TY - JOUR
T1 - Bone Marrow versus Peripheral Blood Grafts for Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide
T2 - R. S. Mehta et al
AU - Mehta, Rohtesh S.
AU - Saliba, Rima M.
AU - Alsfeld, Leonard C.
AU - Jorgensen, Jeffrey L.
AU - Wang, Sa A.
AU - Anderlini, Paolo
AU - Al-Atrash, Gheath
AU - Bashir, Qaiser
AU - Ciurea, Stefan O.
AU - Hosing, Chitra M.
AU - Im, Jin S.
AU - Kebriaei, Partow
AU - Khouri, Issa
AU - Marin, David
AU - Nieto, Yago
AU - Olson, Amanda
AU - Oran, Betul
AU - Popat, Uday R.
AU - Qazilbash, Muzaffar H.
AU - Ramdial, Jeremy
AU - Rondon, Gabriela
AU - Saini, Neeraj
AU - Srour, Samer A.
AU - Rezvani, Katayoun
AU - Shpall, Elizabeth J.
AU - Champlin, Richard E.
AU - Alousi, Amin M.
N1 - Funding Information:
Financial disclosure: Same as conflicts of interest. No specific financial disclosures otherwise. Conflict of interest statement: R.S.M. has received research funding from CSL Behring, Kadmon, and Incyte. S.O.C. has served as an advisory board member for Hansa, Spectrum, MolMed, Cytosen, Kiadis, Allogene, CareDx, Acrotech, and Cellularity, and has research funding from Miltenyi Biotec and Kiadis. K.R. has received researching funding from Affimed Therapeutics and Pharmacyclics; has served on advisory boards for Adicet Bio, ViroGen, and GemoAb; holds a patent on the generation of BKV CTLs for the treatment of HC or PML and a patent on the generation of CAR NK cells; and has license and research agreements with Takeda to develop CB-CAR NK cells for the treatment of B cell malignancies and other cancers. The other authors have no conflicts of interest to report. Authorship statement: R.S.M. conceptualized the study design, collected the data, helped with interpretation of data, and wrote the manuscript; R.M.S. contributed to data analysis and figures and wrote the statistical section of the manuscript; L.C.A. helped with the collection of quality of life data; J.J. and K.R. designed the flow cytometry panel; S.A.W. established quality control for the flow cytometry and trained the laboratory staff; P.A. G.A. Q.B. S.O.C, C.M.H, J.S.I, P.K. I.K. D.M. Y.N. A.O. B.O. U.P. M.H.Q. J.R. G.R. N.S. S.A.S. K.R. E.J.S. R.E.C. enrolled patients in the study and monitored responses. A.A.A. offered critical feedback on GVHD staging, grading and management, enrolled patients in the study, monitored responses, and supervised the study. R.S.M. and R.M.S. had full access to the raw data. All authors approved the manuscript. The corresponding author had the final responsibility to submit for publication. Data availability statement: Deidentified data may be available upon request to the study's principal investigator and will require Institutional Review Board approval. Financial disclosure: See Acknowledgments on page 1003.e13.
Funding Information:
Conflict of interest statement: R.S.M. has received research funding from CSL Behring, Kadmon, and Incyte. S.O.C. has served as an advisory board member for Hansa, Spectrum, MolMed, Cytosen, Kiadis, Allogene, CareDx, Acrotech, and Cellularity, and has research funding from Miltenyi Biotec and Kiadis. K.R. has received researching funding from Affimed Therapeutics and Pharmacyclics; has served on advisory boards for Adicet Bio, ViroGen, and GemoAb; holds a patent on the generation of BKV CTLs for the treatment of HC or PML and a patent on the generation of CAR NK cells; and has license and research agreements with Takeda to develop CB-CAR NK cells for the treatment of B cell malignancies and other cancers. The other authors have no conflicts of interest to report.
Publisher Copyright:
© 2021 The American Society for Transplantation and Cellular Therapy
PY - 2021/12
Y1 - 2021/12
N2 - In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.
AB - In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.
KW - Bone marrow
KW - Chronic GVHD
KW - Haploidentical
KW - PTCy
KW - Peripheral blood
KW - Steroid-refractory GVHD
UR - http://www.scopus.com/inward/record.url?scp=85120729879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85120729879&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2021.09.003
DO - 10.1016/j.jtct.2021.09.003
M3 - Article
C2 - 34537419
AN - SCOPUS:85120729879
SN - 2666-6367
VL - 27
SP - 1003.e1-1003.e13
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 12
ER -