Frequency and Risk Factors Associated with Cord Graft Failure after Transplant with Single-Unit Umbilical Cord Cells Supplemented by Haploidentical Cells with Reduced-Intensity Conditioning

Tsai, Stephanie B.; Liu, Hongtao; Shore, Tsiporah B.; Fan, Yun; Bishop, Michael; Cushing, Melissa M.; Gergis, Usama; Godley, Lucy A.; Kline, Justin; Larson, Richard A.; Martinez, Guadalupe; Mayer, Sebastian; Odenike, Olatoyosi; Stock, Wendy; Wickrema, Amittha; Besien, Koen van; Artz, Andrew S.

doi:10.1016/j.bbmt.2016.02.010

Cited by 17 publications

(12 citation statements)

References 59 publications

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“…We continue efforts to enhance UCB engraftment in this setting by limiting the cell dose of the haplo-identical graft, 4;6 avoiding haplo-grafts which are matched to the recipient at more than 5 of 8 HLA-alleles, 44 by avoiding grafts targeted by donor specific antibodies and by selecting appropriate cord blood units. 9 …”

Section: Discussionmentioning

confidence: 99%

“…But there are occasional cases where the cord blood graft fails and recipients are left with a permanent adult mismatched graft, or more commonly mixed chimerism. 6 In a previous report, we analyzed causes of umbilical cord graft failure. 6 Here we studied the implications of patterns of engraftment on disease recurrence in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).…”

Section: Introductionmentioning

confidence: 99%

“…6 In a previous report, we analyzed causes of umbilical cord graft failure. 6 Here we studied the implications of patterns of engraftment on disease recurrence in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To this purpose we focused on patients who were in remission with functioning grafts two months after transplant ensuring the study of durable patterns of chimerism.…”

Section: Introductionmentioning

confidence: 99%

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Cord blood chimerism and relapse after haplo-cord transplantation

Besien

Koshy

Gergis

et al. 2016

Leukemia & Lymphoma

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Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic GVHD. But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with AML and MDS, engrafted and in remission at 2 months. Median age was 66 (18-72) and all had intermediate, high, or very high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% vs 11% P<0.0001) and decrease in one year progression-free (20% vs 55%, P=0.004) and overall survival (30% vs 62%, P=0.02). Less than 100% UCB chimerism in the CD3 lineage was associated with increase rate of disease recurrence (46% vs 12%, P=0.007) Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% vs 15%, P=0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful GVL effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cord blood chimerism and relapse after haplo-cord transplantation

Besien

Koshy

Gergis

et al. 2016

Leukemia & Lymphoma

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“…5, 6,7,8,9 To improve the neutrophil and platelet engraftment and take advantage of the low incidence of graft-versus-host-disease (GVHD), we and others previously reported combining haploidentical donor grafts with cord blood stem cells. 10–14 The haploidentical graft provides a “myeloid bridge” that allows for rapid neutrophil and platelet recovery and that –with rare exceptions 15 - is eventually replaced by the cord blood cells. We and other have previously reported on patterns of chimerism, 14, 16–18 its consequences and of immune reconstitution 19, 20 after this procedure.…”

Section: Introductionmentioning

confidence: 99%

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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“…In previous studies we found that patients who received very high CD34 doses from the haplo-identical donor had impaired/delayed umbilical cord blood engraftment. 6 More recently we have limited the cell dose of the haplo-graft to ~3 ×10 6 CD34/kg rec . But occasional cases of haplo-dominance continue to occur.…”

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confidence: 99%