Increasing Efficacy of Autologous Haematopoetic Cell Transplantation in Acute Myeloblastic Leukaemia; a Single Centre Experience in 141 Patients.

According to the EBMT activity survey in 2005 autologous hematopoietic cell transplantation - AHCT was performed in 24.4% out of 3573 AML patients treated with HCT, and a similar proportion of 20,1% is reported by CIBMTR. However, the role of AHCT in AML remains controversial. The recent trials focused on efficacy of AHCT in comparison to allotransplantation or chemotherapy in general demonstrate advantage of AHCT versus chemotherapy in disease free survival (DFS) and prove the feasibility of AHCT even in patients >60 y. The transplant related mortality - TRM is about 5%. The goal of this study was to evaluate the efficacy of AHCT in adult AML and to see weather the quality of the results improved with time. Among over 1700 patients treated in our department with HCT between 1991 and 2007 there were 335 AML patients; 194 allografted (66 from URD) and 141 treated using auto-transplantation. This analysis concerns AML patients treated with AHCT; age 16–61 y (median 38), M/F =73/68, 125 in CR 1 and 16 in CR >1. In 124 cases the conditioning regimen was BuCy 4+2, in 3 with additional AraC and in 14 the CAV protocol. The median numbers of transplanted cells (cryopreserved, unpurged) were following: NC 2,3 (0,4–20) x10e8/kg; CD34+ 2,1 (0,5–13) x 10e6/kg. Results. The median regeneration time of granulocytes up to >0.5 G/l and of platelets to >50 G/l equaled 20 (10–59) and 53 (11–374) days respectively. In CR1 patients at median observation time of 6.5 y the probability of 10 y OS and DFS equalled 47% and 43% respectively and the 100 day TRM was 6.3%. In the CR>1 group the corresponding values were 10%, 17% and 6%. The results obtained with CAV conditioning were distinctly worse if compared to BuCy. The TRM was related to oral Bu + Cy regimen toxicity and subsequent infections. The analysis of AML patients transplanted before and after 2000 y revealed that the proportion of autologous transplantation’s decreased in these time periods from 61% to 29% in favour of allografts. Patients auto-transplanted after 2000 were older with median age 48 y (16–61) versus 29 y (16–58) <0,000001, and were more frequently transplanted with peripheral blood cells than with bone marrow 83% vs. 23% p<0,00001. The results obtained in 57 patients treated using AHCT after 2000 were in spite of older age better if compared to 84 patients auto-grafted earlier; the TRM decreased from 8.3% to 3.5%, whereas the probability of OS improved from 37% (27–47) to 57% (42–71), p = 0,03 and DFS from 33% (23–43) to 49% (35–63), p=0,09. The multivariate analysis revealed two independent factors influencing OS: CR1 versus CR2 status (HR=2,1, p=0,02) and the transplantation period </>2000y (HR=0,6, p=0,04) whereas only CR status influenced the DFS (HR=2,2, p=0,003). Our observation demonstrates that AHCT is an effective and well tolerated option for patients not eligible for allotransplantation because of age, co-morbidity or lack of the donor and the results of this procedure improved in the last decade. Clinical trials evaluating AHCT in subgroups stratified according to the new molecular risk criteria’s, introduction of less toxic conditioning and development of post-transplant treatments preventing from relapses are keys for AHCT to become still more effective treatment.