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Impact of bone marrow hematogones on umbilical cord blood transplantation outcomes in patients with acute myeloid leukemia.

ABSTRACT: Early after umbilical cord blood transplantation, patients show marked differences in bone marrow (BM) hematogone percentages. Little is known about whether these differences are clinically relevant. We hypothesized that early recovery of hematogones may be associated with improved transplantation outcomes. BM aspirates were assessed from 88 patients with acute myeloid leukemia by two independent reviewers at day 21 and 100 after umbilical cord blood transplantation. Interobserver variability for BM hematogone percentages at these time points showed correlation coefficients of 0.83 and 0.98, respectively (P ? .01 for both). A high percentage of hematogones at day 21 was associated with less acute graft-versus-host disease grade 3 to 4 (P = .01). At day 100, a high percentage of BM hematogones was associated with improved overall survival (P = .02) and lower treatment-related mortality (P ? .01). This study shows that BM hematogone percentages may be useful prognostic indicators in patients with acute myeloid leukemia after umbilical cord blood transplantation and should be routinely reported in BM differential counts.

SUBMITTER: Honebrink T

PROVIDER: S-EPMC4378716 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Impact of bone marrow hematogones on umbilical cord blood transplantation outcomes in patients with acute myeloid leukemia.

Honebrink Theodore T Dayton Vanessa V Burke Michael J MJ Larsen Karen K Cao Qing Q Brunstein Claudio C Weisdorf Daniel D Miller Jeffery S JS Wagner John E JE Verneris Michael R MR

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20111120 6

Early after umbilical cord blood transplantation, patients show marked differences in bone marrow (BM) hematogone percentages. Little is known about whether these differences are clinically relevant. We hypothesized that early recovery of hematogones may be associated with improved transplantation outcomes. BM aspirates were assessed from 88 patients with acute myeloid leukemia by two independent reviewers at day 21 and 100 after umbilical cord blood transplantation. Interobserver variability fo ...[more]

PMID: 22108570

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Project description: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.

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

Impact of bone marrow hematogones on umbilical cord blood transplantation outcomes in patients with acute myeloid leukemia.

Publications

Impact of bone marrow hematogones on umbilical cord blood transplantation outcomes in patients with acute myeloid leukemia.

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