Abstract

Modern extensive treatment of acute myeloid leukemia (AML) consists of three steps: First: induction chemotherapy composed of 3 days of daunorubicin and 7 days of cytarabine (Ara-C), (DA protocol), aimed at achieving a complete hematological remission (CR). Second: two cycles of consolidation chemotherapy aimed at further reduction of leukemic cells. Third: postremission therapy aimed at long-term disease free survival. The postremission therapy includes either maintenance therapy administered for two years or alternatively bone marrow transplantation (BMT), which might be autologous or allogeneic. Although achieving a complete remission is essential to proceed through all phases of AML treatment, the last part (postremission therapy) is in fact critical to accomplish long-term survival. The choice between maintenance therapy, autologous and allogeneic BMT is not straightforward since for a given individual patient advantages and disadvantages of each type of treatment as well as the risk of the leukemia must be taken into account. The probability of leukemia recurrence is the lowest after allogeneic BMT, increases after autologous BMT and is the highest in patients treated only with maintenance therapy. However, treatment related complications increase for each type of therapy conversely to the benefits obtained from the lower probability of leukemia relapse. Here we analyzed the results of AML therapy in 62 patients aged 18-60 (median 46) years treated in the Department of Hematology, Medical University of Gdańsk between 1999-2005. Specifically we were interested what is the role of autologous and allogeneic BMT for the long-term cure. We compared our results to the results of patients treated 15 years ago, when BMT was not accessible at our center. Our patients were treated as a part of a multicenter national trial, which asked if addition of cladribine to the standard induction treatment (DAC protocol) increases the chance of obtaining CR. However the choice of postremission therapy, which is the subject of our analysis, was taken at the discretion of each center. Complete remission after induction therapy was achieved in 78% of patients. Nine (14%) patients died during the induction, whereas 5 failed to achieve CR. The percentage of complete remissions was similar in patients treated with DA and DAC: 80% and 75%, respectively. These results improved almost twice if compared to that obtained 15 years ago. Four patients died during consolidation therapies, one relapsed. Thus 43 patients remaining in CR proceeded to the postremission therapy. The choice of treatment at this stage was based on the type of leukemia (according to the FAB classification) and risk of leukemia based on cytogenetic marrow analysis (if such result was available), quality of chemotherapy response, patient’s age, clinical condition and co-morbidities as well as patient’s decision. Since cytogenetic marrow analysis was not performed in more than 50% of patients decisions which therapy should be chosen were guided mainly by the clinical judgment. Such approach explains the 20-year difference between patients’ age treated with allogeneic BMT and maintenance therapy. In addition to 43 CR patients, one patient without CR received BMT from his brother. His results were analyzed with other allogeneic patients. Altogether fourteen patients received allogeneic BMT from 11 related and 3 unrelated donors (group ALLO), 16 patients autologous BMT (group AUTO), and 14 patients were treated with maintenance therapy (group NON-BMT). Six (42%) patients died in ALLO group (5 from leukemia recurrence and one from transplant related complications), 10 (62%) patients in AUTO group (8 from leukemia recurrence and 2 from transplant related complications) and 6 (43%) patients in NON-BMT group all from leukemia recurrence. Probability of 5-year survival was not statistically significantly different (p=0.7, test log-rank) and equaled 0.48 (95% CI: 0.19–0.79) for ALLO, 0.37 (95% CI 0.14–0.61) for AUTO and 0.49 (95% CI: 0.2–0.78) for NON-BMT group. Overall, the probability of long-term survival for all analyzed patients irrespective of type of postremission therapy was 0.42 (95% CI 0.26–0.52). This result is of great improvement compared to that less than 0,1 obtained when maintenance chemotherapy was the only postremission therapy available. Further improvements in long-term survival can be achieved providing the proper selection of patients for each type of transplant (based on the cytogenetic and molecular risk stratification) is available and the number of transplants particularly from unrelated donors increases.

Adres: dr hab. Jan Maciej Zaucha
e-mail: jzaucha@gumed.edu.pl
Klinika Hematologii AMG