Cytogenetic evolution in acute leukemia at relapse after allogeneic hematopoietic cell transplantation: association with regimen conditioning and effect on survival
The aim of this study was to characterize patterns of cytogenetic changes in patients with acute leukemia who relapsed after allo-HSCT, to assess the effect of сytogenetic evolution upon survival; and to elucidate associations of cytogenetic evolution with conditioning regimen.
Materials and methods
Our study included seventy-three patients (35 females and 38 males, at the age of 0.8 to 60 years) diagnosed with acute myeloblastic leukemia (AML) or acute lymphoblastic leukemia (ALL) who underwent allo-HSCT at our University from 2009 to 2016. The bone marrow karyotypic changes in posttransplant relapse (PTR) were compared with those observed before allo-HSCT. Median time from transplant to relapse was 87 days (range, 18 to 1280). Myeloablative conditioning and reduced intensity conditioning was performed in 39 (53%) and 34 (47%) patients, respectively.
Karyotypic changes at PTR were noted in 29 AML patients (71%) and 23 ALL patients (72%). The cytogenetic changes were divided into five following groups: a) clonal evolution of karyotype at PTR (n=30); b) clonal regression (n=1); c) new unrelated clones (n=5); d) clonal evolution of karyotype, combined with clonal regression (n=15); and e) changing of normal karyotype into abnormal at PTR (n=1). Moreover, two or more cytogenetic subclones were detected in 6 (8%) patients before allo-HSCT and in 24 (33%) patients at PTR (p<0.0002). Eight different ways of subclone formation has been identified. Acquisition of 3 or more new chromosomal abnormalities was the most frequent cytogenetic change, followed by acquisition of both unbalanced abnormalities and aneuploidy. The common losses in AML patients were 1q, 2q, 3q 5q, 7q, 9q, 11p, 13q, 14q, 17p, and 20q, whereas gains concerned 1q, 11q 13q, 15q, and 21q. The common losses in ALL patients were 1p, 8p, 11p, 11q, 17p, whereas the gains concerned 1q, 8q, 18p, 18q, 21q, and Xp. In the group with cytogenetic evolution at PTR, myeloablative conditioning was used more often (p=0.01). Cytogenetic clonal evolution frequently occurred in an unfavorable pre-transplant group with complex chromosome aberrations (3 and more per metaphase) (p=0.02). Overall survival after HSCT and survival after PTR were shortened in the group of patients with karyotype changes in PTR (38% vs. 17%, p=0.03 and 41% vs. 6%, p=0.006, respectively) as well as in the group of patients with two or more abnormal cytogenetic clones in PTR (31% vs. 9%; р=0.04 only for OS). The emergence of a new unrelated clone was associated with decreasing of survival after PTR (17% vs. 0%, p=0.04).
We have revealed evidence for a significant impact of cytogenetic evolution to clinical progression in acute leukemia treated with allo-HSCT.
Acute leukemia, posttransplant relapse, cytogenetic evolution, conditioning regimen, outcomes.