Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors

Kanate, Abraham S.; Mussetti, Alberto; Kharfan‐Dabaja, Mohamed A.; Ahn, Kwang Woo; DiGilio, Alyssa; Beitinjaneh, Amer; Chhabra, Saurabh; Fenske, Timothy S.; Freytes, César O.; Gale, Robert Peter; Ganguly, Siddhartha; Hertzberg, Mark; Klyuchnikov, Evgeny; Lazarus, Hillard M.; Olsson, Richard F.; Perales, Miguel Angel; Rezvani, Andrew R.; Riches, Marcie L.; Saad, Ayman; Slavin, Shimon; Smith, Sonali M.; Sureda, Anna; Yared, Jean A.; Ciurea, Stefan O.; Armand, Philippe; Salit, Rachel B.; Bolaños-Meade, Javier; Hamadani, Mehdi

doi:10.1182/blood-2015-09-671834

Cited by 253 publications

(175 citation statements)

References 35 publications

(70 reference statements)

Supporting

Mentioning

150

Contrasting

Unclassified

Order By: Relevance

“…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%

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

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

show abstract

“…[1][2][3][4][5][6] outcomes for haplo T-cell-replete transplantation with PT-Cy, donor prioritization strategies are extrapolated from HLA-matched related and unrelated donor transplantation. 7 The Baltimore group's selection algorithm for haplo donors incorporates donor-specific antibodies, donor-recipient ABO match, donor age, donor sex, and cytomegalovirus (CMV) serostatus match.…”

Section: Introductionmentioning

confidence: 99%

Effect of donor characteristics on haploidentical transplantation with posttransplantation cyclophosphamide

McCurdy

Zhang²,

Martin

et al. 2018

Blood Advances

Self Cite

View full text Add to dashboard Cite

Key Points• The effect of donor age on survival is negated by the effect of patient age.• Survival did not differ between sibling and offspring donor transplantation.We studied the association between non-HLA donor characteristics (age, sex, donor- Two-year survival adjusted for CMV seropositivity, disease, and disease risk index was lower in patients aged 55 to 78 years after transplantation of grafts from donors younger than 30 years (53%) or aged at least 30 years (46%) compared with younger patients who received grafts from donors younger than 30 years (61%) and at least 30 years (60%; P , .0001).Similarly, 2-year survival in patients aged 55 to 78 years was lower after transplantation of grafts from siblings (45%) or offspring (48%) compared with patients aged 18 to 54 years after transplantation of grafts from siblings (62%), offspring (58%), and parents (61%; P , .0001). Graft failure was higher after transplantation of grafts from parents (14%) compared with siblings (6%) or offspring (7%; P 5 .02). Other non-HLA donor characteristics were not associated with survival or graft failure. The current analyses suggest patient and disease, rather than non-HLA donor characteristics, predominantly influence survival in adults.

show abstract

“…11 Although single-institution studies 12,13 have shown encouraging results of Haplo-HCT with PT-Cy in lymphoma, and although a recent registry analysis has reported comparable outcomes of Haplo-HCT versus matched URD allo-HCT in patients with lymphoma, 14 it remains unclear whether the greater degree of HLA disparity associated with haploidentical allografts results in higher NRM and inferior survival when compared with MSD-HCT, the established standard for allo-HCT. To address this question, we compared the outcomes of Haplo-HCT against MSD-HCT in patients with lymphoma, using the observational database of the Center for International Blood and Marrow Transplant Research.…”

Section: Introductionmentioning

confidence: 99%

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

Karmali

Rocha

et al. 2016

JCO

Self Cite

219

129

View full text Add to dashboard Cite

Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and MethodsWe evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versushost disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. ResultsMedian follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P , .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P , .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/ progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). ConclusionHaplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD.

show abstract

Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors

Cited by 253 publications

References 35 publications

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

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

Effect of donor characteristics on haploidentical transplantation with posttransplantation cyclophosphamide

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

Contact Info

Product

Resources

About