Use of RIC-Allosct In Patients Younger Than 45 Years Old Affected by MDS and Leukemia: A Monocenter Retrospective Analysis.
Authors: Crocchiolo Roberto , Castagna Luca , Furst Sabine , Cheikh Jean El , Faucher Catherine , Devilliers Raynier , Vazquez Alberto , Belmecheri Nawel , Granata Angela , D'Incan Evelyne , Vey Norbert , Blaise Didier 
Published: October 2019

Abstract
Abstract 1316

Introduction:
reduced-intensity conditioning (RIC) for allogeneic hematopoietic stem cell transplantation (AlloSCT) are usually used in non-fit or elderly patients (pts) as alternative to myeloablative conditoning (MAC). As a consequence, most of these pts are ’ 45 years old, since pts ≤ 45 years old are likely to receive a MAC. Here we analyse our cohort of younger pts (i.e. ≤ 45 years old) who received a RIC for a hematological malignancy, in order to evaluate transplant outcome.

Patients and Method:
data on pts ≤ 45 years old who received AlloSCT after a RIC conditioning between Jan 2000 and Jan 2010 were collected. Only diagnoses of acute leukemia (both AML and ALL), MDS, CML or other myeloproliferative syndromes were retained. Outcomes were analyzed with Kaplan-Meier and cumulative incidence methods, log-rank was used to compare groups. Patients were classified according to the reason of RIC. Disease status at AlloSCT, cytogenetics and molecular markers at diagnosis, use of busulphan during conditioning regimen were also evaluated for final outcome. Sorror score were included when available.

Results:
a total of 45 pts were identified; median age at transplant was 40 (18-45), median follow-up was 757 days (449-3236). Main characteristics are shown in table 1[DB1]. OS, PFS, NRM and relapse incidence of the entire cohort were 56%, 48%, 10% and 43% respectively. Grade 2–4 aGvHD occurred in 10 patients (25%) while severe, grade 3–4 aGvHD occurred in only two pts (5%). Nineteen pts (47%) developed cGvHD, of whom 13 (32%) an extensive form. When considering disease status at AlloSCT, a difference in 2-year OS, PFS and NRM was observed between pts with acute leukemia in CR1 or CR2 (“early disease”) vs. others: 64% vs. 46% (p=0.07), 61% vs. 36% (p=0.06) and 4% vs. 20% (p=0.06) respectively. We observed a strong impact of cytogenetics on OS among pts with early disease (n=23), with survival rates 71% vs. 17% and relapse 29% vs. 67% for favourable[DB2] cytogenetics/normal caryotype (FN) and unfavourable group (U) (see table 1) pts respectively (p=0.06 and p=0.12). Interestingly, no toxic deaths were observed among the 17 patients with early disease, FN pts. The use of busulfan (N=32) during conditioning appeared to confer superior disease control as compared with other conditioning regimens (relapse incidence: 32% vs. 67% and 27% vs. 69% in early and advanced disease group respectively[DB3], p=0.15 and p=0.13) without affecting NRM that was similar in both group. Due to availability of molecular markers in only 22 (49%) pts, analysis was not possible. Sorror score and reason for RIC were not predictive of final outcome, with exception of pts undergoing second AlloSCT who had inferior OS compared with all others: 15% vs. 50%, p=0.07.

Conclusions:
present results confirm a low incidence of aGvHD and NRM among pts undergoing RIC-AlloSCT, despite of a relatively high relapse risk. Disease status at AlloSCT and cytogenetics at diagnosis were the main factors affecting outcome, while no impact of comorbidity score or therapy/infectious complications before AlloSCT was observed. Although our data show a very high relapse incidence, notably in pts with unfavorable cytogenetics, it should be noted that the use of busulfan in the conditioning regimen represented a factor of disease control; therefore it could represents a valid approach for those pts with early disease status at AlloSCT and favourable cytogenetics [DB4] or normal caryotype at diagnosis, with 71% OS and 0% NRM in our series. Further approaches, tuning the dose of busulfan doses on disease control, are warranted and ongoing in our program.

Disclosures:
Off Label Use: Zevalin is off-label use in conditioning regimen in France.