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Allogeneic transplantation for advanced acute myeloid leukemia: The value of complete remission.

ABSTRACT: BACKGROUND:Patients with acute myeloid leukemia (AML) without complete remission (CR) or in first relapse (Rel1) can have extended leukemia control and survival after allogeneic hematopoietic cell transplantation (HCT). For patients in Rel1 or primary induction failure (PIF), transplantation versus treatment to achieve a second CR (CR2) and subsequent HCT might yield similar outcomes, but available comparative data are scarce. METHODS:Survival was analyzed in 4682 HCT recipients according to disease status: PIF (N = 1440), Rel1 (failing ?1 reinduction; N = 1256), and CR2 (N = 1986). RESULTS:Patient, disease, and transplantation characteristics were similar, except that patients in CR2 more often had performance scores of 90% to 100%, de novo AML, and longer CR1 duration. Adverse cytogenetics were more common in patients who experienced PIF. The 5-year survival rate adjusted for performance score, cytogenetic risk, and donor type for CR2 was 39% (95% confidence interval [CI], 37%-41%) compared with 18% (95% CI, 16%-20%) for HCT in Rel1 and 21% (95% CI, 19%-23%) in PIF (P < .0001). CONCLUSIONS:Although survival is superior for patients who undergo HCT in CR2, transplantation for selected patients in Rel1 or PIF may still be valuable. These data can guide decision making about additional salvage therapy versus prompt HCT for patients not in CR, but they also highlight that AML is intrinsically more treatable in patients who have favorable-risk cytogenetics, those with longer CR1 duration, and younger patients with better performance status. Cancer 2017;123:2025-2034. © 2017 American Cancer Society.

SUBMITTER: Weisdorf DJ

PROVIDER: S-EPMC5445001 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Allogeneic transplantation for advanced acute myeloid leukemia: The value of complete remission.

Weisdorf Daniel J DJ Millard Heather R HR Horowitz Mary M MM Hyare Parvinder S PS Champlin Richard R Ho Vincent V Mielcarek Marco M Rezvani Andrew A Stockerl-Goldstein Keith K Khoury Hanna J HJ De Lima Marcos M Saber Wael W Sandmaier Brenda B Zhang Mei Jie MJ Eapen Mary M

Cancer 20170124 11

<h4>Background</h4>Patients with acute myeloid leukemia (AML) without complete remission (CR) or in first relapse (Rel1) can have extended leukemia control and survival after allogeneic hematopoietic cell transplantation (HCT). For patients in Rel1 or primary induction failure (PIF), transplantation versus treatment to achieve a second CR (CR2) and subsequent HCT might yield similar outcomes, but available comparative data are scarce.<h4>Methods</h4>Survival was analyzed in 4682 HCT recipients a ...[more]

PMID: 28117884

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Project description:To identify favored choice of transplantation in patients with acute promyelocytic leukemia (APL) in second complete remission, we studied 294 patients with APL in second complete remission (CR2) receiving allogeneic (n = 232) or autologous (n = 62) hematopoietic cell transplantation (HCT) reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR) from 1995 to 2006, including 155 with pre-HCT PML/RAR? status (49% of allogeneic and 66% of autologous). Patient characteristics and transplantation characteristics, including treatment-related mortality, overall survival (OS), and disease-free survival, were collected and analyzed for both univariate and multivariate outcomes. With median follow-up of 115 (allogeneic) and 72 months (autologous), 5-year disease-free survival (DFS) favored autologous with 63% (49% to 75%), compared with allogeneic at 50% (44% to 57%) (P = .10). OS was 75% (63% to 85%) versus 54% (48% to 61%) (P = .002), for autologous and allogeneic transplantation, respectively. Multivariate analysis showed significantly worse DFS after allogeneic HCT (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.16 to 3.06; P = .011) and age > 40 years (HR, 2.30; 95% CI, 1.44 to 3.67; P = .0005). OS was significantly worse after allogeneic HCT (HR, 2.66; 95% CI, 1.52 to 4.65; P= .0006); age > 40 (HR, 3.29; 95% CI, 1.95 to 5.54; P < .001), and first complete remission < 12 months (HR, 1.56; 95% CI, 1.07 to 2.26; P = .021). Positive pre-HCT PML-RAR? status in 17 of 114 allogeneic and 6 of 41 receiving autologous transplantation did not influence relapse, treatment failure, or survival in either group. The survival advantage for autografting was attributable to increased treatment-related mortality (TRM) in the allogeneic group of 30% compared to 2% in the autologous group, in addition to the added mortality associated with GVHD. We conclude that autologous HCT yields superior OS for APL in CR2. Long-term DFS in autologous recipients, even with minimal residual disease-positive grafts, remains an important subject for further study.

Project description:Hematopoietic stem cell transplantation (HSCT) and consolidation chemotherapy have been used to treat intermediate-risk acute myeloid leukemia (AML) patients in first complete remission (CR1). However, it is still unclear which treatments are most effective for these patients. The aim of our study was to analyze the relapse-free survival (RFS) and overall survival (OS) benefit of allogeneic HSCT (alloHSCT) for intermediate-risk AML patients in CR1. A meta-analysis of prospective trials comparing alloHSCT to non-alloHSCT (autologous HSCT [autoHSCT] and/or chemotherapy) was undertaken. We systematically searched PubMed, Embase, and the Cochrane Library though October 2014, using keywords and relative MeSH or Emtree terms, 'allogeneic'; 'acut*' and 'leukem*/aml/leukaem*/leucem*/leucaem*'; and 'nonlympho*' or 'myelo*'. A total of 7053 articles were accessed. The primary outcomes were RFS and OS, while the secondary outcomes were treatment-related mortality (TRM) and relapse rate (RR). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for each outcome. The primary outcomes were RFS and OS, while the secondary outcomes were TRM and RR. We included 9 prospective controlled studies including 1950 adult patients. Patients with intermediate-risk AML in CR1 who received either alloHSCT or non-alloHSCT were considered eligible. AlloHSCT was found to be associated with significantly better RFS, OS, and RR than non-alloHSCT (HR, 0.684 [95% CI: 0.48, 0.95]; HR, 0.76 [95% CI: 0.61, 0.95]; and HR, 0.58 [95% CI: 0.45, 0.75], respectively). TRM was significantly higher following alloHSCT than non-alloHSCT (HR, 3.09 [95% CI: 1.38, 6.92]). However, subgroup analysis showed no OS benefit for alloHSCT over autoHSCT (HR, 0.99 [95% CI: 0.70, 1.39]). In conclusion, alloHSCT is associated with more favorable RFS, OS, and RR benefits (but not TRM outcomes) than non-alloHSCT generally, but does not have an OS advantage over autoHSCT specifically, in patients with intermediate-risk AML in CR1.

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Allogeneic transplantation for advanced acute myeloid leukemia: The value of complete remission.

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Allogeneic transplantation for advanced acute myeloid leukemia: The value of complete remission.

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