Faster Registration on International Donor Registries and Shorter Time to Allogeneic Hematopoietic Stem Cell Transplantation After Having Found a Donor Confers Better Outcome In Acute Leukemia Patients
Authors: Michallet Mauricette , Sobh Mohamad , Morisset Stephane , Thomas Xavier , Chelghoum Youcef , Labussiere Helene , Nicolini Franck E , Ducastelle Sophie , Barraco Fiorenza , Tedone Nathalie , Fatoum Jihane , Detrait Marie , Rey Sylvie , Dubois Valerie 
Published: October 2019

Abstract
Abstract 2371

Background:
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) appears to offer a potential advantage in terms of event free survival (EFS) and overall survival (OS) in patients with acute leukemia (AL) with bad prognostic factors. The main issue is to find a donor; usually, a patient has 30% chance to find an HLA identical sibling donor (SD) and approximately 40% chance to find a suitable unrelated donor (UD) from international registries. Unfortunately, 40% of registered patients relapse or die before finding a donor.

Aim:
Our objective was to evaluate the outcome (OS & EFS) in AL patients, whether they had an HLA identical SD, an UD or no donor (ND) after registration on France Greffe de Moelle (FGM) registry, either transplanted later or not. Our secondary objective was to evaluate the impact of interval between, diagnosis and allo-HSCT, donor finding and allo-HSCT, interval registration-allo-HSCT, on OS and EFS.

Methods:
We have analyzed 251 AL patients diagnosed between January 2000 and December 2008, for whom a search for a donor was initiated for a required allo-HSCT. There were 117 (47%) males and 134 females with a median age at diagnosis of 40 years [16-66], 177 (71%) were AML (prognosis according to cytogenetics & molecular markers: 59 were good, 97 poor and 21 not done) 75 were ALL (prognosis according to cytogenetics & molecular markers: 33 were good, 16 poor and 26 not done). Seventy six (30%) patients had an available SD and received allo-HSCT within a median time of 3.5 months (0.5 – 43) (59 AML & 17 ALL), and 38 (15%) with SD but were not transplanted due to early relapse and/or death. For patients with no available SD, a registration on FGM registry was done. One hundred thirty seven patients were registered after a median interval of 2.3 months (0.4-135) from diagnosis, 33 (13%) patients (24 AML & 9 ALL) did not find any donor, have not been transplanted and they received the standard of care. One hundred and four (41%) patients (62 AML & 42ALL) found an UD or cord blood cell (CBC) unit after a median registration time of 1.6 months (0.3 – 26): 86 with UD of which only 60 have been transplanted within a median time of 2.3 months (0.4 – 14), 18 with CBU of which only 17 were transplanted. Among transplanted patients, 113 (74%) were in complete response (CR) at transplantation, and 40 were in less than CR. Fifty (33%) received peripheral blood (PBSC) (23 UD & 27 SD), 86 (57%) received bone marrow (BM) (37 UD & 49 SD) and 17 (10%) CBC units. For conditioning, 56 (37%) were reduced intensity (29 SD & 27 UD) and 96 standard (47SD & 50 UD). For HLA, there were 45 HLA 10/10, (27BM & 18 PBSC), 14 HLA 9/10 (9BM 5PBSC) 1 HLA 8/10 (BM) and for CBC 14 HLA 4/6 and 3 HLA 5/6.

Results:
After a median follow-up of 25 months (0.2- 234), the median OS was 78 months (51 – 133) for transplanted patients with SD (3years OS: 68%), it was 33 months (27 – 47) for transplanted patients with UD (3years OS: 44%), 21 months (15 – 37) for not transplanted patients with available SD or UD (3years OS: 34%) and finally it was 31 months (23-221) for patients with ND (3years OS: 45%). The median EFS for the same groups was 38 months (23 – 133), 24 months (17 – 36), 15 months (11-24) and 23 months (14 – 48) respectively. The only factors negatively affecting OS in multivariate analysis (studying age, sex, AL type, cytogenetics, donor or no donor, transplanted or not, UD or SD) were age and allo-transplanted from UD. When adjusting only on transplanted patients, taking into account in addition to previous factors, the time between diagnosis-registration, time between registration-allo-HSCT, disease status at allo-HSCT, stem cell source, conditioning; three significant factors affected OS: disease status (<CR) HR= 2.8 [1.5-5.3] p<0.001; long interval between diagnosis-registration HR= 2 [1.2-3.6] p=0.001 and conditioning (standard) HR=0.27 [0.1-0.8] p=0.02. (3years OS for SD allo-HSCT, UD allo-HSCT late and early registration: 59%, 29% and 47% respectively).

Conclusion:
The results of our first analysis seemed surprising regarding our knowledge of outcome in allo-HSCT from SD and UD, which led us to investigate on unusual interfering factors. We have explored the relation between the interval diagnosis-registration for a donor search and the interval registration-allo-HSCT that appeared as major factors affecting survival in UD allo-HSCT settings.

Disclosures:
No relevant conflicts of interest to declare.