A Prospective Study on the Feasibility of Related and Unrelated Donor Search and Hematopoietic Cell Transplantation for Adults with Acute Leukemia at 31 European Transplant Centers
Authors: Rocha Vanderson , Arat Mutlu , Koza Vladimir , Gorin Norbet C , Ferrant Augustin , Schäfer-Eckart Kerstin , Ebeling Freja , Milone Giuseppe , de Fabritiis Paolo , Verdonck Leo , Bosi Alberto , Esteve Jordi , Allione Bernardino , Maertens Johan , Olivieri Attilio , Pilatrino Chiara , Herr-Bellon Andree-Laure , Pinto Fernando , Arrais Celso , Nabhan Samir , Socié Gerard , Dini Giorgio , Gluckman Eliane , Polge Emmanuelle , Labopin Myriam 
Published: April 2020

Abstract
Currently, a donor can be virtually found for all patients with an indication for allo-transplantation due to the increased number of hematopoietic stem cell (HSC) donors and increasing use of umbilical cord blood and haplo-transplants. In this study, we have addressed the question of the feasibility of searching HSC donors grafts [HLA-matched sibling donor (MSD), and alternative donors] and performing such transplants or other treatments (such as autologous HSC transplant or chemotherapy) for adults with acute leukemia for whom an indication of allo-HSCT could be planned during the course of their disease. The second objective was to compare in an “intent to treat” analysis, LFS according to planned strategy treatment. Patients were included at HLA typing test. A specific questionnaire was completed specifying the initial strategies planned for each patient and their changes over the period: at HLA typing, after 3, 6, 9, 12 months after the registration, and twice a year for the following 2 years. From 2003 to 2006, 702 adults were enrolled by 31 EBMT centres, 490 had AML, 212 ALL. HLA typing was performed for 443 patients at diagnosis, 172 after first CR, 11 after CR2, and 64 in more advanced phase. Median follow-up was 31 months, median age was 42-years (18–75); 207 patients were aged more than 50 years. A MSD was found for 309 patients (44%). Of 309 patients, 290 patients had 1 MSD, 17 patients 2 MSD and only 2 patients more than 2 donors. In 40 cases where the MDS was found the transplant centres did not planned to perform the transplant. A transplant using a haploidentical donor was planned in 4 cases. At the end, 273 patients were planned to be transplanted from a family donor (269 from a MSD and 4 from an haplo). For the remaining 429 patients, the indication of an auto-HCT was made in 85 (20%) patients, use of chemotherapy as post-remission therapy in 142 (33%) and indication of an allo-HSCT with an alternative donor in 202 (47%). Of those 202 patients, the transplant centres were keen to search for a cord blood donor in 72 cases and for a haplo donor in 11 cases. Analysing the treatment received at the last follow-up and comparing with the strategy planned at the registration, 215 of 270 (80%) patients were transplanted with a family donor, 112 of 142 (79%) patients were still receiving chemotherapy, 53 of 85 (62%) received an autograft and 118 of 202 (58%) received an unrelated transplant. At last follow-up, 448 patients of 702 patients included received an HSCT (64%). Probability of survival at 2 years for 702 patients was 55%. Interval from HLA typing and HSCT was 125 days for MSD, 148 days for unrelated donor, 167 days for unrelated cord blood and 149 days for autologous transplantation. Cumulative incidence function at one year (CIF; using death as a competing event) for receiving an allograft was 81% if the strategy planned was an allograft with a MSD, 57% for those patients for whom an alternative donor was searched and 6% for those patients for whom an allo-transplant was not planed at inclusion. However, CIF at 1-year for really receiving an allograft was 74% in case of MSD, and only 30% for those patients not having an HLA identical siblingAt 2-years, LFS by initial planned strategy at HLA typing was 43% for those patients in whom a donor search was planned, 47% for those with a planned autologous HSCT, 46% for those with planned chemotherapy and 49% for those with a family transplant. In conclusion, the majority of patients (80%) with AL in European centres are HLA typed at diagnosis or CR1. The majority of patients received a MSD as planned treatment in the first year after HLA typing, in the absence of MSD an alternative donor was searched only for 51% of patients and CIF at one year for performing an allotransplant was 30% however in case of searching for alternative donor, transplantation could be performed in 57% of the cases in the first year. Surprisingly, searching for other alternative donors such as unrelated cord blood or haplo-identical donors, was only done for a small proportion of patients, in spite of encouraging results with both strategies. Therefore, in retrospective studies comparing outcomes of HLA identical sibling, and other alternative donor transplants there is a potential bias linked to the decision to search or not in half of the cases, that is probably linked to patients-, disease- and centre-related factors.