TY - JOUR
T1 - Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease
AU - Ngwube, Alexander
AU - Shah, Niketa
AU - Godder, Kamar
AU - Jacobsohn, David
AU - Hulbert, Monica L.
AU - Shenoy, Shalini
N1 - Funding Information:
Conflict-of-interest disclosure: M.L.H. has a spouse employed by Pfizer, Inc.; receives research funding from Global Blood Therapeutics;
Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/8/25
Y1 - 2020/8/25
N2 - We report results of a phase 1 multicenter stem cell transplantation (SCT) trial from HLAmatched (n 5 7) or one-antigen-mismatched (n 5 7) unrelated donors (URD) using bone marrow or cord blood as stem cell source, following reduced-intensity conditioning (RIC) in severe sickle cell disease (SCD). Conditioning included distal alemtuzumab, fludarabine, and melphalan (matched donors), with thiotepa (mismatched donors). Abatacept, a selective inhibitor of T cell costimulation, was added to tacrolimus and methotrexate as graft-versushost disease (GVHD) prophylaxis to offset GVHD risks, and was administered for longer duration in bone marrow recipients than in cord blood recipients because of increased incidence of chronic GVHD with bone marrow. Median age at transplant was 13 years (range, 7-21 years). The incidence of grades II to IV and grades III to IV acute GVHD at day 1100 was 28.6% and 7%, respectively. One-year incidence of chronic GVHD was 57% and mild/limited in all but 1 patient who received abatacept for a longer duration. Only 1 patient developed reversible posterior encephalopathy syndrome and recovered. With a median follow-up of 1.6 years (range, 1-5.5 years), the 2-year overall and disease-free survival was 100% and 92.9%, respectively. The encouraging results from the phase 1 portion of this RIC SCT trial, despite risk factors such as older age, URD, and HLA-mismatch, support further evaluation of URD SCT in clinical trial settings. The phase 2 portion of the trial is in progress. This trial was registered at www.clinicaltrials.gov as NCT03128996.
AB - We report results of a phase 1 multicenter stem cell transplantation (SCT) trial from HLAmatched (n 5 7) or one-antigen-mismatched (n 5 7) unrelated donors (URD) using bone marrow or cord blood as stem cell source, following reduced-intensity conditioning (RIC) in severe sickle cell disease (SCD). Conditioning included distal alemtuzumab, fludarabine, and melphalan (matched donors), with thiotepa (mismatched donors). Abatacept, a selective inhibitor of T cell costimulation, was added to tacrolimus and methotrexate as graft-versushost disease (GVHD) prophylaxis to offset GVHD risks, and was administered for longer duration in bone marrow recipients than in cord blood recipients because of increased incidence of chronic GVHD with bone marrow. Median age at transplant was 13 years (range, 7-21 years). The incidence of grades II to IV and grades III to IV acute GVHD at day 1100 was 28.6% and 7%, respectively. One-year incidence of chronic GVHD was 57% and mild/limited in all but 1 patient who received abatacept for a longer duration. Only 1 patient developed reversible posterior encephalopathy syndrome and recovered. With a median follow-up of 1.6 years (range, 1-5.5 years), the 2-year overall and disease-free survival was 100% and 92.9%, respectively. The encouraging results from the phase 1 portion of this RIC SCT trial, despite risk factors such as older age, URD, and HLA-mismatch, support further evaluation of URD SCT in clinical trial settings. The phase 2 portion of the trial is in progress. This trial was registered at www.clinicaltrials.gov as NCT03128996.
UR - http://www.scopus.com/inward/record.url?scp=85090351259&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2020002236
DO - 10.1182/bloodadvances.2020002236
M3 - Article
C2 - 32813873
AN - SCOPUS:85090351259
SN - 2473-9529
VL - 4
SP - 3894
EP - 3899
JO - Blood Advances
JF - Blood Advances
IS - 16
ER -