TY - JOUR
T1 - Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide Plus Thiotepa Improves Donor Engraftment in Patients with Sickle Cell Anemia
T2 - Results of an International Learning Collaborative
AU - de la Fuente, Josu
AU - Dhedin, Nathalie
AU - Koyama, Tatsuki
AU - Bernaudin, Francoise
AU - Kuentz, Mathieu
AU - Karnik, Leena
AU - Socié, Gérard
AU - Culos, Kathryn A.
AU - Brodsky, Robert A.
AU - DeBaun, Michael R.
AU - Kassim, Adetola A.
N1 - Funding Information:
Financial disclosure: The work was supported by an intramural grant from the Department of Hematology/Stem Cell Transplantation, Vanderbilt University Medical Center. Our group is supported by several grants from the Hospital Clinical Research Program of the French National Cancer Institute (to M.M.).
Funding Information:
Financial disclosure: The work was supported by an intramural grant from the Department of Hematology/Stem Cell Transplantation, Vanderbilt University Medical Center. Our group is supported by several grants from the Hospital Clinical Research Program of the French National Cancer Institute (to M.M.). Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: R.A.B. MRD, A.A.K. J.D. F.B., M.K. and N.D. designed the study, analyzed data, and wrote the manuscript. L.K. and S.G. analyzed data, and reviewed the manuscript. T.K. provided statistical input and reviewed the manuscript. Phillips Family Foundation provided support for MRD. Financial disclosure: See Acknowledgments on page 1208.
Publisher Copyright:
© 2018 American Society for Blood and Marrow Transplantation
PY - 2019/6
Y1 - 2019/6
N2 - Curative therapy for individuals with severe sickle cell disease (SCD) who lack an HLA-identical sibling donor has been frustratingly elusive. In with the goal of improving engraftment while minimizing transplantation-related morbidity, a multi-institutional learning collaborative was developed in the context of a Phase II clinical trial of nonmyeloablative, related HLA-haploidentical (haplo) bone marrow transplantation (BMT) with post-transplantation cyclophosphamide. All eligible participants had hemoglobin SS, and 89% (16 of 18) had an identifiable donor. The median patient age was 20.9 years (IQR, 12.1 to 26.0 years), and the most common indication for transplantation was overt stroke (in 69%; 11 of 16). In the first 3 patients, the conditioning regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and low-dose total body irradiation. Graft-versus-host disease (GVHD) prophylaxis included post-transplantation cyclophosphamide, mycophenolate mofetil, and sirolimus. Primary graft rejection occurred in 2 of the 3 patients (67%), which triggered the study-stopping rule. To reduce graft rejection risk, thiotepa was added to the conditioning regimen, and then 15 patients (including 2 with previous graft rejection) underwent haplo-BMT with this thiotepa-augmented conditioning regimen. At a median follow-up of 13.3 months (interquartile range [IQR], 3.8 to 23.1 months), 93% (14 of 15) had >95% stable donor engraftment at 6 months, with 100% overall survival. The median time to neutrophil engraftment (>500) was 22 days (IQR, 19 to 27 days), and that for platelet engraftment (>50 x 109/L) was 28 days (IQR, 27 days to not reached). Two patients had grade III-IV acute GVHD, 1 patient had mild chronic GVHD, and 86% of patients (6 of 7) were off immunosuppression therapy by 1-year post-transplantation. Our data suggest that haplo-BMT with post-transplantation cyclophosphamide and thiotepa improves donor engraftment without significantly increasing morbidity or mortality and could dramatically expand curative options for individuals with SCD.
AB - Curative therapy for individuals with severe sickle cell disease (SCD) who lack an HLA-identical sibling donor has been frustratingly elusive. In with the goal of improving engraftment while minimizing transplantation-related morbidity, a multi-institutional learning collaborative was developed in the context of a Phase II clinical trial of nonmyeloablative, related HLA-haploidentical (haplo) bone marrow transplantation (BMT) with post-transplantation cyclophosphamide. All eligible participants had hemoglobin SS, and 89% (16 of 18) had an identifiable donor. The median patient age was 20.9 years (IQR, 12.1 to 26.0 years), and the most common indication for transplantation was overt stroke (in 69%; 11 of 16). In the first 3 patients, the conditioning regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and low-dose total body irradiation. Graft-versus-host disease (GVHD) prophylaxis included post-transplantation cyclophosphamide, mycophenolate mofetil, and sirolimus. Primary graft rejection occurred in 2 of the 3 patients (67%), which triggered the study-stopping rule. To reduce graft rejection risk, thiotepa was added to the conditioning regimen, and then 15 patients (including 2 with previous graft rejection) underwent haplo-BMT with this thiotepa-augmented conditioning regimen. At a median follow-up of 13.3 months (interquartile range [IQR], 3.8 to 23.1 months), 93% (14 of 15) had >95% stable donor engraftment at 6 months, with 100% overall survival. The median time to neutrophil engraftment (>500) was 22 days (IQR, 19 to 27 days), and that for platelet engraftment (>50 x 109/L) was 28 days (IQR, 27 days to not reached). Two patients had grade III-IV acute GVHD, 1 patient had mild chronic GVHD, and 86% of patients (6 of 7) were off immunosuppression therapy by 1-year post-transplantation. Our data suggest that haplo-BMT with post-transplantation cyclophosphamide and thiotepa improves donor engraftment without significantly increasing morbidity or mortality and could dramatically expand curative options for individuals with SCD.
KW - Bone marrow transplantation
KW - Haploidentical
KW - Post-transplantation cyclophosphamide
KW - Sickle cell disease
KW - Thiotepa
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UR - http://www.scopus.com/inward/citedby.url?scp=85060052698&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2018.11.027
DO - 10.1016/j.bbmt.2018.11.027
M3 - Article
C2 - 30500440
AN - SCOPUS:85060052698
SN - 1083-8791
VL - 25
SP - 1197
EP - 1209
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 6
ER -