Immune Recovery (IR) Following Allogeneic Stem Cell Transplant (Allo-SCT): A Comparison of Three Different Transplant Strategies at a Single Transplant Center

Introduction: Favorable IR after allo-SCT has been reported after reduced intensity conditioning (RIC); however, T-cell depletion and cord blood (CB) SCT have been associated with delay in IR. The goal of this study is to compare the rates of IR using three different transplant strategies employed at UMass Memorial Medical Center.

Patients & Methods:We retrospectively analyzed data of all patient who underwent allo-SCT at our institution since April 2009 using either RIC with thiotepa/fludarabine/melphalan followed by post-transplant cylophosphamide (TFM/Cy arm), RIC with Fludarabine/Busulfanx2/antithymocyte globulin (FluBu2/ATG arm) or CB transplant with TFM/ATG regimen. IR was assessed by rates of recovery of lymphocyte subsets (CD3, CD4, CD19, CD25+127- and NK-cells) and serum immunoglobulins (Ig’s) at D30, D100 and 1 year post transplant.

Results: 102 patients were identified from the database. 38 patients (37.2%) were included in the TFM/Cy arm, 38 patients (37.2%) in the FluBu2/ATG arm and 26 patients (25.5%) in the CB arm. Median age of all patients was 62.2 years (range 18.4 – 83.5) and 52.4, 67.5, and 63 years in the TFM/Cy, FluBu2/ATG and CB arms, respectively. Median lymphocyte subset counts and Ig levels at different post transplant points are detailed in Table-1. CD3 and CD4 recovery was significantly inferior in the CB arm at D30 and D100. There was a trend towards delayed IR of regulatory T-cells (CD25+127-) in the CB arm at all points. CD19 and NK-cell recovery was superior in the CB arm at all points, but NK-cell recovery did not reach statistical significance at 1 year. Recovery of serum Ig’s was noted to be faster in the FluBu2/ATG arm early on post transplant. At 1-year post allo-SCT, Ig values were comparable in all arms.

Conclusion: Our results show that CB allo-SCT with TFM/ATG conditioning was associated with faster recovery of NK-cells and CD19 cell; however with delayed recovery of T-lymphocyte subsets. Recovery of T-lymphocyte subsets was almost comparable in both arms receiving allo-SCT with RIC regimen regardless of the use of post-tx Cy vs ATG.  FluBu2/ATG regimen was associated with faster recovery of serum Ig’s in the early post-transplant period. 

 

Cells/mm3	All Patients	TFM/Cy	FluBu2/ATG	CB	P value
CD3-  D30           D100           1 year	284 518 669	376 598.5 744.5	277 1159 690	16.5 125 244	<0.0001 <0.0001 0.13
CD4-  D30           D100           1 year	100 175 251	111 189 293	129.5 276 269	4 53 141	<0.0001 <0.0001 0.08
CD19-  D30            D100            1 year	2 41.5 184.5	1 24 204	8 73.5 96	2 273.5 925	<0.0001 0.03 0.01
T-reg   D30            D100            1 year	14 18.5 22	16 20 21.5	10.5 29.1 38	2 5.5 12.5	0.06 0.13 0.14
NK-cells- D30               D100               1 year	136 150 143	29 110 132.5	205 201 148	264 269 166	<0.0001 0.001 0.53
IgA- D30         D100         1 year	59 60.5 58	46 26 51	147 131 45	54 33.5 77.5	<0.0001 <0.0001 0.13
IgG- D30         D100         1 year	593 612 760	534 494 784	763 656 742	548 592 878	0.01 0.45 0.46
IgM-  D30          D100          1 year	29 30.2 52.2	23.1 17.0 42.2	58.6 80.2 53.8	28.1 58.9 81.1	0.01 <0.0001 0.25