Prognostic Significance of CD20 Expression in Adult B-Cell Precursor Acute Lymphoblastic Leukemia.
Authors: Maury Sébastien , Huguet Françoise , Pigneux Arnaud , Raffoux Emmanuel , Thomas Xavier , Beldjord Kheira , Delabesse Eric , Chevallier Patrice , Buzyn Agnès , Delannoy André , Chalandon Yves , Vernant Jean-Paul , Rousselot Philippe , Lafage-Pochitaloff Marina , Chassevent Agnès , Lheritier Véronique , Macintyre Elizabeth , Ifrah Norbert , Dombret Herve , Béné Marie-Christine 
Published: October 2019

Abstract
Introduction: CD20 expression is classically considered to be associated with inferior survival in adults with B-cell precursor acute lymphoblastic leukemia (ALL) but this notion is not strongly sustained in the literature. A recent pediatric study performed at St Jude’s Children’s Research Hospital reports that CD20 expression does not appear to be associated with inferior outcome in a cohort of 359 patients treated with contemporary regimens. This question is of importance notably since favorable experience has been reported for the use of rituximab, a chimeric monoclonal antibody to CD20, in combination with chemotherapy in mature B-cell lymphoma and leukemia, and possibly also in adult B-cell precursor ALL.
Method: To determine the prognostic impact of CD20 expression in adult patients with B-cell precursor ALL and therefore the potential utility of rituximab in this subset of patients, we studied 143 patients treated in the GRAALL-2003 trial, designed to offer a dose-intensive pediatric-like approach in adults with Ph-negative ALL until 55 years of age.
Results: CD20 positivity, defined as expression of CD20 in more than 20% of leukemia blasts, was observed in 49 patients (34%). There was no association between CD20 expression and patient age, white blood cell count at diagnosis, E2A-PBX, or ploidy. None of 21 patients with MLL-AF4 expressed CD20 (p<0.001). Even if CD20 expression tended to be associated with corticoresistance (24% in CD20+ cases vs. 14% in others, p=0.16), it was not associated with chemoresistance, overall early response (cortico- and/or chemoresistant ALL), CR rate, or post-induction MRD >10-3, as assessed by clonal Ig rearrangements quantification. However, the cumulative incidence of relapse at 30 months was significantly higher in CD20+ cases (39% [95% CI, 25 to 55] vs. 20% [95% CI, 13 to 31], p=0.02). Interestingly, a negative impact of corticoresistance and high white blood cell count at diagnosis on the cumulative incidence of relapse was only observed in this population of CD20+ patients (p=0.05 and p<0.001, respectively), but not in CD20neg patients (p=0.85 and 0.67). These data suggest either an intrinsic resistance of CD20+ leukemic cells or a lack of impact on these cells of the dose intensification (reinforcement of the induction course with a sequential bolus administration of cyclophosphamide) applied to corticoresistant patients. Disease-free survivals at 30 months were of 57% [95% CI, 40 to 70] and 64% [95% CI, 52 to 74] in CD20+ and CD20neg groups, respectively (p=0.36).
Conclusion: In contrast to pediatric ALL, CD20 expression appears to be associated with inferior outcome in adult ALL with a significantly higher cumulative incidence of relapse in this group of patients. This reinforces the interest of evaluating the effect of rituximab combined to chemotherapy in adult ALL.