Double cord blood transplantation: extending the use of unrelated umbilical cord blood cells for patients with hematological diseases

Rocha, Vanderson; Crotta, Alessandro; Ruggeri, Annalisa; Purtill, Duncan; Boudjedir, Karim; Herr, Andrée-Laure; Ionescu, Irina; Gluckman, Éliane

doi:10.1016/j.beha.2010.07.005

Cited by 56 publications

(54 citation statements)

References 19 publications

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“…Only 1 of 17 patients receiving RCD grafts developed acute GvHD, and 1 of 11 evaluable patients developed chronic GvHD; frequencies much lower than previously reported even when ATG has been used [3,36,38]. Further studies with more patients are required to confirm this observation.…”

Section: Discussionmentioning

confidence: 73%

“…Delayed engraftment, however, remains a significant limitation due to low cell doses in UCB units. Strategies to overcome this limitation include use of multiple cord blood units [2,3], ex vivo expansion of UCB stem cells [4], and co-infusion of third party haploidentical CD34 + cells [5,6], but technical obstacles, complexity of procedures, and/or economic considerations may limit their widespread use.…”

Section: Introductionmentioning

confidence: 99%

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In Vivo DPP-4 Inhibition to Enhance Engraftment of Single-Unit Cord Blood Transplants in Adults with Hematological Malignancies

Farag

Srivastava

Messina-Graham

et al. 2013

Stem Cells and Development

119

117

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Delayed engraftment is a significant limitation of umbilical cord blood (UCB) transplantation due to low stem cell numbers. Inhibition of dipeptidyl peptidase (DPP)-4 enhanced engraftment in murine transplants. We evaluated the feasibility of systemic DPP-4 inhibition using sitagliptin to enhance engraftment of single-unit UCB grafts in adults with hematological malignancies. Twenty-four patients (21-58 years) received myeloablative conditioning, followed by sitagliptin 600 mg orally days -1 to + 2, and single UCB grafts day 0. Seventeen receiving red cell-depleted (RCD) grafts, matched at 4 (n = 10) or 5 (n = 7) of 6 human leucocyte antigen (HLA) loci with median nucleated cell dose 3.6 (2.5-5.2) · 10 7 /kg, engrafted at median of 21 (range, 13-50) days with cumulative incidence of 94% (95% confidence interval, 84%-100%) at 50 days. Plasma DDP-4 activity was reduced to 23% -7% within 2 h. Area under DPP-4 activity-time curve (AUC A ) correlated with engraftment; 9 of 11 with AUC A < 6,000 activity$h engrafted within £ 21 days, while all 6 with higher AUC A engrafted later (P = 0.002). Seven patients receiving red cell replete grafts had 10-fold lower colony forming units after thawing compared with RCD grafts, with poor engraftment. Systemic DPP-4 inhibition was well tolerated and may enhance engraftment. Optimizing sitagliptin dosing to achieve more sustained DPP-4 inhibition may further improve outcome.

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Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

In Vivo DPP-4 Inhibition to Enhance Engraftment of Single-Unit Cord Blood Transplants in Adults with Hematological Malignancies

Farag

Srivastava

Messina-Graham

et al. 2013

Stem Cells and Development

119

117

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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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“…The possibility of using two cord blood units has extended the use of UCBT to patients for whom a single unit containing a minimum of 2.5x10 7 /kg total nucleated cells is not available. [17][18][19] Studies have been performed comparing outcomes after single (s) UCBT and double (d) UCBT, 20 but, none focused on a homo-geneous population.…”

Section: Introductionmentioning

confidence: 99%

Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France

Labopin¹,

Ruggeri²,

Gorin³

et al. 2013

Haematologica

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IntroductionAllogeneic stem cell transplantation (HSCT) is effective treatment for patients with various hematologic disorders. It is, however, a complex, resource-intense and costly procedure. [1][2][3][4] The cost of HSCT has been previously evaluated, mainly in the setting of HLA identical sibling 5 and matched unrelated donor transplants.The first studies on the cost-efficacy of HSCT compared allogeneic HSCT to chemotherapy in patients with acute leukemia. 7,8 Despite the high cost of HSCT, the results demonstrated the advantages of the procedure due to the impact on long-term survival adjusted to the quality of life. In the first published studies, the estimated costs for HSCT varied greatly (Online Supplementary Table S1) depending on the country in which they were performed, type of donor, transplant center procedures and year of transplantation. 5,7,[9][10][11] A more recent comparative study of autologous and allogeneic HSCT for patients transplanted for hematologic malignancies in the USA estimated a 100-day total cost of US$ 203,026 for allogeneic HSCT. 12 Unrelated donor cord blood transplantation (UCBT) has become a widely accepted transplant modality in the absence of an HLA-matched donor. [13][14][15][16] However, the delay of engraftment and the increased risk of graft failure remain problems in adults transplanted with a single cord blood unit. The possibility of using two cord blood units has extended the use of UCBT to patients for whom a single unit containing a minimum of 2.5x10 7 /kg total nucleated cells is not available. [17][18][19] Studies have been performed comparing outcomes after single (s) UCBT and double (d) UCBT,20 but, none focused on a homo- open-access paper. doi:10.3324/haematol.2013.092254 The online version of this article has a Supplementary Appendix. Manuscript received on May 27, 2013. Manuscript accepted on October 14, 2013 Double cord blood transplantation extends the use of cord blood to adults for whom a single unit is not available, but the procedure is limited by its cost. To evaluate outcomes and cost-effectiveness of double compared to single cord blood transplantation, we analyzed 134 transplants in adults with acute leukemia in first remission. Transplants were performed in France with reduced intensity or myeloablative conditioning regimens. Costs were estimated from donor search to 1 year after transplantation. A Markov decision analysis model was used to calculate qualityadjusted life-years and cost-effectiveness ratio within 4 years. The overall survival at 2 years after single and double cord blood transplants was 42% versus 62%, respectively (P=0.03), while the leukemia-free-survival was 33% versus 53%, respectively (P=0.03). The relapse rate was 21% after double transplants and 42% after a single transplant (P=0.006). No difference was observed for non-relapse mortality or chronic graft-versus-host-disease. The estimated costs up to 1 year after reduced intensity conditioning for single and double cord blood transplantation were € 165,253 and €191,...

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Double cord blood transplantation: extending the use of unrelated umbilical cord blood cells for patients with hematological diseases

Cited by 56 publications

References 19 publications

In Vivo DPP-4 Inhibition to Enhance Engraftment of Single-Unit Cord Blood Transplants in Adults with Hematological Malignancies

In Vivo DPP-4 Inhibition to Enhance Engraftment of Single-Unit Cord Blood Transplants in Adults with Hematological Malignancies

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

Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France

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