Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia

TLDR

Cytogenetic determination of modal chromosome number is essential at diagnosis to stratify hypodiploid acute lymphoblastic leukaemia patients into appropriate risk groups. Patients were classified into near‑haploidy (23–29 chromosomes), low hypodiploidy (33–39 chromosomes), and high hypodiploidy (42–45 chromosomes) based on chromosome count. In the largest hypodiploid ALL series (5% incidence), near‑haploid and low hypodiploid subgroups exhibited chromosomal gains, frequent structural abnormalities, and poorer survival compared to the high hypodiploid group, which had complex karyotypes involving chromosomes 7, 9, and 12.

Abstract

Summary This study of children and adults with acute lymphoblastic leukaemia (ALL) is the largest series of patients with hypodiploidy (<46 chromosomes) yet reported. The incidence of 5% was independent of age. Patients were subdivided by the number of chromosomes; near‐haploidy (23–29 chromosomes), low hypodiploidy (33–39 chromosomes) and high hypodiploidy (42–45 chromosomes). The near‐haploid and low hypodiploid groups were characterized by their chromosomal gains and a doubled hyperdiploid population. Structural abnormalities were more frequent in the low hypodiploid group. Near‐haploidy was restricted to children of median age 7 years (range 2–15) whereas low hypodiploidy occurred in an older group of median age 15 years (range 9–54). Patients with 42–45 chromosomes were characterized by complex karyotypes involving chromosomes 7, 9 and 12. The features shared by the few patients with 42–44 chromosomes and the large number with 45 justified their inclusion in the same group. Survival analysis showed a poor outcome for the near‐haploid and low hypodiploid groups compared to those with 42–45 chromosomes. Thus cytogenetics, or at least a clear definition of the modal chromosome number, is essential at diagnosis in order to stratify patients with hypodiploidy into the appropriate risk group for treatment.