Synapse - High progression-free survival after intermediate intensity double unit cord blood transplantation in adults

High progression-free survival after intermediate intensity double unit cord blood transplantation in adults Journal Article

Authors:	Barker, J. N.; Devlin, S. M.; Naputo, K. A.; Skinner, K.; Maloy, M. A.; Flynn, L.; Anagnostou, T.; Avecilla, S. T.; Scaradavou, A.; Cho, C.; Dahi, P. B.; Giralt, S. A.; Gyurkocza, B.; Hanash, A. M.; Hsu, K.; Jakubowski, A. A.; Papadopoulos, E. B.; Peled, J. U.; Perales, M. A.; Sauter, C. S.; Shah, G. L.; Shaffer, B. C.; Tamari, R.; Young, J. W.; Roshal, M.; O'Reilly, R. J.; Ponce, D. M.; Politikos, I.
Article Title:	High progression-free survival after intermediate intensity double unit cord blood transplantation in adults
Abstract:	Cord blood transplantation (CBT) after high intensity or nonmyeloablative conditioning has limitations. We investigated cyclosporine-A/mycophenolate mofetil-based intermediate intensity (cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, thiotepa 10 mg/kg, total body irradiation 400 cGy) unmanipulated double-unit CBT (dCBT) with prioritization of unit quality and CD341 cell dose in graft selection. Ninety adults (median age, 47 years [range, 21-63]; median hematopoietic cell transplantation comorbidity index, 2 [range, 0-8]; 61 [68%] acute leukemia) received double-unit grafts (median CD341 cell dose, 1.3 3 105/kg per unit [range, 0.2-8.3]; median donor-recipient human leukocyte antigen (HLA) match, 5/8 [range 3-7/8]). The cumulative incidences of sustained CB engraftment, day 180 grade III-IV acute, and 3-year chronic graft-versus-host disease were 99%, 24%, and 7%, respectively. Three-year transplant-related mortality (TRM) and relapse incidences were 15% and 9%, respectively. Three-year overall survival (OS) is 82%, and progression-free survival (PFS) is 76%. Younger age and higher engrafting unit CD341 cell dose both improved TRM and OS, although neither impacted PFS. Engrafting unit-recipient HLA match was not associated with any outcome with a 3-year PFS of 79% in 39 patients engrafting with 3-4/8 HLA-matched units. In 52 remission acute leukemia patients, there was no association between minimal residual disease (MRD) and 3-year PFS: MRD negative of 88% vs MRD positive of 77% (P 5.375). Intermediate intensity dCBT is associated with high PFS. Use of highly HLA mismatched and unmanipulated grafts permits wide application of this therapy, and the low relapse rates support robust graft-versus-leukemia effects even in patients with MRD. © 2020 by The American Society of Hematology
Keywords:	adult; middle aged; major clinical study; overall survival; myeloproliferative disorder; fludarabine; mortality; drug withdrawal; imatinib; progression free survival; lung toxicity; maintenance therapy; cyclophosphamide; hematopoietic stem cell transplantation; dasatinib; chronic myeloid leukemia; retrospective study; thiotepa; acute lymphoblastic leukemia; age; acute graft versus host disease; acute leukemia; chronic graft versus host disease; cord blood stem cell transplantation; engraftment; graft failure; hla matching; myelodysplastic syndrome; whole body radiation; minimal residual disease; graft versus host reaction; leukemia relapse; granulocyte colony stimulating factor; cyclosporine; vascular disease; leukemia remission; immune reconstitution; acute myeloid leukemia; mycophenolate mofetil; quizartinib; ponatinib; human; male; female; priority journal; article; double unit cord blood transplantation; transplant related mortality
Journal Title:	Blood Advances
Volume:	4
Issue:	23
ISSN:	2473-9529
Publisher:	American Society of Hematology
Date Published:	2020-12-08
Start Page:	6064
End Page:	6076
Language:	English
DOI:	10.1182/bloodadvances.2020003371
PUBMED:	33290545
PROVIDER:	scopus
PMCID:	PMC7724901
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85098055648&doi=10.1182%2fbloodadvances.2020003371&partnerID=40&md5=27011821f961228ecde499ed96c8f354
Notes:	Article -- Export Date: 4 January 2021 -- Source: Scopus