CD371+ pediatric B-cell acute lymphoblastic leukemia: propensity to lineage switch and slow early response to treatment
Abstract
In the effort to improve immunophenotyping and minimal residual disease (MRD) assessment in acute lymphoblastic leukemia (ALL), the international Berlin-Frankfurt-Münster (iBFM) Flow Network introduced the myelomonocytic marker CD371 in 2014, for a large prospective characterization with a long follow-up. In the present study, we aimed to investigate the clinical and biological features of CD371-positive (CD371pos) pediatric BCP-ALL.
From June 2014 to February 2017, 1812 pediatric patients with newly diagnosed BCP-ALLs enrolled in trial AIEOP-BFM ALL 2009 were evaluated as either screening (n=843, Italian centers) or validation cohort (n=969, other iBFM centers). Laboratory assessment at diagnosis consisted of morphological, immunophenotypic, and genetic analysis on bone marrow or peripheral blood samples.
Response assessment relied on morphology, multiparametric flow-cytometry (MFC), and PCR-MRD. Overall, 160/1812 (8.8%) BCP-ALLs were CD371pos at diagnosis.
This finding correlated with older age (p<0.001), lower ETV6::RUNX1 frequency (p<0.001), immunophenotypic immaturity (p<0.001), strong expression of CD34 and of CD45 (p<0.05). During induction therapy, CD371pos BCP-ALLs showed a transient myelomonocytic switch (mm-SW: up to 65.4% of samples at Day 15) and frequently an inferior response to chemotherapy [Slow Early Response by PCR-MRD, p<0.001].
However, the 5-year event-free survival was 88.3%. Among 420 patients from the validation cohort, 27/28 (96.4%) cases positive for DUX4-fusions were CD371pos.
In conclusion, we comprehensively characterized CD371pos BCP-ALL in the largest pediatric cohort. CD371 is the most sensitive marker of transient mm-SW, whose recognition is essential for proper MFC-MRD assessment.
CD371pos is associated to poor early-treatment response, although a good outcome can be reached after MRD-based ALL-related therapies.