Early Assessment of Minimal Residual Disease (MRD) by Qualitative PCR for NPM-ALK Identifies Patients At Very High Risk of Relapse in Anaplastic Large Cell Lymphoma

Abstract 1565

25–35% of children and adolescents with ALK-positive anaplastic large cell lymphoma (ALCL) suffer a relapse. Detection of minimal disseminated disease (MDD) by qualitative RT-PCR for NPM-ALK in bone marrow (BM) or blood (PB) confers a relapse risk of 50%. We set out to address the issue of whether detection of minimal residual disease (MRD) by qualitative RT-PCR for NPM-ALK in BM or PB early during treatment allows identification of patients at highest risk of relapse.

ALCL-patients were treated according to protocols NHL-BFM95, LNH97 or ALCL99, all BFM-type protocols consisting of comparable cytoreductive prephase and chemotherapy courses between 8/1998 and 12/2008. The qualitative RT-PCR for NPM-ALK with a sensitivity of 10⁻⁵ was applied as previously described. PB and/or BM of 184 patients with NPM-ALK-positive ALCL were screened for the presence of NPM-ALK transcripts (MDD) at diagnosis. BM or PB was requested from those patients with detectable MDD in BM or PB for the measurement of MRD before the second course of chemotherapy (course 2).

MDD was detected in BM or PB or both media in 103 of 184 patients with NPM-ALK positive ALCL. The cumulative incidence of relapse (CIR) of 81 MDD-negative patients was 16±5% compared to 51±5% of 103 patients who were MDD-positive in either BM or PB or both (p<.001). MRD before course 2 could be evaluated in either BM or PB of 52 MDD-positive patients. CIR of the 26 MRD-positive patients (81±8%) was significantly higher than CIR of the 26 MDD-positive, but MRD-negative patients (31±9%) (p<.001). CIR of MDD-positive patients without material for MRD available was 35±7%. 5-year survival of MDD-negative patients and MDD-positive but MRD-negative patients were similar (92±2% and 92±5%, respectively) whereas survival of MRD-positive patients was 65±9% (p<.001).

Our data suggest that early evaluation of MRD by a sensitive RT-PCR in NPM-ALK positive ALCL with detectable MDD at diagnosis identifies patients with a very high risk of relapse.