Prevalence and clinical implications of bone marrow involvement in pediatric anaplastic large cell lymphoma

Anaplastic large cell lymphoma ( ALCL) harbors the reciprocal chromosomal translocation t( 2; 5)( p23; q35) in approximately 80% of the cases. The genes involved are nucleophosmin ( NPM) and anaplastic lymphoma kinase ( ALK) and the resulting chimeric NPM - ALK protein is thought to play a key role in the pathogenesis of t( 2; 5) positive ALCL. Few data on bone marrow ( BM) involvement in ALCL have been published and they mostly rely on morphological examination of BM smears. We studied 52 ALCL for NPM - ALK expression by RT- PCR: 47/52 biopsies were positive. In 41 of the 47 cases we obtained the BM at diagnosis and investigated the prevalence of minimal BM infiltration by RT-PCR and real-time PCR. Minimal disseminated disease was positive in 25/41 patients ( 61%), of whom six had morphologically infiltrated BM. Survival analysis demonstrated a 5-year progression-free survival of 41 +/- 11% for patients with molecularly positive BM vs 100% for patients with negative BM ( P = 0.001). These results suggest that minimal BM involvement at diagnosis is a common event in pediatric ALCL and that minimal BM disease monitoring could identify patients at risk of relapse.