Immune Reconstitution In Anti-Thymocyte Globulin Conditioned Unrelated Donor Stem Cell Transplantation

• Published in: Blood 2013-11, Vol.122 (21), p.2071-2071
• Main Authors: Kobulnicky, David Jared, Sabo, Roy T, Scalora, Allison F, Portier, David, Fletcher, Devon, Tessier, Jeffrey M, Clark, William B, Chung, Harold M, McCarty, John M, Roberts, Catherine H, Toor, Amir A
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.2071.2071

Anti-thymocyte globulin (ATG) is widely used for in vivo T cell depletion and immunomodulation in unrelated donor (URD) stem cell transplantation (SCT) to reduce the risk of graft vs. host disease (GVHD). However, despite the reduction in GVHD risk, outcomes are generally not superior to matched related donor (MRD) SCT conditioned without ATG. This is primarily because of defective immune reconstitution and high rates of opportunistic infections in ATG recipients. We have previously reported equivalent outcomes in URD SCT recipients conditioned with ATG when compared to MRD recipients. We now report immune reconstitution in an expanded cohort of these patients. Patients with AML, ALL, MDS, MPD (n=142) transplanted between 2004 and 2011 were included in this retrospective review. Seventy eight received either bone marrow or peripheral blood stem cell (PBSC) grafts from URD and received either 10 or 7.5 mg/kg rabbit ATG (Thymoglobulin, Sanofi-Aventis) during conditioning, those with MRD did not. Conditioning was myeloablative in all patients. Lymphoid recovery was equivalent in the two cohorts during the first year following SCT except in the first month (Figure), when URD recipients had lower absolute lymphocyte count (μ-URD=0.6x103/ μ L, μ-MRD=1.1; repeated measures mixed model p=0.022). Age, CD3/34 cell dose infused, stem cell source and conditioning intensity were not associated with ALC recovery post transplant. In a subset of patients lymphocyte subset enumeration was performed following withdrawal of immunosuppression, at an average 237 days post-SCT. ATG recipients had significantly lower mean CD4+ counts (μ-URD=267 (n=30), μ-MRD =434/ μ L (n=27); ANCOVA p = 0.003), however no significant differences were observed in CD3+, CD8+, CD19+ or CD56+ cell recovery. ATG recipients were significantly more likely to have complete donor T cell chimerism at 1 (OR = 12.5, CI= 2.4, 66.0, p = 0.001) and 2 months post-SCT (OR = 6.5 , CI=1.5, 27.4, p = 0.013), however by 9 months following SCT this trend had reversed with a greater likelihood of mixed T cell chimerism (OR > 100; p = 0.017), suggesting re-emergence of recipient derived T cell clones. Consequently, donor lymphocyte infusions were given significantly more often to ATG recipients (12/78) than to non-recipients (2/64) (OR = 5.64, CI = 1.21, 26.20, p=0.027). High grade CMV viremia (1000 copies/ μL) was significantly more likely in CMV sero-positive ATG recipients (n=18/55) than in non-recipients (n=7/48) (