Comparison of Immune Reconstitution after Umbilical Cord Blood (UCB) and Allogenic Peripheral Blood Stem Cell (APBSC) Transplantation in Patients with Advanced Multiple Myeloma (MM) and Acute Myeloid Leukemia (AML).
Authors: Meniane Jean-Come , Ceballos Patrice , Condomines Maud , Eliaou Jean-françois , Fegueux Nathalie , Klein Bernard , Rossi Jean-françois 
Published: October 2019

Abstract
Background. T-cell reconstitution is usually delayed after UCB transplantation, in addition to an impaired thymopoiesis and late memory T cell skewing. NK cells are usually variable, with an initial increase in % and absolute number. The role of these cells is unclear, particularly on tumor control, maybe participating to the T-cell lymphopenia. Patients and methods. F rom 01/03 to 04/07, we retrospectively analysed data concerning lymphocyte recovery for patients having MM and AML, who received allogenic transplantation (AT). We excluded patients with progressive disease before AT, with short follow-up (<120days) and without dominant donor chimerism. 43 patients (MM, n=19; AML, n=24) were included, and they received UCBT (n=13: MM=7 and AML=6; single: n=2 or double: n=11), all with reduced intensity conditioning (RIC) regimen adapted from the Minneapolis protocol, or APBSC (n=30) [RIC (n=23; MM=12 and AML=11), including ATG (n=12/23; AML=10/11) or myelo-ablative conditioning (MAC: n=7, all having AML,]. Immune reconstitution in PB was followed, including CD3+, CD4+, CD8+, CD3−/CD56+, and CD19+ cells, monthly. Prophylaxis of GVHD included cyclosporin A from d-3 to months +3 or +6, according to clinical manifestations of GVHD, and mycophenolate mofetil from d-3 to d+28 after RIC regimen and standard prophylaxis with cyclosporine and short course methotrexate after MAC regimen. Anti-infectious prophylaxis and follow-up were standard. Results. Median age was comparable between groups (MM: DUCB (57y, 42–61), PBSC (55y, 50–68); AML: DUCB (45y, 30–63), PBSC (53y, 21–64). Sex ratio (F/M) was 6/13 for MM, and 11/13 for AML. In the group MM/UCB, NK cells was above 80/mm3 from D-7 to 1 year and peaked at D260 (median=193/mm3), with no statistical difference with the MM/PBSC group (64 at D-7 to 132/mm3). NK cells were significantly higher (p=0.04) for AML/UBC group (from D90: 187/mm3) to D260: 328/mm3), in comparison to AML/PBSC (from 116 to 138/mm3). For CD4 T-lymphocytes, there was a significant difference between MM/UCB and MM/PBSC during the first 3 months [39 to 75/mm3 vs 152 to 175/mm3, p=0.01]. A more rapid recovery of CD4+ was observed in AML/UBC (from 227 to 829/mm3, D90 to 1y), 2-fold higher than in the AML/PBSC at any time. Those differences could be explained by the high-dose therapy given to patients with MM. In addition, patients who received ATG (all AML/PBSC/RIC) had a delayed CD4 recovery. CD8-cell recovery was delayed for UBC groups with a CD8 cell count >200 starting at D230 as compared to the PBSC group (D150 for MM and D90 for AML). B cell recovery was faster in the UCB group [MM/UCB and AML/UCB, >200/mm3 at D230 and D150 as compared to D300 and D230 respectively in MM/PBSC and AML/PBSC (p=NS)]. Conclusion. NK cells increased after UBC more intensively and rapidly than after PBSC AT. T-cell recovery appeared to be associated to pre-treatment intensity and use of ATG. CD4, CD8 counts were highly reduced in UCB compared to PBSC except for CD4+ in AML/UCB. B-cell recovery is not different between both groups (i.e. UCB and PBSC). NK cells from 2 patients are now collected for analysis of their functions particularly their anti-tumoral effect in vitro.