CD371-positive pediatric B-cell acute lymphoblastic leukemia: propensity to lineage switch and slow early response to treatment

• Published in: Blood 2024-04, Vol.143 (17), p.1738-1751
• Main Authors: Buldini, Barbara, Varotto, Elena, Maurer-Granofszky, Margarita, Gaipa, Giuseppe, Schumich, Angela, Brüggemann, Monika, Mejstrikova, Ester, Cazzaniga, Giovanni, Hrusak, Ondrej, Szczepanowski, Monika, Scarparo, Pamela, Zimmermann, Martin, Strehl, Sabine, Schinnerl, Dagmar, Zaliova, Marketa, Karawajew, Leonid, Bourquin, Jean-Pierre, Feuerstein, Tamar, Cario, Gunnar, Alten, Julia, Möricke, Anja, Biffi, Alessandra, Parasole, Rosanna, Fagioli, Franca, Valsecchi, Maria Grazia, Biondi, Andrea, Locatelli, Franco, Attarbaschi, Andishe, Schrappe, Martin, Conter, Valentino, Basso, Giuseppe, Dworzak, Michael N.
• Format: Article
• Language: English
• Subjects: Adolescent; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cell Lineage; Child; Child, Preschool; Female; Humans; Immunophenotyping; Infant; Male; Neoplasm, Residual - diagnosis; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy; Tetraspanins - genetics; Tetraspanins - metabolism
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2023021952

•Pediatric CD371-positive B-cell precursor acute lymphoblastic leukemia shows transient lineage switch and slow early response to treatment.•Accurate immunophenotypic identification of lineage switch is mandatory to properly assess MRD by flow cytometry. [Display omitted] 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 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 B-cell precursor ALL (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 part of either a screening (n = 843, Italian centers) or validation cohort (n = 969, other iBFM centers). Laboratory assessment at diagnosis consisted of morphological, immunophenotypic, and genetic analysis. Response assessment relied on morphology, multiparametric flow cytometry (MFC), and polymerase chain reaction (PCR)-MRD. At diagnosis, 160 of 1812 (8.8%) BCP-ALLs were CD371pos. This correlated with older age, lower ETV6::RUNX1 frequency, immunophenotypic immaturity (all P < .001), and strong expression of CD34 and of CD45 (P < .05). During induction therapy, CD371pos BCP-ALLs showed a transient myelomonocytic switch (mm-SW: up to 65.4% of samples at day 15) and an inferior response to chemotherapy (slow early response, P < .001). However, the 5-year event-free survival was 88.3%. Among 420 patients from the validation cohort, 27 of 28 (96.4%) cases positive for DUX4-fusions were CD371pos. In conclusion, 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.