Impact of Hematopoietic Stem Cell (HSC) Recruitment and Graft Composition on Transplant Outcome after Reduced Intensity Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT): A Study of the Société Française de Greffe de Moelle Osseuse et de Thérapie Cellulaire (SFGM-TC) Registry.
Authors: Prebet Thomas , Le Quoc-Hung , Boiron Jean-Michel , Blaise Didier , Huynh Anne , Yakoub-Agha Ibrahim , Esperou Hélène , Garban Fréderic , Bourhis Jean Henri , Michallet Mauricette 
Published: April 2020

Abstract
Evidence of an impact of graft product on transplant outcome after PBSCT is actually rising. Here, we investigated retrospectively the potential impact of HSC recruitment procedure (i.e. G-CSF stimulation schedule and apheresis number) and graft composition (CD34+ and CD3+ cell number) on transplant outcome (GVHD, OS, EFS). Our analysis concerned 488 HLA matched sibling allogeneic reduced intensity conditioning (RIC) PBSCT for hematological malignancies (116 MM, 110 AML, 109 NHL, 41 CLL, 41 MDS, 24 CML, 19 HD, 17 ALL and 11 MPS) reported on the SFGM-TC registry between 1998 and 2004. Follow-up was updated in April 2005. RIC-PBSCT was performed during first line treatment in 225 (49%) patients and a previous HSCT was recorded in 55% of the cases. Before RICT, 161 patients were in Complete Response, 161 in Partial Response, 34 in Stable Disease and 132 in Progressive Disease. Regarding donors, median age was 49 years, sex mismatching and ABO incompatibility were seen in 222 and 162 patients respectively. CMV status was positive either in donor or recipient in 152 cases. G-CSF median duration was 5 days (3–7days) at a median dose of 10μg/kg/day (4.6–16). G-CSF was given bid in 40% of the stimulations. Filgrastim was used in 59% of the donors and Lenograstim in 41% of the donors. A single apheresis was performed in 107 donors, 2 in 298 donors, more than 2 in 93 donors. The median number of CD34+ cells infused was 5.6x106 CD34+/kg (1–26) and the median CD3+ cells was 302x106 CD3+/kg (63–996). Conditioning regimen was most frequently an association of Fludarabine Busulfan and Anti Thymocyte Globuline (246 cases, duration of ATG 1 day: 18%, 2 days: 20%, 3 days: 20%, 4 days: 8% 5 days: 33%) or Fludarabine + TBI 2 Gy (123 patients). GVHD prophylaxis was a cyclosporine based treatment in 478 patients [95% of the cases (+ Methotrexate: 29%, + Mycophenolate Mofetil: 26%)]. Median follow-up after transplantation was 35 months (range: 0–86). Acute GVHD (grade II-IV) and cGVHD incidences were 35% (n=163 on 488 patients) and 50% (n=217 on 430 patients) respectively. The 3-year OS was 40% and the 3-year EFS was 34%. Treatment related mortality was 12% at 1 year and 15% at 3 years. In multivariate analysis studying pre and post transplant factors, a significant impact was shown of G-CSF duration (HR: 0.79 (0.62–1) p=0,05), G-CSF daily dose (HR: 1.13 (1–1.28) p=0,04) on OS. Other variables also influenced OS (NHL vs AML, aGVHD grade II vs 0-I and III-IV vs 0-I and cGVHD: yes vs no) and EFS (Sex mismatch, ABO incompatibility, NHL vs AML, FBS ATG duration: 5 days vs 2 days, aGVHD grade II vs 0-I and III-IV vs 0-I and cGVHD: yes vs no). No influence of graft composition or stem cell recruitment was demonstrated on aGVHD and cGVHD incidences although we found a significant impact of conditioning (FBS ATG 1 day vs 2days and 5days vs 2days). In conclusion, this study demonstrates that, surprisingly, graft composition has no impact on transplant outcome. Prolonged administration of moderate dose of G-CSF seems to be the best schedule for PBSC recruitment.