General AML

The impact of abnl(17p) on the outcomes of AML patients receiving allogenic HSCT – A Japanese study.

Acute Myeloid Leukemia (AML) patients with abnormalities in the short arm of chromosome 17 (abnl[17p]) have been reported to have poor outcomes after Allogenic Hematopoietic Stem Cell Transplantation (allo-HSCT).1 However, comparative studies on the impact of abnl(17p) on the outcomes of allo-HSCT in AML patients is lacking hence the rationale of this study.

Jinichi Mori from The University of Tokyo and colleagues retrospectively studied the outcomes of allo-HSCT in AML patients with or without abnl(17p). The results of the study were published in Biology of Blood and Bone Marrow Transplantation. 2

Using the Transplant Registry Unified Management Program (TRUMP), the authors collected clinical data of 10,923 AML patients who were either with (n = 262) or without (n = 10,661) abnl (17p) and received allogenic HSCT between January 1975–December 2014. Using the National Comprehensive Cancer Network guidelines, patients were grouped into three risk groups; favorable, intermediate and poor cytogenetic risk groups. Median follow-up length of the study was 1,425 days (range, 0–8758 days).

The key results of the study were:
  • 5-year Overall Survival (OS) in poor cytogenetic risk patients that are with (n = 235) or without (n = 1959) abnl(17p); 9.2% vs 27.4%; P < 0.001
  • 5-year Disease Free Survival (DFS) in poor cytogenetic risk patients that are with or without abnl(17p) were 7.8% and 25.0% respectively; P < 0.001
  • Cumulative Incidence of relapse at 5 years post- allogenic HSCT in poor cytogenetic risk patients that are with or without abnl(17p); 66.6% vs 49.4% respectively; P < 0.001
  • Non-Relapse Mortality (NRM) rates 5 years post- allogenic HSCT in poor cytogenetic risk patients that are with or without abnl(17p) were 25.6% and 25.6% respectively; P = 0.648
  • Poor survival was significantly associated with non-remission status at transplantation (HR = 2.61, P < 0.001), poor cytogenetic risk group (HR = 3.02, P < 0.004) and male sex (HR = 1.46, P < 0.014)

 In summary, “the presence of an abnl(17p) negatively affects allo-HSCT outcomes” in AML patients.

Abstract

We retrospectively analyzed a Japanese nationwide database to elucidate the impact of abnormalities in the short arm of chromosome 17 (abnl[17p]) on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia. Of 10923 patients, 262 (2.4%) had abnl(17p), 235 of whom were classified into the poor cytogenetic risk group according to the National Comprehensive Cancer Network criteria. The median follow-up period was 1425 days. In abnl(17p) vs. non-abnl(17p) patients of poor cytogenetic risk group, overall survival (OS), disease-free survival, cumulative incidence of disease relapse, and non-relapse mortality rates at 5 years post-allo-HSCT were 9.2% vs. 27.4%, 7.8% vs. 25.0%, 66.6% vs. 49.4%, and 25.6% vs. 25.6%, respectively. In contrast to the other types of abnl(17p), isochromosome 17q rarely encompassed the poor cytogenetic risk traits and did not adversely affect OS. Among the abnl(17p) patients, male sex, non-remission disease status at transplantation and poor cytogenetic risk group were significantly associated with shorter OS. In conclusion, the presence of an abnl(17p) negatively affects allo-HSCT outcomes, which in turn are influenced by the type of abnormality. Prompt initiation of allo-HSCT during complete remission may improve outcomes.

References
  1. Middeke J. M. et al. Outcome of patients with abnl(17p) acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Blood. 2014 May 8. 123 (19): 2960–7. DOI: 10.1182/blood-2013-12-544957. Epub 2014 Mar 20.
  2. Mori J. et al. Outcomes of Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Patients with Abnormalities of the Short Arm of Chromosome 17. Biol Blood Marrow Transplant. 2017 Apr 25. DOI: 10.1016/j.bbmt.2017.04.020. [Epub ahead of Print].