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. 2020 Dec 8;4(23):6064-6076.
doi: 10.1182/bloodadvances.2020003371.

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

Juliet N Barker  1   2 , Sean M Devlin  3 , Kristine A Naputo  1 , Kelcey Skinner  1 , Molly A Maloy  1 , Lisa Flynn  1 , Theodora Anagnostou  1 , Scott T Avecilla  4 , Andromachi Scaradavou  5   6 , Christina Cho  1   2 , Parastoo B Dahi  1   2 , Sergio A Giralt  1   2 , Boglarka Gyurkocza  1   2 , Alan M Hanash  1   2 , Katharine Hsu  1   2 , Ann A Jakubowski  1   2 , Esperanza B Papadopoulos  1   2 , Jonathan U Peled  1   2 , Miguel-Angel Perales  1   2 , Craig S Sauter  1   2 , Gunjan L Shah  1   2 , Brian C Shaffer  1   2 , Roni Tamari  1   2 , James W Young  1   2 , Mikhail Roshal  7 , Richard J O'Reilly  5   6 , Doris M Ponce  1   2 , Ioannis Politikos  1   2
Affiliations

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

Juliet N Barker et al. Blood Adv. .

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 CD34+ 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 CD34+ cell dose, 1.3 × 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 CD34+ 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 = .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.

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Conflict of interest statement

Conflict--interest disclosure: J.N.B. has received clinical trial funding from Angiocrine Bioscience and an unrestricted educational grant from Merck. S.T.A. has received honoraria from Abbott Laboratories. A.S. was the Medical Director of the National Cord Blood Program until 1/2020 and serves as a consultant at the Scientific Advisory Board of ExCellThera. S.A.G. has served as a consultant for Amgen, Actinium, Celgene, Johnson & Johnson, Jazz Pharmaceutical, Takeda, Novartis, Kite, and Spectrum Pharma and has received research funding from Amgen, Actinium, Celgene, Johnson & Johnson, Miltenyi, and Takeda. J.U.P. reports research funding, intellectual property fees, and travel reimbursement from Seres Therapeutics and consulting fees from DaVolterra. M.-A.P. has received honoraria from Abbvie, Bellicum, Bristol-Myers Squibb, Incyte, Kite (Gilead), Merck, Novartis, Nektar Therapeutics, and Takeda; serves on data and safety monitoring boards for Servier, Cidara Therapeutics and Medigene; serves on the scientific advisory boards of MolMed and NexImmune; and has received research support for clinical trials from Incyte, Kite (Gilead) and Miltenyi Biotec. C.S.S. has served as a paid consultant on advisory boards for Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite/a Gilead Company, Celgene, Gamida Cell, and GSK, and has received research funds for clinical trials from Juno Therapeutics, Celgene, Bristol-Myers Squibb, Precision Biosciences, and Sanofi-Genzyme. R.J.O. receives royalties from Atara Biotherapeutics. I.P. has received research funding from Merck and serves as a member on a data and safety monitoring board for ExcellThera. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Transplant outcomes after intermediate intensity dCBT. (A) Cumulative incidence of neutrophil engraftment in patients who received dCB grafts only (n = 47). Patients who received dCB grafts combined with haplo-identical CD34+ cells were excluded because of transient haploidentical donor-derived myeloid bridging before sustained CB engraftment. (B) Cumulative incidence of acute GVHD by 180 days after transplant (n = 90). (C) Three-year cumulative incidence of chronic GVHD (n = 90). (D) Three-year cumulative incidence of TRM (n = 90). (E) Three-year cumulative incidence of relapse (n = 90). (F) Loess-smoothed averages of lymphocyte subset recovery including CD4+-, CD8+-, NK-, and B-cell subsets. As there were no differences in recovery after dCBT and dCBT combined with haplo-identical cells, these patients were combined (n = 90).
Figure 2.
Figure 2.
Three-year probabilities of PFS after intermediate intensity dCBT (n = 90). Three-year PFS and OS (A), 3-year GRFS (B), 3-year PFS according to age (split at 50 years) (C), European vs non-European ancestry (D), HCT-CI (low score of 0-2 vs 3-8) (E), rDRI (low-intermediate vs high-very high) (F), engrafting unit infused CD34+ cell dose (split at the median) (G), and engrafting unit-recipient 8-allele HLA match (H).
Figure 3.
Figure 3.
Three-year probabilities of PFS in patients with acute leukemia after intermediate-intensity dCBT. (A) Three-year PFS according to pretransplant MRD status in the 52 patients with acute leukemia in complete remission. (B) Three-year PFS in 40 AML patients transplanted in CR according to their ELN 2010 genetic risk classification at diagnosis.
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References

    1. Ponce DM, Hilden P, Devlin SM, et al. . High disease-free survival with enhanced protection against relapse after double-unit cord blood transplantation when compared with T cell-depleted unrelated donor transplantation in patients with acute leukemia and chronic myelogenous leukemia. Biol Blood Marrow Transplant. 2015;21(11):1985-1993. - PMC - PubMed
    1. Brunstein CG, Gutman JA, Weisdorf DJ, et al. . Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood. 2010;116(22):4693-4699. - PMC - PubMed
    1. Milano F, Gooley T, Wood B, et al. . Cord-blood transplantation in patients with minimal residual disease. N Engl J Med. 2016;375(10):944-953. - PMC - PubMed
    1. Sharma P, Purev E, Haverkos B, et al. . Adult cord blood transplant results in comparable overall survival and improved GRFS vs matched related transplant. Blood Adv. 2020;4(10):2227-2235. - PMC - PubMed
    1. Barker JN, Weisdorf DJ, DeFor TE, et al. . Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005;105(3):1343-1347. - PubMed

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