The poor prognosis of low hypodiploidy in adults with B‐cell precursor acute lymphoblastic leukaemia is restricted to older adults and elderly patients

Abstract

Summary The prognostic significance of low‐hypodiploidy has not been extensively evaluated in minimal residual disease (MRD)‐oriented protocols for adult acute lymphoblastic leukaemia (ALL). We analysed the outcome of hypodiploid adult ALL patients treated within Programa Español de Tratamientos en Hematología (PETHEMA) protocols. The 5‐year cumulative incidence of relapse (CIR) of low‐hypodiploid B‐cell precursor (BCP)‐ALL was significantly higher than that of high‐hypodiploids (52% vs. 12%, P = 0.013). Low‐hypodiploid BCP‐ALL patients aged ≤35 years showed superior survival (71% vs. 21%, P = 0.026) and lower 5‐year CIR (17% vs. 66%, P = 0.090) than low‐hypodiploids aged >35 years. Older adults and elderly low‐hypodiploid BCP‐ALL patients show dismal prognosis although achieving an end‐induction good MRD response.

Near-Haploidy and Low-Hypodiploidy in B-Cell Acute Lymphoblastic Leukemia: When Less Is Too Much

“…It has been reported that pediatric patients with B-ALL with <36 chromosomes may show additional structural chromosome aberrations more frequently when compared with those with ≥36 [ 22 ]. It would be interesting to learn whether pediatric patients with additional structural alterations are also older than those without them, which would be consistent with different reports on adult B-ALL showing structural chromosome aberrations, especially unbalanced translocations and losses of chromosome arms, in 50% of low-hypodiploid cases [ 35 , 38 ].…”

“…Although traditionally defined as the loss of one or more chromosomes in a cell [ 34 ], hypodiploidy has been classified according to diverse criteria in different studies to define different hypodiploid B-ALL subtypes ( Table 3 ), and a clear distinction between those cases with <40 chromosomes and those with 40–45 chromosomes has become generally accepted based on the evident differences in treatment response [ 21 , 35 ]. Hypodiploid cases with <40 chromosomes can be further subdivided into two groups based on the bimodal distribution of chromosome numbers: (i) near-haploidy, with 24–29 chromosomes ( Figure 2 A), and (ii) low-hypodiploidy, with 30–39 chromosomes ( Figure 2 B,C) [ 27 ] ( Table 3 ).…”

“…Furthermore, the doubled clone may be the only one detected at diagnosis, leading to the manifestation known as “masked hypodiploidy”, which is clinically challenging since patients can be erroneously classified and treated for high-hyperdiploid B-ALL while being at higher risk of treatment failure. It has been reported that there is no difference in clinical outcome for patients with “masked hypodiploidy”, those who are mosaic for a doubled clone and a hypodiploid clone, and those who have only a hypodiploid clone [ 22 , 35 , 41 ]. In addition, the hypodiploid clone tends to be quantitatively more frequent at relapse, suggesting that the actual hypodiploid clones may be more chemoresistant than their hyperdiploid (doubled) counterparts [ 20 , 44 ].…”

Biologic and Therapeutic Implications of Genomic Alterations in Acute Lymphoblastic Leukemia

“…Moreover, for patients who achieve MRD-negative status after induction, allogeneic transplantation has been shown to be not successful in improving overall survival [31,32]. Although MRD-oriented protocols, older adults and elderly patients with low hypodiploidy do fairly poor with higher five-year cumulative incidence of relapse compared to high hypodiploid cases [33], making them candidates for different treatment approaches (e.g., immunotherapy and targeted therapies). Among those, preclinical studies have shown that hypodiploid ALL cells are sensitive to Phosphoinositide 3-kinase (PI3K) and BCL2 Apoptosis Regulator (BCL2) inhibitors [27,34].…”

Adult hypodiploid B‐acute lymphoblastic leukaemia and stem cell transplantation

“…In this issue of the Journal, Ribera et al () present a retrospective study designed to determine the influence on prognosis of low‐hypodiploidy in 56 adults with Philadelphia chromosome (Ph)‐negative B‐cell precursor acute lymphoblastic leukaemia (ALL). The patients were treated on minimal residual disease (MRD)‐oriented Programa Español de Tratamientos en Hematología (PETHEMA) protocols between 1993 and 2017.…”