EBMT 2018 | Chromosomal abnormalities as risk factors for allo-HSCT ATL patients

At the oral session on lymphoma at the 44^th European Society for Blood and Marrow Transplantation (EBMT) annual meeting on 19 March 2018, Abstract OS1-5 was presented by Nobuaki Nakano from the Imamura General Hospital, Kagoshima, Japan, on behalf of the Japanese Society for Hematopoietic Cell Transplantation (JSHCT) ATL working group. During this oral presentation, the impact of chromosomal abnormalities on adult T-cell leukemia/lymphoma (ATL) patients’ survival following allogeneic HSCT (allo-HSCT) was discussed.

Results from their previous study reported the deleterious effects of chromosomal abnormalities on the survival of newly-diagnosed ATL patients, who received conventional chemotherapy but not allo-HSCT. Building upon these outcomes, the authors performed a large scale evaluation of the presence and effects of chromosomal abnormalities on the survival of ATL patients from the Transplant Registry Unified Management Program (TRUMP) that received allo-HSCT. The primary endpoint of the study was overall survival (OS).

Patient characteristics & study design

• N = 300 ATL patients (170 males, 130 females; excluding multiploid, without mitosis, no clonality, without bone marrow invasion and insufficient information by G-banding, patient samples)
• Of those: n = 208 presented with abnormal karyotype and n = 92 had a normal karyotype
• Median patient age (range): 55 (24-70) years
• Diagnosis (ATL clinical variants):
  • Acute ATL: n = 183
  • Lymphoma-type ATL (lymphomatous): n = 70
  • Chronic-type ATL: n = 33
  • Smoldering-type ATL: n = 14
• Myeloablative conditioning (MAC): n = 118 patients or reduced-intensity conditioning (RIC): n = 182 patients
• Chromosomal analysis samples were taken from bone marrow (n=166), lymph nodes (n=86), peripheral blood (n=41), and others (n=7)
• Karyotype with ≥ 3 abnormalities was defined as complex
• Chromosomal abnormalities with frequency > 15 were used as OS variables

Key findings

• Any kind of karyotypic abnormality was detected in n = 280 patients
• Most frequent numerical chromosomal abnormalities (n > 20): -14, +3, -13, and –Y
• Most frequent structural breakpoints (n > 40) located at 6q, 9q, 1q, 2q, 3q and 14q
• OS negatively-associated with breakpoints at 2q (HR, 1.5; 95% CI [1.023-2.198]; P = 0.038) and 5q (HR, 2.17; 95% CI [1.22-3.85]; P = 0.008)
• OS was positively-associated with breakpoints at 3p (HR, 1.47; 95% CI [0.940-2.283]; P = 0.002) and -6 numerical abnormality (HR, 1.88; 95% CI [0.994-3.566]; P = 0.052)
• On the contrary, factors negatively-associated with ATL-related mortality were -14 numerical abnormality (HR, 1.74; 95% CI [1.008-2.993]; P = 0.047) and breakpoints at 3p (HR, 1.47; 95% CI [1.023-2.198]; P = 0.002), at 5q (P = 4.14e-06) and at 6q (P = 0.0335)
• Complex karyotype in whole was not associated negatively with OS (HR, 1.286; 95% CI [0.9626-1.718]; P = 0.089)
• However, subsets of complex karyotypes like breakpoints at 5q or 3p-6q co-existence had a negative impact on OS and ATL-related death

This study demonstrated the existence of multiple numerical and structural chromosomal abnormalities in samples from a large cohort of ATL patients that received allo-HSCT. Moreover, evidence was provided for the negative impact of certain chromosomal abnormalities on ATL patient survival, like break points at 2q and 5q that were negatively-associated with OS. These breakpoints represented independent risk factors for OS in ATL patients post allo-HSCT.