Early Allogeneic Blood Stem Cell Transplantation after Melphalan-Induced Aplasia for Patients with Primary Refractory or Relapsed Acute Myeloid Leukemia - Results of a Retrospective Single Center Analysis
Authors: Schaefer-Eckart Kerstin , Wendelin Knut , Dressler Sabine , Martina Starke , Wilhelm Martin 
Published: November 2019

Abstract
Introduction
Patients (pts) with acute myeloid leukemia (AML) and induction failure or relapse have a dismal prognosis. In 2010 we started to offer an allogeneic transplantation (tx) in aplasia to all eligible patients with an HLA-compatible donor as soon as possible after diagnosis of refractory or relapsed AML. Here we report the results of a retrospective analysis.
Patients and treatment
25 pts (median age 51; 24-71) received an allogeneic tx in aplasia. Diagnoses were primary AML in 20 pts, t-AML in 3 and s-AML in 2 patients. 20 pts were transplanted because of primary refractory AML, in 5 pts the indication was relapsed AML. ELN classification was favorable in 3 (all NPM pos), intermediate-1 in 7, intermediate-2 in 4 and adverse in 11 pts. First induction therapy consisted of daunorubicin and Cytarabin (3+7) in all but one pt. A second induction with high-dose Cytarabin was given in 9/20 pts with induction failure. The search for a stem cell donor was started immediately after results of high-risk cytogenetic, no achievement of bone marrow aplasia on day 14 of induction therapy or in case of induction failure. Four patients had a related 10/10 donor, for 11 patients a 10/10 matched unrelated donor was identified and 10 patients received a transplant from a 9/10 unrelated donor. The interval between diagnosis and tx was 3 (1-4) months (mo) for patients with primary refractory AML as well as relapsed AML. In 21 patients melphalan (100-140 mg/m²) was used to induce an aplasia before starting conditioning therapy. The interval between melphalan and conditioning therapy was 13 (9-21) days. 3 pts started the conditioning therapy while in aplasia after previous chemotherapy. The conditioning therapy was of reduced intensity in all pts. and consisted of Treosulfan (30g/m²)/Fludarabin in 18 pts, TBI(8Gy)/Fludarabin in 5 pts and Busulfan(8m/(kg)/Fludarabin in 2 pts, respectively. Most pts (17/25) had a severe neutropenia below 0,5/nl (med 0,2; 0,1-5,2) before starting melphalan because of refractory leukemia.
Results
After a median follow-up of 31 (10-60) mo 6 pts (24%) are alive without relapse. 5 (20%) pts died because of a relapse after a median of 6 (2-18) mo. The non-relapse mortality was 44% (14/25 pts). Most of these pts (9/19, 47%) died because of infectious complications early after transplantation (med 1; 0-11) mo). Two patients developed pulmonary toxicity and died 1, respectively 19 mo after tx. In 3 pts acute gvhd was the main cause of mortality. The results for patients with 10/10 or 9/10 donors were comparable.
Conclusion
In this retrospective "real-life" analysis we showed that an early allogeneic transplantation is feasible for patients with primary refractory and relapsed AML. A reduced intensity conditioning after induction of aplasia with melphalan offers a chance of long-term relapse-free survival for about a quarter of patients with an otherwise dismal prognosis. NRM is high, especially because of infectious complications early after transplantation, probably related to the long period of severe neutropenia. Therefore, the focus has to be set on early recognition and intervention of infectious complications.

Disclosures
No relevant conflicts of interest to declare.