High-hyperdiploidy in Philadelphia positive adult acute lymphoblastic leukaemia: case-series and review of literature

Abstract

Summary:Patients with Philadelphia positive (Ph + ) adult acute lymphoblastic leukaemia (ALL) have a poor prognosis. Stem cell transplantation (SCT) is increasingly being recognised as the treatment of choice in eligible patients with Ph + ALL, but disease-relapse remains a problem in a proportion of patients prior to and after SCT. Genetic abnormalities in addition to the Ph chromosome may influence the biology and clinical course of ALL, but there are not many studies on the potential genetic heterogeneity of adult Ph + ALL and clinical outcomes. Here, we report on five patients with ALL who were double Ph + and also had a high-hyperdiploid karyotype (Ph + / hyperdiploid) at diagnosis. In contrast to the presence of the Ph + chromosome, high-hyperdiploidy (450 chromosomes) as the sole karyotypic abnormality in ALL is associated with a favourable clinical outcome. In our series, four patients with a Ph + /hyperdiploid karyotype achieved a cytogenetic remission after induction chemotherapy and proceeded to stem cell transplantation (SCT). The fifth had five subclones including Ph + / hyperdiploid, as well as those that were only Ph + ; the latter emerged as the dominant clone after induction therapy and the patient died of disease-relapse. Of the patients who underwent SCT, only one relapsed, but achieved a durable remission with donor lymphocyte infusions. Thus, it is conceivable that the presence of high-hyperdiploidy as an additional karyotypic abnormality may confer a better prognosis to Ph + ALL, presumably by altering the kinetics of Ph + neoplastic cells. We have discussed these results in the context of recent studies on the significance of high-hyperdiploidy in Ph + adult ALL.

Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993

“…The impact of additional chromosome abnormalities and BCR breakpoint on OS, EFS, RFS, and death in remission were examined by univariate analysis (Table 4). Both an extra Ph chromosome [ϩder (22)] and high hyperdiploidy (HeH) were associated with a significantly better RFS. It should be noted that 25 of 28 (89%) cases with HeH also had ϩder (22).…”

“…Both an extra Ph chromosome [ϩder (22)] and high hyperdiploidy (HeH) were associated with a significantly better RFS. It should be noted that 25 of 28 (89%) cases with HeH also had ϩder (22). The RFS results were broadly consistent with the effects seen on OS and EFS, but these did not reach statistical significance.…”

Supernumerary Philadelphia Positive Hyperdiploid Acute Lymphoblastic Leukemia: A Bad or A Good Prognosis? Single Case and Review of Literature

“…High-hyper diploid ALL cases have shown that blasts have a marked propensity for apoptosis in vitro, which has been related to the relatively good in vivo response to chemotherapy. Reports from the literature also make it conceivable that the presence of high-hyper diploidy as an additional karyotypic abnormality may confer a better prognosis to Ph(+) ALL, presumably by altering the kinetics of Ph(+) neoplastic cells [11]. Chilton et al suggested, High-hyper diploidy is an important subtype of ALL at all ages and displays outcome heterogeneity according to chromosomal gain, however they did not find overall survival differences between Ph-positive HeH patients and Ph-negative patients (P=0.2: 50 vs 57% at 5 years) [12].…”

“…Metaphases were G-banded and the karyotype was described according to the ISCN 1995 [5]. 20 metaphases were analyzed which revealed the karyotype: 46,XY,t(9;22)(q34;q11) [4]/53,XY,+2,+4,+5,t(9;22)(q34;q11),+11,+14,+21,+der(22) t(9;22)(q34;q11) [14]/46,XY [2].…”

“…Translocation t (9; 22) or Philadelphia chromosome is a common structural aberration found in patients, who present with hyper diploidy [2,3]. It is conceivable that the simultaneous presence of additional karyotypic abnormalities may alter the biological properties of Ph+ cells and influence clinical outcomes [4]. In this context, the coexistence of a high-hyper diploid (53 chromosomes) karyotype with double Ph+ chromosomes is of interest since high-hyper diploidy as the sole cytogenetic abnormality in ALL is associated with a good prognosis [4], while Philadelphia positivity confers a worse prognosis.…”