Adaptation of Augmented Berlin-Frankfurt-Munster (ABFM) Therapy in Adolescents and Young Adults with Acute Lymphoblastic Leukemia (ALL).

Comparisons of survival of adolescents up to age 21 years of age treated on either pediatric or adult ALL protocols so far show improved survival for patients (pts) treated with pediatric therapies. ABFM therapy has been shown to be effective therapy for teen-aged pts up to age 21, and is the standard therapy arm of the current Children’s Oncology Group high-risk ALL trial. We have initiated a trial of ABFM based therapy for pts up to the age of 30 with lymphoblastic leukemia. Pts receive four drug induction with prednisone 60 mg/m2 daily for 28 days, daunorubicin 25 mg/m2 weekly for four doses, vincristine 2 mg weekly for four doses, and a single dose of intravenous pegylated asparaginase (PEG-asp) in week one of therapy. Intrathecal (IT) cytarabine is given on day one, and IT methotrexate is given on days 8 and 29. IT therapy is intensified depending on the presence of spinal fluid blasts. Induction is extended by two weeks for patients who do not acheive a bone marrow morphologic remission (MR) by day 29. Pts that are in MR by day 15 are rapid early responders; they receive one phase of delayed intensification. Pts who are not in MR by day 15 but enter MR by day 29 or 42 are slow early responders; they receive two delayed intensifications. Upon completion of induction, pts continue with intensive phases of chemotherapy for approximately 6 months. They then start 24 months of maintenance therapy. 13 patients with newly diagnosed ALL have been enrolled with a planned enrollment of 80. The median age is 20 (range 14–28). 10(77%) have pre-B ALL and 3(23%) have T-ALL. 12(92%) are rapid early responders. All pts are in MR by day 29. Minimal residual disease (MRD) status is evaluated at day 29 and day 84 by four-color flow cytometry. 8(62%)pts are MRD negative by day 29. All pts so far are MRD negative by day 84. One pt has relapsed. There are no treatment related deaths. Treatment delays for bone marrow suppression are common. There has been 1 allergic reaction to PEG-asp and 2 cases of clinical pancreatitis. 2 pts have had stroke-like symptoms with MRI findings compatible with treatment toxicity; complete clinical resolution has occurred in both. 4 pts have had grade (Gr) 3–4 hyperglycemia. 2 pts have had Gr 3–4 hyperbilirubinemia. 2 patients have been non-compliant. One pt has had Gr 4 sepsis. Other infectious complications are not common. Early evaluation indicates that ABFM therapy is effective in inducing rapid MR in young adults with ALL. The regimen appears tolerable, but morbidity is frequent. Gr 3–4 toxicity occurs more often than recently reported for similar therapy in adults with ALL (