OUTCOME of Allogeneic Hematopoietic CELL TRANSPLANTATION for AML: A Single CENTER Retrospective ANALYSIS.
Authors: Sakellari Ioanna , Apostolou Chrisa , Mallouri Despina , Athanasiadou Anastasia , Batsis Ioannis , Smias Christos , Yannaki Evangelia , Lalayanni Chrisavgi , Syrigou Antonia , Stavrogianni Niki , Vadikolia Chrisanthi , Saloum Riant , Fassas Athanasios , Anagnostopoulos Achilles 
Published: October 2019

Abstract
Abstract 4567

Background:
Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for patients (pts) suffering of AML with high risk features at diagnosis and beyond 1st complete remission (CR1) it remains the sole rescue treatment. In this retrospective study we analysed the data of all pts (149) allografted concecutively in our BMT unit for AML from 1991 to 2009. The aim of the study was to estimate the outcome in terms of overall survival (OS), disease free survival (DFS), relapse rate (RR) and non relapse mortality (NRM). Sixty-three pts of a median age 35 (8-63) years suffered from de novo (58), secondary (4) and biphenotypic AML (1) were transplanted in CR1. Cytogenetic analysis was available in 40/63 pts (intermediate 32, poor risk 8). Donors were siblings in 55, relative (1 antigen mismatch) in 3, unrelated (4 mismatched with 1–2 alleles) in 8 pts. Graft source was bone marrow (BM) in 12 and peripheral blood (PB) in 51 pts. Fifty-six received a myeloablative (MA) and 7 non- myeloablative (NMA) conditioning regimen. Eighty-six pts were allografted beyond CR1. Disease status was primary refractory (Prim. Ref) in 42/86, CR2 in 15, 1st refractory after re-induction relapse (Rel1) in 23 and advanced (CR3; Rel2+) in 6 pts. Three pts were retransplanted from the original donor for relapsed disease after alloHCT. In the cohort of pts with disease beyond CR1, cytogenetic analysis was available in 71 (favourable 4, intermediate 53, poor risk 14). Donors were siblings in 58, syngeneic (1 antigen mismatch) in 8, unrelated (3 with mismatch) in 17, unrelated double cord blood (CB) in 1, haploidentical in 5 pts. The majority of the pts received mobilized PB (72) as graft source and myeloablative conditioning regimen (82).

Results:
For pts transplanted in CR1 OS was 63%, NRM 23%, DFS 60% and RR 21% at 13 years. Seventeen pts transplanted before 2000 had an estimated OS and DFS 59%, RR 9% and NRM 35% whereas for forty-six pts transplanted after 1999 the OS was 64%, DFS 61%, NRM 17% and RR 25% at 9 years. DFS for pts in CR1 with an unrelated donor was 47% and 62% for siblings. Myeloablative regimen resulted in 65% DFS while NMA in lower DFS (21%) due to higher RR. According to cytogenetics OS and DFS were 62% and 64% for the intermediate risk group (n=32), 44% and 45% for the poor risk (n=8) respectively. For the cohort of pts transplanted for Prim. Ref. disease (n=42) OS was 20% (plateau at 3 years), DFS 17% (plateau at 2 years), RR 78% and NRM 34% at 12 years. Despite the small number of pts with poor risk karyotype (n=7) the prognosis seemed to be dismal (DFS and OS 0%) versus 25% and 31% respectively for the intermediate risk group (n=28). For pts transplanted in CR2 (n=15) OS was 51% and DFS 46% (plateau at 1year), RR 43% and NRM 16%. For pts in REL1 (n=23) OS was 15%, NRM 56%, DFS 4% and RR 86%. For the 6 pts transplanted for advanced disease (CR3; REL2+) OS was 17%, DFS 17%, RR 67% and NRM 50%. The 5 pts undergone haploidentical alloHCT (2 Prim. Ref., 2 CR2, 1 CR3) after TBI 8/thiotepa/fludara/ATG had OS and DFS 40% at 8 years. One of 3 pts retransplanted is alive in CR and the rest succumbed to their disease.

Discussion:
In 2010 when the use of alternative transplantation has been expanted the selection of pts upon the best stratification and the timing of the transplantation still remain open questions. The majority of patients are classified in the intermediate risk group with normal karyotype. According to our experience during the last two decades alloHCT for AML in early disease phase (CR1) can offer the best results and possibly cure in a significant number of patients (60%). Transplantation procedures have been continuously improved over time leading to improvement of the outcome mostly in the era of alternative donor alloHCT. For poor risk pts in CR1 and for all pts with AML beyond CR1 (apart from acute promyelocytic leukemia in molecular remission) alloHCT remains the only treatment option. In this cohort of pts results from our data indicate that pts in CR2 may attain long term survival after alloHCT (OS 51%, NRM 16%). Among pts refractory to induction and salvage treatment therapies (> CR2, Prim Ref., REL) a small proportion of pts (15-20%) may be rescued by alloHCT.

Disclosures:
No relevant conflicts of interest to declare.