No impact of high‐dose cytarabine on the outcome of patients transplanted for acute myeloblastic leukaemia in first remission

Abstract

High‐dose cytarabine is currently used in combination with anthracycline in the treatment of acute myeloblastic leukaemia (AML). Moreover, high‐dose cytarabine has been reported to produce long‐term disease‐free survival in a proportion of patients, especially in certain subtypes of AML. However, it remains unknown whether the outcome of patients undergoing allogeneic or autologous stem cell transplantation is influenced by previous treatment with high‐dose cytarabine. To this end, 1672 patients with AML in first remission who were reported to the Acute Leukaemia Working Party registry of the European Group for Blood and Marrow Transplantation (EBMT) and who were transplanted between 1980 and 1995 were analysed according to the dose intensity of cytarabine given at induction and/or consolidation. Autologous stem cell transplantation (ABMT) was performed in 846 patients and allogeneic bone marrow transplantation (BMT) in 826 patients. This study shows that the dose of cytarabine (Ara‐C) given at induction and/or consolidation did not influence the relapse incidence in patients subsequently allografted or autografted. In addition, it did not give any advantage in terms of overall outcome. Therefore, high‐dose (HD) Ara‐C may not be needed for patients who have a planned stem cell transplantation (SCT) as post‐remission therapy. Nevertheless, HD Ara‐C may be utilized in certain subtypes of AML that are believed to be curable by chemotherapy alone.

Improved efficiency of remission induction facilitates autologous BMT harvesting and improves overall survival in adults with AML: 108 patients treated at a single institution

“…It is noteworthy that in our study, age above 50 years did not really impair the results, contrasting with other trials where the rate of CR and the OS declined with age. 18,22,23,28 All these findings are consistent with two recent reports from the EBMT: a first one indicating that very high-dose aracytine given in the period preceding transplant does not improve outcome post transplant, 29 which supports our use of intermediate-dose aracytine; and a second one indicating feasibility and recent outcome improvement following ABMT in patients older than 60 years of age, indeed up to 77 years. 30 In conclusion, we show that a global approach, carefully combining and balancing the reinforcement of induction, semi-intensive consolidation and marrow grafting can bring about a consistent improvement in initial anti-leukemic efficacy while taking into account the need to maintain sufficient hematopoietic reserve to make autografting likely to be feasible.…”

Allogeneic bone marrow transplantation for acute myeloblastic leukaemia in remission: risk factors for long-term morbidity and mortality

“…In two studies, the impact of HiDAC before transplant failed to result in any difference in patient outcome. 37,38 In our study, long-term outcome of patients treated with HiDAC (mostly adults in CR2) was identical to that of those who did not receive HiDAC. In contrast, multiple chemotherapy courses seemed deleterious in our patients, as already suggested by others.…”

Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia

“…To date, studies evaluating the role of post-remission chemotherapy before HCT with myeloablative or reduced intensity conditioning have not shown any improvement in post-transplantation outcomes. [41][42][43][44] Information on MRD at HCT was not available in any of those retrospective studies and it is unknown whether additional post-remission therapy before HCT could benefit a subset of patients who are MRD-positive.…”