Topping it up: methods to improve cord blood transplantation outcomes by increasing the number of CD34+ cells

Lindemans, Caroline A.; Besien, Koen van

doi:10.1016/j.jcyt.2015.02.005

Cited by 8 publications

(7 citation statements)

References 47 publications

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“…1–3 This combination allows faster count recovery than is observed after transplantation of single or double UBC by providing initial engraftment of the third party source, followed by permanent UCB engraftment. 4;5 It also allows the use of smaller better HLA-matched UCB grafts thus leading to a low rate of acute and chronic graft-versus-host disease (GVHD).…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

Cord blood chimerism and relapse after haplo-cord transplantation

Besien

Koshy

Gergis

et al. 2016

Leukemia & Lymphoma

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“…In its absence, severe rejection and prolonged second nadirs have been reported. 15,34 The use of ATG has been controversial because of concerns over higher rates of disease recurrence and increased rates of infections, toxicity and post-transplant lymphoproliferative disease. 35 Increasing evidence, supported by our findings, suggests that many side-effects are dose related and that with appropriate dosing and monitoring, rabbit ATG is safe and not associated with increased rates of disease recurrence.…”

Section: Discussionmentioning

confidence: 99%

“…10 We and others have investigated an alternative strategy: the use of third-party CD34 selected adult haplo-identical stem cells to supplement a single UCB stem cell graft. [11][12][13][14][15] In an initial report using a reduced intensity conditioning approach, we showed encouraging rates of engraftment and of long-term outcome. 16 We also showed how the initial engraftment of the haplo-identical stem cells was, in the large majority of cases, ultimately superseded by the outgrowth of UCB cells.…”

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confidence: 99%

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

et al. 2016

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Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant).Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II-IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. ABSTRACT

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“…Eapen et al37 found that with the TNC >3.0×10 7 /kg, the overall outcome significantly improved in children with acute leukemia. The CD34 + dose in a CB graft is on average 1–2 log smaller than in an unrelated BM or peripheral blood stem cell graft 38. Many strategies mentioned in the Introduction are utilized to overcome the low dose limitation in CB.…”

Section: Discussionmentioning

confidence: 99%

Umbilical cord blood transplantation supplemented with the infusion of mesenchymal stem cell for an adolescent patient with severe aplastic anemia: a case report and review of literature

Luan¹,

Chen²,

Chen³

et al. 2015

PPA

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Delayed hematopoietic recovery and increased rate of engraftment failure limit the use of umbilical cord blood transplantation (UCBT). We describe a case of severe aplastic anemia treated by UCBT combined with mesenchymal stem cells. Our case reveals that infusing mesenchymal stem cells early (about 40 days) after UCBT may promote hematopoietic recovery. This experience will guide clinical scientists, especially hematologists, to deal with similar situations and encourage them to widen this strategy.

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Topping it up: methods to improve cord blood transplantation outcomes by increasing the number of CD34+ cells

Cited by 8 publications

References 47 publications

Cord blood chimerism and relapse after haplo-cord transplantation

Cord blood chimerism and relapse after haplo-cord transplantation

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

Umbilical cord blood transplantation supplemented with the infusion of mesenchymal stem cell for an adolescent patient with severe aplastic anemia: a case report and review of literature

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Topping it up: methods to improve cord blood transplantation outcomes by increasing the number of CD34+ cells

Cited by 8 publications

References 47 publications

Cord blood chimerism and relapse after haplo-cord transplantation

Cord blood chimerism and relapse after haplo-cord transplantation

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

Umbilical cord blood transplantation supplemented with the infusion of mesenchymal stem cell for an adolescent patient with severe aplastic anemia: a case report and review of&nbsp;literature

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Umbilical cord blood transplantation supplemented with the infusion of mesenchymal stem cell for an adolescent patient with severe aplastic anemia: a case report and review of literature