Post-transplant relapse is a main cause of treatment failure in patients with complex karyotype AML

In the February 2018 issue of Cancer, Stephan O. Ciurea from The University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, and colleagues reported results from their study which retrospectively evaluated factors predicting post-transplantation outcomes in a large cohort of patients with complex karyotype (CK) acute myeloid leukemia (AML).  

In total, 1,342 de novo (n = 1,099) or secondary (n = 239) CK-AML patients (median age = 52 years, range:  18–76) who underwent allogenic hematopoietic stem cell transplantation (allo-HSCT) from either a matched-related donor (MRD, n = 749), matched unrelated donor (MUD, n = 513) or a mismatched-unrelated donor (MMUD, n = 80) between January 2000 – December 2015 and were reported to the European Blood and Marrow Transplantation (EBMT) and MDACC databases, were retrospectively analyzed in this study.

Patients underwent transplant either at first complete remission (CR1, n = 877), second CR (CR2, n = 77) or had active disease (n = 388).

Key findings:

• 2-year post-transplantation outcomes for all patients
  • Non relapse mortality (NRM) rate: 17.6% (95% CI, 15.6%–19.7%)
  • Cumulative incidence of relapse: 51.1% (95% CI, 48.3%–53.9%)
  • Leukemia free survival (LFS): 31.3% (95% CI, 28.7%–33.9%)
  • Overall survival (OS): 36.8% (95% CI, 34.1%–39.5%)
  • GvHD free/relapse free survival: 19.8% (95% CI, 5.2%–26.6%)
• 2-year cumulative incidence of relapse in patients in CR1, CR2 and with active disease: 46% vs 48.2% vs 63.5% respectively, P < 0.001
• 2-year LFS rates in patients in CR1, CR2 and with active disease: 38.4% vs 33.3% vs 14.6% respectively, P < 0.001
• Factors associated with increased risk of relapse include age (HR = 1.1 per 10 years, P = 0.02), secondary AML (HR = 1.33, P = 0.01), active disease at transplantation (HR = 1.98, P < 0.01), and the presence of deletion/monosomy 7 (HR = 1.41, P = 0.02) 
• Factors associated with inferior LFS include age (HR = 1.5, P < 0.001), secondary AML (HR = 1.36, P = 0.001), active disease at transplantation (HR = 2.11, P < 0.001), presence of deletion/monosomy 7 (HR = 1.24, P = 0.008) and the presence of deletion/monosomy 5 (HR = 1.26, P = 0.005)

In summary, relapse was the main cause of treatment failure for patients with CK-AML after transplantation. The authors suggested that “conditioning regimens or cellular therapy that can effectively eradicate resistant leukemic clones” and prevent post-transplantation relapse are urgently needed to improve transplantation outcomes in CK-AML patients.