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.
Early morbidity and mortality in childhood acute lymphoblastic leukemia with very high white blood cell count
