Early Marrow Response in CCG-1952: The Prognostic Impact of Poor Day 14 Marrow Response Is Powerful and Only Partially Reversible with Intensified Therapy.

Microscopic assessment of bone marrow response on Day 7 and/or Day 14 of induction therapy remains a powerful predictor of long-term outcome in childhood acute lymphoblastic leukemia (ALL). Between 1996 and 2000, 2175 Rome/NCI standard risk children, i.e., age >1 and <10 years with presenting WBC <50,000/ul, entered CCG-1952 and received induction therapy with vincristine, native asparaginase, prednisone, and intrathecal cytarabine and methotrexate. Bone marrow status was assessed on Day 7 and Day 28. Patients with blasts >5% on Day 7 had an additional evaluation on Day 14. Patients with blasts >25% (M3) on Day 14, adverse cytogenetics (i.e., t(9;22), t(4;11), or severe hypodiploidy (modal chromosome numbers <45) received daunomycin on day 19 of induction and the augmented intensive regimen therafter (

Day 7 M1 patients had better EFS than Day 7 M2 or M3 patients who did not achieve M1 status until Day 14. Induction daunomycin and stronger post induction intensification therapy may have rescued Day 7 M3/Day 14 M3 patients, who had a better EFS than the more rapidly responding Day 7 M3/Day 14 M2 patients, who received only standard strength intensification. Day 7 M3/Day 14 M2 patients received ‘augmented therapy’ on the subsequent study, CCG-1991. In summary, microscopic assessment of marrow response remains a powerful predictor of long-term outcome. Outcomes may be modified by more effective subsequent therapy.