Abstract 2185: Childhood obesity is associated with persistent minimal residual disease (MRD) following induction therapy for pediatric acute lymphoblastic leukemia

Purpose Our aim was to determine the role of end-of-induction (EOI) minimal residual disease (MRD) assessment in the identification and stratification of induction failure in patients with pediatric acute lymphoblastic leukemia (ALL) and to identify genetic abnormalities that drive disease in these patients. Patients and Methods Analysis included 3,113 patients who were treated in the Medical Research Council UKALL2003 multicenter randomized trial (NCT00222612) between 2003 and 2011. MRD was measured by using standardized real-time quantitative PCR. Median follow-up was 5 years 9 months. Results Fifty-nine patients (1.9%) had morphologic induction failure with 5-year event-free survival (EFS) of 50.7% (95% CI, 37.4 to 64.0) and 5-year overall survival of 57.7% (95% CI, 44.2 to 71.2). Of these, a small proportion of patients with M2 marrow (6 of 44) and a low EOI MRD level (< 0.01%) had 5-year EFS of 100%. Conversely, among patients with morphologic remission 2.3% (61 of 2,633) had high MRD (≥ 5%) and 5-year EFS of 47.0% (95% CI, 32.9 to 61.1), which was similar to those with morphologic induction failure. Redefining induction failure to include morphologic induction failure and/or MRD ≥ 5% identified 3.9% (120 of 3,133 patients) of the trial cohort with 5-year EFS of 48.0% (95% CI, 39.3 to 58.6). Induction failure (morphologic or MRD ≥ 5%) occurred most frequently in T-ALL (10.1%; 39 of 386 T-ALL cases) and B-other ALL, that is, lacking established chromosomal abnormalities (5.6%; 43 of 772 B-other cases). Genetic testing within the B-other group revealed the presence of PDGFRB gene fusions, particularly EBF1-PDGFRB, in almost one third of B-other ALL cases. Conclusion Integration of EOI MRD level with morphology identifies induction failure more precisely than morphology alone. Prevalence of EBF1-PDGFRB fusions in this group highlights the importance of genetic screening to identify abnormalities that may be targets for novel agents.

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CD11b is a therapy resistance– and minimal residual disease–specific marker in precursor B-cell acute lymphoblastic leukemia

Blood ◽

10.1182/blood-2009-10-247585 ◽

2010 ◽

Vol 115 (18) ◽

pp. 3763-3771 ◽

Cited By ~ 13

Author(s):

Peter Rhein ◽

Rita Mitlohner ◽

Giuseppe Basso ◽

Giuseppe Gaipa ◽

Michael N. Dworzak ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

B Cell ◽

Minimal Residual Disease ◽

Induction Therapy ◽

Residual Disease ◽

Lymphoblastic Leukemia ◽

Consolidation Therapy ◽

Cd11b Expression ◽

Cell Acute Lymphoblastic Leukemia ◽

Minimal Residual

Abstract A consistently increased mRNA expression of the adhesion receptor CD11b is a hallmark of the reported genomewide gene expression changes in precursor B-cell acute lymphoblastic leukemia (PBC-ALL) after 1 week of induction therapy. To investigate its clinical relevance, CD11b protein expression in leukemic blasts has been prospectively measured at diagnosis (159 patients) and during therapy (53 patients). The initially heterogeneous expression of CD11b inversely correlated with cytoreduction rates measured at clinically significant time points of induction therapy in the ALL–Berlin-Frankfurt-Münster 2000 protocol. CD11b positivity conferred a 5-fold increased risk of minimal residual disease (MRD) after induction therapy (day 33) and of high-risk group assignment after consolidation therapy (day 78). In the multivariate analysis CD11b expression was an independent prognostic factor compared with other clinically relevant parameters at diagnosis. During therapy, CD11b expression increased early in most ALL cases and remained consistently increased during induction/consolidation therapy. In more than 30% of MRD-positive cases, the CD11b expression on blast cells exceeded that of mature memory B cells and improved the discrimination of residual leukemic cells from regenerating bone marrow. Taken together, CD11b expression has considerable implications for prognosis, treatment response monitoring, and MRD detection in childhood PBC-ALL.

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