Haploidentical stem cell transplantation augmented by CD45RA negative lymphocytes provides rapid engraftment and excellent tolerability

DR Shook, BM Triplett, PW Eldridge… - Pediatric blood & …, 2015 - Wiley Online Library
DR Shook, BM Triplett, PW Eldridge, G Kang, A Srinivasan, W Leung
Pediatric blood & cancer, 2015Wiley Online Library
Background Haploidentical donors are being increasingly used for allogeneic hematopoietic
cell transplantation (HCT). However, the requisite T‐cell depletion results in a profound and
often long‐lasting immunocompromised state, and donor lymphocyte infusions bring a risk
of graft‐versus‐host disease (GVHD). Naļve T‐cells are believed to be among the most
alloreactive T‐cell subset and can be identified by CD45RA expression. Allogeneic HCT
using CD45RA depletion has not been previously described for haploidentical donors …
Background
Haploidentical donors are being increasingly used for allogeneic hematopoietic cell transplantation (HCT). However, the requisite T‐cell depletion results in a profound and often long‐lasting immunocompromised state, and donor lymphocyte infusions bring a risk of graft‐versus‐host disease (GVHD). Naļve T‐cells are believed to be among the most alloreactive T‐cell subset and can be identified by CD45RA expression. Allogeneic HCT using CD45RA depletion has not been previously described for haploidentical donors.
Procedure
Eight children with relapsed or refractory solid tumors were transplanted following myeloablative conditioning. Each patient received two cell products, one created by CD3 depletion and the other through CD45RA depletion.
Results
Median CD34 recovery was 59.2% with CD45RA depletion, compared to 82.4% using CD3 depletion. Median CD3+ T‐cell dose after CD45RA reduction was 99.2 × 106 cells/kg, yet depletion of CD3+ CD45RA+ cells exceeded 4.5 log. CD45RA depletion also resulted in substantial depletion of B‐cells (median 2.45 log). All eight patients engrafted within 14 days and rapidly achieved 100% donor chimerism. No acute GVHD or secondary graft failure was observed.
Conclusions
CD45RA depletion is a novel approach to haploidentical HCT that offers rapid engraftment with minimal risk of GVHD. Pediatr Blood Cancer 2015;62:666–673. © 2014 Wiley Periodicals, Inc.
Wiley Online Library