Prognostic impact of t(1;19)/TCF3–PBX1in childhood acute lymphoblastic leukemia in the context of Berlin–Frankfurt–Münster-based protocols

Abstract

Historically, t(1;19)(q23;p13.3) has been related to pre-B acute lymphoblastic leukemia (ALL) and associated with a poor prognosis. Current treatments have overcome this dismal outcome, but advantages in survival for the unbalanced group have been reported. We compared the outcome of balanced and unbalanced der(19)t(1;19) cases and also patients with t(1;19)/TCF3-PBX1 versus patients without this translocation, to assess its prognostic value. From January 1990 to December 2010, t(1;19)(q23;p13)/TCF3-PBX1 was detected in 48 cases. Patients were treated with Berlin-Frankfurt-Münster (BFM)-based protocols and classified into balanced (n = 17) and unbalanced (n = 23) groups. The probability of event-free survival (pEFS) (standard error) of patients with t(1;19)/TCF3-PBX1 was 85% (6%), for the unbalanced group 78% (10%), and 88% (8%) for the balanced. The pEFS of patients with t(1;19)/TCF3-PBX1 was significantly superior to that of patients without t(1;19)/TCF3-PBX1 (p-value <0.0001). Patients with t(1;19)/TCF3-PBX1 presented a good outcome with no differences between balanced and unbalanced subgroups. Thus, risk-adjustment therapy would not be necessary for cases with t(1;19)/TCF3-PBX1.

E2A-PBX1 exhibited a promising prognosis in pediatric acute lymphoblastic leukemia treated with the CCLG-ALL2008 protocol

“…In an Australian cohort, the implementation of early-dose-intensified remission induction to the ALL-Berlin-Frankfurt-Münster (BFM) trial was highly effective in children with E2A-PBX1, with the 5-year EFS reaching 90%±5% 7. Felice et al8 also reported a BFM-based protocol, with which the probability of event-free survival (pEFS) of patients with t(1;19)/E2A-PBX1 was 85% and significantly superior to that of patients without t(1;19)/E2A-PBX1 ( P <0.0001).…”

“…Patients with E2A-PBX1 gene expression usually had a more aggressive disease course and received an intensive chemotherapy 6. However, benefiting from the investigation of the pathological mechanism of E2A-PBX1-positive B-ALL and appropriate treatment till now, patients obtained an exciting survival outcome 7,8…”

Childhood acute lymphoblastic leukemia: Integrating genomics into therapy

“…Other recurrent chromosomal translocations in B‐ALL include t(1;19)(q23;p13.3) resulting in transcription factor 3/pre‐B–cell leukemia homeobox 1 ( TCF3‐PBX1 [ E2A‐PBX1 ]) fusion, rearrangement of lysine (K)‐specific methyltransferase 2A ( KMT2A ) (formerly myeloid/lymphoid or mixed‐lineage leukemia [ MLL ]; 11q23), and t(9;22)(q34;q11.2) (Philadelphia chromosome [Ph]‐positive), resulting in a breakpoint cluster region/Abelson 1 proto‐oncogene ( BCR‐ABL1 ) fusion. Although TCF3‐PBX1 ALL was previously associated with an intermediate or unfavorable prognosis, modern therapeutic regimens have improved outcomes, and TCF3‐PBX1 fusion is no longer considered for risk stratification . Children with TCF3‐PBX1 ALL appear to have a higher risk of CNS relapse and may merit intensification of CNS‐directed therapy .…”

Beyond the 2008 World Health Organization classification: the role of the hematopathology laboratory in the diagnosis and management of acute lymphoblastic leukemia

“…18 Similarly, t(1;19) was historically considered an adverse prognostic factor, but with current intensive treatment regimens, this is no longer the case. 19–21 More recently, intrachromosomal amplification of chromosome 21 (iAMP21) in the region containing the AML1 gene has been identified as a rare but recurring abnormality in childhood pre-B ALL that is associated with poor outcomes, although response to therapy may identify subsets within this group of patients at higher or lower risk of relapse. 22–24 Another rare but noteworthy translocation is t(17;19) because these patients tend to have very resistant disease and poor outcomes.…”