Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children

Abstract

BackgroundAlthough leukemic blast cells of Pro-B cell acute lymphoblastic leukemia (ALL) are arrested at the same stage of B cell differentiation, the immature B cell subtype is still biologically heterogeneous and is associated with diverse outcomes. This study aimed to explore the clinical-biological characteristics of pediatric pro-B ALL and factors associated with outcomes.MethodsThis study enrolled 121 pediatric patients aged 6 months to 14 years with newly diagnosed CD19+CD10− pro-B cell acute lymphoblastic leukemia (pro-B ALL) treated at Beijing Children’s Hospital from March 2003 to October 2018. Genetic abnormalities, immunophenotypic markers, minimal residual disease (MRD) at early treatment stage and long-term outcomes of children treated on two consecutive protocols were analyzed.ResultsKMT2A rearrangements were the most frequent abnormalities (incidence rate 33.06%), and were associated with lower frequency of CD13, CD33, CD22 and CD34 expression and higher frequency of CD7 and NG2 expression. Higher frequency of CD15 and CD133 expression was found in KMT2A-AFF1+ patients, exclusively. Presence of CD15 and absence of CD34 at diagnosis correlated with the high burden of MRD at the early stage of treatment. Outcomes were more favorable in patients older than 1 year, with absence of CD20 expression and KMT2A rearrangements, and with MRD lower than 1% at the end of induction and 0.1% before consolidation. Increased intensity of chemotherapy based on MRD analysis did not improve outcomes significantly (5-year EFS 73.9 ± 6.5% for BCH-2003 and 76.1 ± 5.3% for CCLG-2008, P = 0.975). Independent adverse prognostic factors were MRD ≥ 0.1% before consolidation and presence of KMT2A gene rearrangements (odds ratios [ORs] 9.424 [95% confidence interval (CI) 3.210, 27.662; P < 0.001]; 4.142 [1.535, 11.715, P = 0.005]; respectively).ConclusionsPediatric pro-B ALL is a heterogeneous disease. Genetic analysis and MRD evaluation can predict patients with dismal prognosis; however, intensive chemotherapy alone does not improve outcomes of these patients and targeted therapy or hematopoietic stem cell transplantation may be required.

Poor treatment responses were related to poor outcomes in pediatric B cell acute lymphoblastic leukemia with KMT2A rearrangements

“…The CR rate in our cohort was 83.33%, and the 5-year pEFS for patients who did not have TRM was 40.84 ± 9.16%. These data were far lower than those of patients with B-ALL with good indicators, ETV6-RUNX1 transcripts or hyperploid karyotypes (> 95%, > 80–90%) [ 6 , 7 , 10 ].…”

“…In our study, 4 patients died of severe infection, and the TRM was 8.33%. The data were higher than those of developed countries, partially due to the socioeconomic conditions in developing countries [ 6 , 8 – 10 , 14 ]. A total of 4 patients, including 3 of 18 infants or 1 of 30 elderly patients, died of TRM in the course of induction remission, which indicated that intensive care, antimicrobial prophylaxis and positive pressure rooms are important for neutropenic conditions.…”

High CD34 surface expression in BCP‐ALL predicts poor induction therapy response and is associated with altered expression of genes related to cell migration and adhesion

“…Two other early studies suggested an association between CD34-positive BCP-ALL and a favorable outcome [49,50] but were limited by reduced sensitivity due to few FCM-acquired cells and/or hemodilution [49], as well as lack of cytogenetic analysis for rearrangements involving KMT2A [49,50]. KMT2A-r BCP-ALL, more common in infants, has a very poor prognosis and often displays a CD10negCD20neg LAIP with around 50% CD34negative cases [51,52]. Thus, the poor prognosis of KMT2A-r could mask an inverse association of CD34 with therapy response in non-KMT2A-r patients.…”

Precursor B-lineage acute lymphoblastic leukemia patients with aberrant natural killer cell and T cell – lineage antigen expression: experience from a tertiary cancer care center

“…English literature regarding aberrant expression of T-cell or natural killer (T/NK)-cell lineage antigens (i.e., CD1a, CD2, CD4, CD5, CD7, CD8 and CD56) in B-ALL patients dates back to 1989. 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 Among this literature, only Seegmiller et al and Hussein et al have documented large cohorts (18 cases each) of T/NK cell antigen-expressing B-ALL patients, with only Hussein et al having compared the clinical-laboratory profile of these patients against conventional B-ALL patients. 2 , 3 Regarding these T/NK cell antigen-expressing B-ALL patients, individual antigen-wise clinical-hematologic profiles and their prognostic relevance is yet to be compared.…”