Characterization of early lymphocyte recovery after reduced-intensity conditioning and matched-sibling hematopoietic stem cell transplant for sickle cell disease

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NHLBI	CLIN/TRANS-26

Authors

• R.P. Weitzel
• A. Biancotto
• M.M. Hsieh
• J.F. Tisdale

Abstract

Currently, hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients suffering from sickle cell disease (SCD). Our protocol employs a reduced-intensity conditioning regimen including alemtuzimab, 300cGy TBI and immunosuppression with Sirolimus (Rapamycin) after transplant. Flow cytometric analyses reveal dramatically high proportion of T-regulatory (6.3%-32.8%) and T-helper-17 (8.2-21.2%) CD4+ lymphocytes between 60 and 100 days post transplant. As expected, CD38, CD39 and CD103 surface expression on CD4+ and CD8+ lymphocytes was strongly elevated. Notably, CD146 surface expression was particularly high in engrafting patients, despite the normal proportion of lymphocytes identified as effector memory cells based on CCR7 expression. Luminex analysis reveals high expression of IL-17 across multiple timepoints in the successfully engrafting patients. Significant differences in T-regulatory-associated cytokines IL-10 and IL-6 were not observed. Interestingly, expression of both T-helper-1-associated and T-helper-2-associated cytokines in patients who ultimately rejected their grafts were among the lowest of all samples in our analyses. Rejecting patients notably expressed high levels of CCL2 around day 60 post transplant. These observations characterizing lymphocyte subpopulations and cytokines at early timepoints after HSCT provide novel insight into the mechanisms of Sirolimus-based immunosupporession and may assist in predicting outcomes before stable chimerism is observed clinically.

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