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Effect of conditioning regimen intensity on acute myeloid leukemia outcomes after umbilical cord blood transplantation.

ABSTRACT: Reduced-intensity conditioning (RIC) umbilical cord blood (UCB) transplantation is increasingly used in hematopoietic stem cell transplantation (HCT) for older and medically unfit patients. Data on the efficacy of HCT after RIC relative to myeloablative conditioning (MAC) are limited. We compared the outcomes of acute myeloid leukemia (AML) patients >18 yrs who received UCB grafts after either RIC or MAC. One hundred nineteen adult patients with AML in complete remission (CR) underwent an UCB transplant after RIC (n =74, 62%) or MAC (n = 45, 38%) between January 2001 and December 2009. Conditioning was either reduced intensity and consisted of cyclophosphamide 50 mg/kg, fludarabine 200 mg/m(2), and total-body irradiation (TBI) 200 cGy or myelablative and consisted for cyclophosphamide 120 mg/kg, fludarabine 75 mg/m(2), and TBI 1200-1320 cGy. All patients received cyclosporine (day -3 to day +180) and mycophenolate mofetil (day -3 to day +45) post-HCT immunosuppression and hematopoietic growth factor. Use of RIC was reserved for patients >45 years (n = 66, 89%) or preexisting severe comorbidities (n = 8, 11%). The 2 groups were similar except for preceding myelodysplastic syndrome (RIC = 28% versus MAC = 4%, P < .01) and age that was dictated by the treatment protocols (median, RIC = 55 years versus MAC = 33years; P < .01). The incidence of neutrophil recovery at day +42 was higher with RIC (94% versus MAC = 82%, P < .1), whereas platelet recovery at the sixth month was similar (RIC = 68% versus MAC = 67%, P = .30). Incidence of grade II-IV acute graft-versus-host disease (aGVHD) (RIC = 47% versus MAC = 67%, P < .01) was decreased with similar incidence of chronic GVHD (cGVHD) (RIC = 30% versus MAC = 34%, P = .43). Median follow-up for survivors was 3.8 and 4.5 years for RIC and MAC, respectively (P = .4). Using RIC, 3-year leukemia-free survival (LFS) was decreased (31% versus MAC = 55%, P = .02) and 3-year relapse incidence was increased (43% versus MAC = 9%, P < .01). Two-year transplant-related mortality (TRM) was similar (RIC = 19% versus MAC = 27%; P = .55). In multivariate analysis, RIC recipients and those in CR2 with CR1 duration <1 year had higher risk of relapse and poorer LFS with no independent predictors of TRM. UCB with RIC extends the use of allogeneic HCT for older and frail patients without excessive TRM with greater benefit for patients in CR1 and CR2 with longer CR1.

SUBMITTER: Oran B

PROVIDER: S-EPMC4130206 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Effect of conditioning regimen intensity on acute myeloid leukemia outcomes after umbilical cord blood transplantation.

Oran Betul B Wagner John E JE DeFor Todd E TE Weisdorf Daniel J DJ Brunstein Claudio G CG

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20110111 9

Reduced-intensity conditioning (RIC) umbilical cord blood (UCB) transplantation is increasingly used in hematopoietic stem cell transplantation (HCT) for older and medically unfit patients. Data on the efficacy of HCT after RIC relative to myeloablative conditioning (MAC) are limited. We compared the outcomes of acute myeloid leukemia (AML) patients >18 yrs who received UCB grafts after either RIC or MAC. One hundred nineteen adult patients with AML in complete remission (CR) underwent an UCB tr ...[more]

PMID: 21232621

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Project description:The high incidence of human herpesvirus-6 (HHV-6) reactivation, potentially interfering with engraftment after umbilical cord blood (UCB) hematopoietic cell transplantation (HCT), remains a major challenge. To potentially address this problem, we evaluated the effect of prophylactic foscarnet administered twice daily beginning on day +7 and continuing through engraftment in 25 patients. To determine the impact of foscarnet on HHV-6, engraftment, and other transplantation outcomes, we compared results in 61 identically treated patients with hematologic malignancies. Treatment and control groups underwent reduced-intensity conditioning UCB HCT with a conditioning regimen of fludarabine, cyclophosphamide, and total body irradiation 200 cGy with or without antithymocyte globulin (ATG), using sirolimus plus mycophenolate mofetil immune suppression. The treatment and control groups were similar in terms of age, disease risk, use of ATG, Hematopoietic Cell Transplantation Comorbidity Index, and graft CD34 cell dose; however, foscarnet-treated patients were less likely to receive a double UCB graft and to be treated more recently (2016 to 2018). The cumulative incidence of HHV-6 reactivation by day +100 was 63% for all patients (95% confidence interval [CI], 51% to 75%) and was not significantly different between the 2 groups. HHV-6 reactivation occurred at a median of 34 days in the foscarnet group and 25.5 days in the control group. The incidence of neutrophil engraftment at day 42 was higher in the foscarnet group compared with the control group (96%; [95% CI, 83% to 100%] versus 75% [95% CI, 64% to 85%]; P< .01). The cumulative incidence of platelet engraftment by 6 months was 92% (95% CI, 69% to 100%) for the foscarnet group versus 75% (95% CI, 60% to 90%) for the control group (P= .08), and multivariate analysis identified the use of foscarnet as an independent predictor of better platelet engraftment. No patients died as a result of graft failure in recipients of foscarnet, whereas 5 patients died from graft failure in the control group. Six-month overall survival (OS) and nonrelapse mortality (NRM) were better in the foscarnet group (96% versus 72% [P= .02] and 4% versus 18% [P= .07], respectively). Even though foscarnet prophylaxis did not prevent HHV-6 viremia, we observed a delay in time to HHV-6 reactivation, a trend toward differences in engraftment, NRM, and OS compared with historical controls.

Project description:For patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation, umbilical cord blood transplantation (UCBT) has become an acceptable alternative donor source in the absence of a matched sibling or unrelated donor. To date, however, there have been few published series dedicated solely to describing the outcomes of adult patients with myelodysplastic syndrome (MDS) who have undergone UCBT. Between 2004 and 2013, 176 adults with MDS underwent UCBT as reported to the Center for International Blood and Marrow Transplant Research. Median age at the time of transplantation was 56 years (range, 18-73 years). The study group included 10% with very low, 23% with low, 19% with intermediate, 19% with high, and 13% with very high-risk Revised International Prognostic Scoring System (IPSS-R) scores. The 100-day probability of grade II-IV acute graft-versus-host disease (GVHD) was 38%, and the 3-year probability of chronic GVHD was 28%. The probabilities of relapse and transplantation-related mortality (TRM) at 3 years were 32% and 40%, respectively, leading to a 3-year disease-free survival (DFS) of 28% and an overall survival (OS) of 31%. In multivariate analysis, increasing IPSS-R score at the time of HCT was associated with inferior TRM (P = .0056), DFS (P = .018), and OS (P = .0082), but not with GVHD or relapse. The presence of pretransplantation comorbidities was associated with TRM (P = .001), DFS (P = .02), and OS (P = .001). Reduced-intensity conditioning was associated with increased risk of relapse (relative risk, 3.95; 95% confidence interval, 1.78-8.75; P < .001), and although a higher proportion of myeloablative UCBTs were performed in patients with high-risk disease, the effect of conditioning regimen intensity was the same regardless of IPSS-R score. For some individuals who lack a matched sibling or unrelated donor, UCBT can result in long-term DFS; however, the success of UCBT in this population is hampered by a high rate of TRM.

Dataset Information

Effect of conditioning regimen intensity on acute myeloid leukemia outcomes after umbilical cord blood transplantation.

Publications

Effect of conditioning regimen intensity on acute myeloid leukemia outcomes after umbilical cord blood transplantation.

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