Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis

Ghosh, Nilanjan; Karmali, Reem; Rocha, Vanderson; Ahn, Kwang Woo; DiGilio, Alyssa; Hari, Parameswaran; Bachanová, Veronika; Bacher, Ulrike; Dahi, Parastoo B.; Lima, Marcos de; D’Souza, Anita; Fenske, Timothy S.; Ganguly, Siddhartha; Kharfan‐Dabaja, Mohamed A.; Prestidge, Tim; Savani, Bipin N.; Smith, Sonali M.; Sureda, Anna; Waller, Edmund K.; Jaglowski, Samantha; Herrera, Alex F.; Armand, Philippe; Salit, Rachel B.; Wagner‐Johnston, Nina D.; Fuchs, Ephraim J.; Bolaños-Meade, Javier; Hamadani, Mehdi

doi:10.1200/jco.2015.66.3476

Cited by 219 publications

(153 citation statements)

References 32 publications

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…[22][23][24][25] Furthermore, HSCT after PD-1 blockade may be associated with lower than expected relapse rates. CIR at 1 year in this study compares favorably to that expected for this cohort based on the Disease Risk Index mix of patients (14% vs 26%).…”

Section: Absolute Cd4+ T Cellsmentioning

confidence: 99%

Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma

Merryman

Kim

Zinzani

et al. 2017

Blood

Self Cite

208

184

View full text Add to dashboard Cite

Key Points• HSCT after PD-1 blockade is feasible, although may be associated with increased early immune toxicity.• PD-1 blockade may cause persistent depletion of PD1 1T cells and alterations in T-cell differentiation impacting subsequent treatment.Anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the 1-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23%, respectively, whereas the 1-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a noninfectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% confidence interval [CI], 74-96) and 76% (95% CI, 56-87), respectively. One-year cumulative incidences of relapse and nonrelapse mortality were 14% (95% CI, 4-29) and 11% (95% CI, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1 1 T cells and decreased ratios of T-regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade. (Blood. 2017;129(10):1380-1388

show abstract

Section: Absolute Cd4+ T Cellsmentioning

confidence: 99%

Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma

Merryman

Kim

Zinzani

et al. 2017

Blood

Self Cite

208

184

View full text Add to dashboard Cite

show abstract

“…66,[80][81][82][83][84] In 475 patients with a variety of hematologic malignancies, Bashey et al showed matched sibling, optimally (10 of 10 HLA allele) matched unrelated donor, and haploidentical transplants all had similar 2-year disease-free survival (ie, 56% vs 50% vs 54%). 80 In 459 patients, Raiola et al showed 4-year disease-free survival was 43% after haploidentical transplantation, 32% after matched sibling transplantation, 36% after matched unrelated donor transplantation, 34% after mismatched unrelated donor transplantation, and 33% after unrelated cord blood transplantation.…”

Section: Haploidentical Vs Matched Hematopoietic Transplantationmentioning

confidence: 99%

“…66 Two studies in lymphoma patients showed similar outcomes after haploidentical transplants with high-dose cyclophosphamide and matched sibling or unrelated donor transplants. 83,84 In a nonrandomized, prospective, multicenter trial in 450 adult AML patients in CR1 at transplant, the Beijing group found 3-year disease-free survival was 74% after haploidentical transplantation and 78% after matched sibling transplantation. 79 A retrospective pair-matched study in adult AML patients in CR1 showed similar results after haploidentical transplants performed in China and matched unrelated donor transplants performed in Europe.…”

Section: Haploidentical Vs Matched Hematopoietic Transplantationmentioning

confidence: 99%

Haploidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation

Mancusi

Ruggeri

Velardi

2016

Blood

View full text Add to dashboard Cite

The present review describes the biology of human leukocyte antigen haplotype mismatched ("haploidentical") transplantation, its translation to clinical practice to cure leukemia, and the results of current transplantation protocols. The 1990s saw what had been major drawbacks of haploidentical transplantation, ie, very strong host-versus-graft and graft-versus-host alloresponses, which led respectively to rejection and graft-versus-host disease (GVHD), being overcome through transplantation of a "mega-dose" of T celldepleted peripheral blood hematopoietic progenitor cells and no posttransplant pharmacologic immunosuppression. The absence of posttransplant immunosuppression was an opportunity to discover natural killer cell alloreactions that eradicated acute myeloid leukemia and improved survival. Furthermore, it also unveiled the benefits of transplantation from mother donors, a likely consequence of the mother-to-child interaction during pregnancy. More recent transplantation protocols use unmanipulated (without ex vivo T-cell depletion) haploidentical grafts combined with enhanced posttransplant immunosuppression to help prevent GVHD. Unmanipulated grafts substantially extended the use of haploidentical transplantation with results than even rival those of matched hematopoietic transplantation. In T cell-depleted haploidentical transplantation, recent advances were made by the adoptive transfer of regulatory and conventional T cells. (Blood. 2016;128(23):2616-2623 Allogeneic hematopoietic stem cell transplantation is the most powerful therapy for high-risk acute leukemia.1 Donor T cells recognize host alloantigens on leukemic cells and eradicate leukemia (graftversus-leukemia [GVL] effect). They also attack nonhematopoietic tissues (such as skin, gut, and liver) and thus mediate graft-versus-host disease (GVHD), a major cause of morbidity and mortality. Matching donor and recipient human leukocyte antigens (HLA) is considered crucial for optimal transplant outcomes with acceptable nonrelapse mortality (NRM).1 However, only 25% of individuals have an HLAidentical sibling who could serve as donor. Alternative stem cell sources (which of course carry increased risk of NRM due to diverse combinations of graft failure, GVHD, veno-occlusive disease, and infections) are matched unrelated volunteers, unrelated umbilical cord blood, and HLA haplotype mismatched ("haploidentical") family members.1,2 In fact, recent years have witnessed tremendous progress in the field of haploidentical transplantation. 3-10The experience of T cell-depleted haploidentical transplantation and the discovery of donor features that improve outcomesHaploidentical transplantation has become a widely used treatment of patients without a matched donor.2-15 Indeed, a haploidentical donor is immediately available in the family for almost all patients, without delay due to registry search. Because of multiple class I and II HLA disparities between donor and recipient, T cell-mediated hostversus-graft and graft-versus-host alloresponses (leading, ...

show abstract

“…Indeed, a recent study of lymphoma patients receiving either haplo SCT with PTCy or HLAmatched sibling SCT came to the same conclusion. 12 It may be argued that the comparison is unfair because the haplo transplants used PTCy, whereas the MUD transplants did not. Support for this argument comes from recent reports showing good survival and low incidence of chronic GVHD after MUD SCT with PTCy.…”

mentioning

confidence: 99%

Related haploidentical donors are a better choice than matched unrelated donors: Point

Fuchs

2017

Blood Advances

View full text Add to dashboard Cite

Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis

Cited by 219 publications

References 32 publications

Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma

Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma

Haploidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation

Related haploidentical donors are a better choice than matched unrelated donors: Point

Contact Info

Product

Resources

About