Haploidentical transplantation using G-CSF-mobilized T-cell replete PBSCs and post-transplantation CY after non-myeloablative conditioning is safe and is associated with favorable outcomes

Bhamidipati, Pavan Kumar; DiPersio, John F.; Stokerl-Goldstein, Keith E.; Rashidi, Armin; Gao, Feng; Uy, Geoffrey L.; Westervelt, Peter; Vij, Ravi; Schroeder, Mark A.; Abboud, Camille N.; Keller, Jesse; Fehniger, Todd A.; Romee, Rizwan

doi:10.1038/bmt.2014.108

Cited by 25 publications

(22 citation statements)

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“…Importantly, despite the advanced age of the patients studied (median age 51 years, with 25% of patients aged more than 65), the comorbidities (approximately two thirds of patients had a Comorbidity-age score of 3 or more), and the relative poor risk status of their malignancies (with the majority of patients having a high or very high DRI), NRM was 12% at 100 days and 17% at 1 year. This is in the range of NRM reported for other PTCy-based approaches [15][16][17]52 . Thus, our results indicate that intensification of the conditioning regimen coupled to the use of PBSC is feasible and does not adversely affect outcomes in the haplo-PTCy context, as also recently reported 18,19,53 .…”

Section: Discussionmentioning

confidence: 56%

“…Recently, different groups have reported encouraging outcomes M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 4 using peripheral blood stem cell (PBSC) grafts [15][16][17] , myeloablative conditioning regimens 18 or a combination of both 19 . Thus, while different conditioning regimens and stem cell sources have been tested in the context of haplo-PTCy, reported GVHD prophylaxis regimens have relied only on calcineurin inhibitors (CNIs) to date.…”

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confidence: 99%

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Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells

Cieri

Greco²,

Crucitti

et al. 2015

Biology of Blood and Marrow Transplantation

130

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Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. Post-HSCT recovery of lymphocyte subsets was broad and fast, with a median time to CD4 > 200/μL of 41 days. Cumulative incidences of grade II to IV and III-IV acute GVHD were 15% and 7.5%, respectively, and were associated with a significant early increase in circulating regulatory T cells at day 15 after HSCT, with values < 5% being predictive of subsequent GVHD occurrence. The 1-year cumulative incidence of chronic GVHD was 20%. Nonrelapse mortality (NRM) at 100 days and 1 year were 12% and 17%, respectively. With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting.

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Section: Discussionmentioning

confidence: 56%

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confidence: 99%

Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells

Cieri

Greco²,

Crucitti

et al. 2015

Biology of Blood and Marrow Transplantation

130

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“…5 Moreover, we have recently reported encouraging results in a haploidentical setting with the combination of PTCy and sirolimus as GVHD prophylaxis (Sir-PTCy), 6 with a potential reduced transplant-related mortality (TRM) and GVHD incidence over a GVHD prophylaxis based on sirolimus-antithymocyte globulin. 7 PTCy has been widely investigated in in the haploidentical context, with bone marrow as a source and in association with calcineurin inhibitors (CNIs), 4,[8][9][10] but limited series have been reported after HLAmatched HSCT with peripheral blood as a source or CNI-free GVHD prophylaxis. 11 Mielcarek et al recently reported their experience on PTCy followed by cyclosporine in HLA-matched mobilized blood cell grafts.…”

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confidence: 99%

Posttransplantation cyclophosphamide and sirolimus for prevention of GVHD after HLA-matched PBSC transplantation

Greco¹,

Lorentino²,

Morelli³

et al. 2016

Blood

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Graft-versus-host disease (GVHD), both acute and chronic, is still a leading cause of nonrelapse mortality after transplantation. 1 Highdose, posttransplantation cyclophosphamide (PTCy) is an attractive approach for in vivo allodepletion across the HLA barrier in allogeneic hematopoietic stem cell transplantation (HSCT), aimed at inducing a state of immunologic tolerance and preventing GVHD.2 This clinical platform was demonstrated first in the reduced-intensity conditioning, haploidentical allogeneic HSCT setting 3,4 and later as single-agent GVHD prophylaxis after myeloablative conditioning and HLAmatched-related or -unrelated bone marrow allografting.5 Moreover, we have recently reported encouraging results in a haploidentical setting with the combination of PTCy and sirolimus as GVHD prophylaxis (Sir-PTCy), 6 with a potential reduced transplant-related mortality (TRM) and GVHD incidence over a GVHD prophylaxis based on sirolimus-antithymocyte globulin.

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“…Other studies with myeloablative haploidentical transplantation using peripheral blood stem cell and post-transplant cyclophosphamide showed similar results of low incidence of acute GVHD and a 1 year of EFS in the range of 50%-60% [50,51] . The use of peripheral blood as a source of stem cells in the nonablative haploidentical setting with post-transplant cyclophosphamide will allow wider applicability of this approach [52] .…”

Section: Cyclophosphamide Post Haploidentical Transplantationmentioning

confidence: 99%

Haploidenticalvscord blood transplantation for adults with acute myelogenous leukemia

Solh

2014

WJSC

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Hematopoeitic cell transplantation is established as a curative treatment for patients w acute myelogenous leukemia. Haploidentical family donor and umbilical cord blood (UCB) are alternative sources of stem cells for patients lacking a matched sibling or unrelated donor. The early challenges of transplant complications related to poor engraftment and graft-vs -host disease have been overcome with new strategies such as using 2 units and increased cell dose in UCB and T-cell depletion and post transplantation cyclophosphamide in haploidentical transplantation. The outcomes of alternative transplantation for acute leukemia were compared to other traditional graft sources. For patients lacking a matched sibling or unrelated donor, either strategy is a suitable option. The choice should rely mostly on the urgency of the transplantation and the available cell dose as well as the expertise available at the transplant center. This manuscript reviews the options of alternative donor transplantation and highlights recent advances in each of these promising transplantation options.© 2014 Baishideng Publishing Group Inc. All rights reserved. Key words: Umbilical cord blood transplantation; Haploidentical transplantation; LeukemiaCore tip: Allogeneic hematopoeitic cell transplantation is a curative treatment for patients with acute leuekemia. Many patients lack a suitable matched donor and require another stem cell source. The choice between cord blood and mismatched relative is challenging as there is no direct comparison between the two transplantation modalities. This manuscript highlights the studies and current innovative approaches with either modality with an emphasis on the recent studies aiming at decreasing complications, enhancing engraftment and speeding immune recovery.Solh M. Haploidentical vs cord blood transplantation for adults with acute myelogenous leukemia. World J Stem Cells

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Haploidentical transplantation using G-CSF-mobilized T-cell replete PBSCs and post-transplantation CY after non-myeloablative conditioning is safe and is associated with favorable outcomes

Cited by 25 publications

References 8 publications

Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells

Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells

Posttransplantation cyclophosphamide and sirolimus for prevention of GVHD after HLA-matched PBSC transplantation

Haploidenticalvscord blood transplantation for adults with acute myelogenous leukemia

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