Transplant Outcome of Unrelated Hematopoietic Stem Cell Transplantation (HSCT) after Myelo-Ablative or Reduced Intensity Conditioning (RIC) for Chronic Lymphocytic Leukemia(CLL). A Study of EBMT Registry.
Authors: Michallet Mauricette , Prebet Thomas , Le Quoc-Hung , Michallet Anne-Sophie , Van Biezen Anja , Brand Ronald , Dreger Peter , Niederwieser Dietger W. 
Published: April 2020

Place of allogeneic HSCT in the therapeutical strategy of CLL remains still controversial and unrelated allogeneic transplantation has to be better explored. This retrospective analysis concerned 214 patients (164 males and 50 females) who underwent allogeneic HSCT for CLL from unrelated donors (150 males and 64 females) and who were reported on EBMT registry. The median age was 49 years. Fifty two patients received bone marrow (BM) and 162 peripheral blood stem cells (PBSC) from 48 HLA mismatched and 166 HLA matched unrelated donors. Sex mismatch and ABO incompatibility were found in 33% and 52% of cases respectively. On 194 evaluated patients for conditioning, 80 received a myelo-ablative regimen, 114 a reduced intensity conditioning and a Total Boby Irradiation was performed in 70 cases. After transplant, 72 patients (37%) developed an acute GVHD grade II-IV (36% in BM patients and 37% in PBSC patients; 49% in myelo-ablative group and 28% in RIC group). On evaluated patients, a chronic GVHD was present in 61% of the patients (50% in BM patients and 67% in PBSC patients, 66% in myelo-ablative group and 63% in RIC group). With a median follow-up of 20 months, we found no significant difference for 3-year probability of Overall Survival between myelo-ablative group (59%, 46–76) and RIC group (48%, 37–63). No significant difference was observed when comparing BM and PBSC patients whatever the conditioning they received. OS was significantly better in HLA matched compared to HLA mismatched patients in RIC population (51% vs 36%, p=0.01) but not in myelo-ablative population. In multivariate analysis (table 1) studying pre and post transplantation factors, a significant impact of 2 variables, age and aGVHD (grade III-IV vs 0-I), was shown on OS for the global population, myelo-ablative and RIC groups. Other variables influenced also significantly the OS: HLA matching (global and RIC populations), sex matching (myelo-ablative and RIC), TBI (myelo-ablative group). Concerning BM and PBSC groups, we demonstrated the influence of age and aGVHD. In conclusion, besides the known influence of severe aGVHD on survival, this study points out the importance of age and HLA matching in allogeneic unrelated HSCT transplantation setting for CLL. No difference was found regarding conditioning regimen and further studies are needed to determine the most adequate regimen for this disease.

Multivariate analyses Variables OS (HR) p Global population Age 1.04 (1-1.07) 0.05 HLA matching: yes vs no 0.44 (0.22-0.89) 0.02 aGVHD grade III-IV vs 0-I 1.37 (1.1-1.74) 0.01 Myelo-ablative group Age 1.07 (1-1.13) 0.04 Sex Mismatch: F to M vs F to F 6.26 (1.53-25.6) 0.01 TBI: yes vs no 16.3 (3.26-80.2) 0.0006 aGVHD grade III-IV vs 0-I 1.9 (1.18-3.06) 0.008 RIC group Age 1.05 (1-1.1) 0.05 HLA matching: yes vs no 0.28 (0.1-0.76) 0.01 Sex Mismatch M to F vs F to F 0.63 (0.42-0.96) 0.03 aGVHD grade III-IV vs 0-I 1.66 (1.16-2.39) 0.005 BM group Age 1.12 (1-1.24) 0.03 aGVHD grade III-IV vs 0-I 1.88 (1-1.36) 0.05 PBSC group aGVHD grade III-IV vs 0-I 1.38 (1.02-1.86) 0.03