy 3 (0-7) units of red blood cell concentrates was transfused in the group with purine analogues compared to 2 (0-5) in the group without purine analogues, p = 0.03. Number of transfused platelet concentrates bags in the group treated with purine analogues was 3 (1-12) vs. 3 (1-6) in the group without purine analogues, p = 0.61. In the course of HD Ara-C consolidation treatment 0 (0-9) units of fresh frozen plasma was transfused in the group with purine analogues compared to 0 (0-11) in the group without purine analogues, p=0,34.

Conclusions
The vast majority of the obtained results did not reveal any significant differences between the group of AML patients treated with or without purine analogues.
During HAM consolidation treatment statistical significance for more fresh frozen plasma units transfused was shown in the patients treated with purine analogues, although the median value was the same in both groups (0). This situation was random and independent of prior use of purine analogues in the induction therapy, because in one of the woman-patient gynecological complications and DIC occurred (bleeding from uterine fibroids). This situation required intensive supportive therapy including fresh frozen plasma transfusions. In one case 56 units of fresh frozen plasma was transfused and in second arm of the study was not applied a plasma transfusions in any patient.
Also during second (HD Ara-C) consolidation treatment number of transfused units of RBC's concentrates was significant higher in the group of patients treated with purine analogues, although the median values were similar (3 vs 2). These differences may arise from the fact that in some patients - especially in group of patients treated with purine analogues who obtained the better results of therapy – second HD Ara-C treatment was also more often followed by mobilization and collection of stem cells from peripheral blood for transplantation. In the procedure of stem cells collection a higher hematocrit value is recommended – so frequent decision for RBC's transfusions was made in this group of patients.
We conclude that the use of purine analogues in the treatment of AML patients does not increase the need for more frequent transfusions of red blood cell concentrates, platelet concentrates and fresh frozen plasma.

Disclosures:
No relevant conflicts of interest to declare.