Halfway there: the past, present and future of haploidentical transplantation

Slade, Michael; Fakhri, Bita; Savani, Bipin N.; Romee, Rizwan

doi:10.1038/bmt.2016.190

Cited by 21 publications

(11 citation statements)

References 90 publications

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“…In the past years haploidentical transplantations with posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis have shown promising results in the treatment of many hematologic diseases, including some cases of graft failure [5,6]. Furthermore, most patients have a haploidentical donor that can be promptly identified and harvested.…”

Section: Introductionmentioning

confidence: 99%

Outcomes of Salvage Haploidentical Transplant with Post-Transplant Cyclophosphamide for Rescuing Graft Failure Patients: a Report on Behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Prata

Resche‐Rigon

Blaise

et al. 2019

Biology of Blood and Marrow Transplantation

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Prognosis of patients with graft failure is dismal, and retransplantation is the sole option for long-term survival. To address the interest of haploidentical transplantation as a salvage option in this context, we analyzed data from 24 patients with graft failure or loss retransplanted with a haploidentical donor who received post-transplant cyclophosphamide (PTCy) as graft-versus-host disease prophylaxis (GVHD). Fludarabine-based reduced-intensity conditioning was used in 23 patients and the Baltimore regimen in 14 patients. The median delay between previous and salvage transplantation for graft failure was 63 days (range, 39 to 98). In addition to PTCy, all patients received cyclosporine, and 22 patients also received mycophenolate mofetil for GVHD prophylaxis. With a median followup of 353 days (range, 16 to 2010), 1-year overall survival (OS) was 56% (95% confidence interval, 38% to 81%). Transplant complications accounted for 80% of deaths. The cumulative incidence of neutrophil engraftment at day +30 was 79%. Cumulative incidence of grades II to IV acute GVHD at day 100 was 14%, and 1-year cumulative incidence of chronic GVHD was 31%. One-year cumulative incidence of relapse was 13%. Stem cell source did not impact on engraftment, GVHD, relapse, or OS. Salvage haploidentical transplant with PTCy for rescuing graft failure patients leads to an acceptable 1-year OS and might be a valid option in this poor situation.

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Section: Introductionmentioning

confidence: 99%

Outcomes of Salvage Haploidentical Transplant with Post-Transplant Cyclophosphamide for Rescuing Graft Failure Patients: a Report on Behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Prata

Resche‐Rigon

Blaise

et al. 2019

Biology of Blood and Marrow Transplantation

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“…Allogeneic hematopoietic cell transplantation (HCT) is the only known potentially curative therapy. While a HLA‐matched sibling donor remains the preferred option for transplantation, there is a substantial lack of this donor population for sAML patients with rates estimated to be as high as 70% …”

Section: Introductionmentioning

confidence: 99%

Haploidentical transplantation outcomes for secondary acute myeloid leukemia: Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) study

Labopin

Ciceri

et al. 2018

American J Hematol

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Secondary acute myeloid leukemia (sAML) traditionally has inferior outcomes compared to de novo AML. Allogeneic hematopoietic cell transplantation (HCT) is the sole potentially curative therapy. This study analyzes the outcomes for unmanipulated haploidentical HCT (haploHCT) for sAML using the Acute Leukemia Working Party (ALWP) registry of the European Society for Blood and Marrow Transplantation (EBMT). We identified 154 patients with sAML who underwent haploHCT from 2006 to 2016. Median age at HCT was 60 years with time from diagnosis to HCT 5 months. At transplantation, 69 patients were in first CR and 85 had active disease. Fifty-seven (38.0%) patients underwent myeloablative conditioning and 97 (62.0%) reduced intensity conditioning (RIC) conditioning. Multivariate analysis showed that there was no difference in RI, nonrelapse mortality (NRM), leukemia free survival (LFS), overall survival (OS), or GVHD-free/relapse free survival (GRFS) for conditioning intensity, age, performance status, or graft source. Active disease was associated with higher RI and inferior LFS, OS, and GRFS compared with patients in CR at time of transplant. T-cell depletion with anti-thymoglobulin resulted in higher NRM and inferior LFS, OS, and GRFS compared to post-transplant cyclophosphamide (PTCy) (HR 2.25, 2.01, 2.16, and 1.73, respectively with P values <.05). Our data shows that haploHCT is a feasible alternative for sAML when matched transplantation is unavailable.

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“…[8][9][10] More recently, a revived interest in the use of haplo-identical (haplo) donors has become apparent because of improved transplantation techniques and pharmacological manipulation of host-versus-graft and graftversus-host reactions. 11 Although each type of donor and/or stem cell source has its own advantages and drawbacks, comparative studies evaluating survival estimates in well-defined groups of patients are scarce. Here, we set out to compare outcome in patients with poor-risk AML in CR1 receiving alloHSCT between 2000 and 2014, using either MRD, 10/10 or 9/10 MUDs, haplo, or UCB grafts.…”

Section: Introductionmentioning

confidence: 99%

Alternative donors for allogeneic hematopoietic stem cell transplantation in poor-risk AML in CR1

et al. 2017

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Key Points• The preferred donor for patients with poor-risk AML in CR1 proceeding to alloHSCT include MRD or 10/10 MUD.• Alternative donors are 9/10 MUD, UCB grafts, and especially haplo, but sufficient numbers and follow-up to define a hierarchy are lacking.Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the treatment of choice to consolidate remission in patients with poor-risk acute myeloid leukemia (AML).With increasing alternative donors available, the preferred donor or stem cell source is debated. We set out to study outcome in recipients of alloHSCT with poor-risk AML in first complete remission (CR1) by donor type. A total of 6545 adult patients with poor-risk AML in CR1 receiving an alloHSCT using matched related donor (MRD, n 5 3511) or alternative donors, including 10/10 (n 5 1959) or 9/10 matched unrelated donors (MUDs, n 5 549), umbilical cord blood (UCB) grafts (n 5 333), or haplo-identical (haplo) donors (n 5 193) were compared. Overall survival (OS) at 2 years following MRD alloHSCT was an estimated 59 6 1%, which did not differ from 10/10 MUD (57 6 1%) and haplo alloHSCT (57 6 4%). OS, however, was significantly lower for 9/10 MUD alloHSCT (49 6 2%) and UCB grafts (44 6 3%), respectively (P , .001). Nonrelapse mortality (NRM) depended on donor type and was estimated at 26 6 3% and 29 6 3% after haplo alloHSCT and UCB grafts at 2 years vs 15 6 1% following MRD alloHSCT. Multivariable analysis confirmed the impact of donor type with OS following MRD, 10/10 MUD, and haplo alloHSCT not being statistically significantly different.NRM was significantly higher for alternative donors as compared with MRD alloHSCT.Collectively, these results suggest that alloHSCT with MRDs and 10/10 MUDs may still be preferred in patients with poor-risk AML in CR1. If an MRD or 10/10 MUD is not available, then the repertoire of alternative donors includes 9/10 MUD, UCB grafts, and haplo-identical donors. The latter type of donor is increasingly applied and now approximates results with matched donors.

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Halfway there: the past, present and future of haploidentical transplantation

Cited by 21 publications

References 90 publications

Outcomes of Salvage Haploidentical Transplant with Post-Transplant Cyclophosphamide for Rescuing Graft Failure Patients: a Report on Behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Outcomes of Salvage Haploidentical Transplant with Post-Transplant Cyclophosphamide for Rescuing Graft Failure Patients: a Report on Behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Haploidentical transplantation outcomes for secondary acute myeloid leukemia: Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) study

Alternative donors for allogeneic hematopoietic stem cell transplantation in poor-risk AML in CR1

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