Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide
Ashley T. Munchel,Chimen Kesserwan,Heather J. Symons,Leo Luznik,Yvette L. Kasamon,Richard J. Jones,Ephraim J. Fuchs +6 more
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TLDR
Results suggest that mini-haploBMT with post-transplantation Cy is associated with acceptably low toxicities and can provide longterm survival, if not cure, for many patients with advanced hematologic malignancies.Abstract:
Allogeneic stem cell transplantation (SCT) from an HLA-haploidentical relative provides a potentially curative treatment option for hematologic malignancies patients who lack a suitably HLA-matched donor. The greatest challenge to performing HLA-haploidentical SCT has been high rates of graft failure and severe graft-versus-host disease (GVHD). Our group has been exploring high dose, post-transplantation cyclophosphamide (Cy) as prophylaxis of GVHD after nonmyeloablative, HLA-haploidentical bone marrow transplantation, or mini-haploBMT. Among 210 recipients of mini-haploBMT, 87% of patients have experienced sustained donor cell engraftment. The cumulative incidences of grades II-IV acute GVHD and chronic GVHD are 27% and 13%, respectively. Five-year cumulative incidence of non-relapse mortality is 18%, relapse is 55%, and actuarial overall survival and event-free survivals are 35% and 27%, respectively. These outcomes suggest that mini-haploBMT with post-transplantation Cy is associated with acceptably low toxicities and can provide longterm survival, if not cure, for many patients with advanced hematologic malignancies.read more
Citations
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Journal ArticleDOI
T-Cell–Replete HLA-Haploidentical Hematopoietic Transplantation for Hematologic Malignancies Using Post-Transplantation Cyclophosphamide Results in Outcomes Equivalent to Those of Contemporaneous HLA-Matched Related and Unrelated Donor Transplantation
Asad Bashey,Xu Zhang,Connie A. Sizemore,Karen Manion,Stacey Brown,H. Kent Holland,Lawrence E. Morris,Scott R. Solomon +7 more
TL;DR: Haploidentical transplants performed using T-cell-replete grafts and post-transplantation cyclophosphamide achieves outcomes equivalent to those of contemporaneous transplantation performed using MRDs and MUDs, indicating such transplantation represents a valid alternative for patients who lack a conventional donor.
Journal ArticleDOI
Modern approaches to HLA-haploidentical blood or marrow transplantation
TL;DR: The three most-developed approaches to HLA-haploidentical alloBMT are provided: T-cell depletion with 'megadose' CD34+ cells; granulocyte colony-stimulating factor-primed allografts combined with intensive pharmacological immunosuppression, including antithymocyte globulin; and high-dose, post-transplantation cyclophosphamide.
Journal ArticleDOI
Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation
Xiaoou Zhou,Gianpietro Dotti,Robert A. Krance,Caridad Martinez,Swati Naik,Rammurti T. Kamble,April G. Durett,Olga Dakhova,Barbara Savoldo,Antonio Di Stasi,David M. Spencer,Yu Feng Lin,Hao Liu,Bambi Grilley,Adrian P. Gee,Cliona M. Rooney,Helen E. Heslop,Malcolm K. Brenner +17 more
TL;DR: Alloreplete iC9-T cells can reconstitute immunity posttransplant and administration of CID can eliminate them from both peripheral blood and the central nervous system (CNS), leading to rapid resolution of GVHD and CRS.
Journal ArticleDOI
Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS
Christopher G. Kanakry,Hua Ling Tsai,Javier Bolaños-Meade,B. Douglas Smith,Ivana Gojo,Jennifer A. Kanakry,Yvette L. Kasamon,Douglas E. Gladstone,William Matsui,Ivan Borrello,Carol Ann Huff,Lode J. Swinnen,Jonathan D. Powell,Keith W. Pratz,Amy E. DeZern,Margaret M. Showel,Michael A. McDevitt,Robert A. Brodsky,Mark J. Levis,Richard F. Ambinder,Ephraim J. Fuchs,Gary L. Rosner,Richard J. Jones,Leo Luznik +23 more
TL;DR: The ability to limit posttransplantation immunosuppression makes PTCy a promising transplantation platform for the integration of postgrafting strategies to prevent relapse.
Journal ArticleDOI
Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene.
Xiaoou Zhou,Xiaoou Zhou,Antonio Di Stasi,Antonio Di Stasi,Siok-Keen Tey,Siok-Keen Tey,Robert A. Krance,Robert A. Krance,Caridad Martinez,Caridad Martinez,Kathryn S. Leung,Kathryn S. Leung,April G. Durett,April G. Durett,Meng Fen Wu,Meng Fen Wu,Meng Fen Wu,Hao Liu,Ann M. Leen,Ann M. Leen,Barbara Savoldo,Barbara Savoldo,Yu Feng Lin,Yu Feng Lin,Bambi Grilley,Bambi Grilley,Adrian P. Gee,Adrian P. Gee,David M. Spencer,Cliona M. Rooney,Cliona M. Rooney,Helen E. Heslop,Helen E. Heslop,Helen E. Heslop,Malcolm K. Brenner,Malcolm K. Brenner,Malcolm K. Brenner,Gianpietro Dotti +37 more
TL;DR: Long-term persistence of iC9-modified (iC 9-T) T cells in vivo in the absence of emerging oligoclonality and a robust immunologic benefit are found, supporting the beneficial effects of this approach to immune reconstitution after haplo-HSCT.
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HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide
Leo Luznik,Paul O'Donnell,Paul O'Donnell,Heather J. Symons,Allen R. Chen,M. Susan Leffell,Marianna Zahurak,Ted Gooley,Ted Gooley,S Piantadosi,Michele Kaup,Richard F. Ambinder,Carol Ann Huff,William Matsui,Javier Bolaños-Meade,Ivan Borrello,Jonathan D. Powell,Elizabeth Harrington,Sandy Warnock,Mary E.D. Flowers,Mary E.D. Flowers,Robert A. Brodsky,Brenda M. Sandmaier,Brenda M. Sandmaier,Rainer Storb,Rainer Storb,Richard J. Jones,Ephraim J. Fuchs +27 more
TL;DR: Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD, and there was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttrans transplantation Cy.
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