Treosulfan-Based Myeloablative Conditioning for Autologous Stem Cell Transplantation In Elderly Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome: Data of Feasibility and Efficacy In 10 Patients.
Authors: Bernardi Massimo , Messina Carlo , Tassara Michela , Crotta Alessandro , Giglio Fabio , Assanelli Andrea , Clerici Daniela , Corti Consuelo , Marcatti Magda , Malato Simona , Forno Barbara , Peccatori Jacopo , Ciceri Fabio 
Published: October 2019

Abstract 4596

Background:

consolidation of complete remission (CR) with high-dose chemotherapy and autologous (auto) stem cell transplantation (SCT) can be an alternative option for AML and MDS patients (pts) when allogeneic SCT is not feasible. Elderly pts. are not usually offered a SCT for the high risk of letal toxicities; moreover, their long term survival is less then 10–15% also when a CR after induction chemotherapy has been obtained. New treatment strategies are warranted to improve the outcome of these poor prognosis pts. Treosulfan can induce a myelotoxicity comparable to busulfan, without CNS and mucosal toxicities, known to occur with busulfan. The fludarabine-cytarabine (FLA) association is effective as induction treatment of acute myeloid leukaemia (AML) and myelodisplastic syndrome (MDS). We have combined high-dose treosulfan with FLA in a new conditioning regimen prior to autoSCT for AML and MDS elderly pts.

Aim:

evaluation of preliminary data on toxicity and efficacy of a treosulfan-based conditioning regimen prior to autoSCT in MDS and AML pts.

Methods:

period 7/2006 to 2/2010, 10 pts, median age 68 (60-76). Diagnosis and risk factors: 5 AML with MDS-related changes (1 complex and 4 normal karytotype), 1 AML with minimal differentiation, 1 AMML with hyperleucocytosis (>100.000/microl), 1 AMML with normal karyotype and 1 MDS (RAEB2) with del5q. Chemo cycles before autoSCT: median 2 (range 2–3), at least 1 containing HDara-C (8 gr/sqm total dose). All pts were in CR at autoSCT, 57 days (median, range 44–132) after first CR documentation. Conditioning regimen (FLAT): treosulfan 10 gr/sqm for 3 days, fludarabine 30 mg/sqm for 5 days, cytarabine 2 gr/sqm for 5 days, PEG filgrastim 1 s.c. vial after autoSCT (8 pts). Transplant: PBSC, median 6.2×10e6 CD34+/kg BW (range 3.8–9).

Results:

the overall median toxicity grade (CTC) was 1 (0-3), with hepatic (3 cases) and cardiac (2 cases of reversible atrial fibrillation) involvement. No deaths due to treatment occurred. Grade 4 neutropenia and thrombocytopenia median duration was 12 (range 9–37) and 27 (range 11–71) days, respectively. Grade 4 neutropenia in pts who received PEG filgrastim lasted 10.5 days (range 9–25). Four out of 10 pts did not experience either fever or sepsis. After autoSCT, 5 pts relapsed (4 haematologic, 1 only cytogenetic) and 4 of them died. Six pts are currently alive, 5 in first CR and 1 in second CR (after allogeneic SCT for cytogenetic relapse) 1025 days (median, range 60–1448) after autoSCT. Overall, EFS from autoSCT was 368 days (median, range 60–1448) with a 45% probability of survival at 3 years.

Conclusions:

the FLAT regimen is myeloablative, as demonstrated by the prolonged cytopenia in all pts. It proved to be feasibile anyway, remarkably in these elderly pts. Furthermore, prolonged survival free from disease was achieved. This new regimen is promising for AML/MDS pts as it could be an effective option to intensify the consolidation of their initial CR, with limited extra-hematologic toxicites. A phase II study in pts older than 65 is ongoing at our Center to confirm these data.

Disclosures:

No relevant conflicts of interest to declare.