TY - JOUR
T1 - Timing of Post-Transplantation Cyclophosphamide Administration in Haploidentical Transplantation: A Comparative Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
T2 - Biology of Blood and Marrow Transplantation
AU - Ruggeri, A.
AU - Labopin, M.
AU - Battipaglia, G.
AU - Chiusolo, P.
AU - Tischer, J.
AU - Diez-Martin, J.L.
AU - Bruno, B.
AU - Castagna, L.
AU - Moiseev, I.S.
AU - Vitek, A.
AU - Rovira, M.
AU - Ciceri, F.
AU - Bacigalupo, A.
AU - Nagler, A.
AU - Mohty, M.
N1 - Cited By :1
Export Date: 11 March 2021
CODEN: BBMTF
Correspondence Address: Ruggeri, A.; Hematology and BMT Unit, Piazza di Sant'Onofrio, 4, Italy; email: annalisaruggeri80@hotmail.com
Chemicals/CAS: busulfan, 55-98-1; cyclophosphamide, 50-18-0; cyclosporine, 59865-13-3, 63798-73-2, 79217-60-0; fludarabine, 21679-14-1; mycophenolate mofetil, 116680-01-4, 128794-94-5; tacrolimus, 104987-11-3; thiotepa, 52-24-4
Funding details: Fundación Universitaria de Navarra, FUNA
Funding details: University of Patras
Funding details: Universität Heidelberg
Funding details: King Hussein Cancer Center, KHCC
Funding details: Cliniques Universitaires Saint-Luc
Funding text 1: The authors thank Emmanuelle Polge from the office of the ALWP of the EBMT, and the clinical staff and investigators involved in this research, and especially the patients who took part: Klinikum Grosshadern, Med Klinik III, Munich, Germany; Hospital Gregorio Mara??n, Secci?n de Trasplante de Medula Osea, Madrid, Spain; SSCVD Trapianto di Cellule Staminali, AOU Citta della Salute e della Scienza di Torino, Torino, Italy; Universita Cattolica S Cuore, Istituto di Ematologia, Rome, Italy; Istituto Clinico Humanitas, Transplantation Unit, Department of Oncology and Haematology, Milano, Italy; First State Pavlov Medical University of St Petersburg, Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology, and Transplantation, St Petersburg, Russia; Institute of Hematology and Blood Transfusion, Servicio de Hematolog?a, Prague, Czech Republic; Hospital Clinic, Institute of Hematology & Oncology, Department of Hematology, Barcelona, Spain; CHU Bordeaux, H?pital Haut-leveque, Pessac, France; Baskent University Hospital, Haematology Division, BMT Unit, Haemaology Reserach Laboratory, Training & Medical, Adana, Turkey; D?partement d`Oncologie, Service d`H?matologie, H?pitaux Universitaires De Gen?ve, Geneva, Switzerland; ASST Papa Giovanni XXIII, Hematology and Bone Marrow Transplant Unit, Bergamo, Italy; Florence Nightingale Sisli Hospital, Hematopoietic SCT Unit, Istanbul, Turkey; Ospedale La Maddalena, Oncologico, Unit? Operativa di Oncoematologia e, Trapianto di Midollo, Palermo, Italy; USD Trapianti di Midollo, Adulti, Universita di Brescia, Brescia, Italy; University Hospital Center Rebro, Zagreb, Croatia; Oslo University Hospital, Rikshospitalet, Clinic for Cancer Medicine, Hematology Department, Section for Stem Cell Transplantation, Oslo, Norway; CHRU, Service des Maladies du Sang, Angers, France; Department of Haematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany; Hematology Service, Hospital Universitari Son Espases, Palma Mallorca, Spain; Hematology Department, Ospedale San Carlo, Potenza, Italy; Hematology Department, University Hospital, Basel, Switzerland; University of Heidelberg, Medizinische Klinik u Poliklinik V, Heidelberg, Germany; CHRU Limoges, Service d`H?matologie Clinique, Limoges, France; King Hussein Cancer Centre, Amman, Jordan; ICO?Hospital Duran i Reynals, L`Hospitalet de Llobregat, Barcelona, Spain; Cl?nica Universitaria de Navarra, Area de Ter?pia Celular, Unidad de Trasplante Hemopoy?tico, Pamplona, Spain; Ospedale Policlinico, Programma di Trapianto Emopoietico Misto e Metropolitano Di Catania, Catania, Italy; S Bortolo Hospital, Department of Hematology, Vicenza, Italy; Department of Hematology, Cliniques Universitaires St Luc, Brussels, Belgium; University Hospital of Patras, Internal Medicine/BMT Unit, Patras, Greece; King Abdul-Aziz Medical City, Riyadh, Saudi Arabia; Birmingham Heartlands Hospital, Department of Haematology, Birmingham, United Kingdom; and Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska Curie National Research Institute of Oncology, Oncology Center, Gliwice, Poland. Financial disclosure: The authors declare no conflict of interest with the study. Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: A.R. and G.B. contributed equally to this work and should be considered co-first authors. A.R. P.C. A.B. F.C. A.N. and M.M. designed the study; M.L. performed the statistical analysis; A.R. and G.B. wrote the manuscript; A.R. G.B. M.L. A.N. and M.M. revised the manuscript; and all the authors reviewed the final version. J.T. J.L.D.M. B.B. P.C. L.C. I.S.M. A.V. M.R. and A.B. were the principal investigators at the centers recruiting the highest number of patients for the study. Financial disclosure: See Acknowledgments on page 1921.
PY - 2020
Y1 - 2020
N2 - The timing of immunosuppressive therapy used in combination with post-transplantation cyclophosphamide (PTCY) in haploidentical hematopoietic stem cell transplant (haplo-HSCT) is not standardized. We evaluated the schedules of immunosuppression therapy after haplo-HSCT in 509 patients with acute leukemia receiving PTCY on days +3 and +4 along with tacrolimus (group 1; n = 215), with cyclosporine A (CSA) and mycophenolate mofetil (MMF) from day +5 (group 2; n = 170), or CSA + MMF from day 0 or 1 with PTCY on days +3 and +5 (group 3; n = 124). Compared with the other 2 groups, patients in group 3 were younger (median age, 46 years; P = .02) and more often received bone marrow (77%; P < .01) and a regimen containing thiotepa, fludarabine, and busulfan (84%; P< .01). At 2 years, overall survival was 44% was in group 1, 48% in group 2, and 59% in group 3 (P= .15); leukemia-free survival (LFS) was 43%, 46%, and 53% (P= .05); and refined graft-versus-host disease-free, relapse-free survival (rGRFS) was 33%, 39%, and 36% (P = .02). The incidence of grade II-IV acute GVHD was 25% in group 1, 39% in group 2, and 18% in group 3 (P< .01); incidence of chronic GVHD was 25%, 21%, and 24% (P= .50); relapse incidence was 36%, 37%, and 26% (P= .02); and nonrelapse mortality was 26%, 20%, and 21% (P= .35). On multivariate analysis, early start of immunosuppression therapy at day +1 followed by PTCY was associated with a better LFS (hazard ratio [HR],. 58; P= .02) and improved rGRFS (HR,. 62; P = .02). In this study, the timing of immunosuppression influenced the outcomes of haplo-HSCT with PTCY. An early start of CSA + MMF with PTCY administered on days +3 and +5 improves LFS and rGRFS. © 2020 American Society for Transplantation and Cellular Therapy
AB - The timing of immunosuppressive therapy used in combination with post-transplantation cyclophosphamide (PTCY) in haploidentical hematopoietic stem cell transplant (haplo-HSCT) is not standardized. We evaluated the schedules of immunosuppression therapy after haplo-HSCT in 509 patients with acute leukemia receiving PTCY on days +3 and +4 along with tacrolimus (group 1; n = 215), with cyclosporine A (CSA) and mycophenolate mofetil (MMF) from day +5 (group 2; n = 170), or CSA + MMF from day 0 or 1 with PTCY on days +3 and +5 (group 3; n = 124). Compared with the other 2 groups, patients in group 3 were younger (median age, 46 years; P = .02) and more often received bone marrow (77%; P < .01) and a regimen containing thiotepa, fludarabine, and busulfan (84%; P< .01). At 2 years, overall survival was 44% was in group 1, 48% in group 2, and 59% in group 3 (P= .15); leukemia-free survival (LFS) was 43%, 46%, and 53% (P= .05); and refined graft-versus-host disease-free, relapse-free survival (rGRFS) was 33%, 39%, and 36% (P = .02). The incidence of grade II-IV acute GVHD was 25% in group 1, 39% in group 2, and 18% in group 3 (P< .01); incidence of chronic GVHD was 25%, 21%, and 24% (P= .50); relapse incidence was 36%, 37%, and 26% (P= .02); and nonrelapse mortality was 26%, 20%, and 21% (P= .35). On multivariate analysis, early start of immunosuppression therapy at day +1 followed by PTCY was associated with a better LFS (hazard ratio [HR],. 58; P= .02) and improved rGRFS (HR,. 62; P = .02). In this study, the timing of immunosuppression influenced the outcomes of haplo-HSCT with PTCY. An early start of CSA + MMF with PTCY administered on days +3 and +5 improves LFS and rGRFS. © 2020 American Society for Transplantation and Cellular Therapy
KW - Acute leukemia
KW - Cyclophosphamide
KW - Haploidentical transplant
KW - busulfan
KW - cyclophosphamide
KW - cyclosporine
KW - fludarabine
KW - mycophenolate mofetil
KW - tacrolimus
KW - thiotepa
KW - acute graft versus host disease
KW - acute leukemia
KW - acute lymphoblastic leukemia
KW - acute myeloid leukemia
KW - adolescent
KW - adult
KW - aged
KW - Article
KW - bone marrow transplantation
KW - cancer free survival
KW - chronic graft versus host disease
KW - early intervention
KW - female
KW - haploidentical transplantation
KW - hematopoietic stem cell transplantation
KW - human
KW - immunosuppressive treatment
KW - major clinical study
KW - male
KW - mortality rate
KW - overall survival
KW - recurrence free survival
KW - retrospective study
KW - survival rate
U2 - 10.1016/j.bbmt.2020.06.026
DO - 10.1016/j.bbmt.2020.06.026
M3 - Article
VL - 26
SP - 1915
EP - 1922
JO - Biol. Blood Marrow Transplant.
JF - Biol. Blood Marrow Transplant.
SN - 1083-8791
IS - 10
ER -