Young Adults with Acute Lymphoblastic Leukemia (ALL) Treated with Adapted Augmented Berlin-Frankfurt-Munster (ABFM) Therapy

The survival of teen-aged patients (pts) with acute lymphoblastic leukemia (ALL) has been analyzed by various groups, with most groups showing improved survival for these pts using pediatric ALL regimens compared to adult treatment regimens. ABFM therapy is an effective therapy for ALL pts up to age 21 and the therapy has acceptable toxicities. We designed a trial of modified ABFM therapy for adolescent/young adults (AYA) up to age 40 with acute lymphoblastic leukemia. Enrollment on the trial began in October 2006. Pts receive four drug induction with prednisone 60 mg/m2 daily for 28 days, daunorubicin 25 mg/m2 weekly for 4 doses, vincristine 2 mg weekly for 4 doses and a single dose of intravenous PEG-asparaginase in week one as well as intrathecal (IT) cytarabine on day one and IT methotrexate on day 8 and 29 depending on the presence of spinal fluid blasts. Induction is extended by two weeks for pts who do not achieve morphologic remission by day 29. Pts who have a morphologic remission by day 15 are classified as rapid early responders, and they receive one phase of delayed intensification. Patients who do not achieve morphologic remission by day 15 but who attain morphologic remission by day 29 or day 42 are slow early responders. Compared to preceding high risk ALL therapy in children, the first year of ABFM treatment uses more vincristine, asparaginase and intravenous methotrexate. As per prior pediatric protocols, central nervous system (CNS) radiation is recommended for pts with CNS involvement at diagnosis and for pts with T-cell ALL and a high presenting white blood cell count. 34 pts have been enrolled. 29 are evaluable (2 with prior relapse, 2 with lymphoblastic lymphoma, and 1 withdrew on day 1 of therapy). The median age is 20 years (range 14–34). 27 (90%) pts are in remission at day 28. Two pts are in remission with extended induction. One pt is refractory to induction. 26 (87%) have rapid early responses by marrow morphology. Minimal residual disease (MRD) testing shows 15/29 positive at day 15, 10/29 positive at day 29, and 3/24 positive at day 84. The most frequent grade 3–4 toxicities are infectious in 19 (65%), elevated transaminases in 17 (58%) patients, hyperglycemia in 13 (44%), and hyperbilirubinemia in 9 (31%). 7 (25%) have Grade 3–4 thrombosis or fatigue. Less frequent but significant toxicities include leukoencephalopathy, osteonecrosis and severe allergic reactions each seen in 3 (10%) pts. One pt had a prolonged delay in chemotherapy due to liver toxicity and relapsed. One pt has CNS relapse, and two have died of leukemia. ABFM therapy in young adults is an effective induction regimen but entails significant hepatic and infectious toxicities. The majority of these toxicities have resolved. Long-term follow-up is needed to determine if this treatment regimen offers an advantage to AYA patients with ALL.