Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood

Brunstein, Claudio G.; Gutman, Jonathan A.; Weisdorf, Daniel J.; Woolfrey, Ann E.; DeFor, Todd E.; Gooley, Theodore A.; Verneris, Michael R.; Appelbaum, Frederick R.; Wagner, John E.; Delaney, Colleen

doi:10.1182/blood-2010-05-285304

Cited by 447 publications

(378 citation statements)

References 37 publications

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“…These include pretransplantation treatment aimed at decreasing MRD levels with new drugs, such as clofarabine 35,36 and nelarabine 37 used in combination with other cytotoxic agents, use of the anti-CD19/antiCD3 bi-specific monoclonal antibody blinatunomab, 38 use of midostaurin for MLL rearranged ALL cases, or use of tyrosine kinase inhibitors for Ph-positive ALL. 39 Less intensive GvHD prophylaxis, rapid withdrawal of immunosuppression, 40 cell-based immunotherapy 41,42 (that is, leukemia-reactive cytotoxic T cells) or use of double UCBT 43,44 can also be useful in the perspective of increasing the GVL effect. However, only well-designed prospective trials may provide sound evidence on the efficacy of these approaches.…”

Section: Discussionmentioning

confidence: 99%

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

et al. 2012

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To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR) ¼ 0.4, P ¼ 0.01) and for those transplanted in CR1 and CR2 (HR ¼ 0.3, P ¼ 0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P ¼ 0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR ¼ 2, P ¼ 0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes.

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Section: Discussionmentioning

confidence: 99%

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

et al. 2012

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“…Long-term survival in patients with UCB appears comparable to those receiving URD transplants; however, nonrelapse mortality is higher, [47] due to slower engraftment and more frequent infection. The use of two separate cord donations in cases where CD34þ cell numbers of individual units is insufficient has improved engraftment and overall results [48].…”

Section: Ucb Donormentioning

confidence: 99%

Concise Review: The Role of Hematopoietic Stem Cell Transplantation in the Treatment of Acute Myeloid Leukemia

Hamilton

Copelan

2012

STEM CELLS

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Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for patients with acute myeloid leukemia (AML). Our understanding of the biology of leukemic stem cells has continued to improve over the last decade and risk stratification using cytogenetics and molecular markers have improved our ability to select patients who would benefit from allogeneic transplantation. Results of HSCT have also improved substantitally, extending the potential application of allogeneic transplant to more patients. This review discusses the theoretical aspects of transplant, analyzes clinical results, and provides recommendations for the use of HSCT in AML. Further study of the biology of leukemic stem cells and the role for HSCT is necessary to optimize outcomes in AML patients.

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“…4 Adult patients treated for AML or ALL have lower relapse rates with UCBT compared with other stem cell sources, but higher treatment-related mortality (TRM) and overall similar survival. 5 Only~30% of patients who require allogeneic stem cell transplantation (alloSCT) will have a matched sibling donor. Many patients without a matched sibling will have an adult MUD, but this is often not the case in patients from ethnic minorities.…”

mentioning

confidence: 99%

Umbilical cord blood graft engineering: challenges and opportunities

Thompson

Rezvani

Hosing

et al. 2015

Bone Marrow Transplant

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We are entering a very exciting era in umbilical cord blood transplantation (UCBT), where many of the associated formidable challenges may become treatable by ex vivo graft manipulation and/or adoptive immunotherapy utilizing specific cellular products. We envisage the use of double UCBT rather than single UCBT for most patients; this allows for greater ability to treat larger patients as well as to manipulate the graft. Ex vivo expansion and/or fucosylation of one cord will achieve more rapid engraftment, minimize the period of neutropenia and also give certainty that the other cord will provide long-term engraftment/immune reconstitution. The non-expanded (and future dominant) cord could be chosen for characteristics such as better HLA matching to minimize GvHD, or larger cell counts to enable part of the unit to be utilized for the development of specific cellular therapies such as the production of virus-specificT-cells or chimeric-antigen receptor T-cells which are reviewed in this study.

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Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood

Cited by 447 publications

References 37 publications

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP–EBMT analysis

Concise Review: The Role of Hematopoietic Stem Cell Transplantation in the Treatment of Acute Myeloid Leukemia

Umbilical cord blood graft engineering: challenges and opportunities

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