Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia

Scaradavou, Andromachi; Brunstein, Claudio G.; Eapen, Mary; Le‐Rademacher, Jennifer; Barker, Juliet N.; Chao, Nelson J.; Cutler, Corey; Delaney, Colleen; Kan, Fangyu; Isola, Luis; Karanes, Chatchada; Laughlin, Mary J.; Wagner, John E.; Shpall, Elizabeth J.

doi:10.1182/blood-2012-08-449108

Cited by 184 publications

(142 citation statements)

References 29 publications

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“…20 There are several differences between that study and the one we report here. The CIBMTR study analyzed patients in all disease states while we focused only on patients given UCBT for acute leukemia in first complete remission.…”

Section: Discussioncontrasting

confidence: 52%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 52%

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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“…Despite the results in univariate analysis showing that double UCBT was associated with improved LFS, graft type was not isolated as a risk factor in the final multivariate model probably because the type of graft was related to the disease status at transplantation, that is, more patients with advanced disease received a single CBU compared with patients transplanted in CR (data not shown). Indeed, in the literature it is still controversial if double CBU is associated with higher a GVL effect and improved outcome; [29][30][31][32][33] and to address this question, a specific study designed to address this question has to be performed.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for outcomes after unrelated cord blood transplantation for adults with acute lymphoblastic leukemia: a report on behalf of Eurocord and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Tucunduva

Ruggeri

Sanz

et al. 2014

Bone Marrow Transplant

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We performed a retrospective analysis on 421 adult patients who underwent unrelated cord blood transplantation (UCBT) for ALL. Median age was 32 years; 46% were in first CR (CR1), 32% in CR2 and 22% had advanced disease. Double UCBT was performed in 173 patients (41%). Myeloablative conditioning (MAC) was given to 314 patients (75%). Cumulative incidence (CI) of 60-day neutrophil recovery was 78%. CI of acute and chronic GVHD was 33 and 26%, respectively. Non-relapse mortality (NRM) at 2 years was 42%. Age ⩾ 35 years (P o 0.0001), advanced disease at UCBT (P o 0.0001) and use of MAC (P o 0.0001) were associated with increased NRM. Relapse incidence (RI) at 2 years was 28%; use of reduced intensity conditioning (RIC) (P = 0.0002) was associated with increased RI. Two-year leukemia-free survival (LFS) was 39% for patients in CR1, 31% for CR2 and 8% for advanced disease. In multivariate analysis, factors associated with decreased LFS rate were: age ⩾ 35 years (P = 0.034), use of MAC (P = 0.032) and advanced disease (P o0.0001). These results show that UCBT is a valuable option to treat high-risk adult ALL when in remission. Strategies to decrease toxicity and relapse are needed to improve final outcomes.

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“…These findings should be externally validated in other large adult cohorts. Recently, transplantation using double UCB units has been increasingly performed in adults in the USA and Europe, as it is difficult to find UCB units capable of providing a sufficiently large total nucleated cell dose per recipient weight in adults, since the average adult body weight is higher than that in Asian countries [37,38]. The impact of HLA mismatch between a recipient and UCB units or between UCB units in double UCBT will also be explored in the future.…”

Section: Effects Of Hla Mismatch In Ucbtmentioning

confidence: 99%

Effect of HLA mismatch on acute graft-versus-host disease

Kanda

2013

Int J Hematol

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HLA matching between donors and recipients is the most important factor associated with acute graftversus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. With improvements in GVHD prophylaxis and supportive care, transplantations from HLA mismatched donors are performed increasingly frequently, drawing greater attention to the effects of HLA mismatch. In related transplantation, HLA 1-antigen mismatch at the HLA-A, HLA-B, and HLA-DR loci is considered acceptable, but the incidence of severe acute GVHD under standard prophylaxis is higher than that for matched related and unrelated transplantation, highlighting the need for a modification of GVHD prophylaxis. Development of new GVHD prophylaxes has now made HLA 2-3-antigen mismatched related transplantation feasible, and has almost overcome the HLA barrier. In unrelated bone marrow or peripheral blood stem cell transplantation, donors matched for HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles are the most preferable. The impact of allele or antigen mismatch has been evaluated in a number of studies, but the results of these have not been consistent, partly due to differences in race and HLA distribution. The effects of HLA mismatch may differ depending on the year of transplantation and the form of GVHD prophylaxis administered. In cord blood transplantation, successful transplantation can be achieved with up to two HLA mismatches. In children, compared to the use of HLA mismatched units, the use of HLA-matched units is associated with a lower risk of acute GVHD and mortality, while in adults HLA mismatches may have a lower impact on outcome. Thus, the effect of HLA matching should be evaluated separately for different stem cell sources.

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Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia

Cited by 184 publications

References 29 publications

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

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

Risk factors for outcomes after unrelated cord blood transplantation for adults with acute lymphoblastic leukemia: a report on behalf of Eurocord and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Effect of HLA mismatch on acute graft-versus-host disease

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