Cord blood chimerism and relapse after haplo-cord transplantation

Besien, Koen van; Koshy, Nebu; Gergis, Usama; Mayer, Sebastian; Cushing, Melissa M.; Rennert, Hanna; Reich-Slotky, Ronit; Mark, Tomer M.; Pearse, Roger; Rossi, Adriana; Phillips, Adrienne A.; Vasovic, Ljiljana V.; Ferrante, Rosanna; Hsu, Yen‐Michael S.; Shore, Tsiporah B.

doi:10.1080/10428194.2016.1190970

Cited by 24 publications

(16 citation statements)

References 44 publications

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“…5,6,16,18 Our own group has shown that persistence of the UCB graft (as contrasted with dominance of the haplo graft) is associated with improved outcomes. 7 Kwon et al, in their comparison of haplo vs haplo-cord, found that, despite higher DRI risk groups, haplo-cord did not have more relapse. 16 Wang et al, from China, also showed that the additional infusion of a CBU with a haplo-graft resulted in reduction of relapse rates and improved OS.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 Many have observed decreases in relapse rates after UCB transplant that may be further enhanced by careful selection of the cord blood graft. [5][6][7] To hasten hematopoietic recovery after UCB transplant, double UCB grafts or in vitro expansion of UCB cells have been used, with varying success. 6,8 The delayed engraftment of cord blood cells can be readily avoided by third-party donor cells, usually derived from family members, but occasionally also from unrelated donors.…”

Section: Introductionmentioning

confidence: 99%

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Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning

et al. 2019

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Haplo-identical transplant with posttransplant cyclophosphamide (haplo) and umbilical cord blood transplant supported by third-party CD34 cells (haplo-cord) are competing approaches to alternative donor transplant. We compared, in adults younger than age 60 years, the outcomes of 170 haplo at 1 institution with that of 137 haplo-cord at 2 other institutions. All received reduced intensity conditioning with fludarabine and melphalan ± total body irradiation. GVHD prophylaxis for haplo consisted of cyclophosphamide, tacrolimus, and mycophenolate, whereas haplo-cord received antithymocyte globulin, tacrolimus, and mycophenolate. Haplo transplant used mostly bone marrow, and peripheral blood stem cells were used in haplo-cord transplants. Haplo-cord were older and had more advanced disease. Haplo-cord hastened median time to neutrophil (11 vs 18 days, P = .001) and platelet recovery (22 vs 25 days, P = .03). At 4 years, overall survival (OS) was 50% for haplo-cord vs 49% for haplo. Progression-free survival (PFS) was 40% for haplo-cord vs 45% for haplo. In multivariate analysis, the disease risk index was significant for OS (hazard ratio, 1.8; 95% confidence interval, 1.48-2.17; P = .00) and PFS. Total body irradiation was associated with decreased recurrence and improved PFS, age >40 with increased nonrelapse mortality. The type of transplant had no effect on OS, PFS, relapse, or nonrelapse mortality. Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) by day 100 was 16% after haplo-cord vs 33% after haplo (P < .0001), but grade 3-4 GVHD was similar. Chronic GVHD at 1 year was 4% after haplo-cord vs 16% after haplo (P < .0001). Haplo or haplo-cord results in similar and encouraging outcomes. Haplo-cord is associated with more rapid neutrophil and platelet recovery and lower acute and chronic GVHD. Institutional review board authorization for this retrospective study was obtained at each institution. Some patients participated in trials registered at www.clinicaltrials.gov as #NCT01810588 and NCT 01050946.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning

et al. 2019

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“…The patterns of chimerism by day 100, are similar to what has been previously described by our group and others. 15, 20, 39 The cumulative incidence of grade II/IV acute GVHD at day 100 was 9.3% and chronic GVHD at 2 years was only 8%. The incidence of both acute and chronic GVHD is lower than that of double cord blood transplant, as we have previously shown.…”

Section: Discussionmentioning

confidence: 98%

Combined Haploidentical and Umbilical Cord Blood Allogeneic Stem Cell Transplantation for High-Risk Lymphoma and Chronic Lymphoblastic Leukemia

Hsu

Artz

Mayer

et al. 2018

Biology of Blood and Marrow Transplantation

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Limited studies have reported on outcomes for lymphoid malignancy patients receiving alternative donor allogeneic stem cell transplants. We have previously described combining CD34-selected haploidentical grafts with umbilical cord blood (haplo-cord) to accelerate neutrophil and platelet engraftment. Here, we examine the outcome of patients with lymphoid malignancies undergoing haplo-cord transplantation at the University of Chicago and Weill Cornell Medical College. We analyzed 42 lymphoma and chronic lymphoblastic leukemia (CLL) patients who underwent haplo-cord allogeneic stem cell transplantation. Patients underwent transplant for Hodgkin lymphoma (n = 9, 21%), CLL (n = 5, 12%) and non-Hodgkin lymphomas (n = 28, 67%), including 13 T cell lymphomas. Twenty-four patients (52%) had 3 or more lines of therapies. Six (14%) and 1 (2%) patients had prior autologous and allogeneic stem cell transplant, respectively. At the time of transplant 12 patients (29%) were in complete remission, 18 had chemotherapy-sensitive disease, and 12 patients had chemotherapy-resistant disease. Seven (17%), 11 (26%), and 24 (57%) patients had low, intermediate, and high disease risk index before transplant. Comorbidity index was evenly distributed among 3 groups, with 13 (31%), 14 (33%), and 15 (36%) patients scoring 0, 1 to 2, and ≥3. Median age for the cohort was 49 years (range, 23 to 71). All patients received fludarabine/melphalan/antithymocyte globulin conditioning regimen and post-transplant graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil. The median time to neutrophil engraftment was 11 days (range, 9 to 60) and to platelet engraftment 19.5 days (range, 11 to 88). Cumulative incidence of nonrelapse mortality was 11.6% at 100 days and 19 % at one year. Cumulative incidence of relapse was 9.3% at 100 days and 19% at one year. With a median follow-up of survivors of 42 months, the 3-year rates of GVHD relapse free survival, progression-free survival, and overall survival were 53%, 62%, and 65%, respectively, for these patients. Only 8% of the survivors had chronic GVHD. In conclusion, haplo-cord transplantation offers a transplant alternative for patients with recurrent or refractory lymphoid malignancies who lack matching donors. Both neutrophil and platelet count recovery is rapid, nonrelapse mortality is limited, excellent disease control can be achieved, and the incidence of chronic GVHD is limited. Thus, haplo-cord achieves high rates of engraftment and encouraging results.

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“…Our group also noted reduced rates of relapse associated with higher cord blood donor chimerism, similarly suggesting that cord engraftment mediates disease control. 11 Drawing from parallel multi-center Phase 2 trials, Brunstein et al 12 reported outcomes of double unit cord blood transplantation and unmanipulated haplo-marrow transplantation with reduce-intensity conditioning. The 1-year NRM and relapse rates were 24% and 31% in the double UCB transplantation trial, respectively, and 7 and 45%, respectively, in the haplo-marrow trial.…”

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confidence: 99%

Against the odds: haplo-cord grafts protect from GvHD and relapse

Choe

Besien

2017

Bone Marrow Transplant

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Two competing technologies, haplo-identical transplantation and umbilical cord blood transplantation offer curative treatments for malignant and non-malignant hematologic conditions in patients who lack HLA-identical donors. The choice between the two approaches is mostly driven by comparison of long-term cure rates and frequency of complications. But short-term factors such as ease of implementation, procedural cost and duration of initial admission also affect centers' choices. Haplo-identical transplantation with post-transplant cyclophosphamide (PTCy-haplo) for graft versus host disease (GvHD) prophylaxis has garnered considerable interest. 1,2 Most patients have haplo-identical family donors. The procedure is straightforward, can be readily implemented and engraftment is relatively fast compared to commonly used single or double umbilical cord blood (UCB) transplantation. Haplo-cord transplantation, the co-infusion of a cord blood graft with CD34-selected cells from a haploidentical related or unrelated donor obviates the prolonged pancytopenia and lengthy initial hospitalizations associated with UCB transplant. 3 But the CD34 selection of the haplo-graft and the purchase of a cord blood graft pose financial and technical barriers to implementation.Kwon et al. 1 are the first to conduct a comparison of the outcomes of haplo-cord transplantation versus haplo-identical transplantation with post-transplant cyclophosphamide. They find similar long-term survival, progression-free survival, non-relapse mortality (NRM) and rates of disease progression. But the comparison is retrospective and the groups are unevenly poised with most imbalances favoring the PTCy-haplo cohort.First, the cohorts were not contemporaneous: the 51 haplo-cord patients were transplanted over the course of 13 years (1999-2012) with a 'significant proportion' more than 10 years ago in the years 1999-2004an era when cord blood selection methods were not optimal. 4 Conversely, the PTCy-haplo transplants were performed between 2012 and 2014 and therefore have benefited from significant improvements in supportive care and rates of survival after allogeneic transplantation that have occurred over the decade. They also have less prolonged follow-up and thus are less at risk for late adverse events. Second, the PTCy-haplo cohort had more favorable disease characteristics. It included fewer patients transplanted beyond CR1 or with active disease, and there were significantly fewer patients with high/very high disease risk index (DRI) classifications. 5 Finally, a quarter of the haplo-cord cohort received TBI based conditioning, which in contrast to the Bu/Cy regimen that 100% of the PTCy-haplo cohort received has been shown to have worse NRM, relapse beyond 1 year, and lower leukemia-free and overall survival (OS). 6 Thus, three important metrics: the era of transplant, patient's disease characteristics and conditioning regimen favor the PTCy-haplo group. The only factor favoring the haplo-cord group was hematopoietic cell transplant-comorbidity inde...

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Cord blood chimerism and relapse after haplo-cord transplantation

Cited by 24 publications

References 44 publications

Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning

Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning

Combined Haploidentical and Umbilical Cord Blood Allogeneic Stem Cell Transplantation for High-Risk Lymphoma and Chronic Lymphoblastic Leukemia

Against the odds: haplo-cord grafts protect from GvHD and relapse

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