Monitoring MRD Guided Treatment Outcome of Adult Patients with Acute Lymphoblastic Leukemia Using ALL-BFM95 Based Protocol

Tremendous achievements have been made in the treatment of childhood ALL within the past decades. However, the same success has not been replicated in adult cases. In addition to more complex genetic abnormalities found in adults vs children, the difference in the hematopoietic affordability, in line with intensive chemo-therapy between childhood and adult patients, raises the concern about whether and how well adult cases could do with childhood ALL protocol, especially among those patients ≥ 30 years old.

Following the successful childhood ALL regimen, reflecting sufficient dose intensity and compact time density, is the key towards the cure of the disease. We utilized BFM95 protocol with modifications and explored its safety and efficiency in the middle age patients with ALL. We designed this single arm study and enrolled 87 patients (ages 30-48 year-old) from 2008 to 2017. The medium follow up time was 62 months (10~101months). Survival was evaluated by Kaplan Meier analysis and Log-Rank test. The BCR-ABL positive patients were excluded from this trial. We changed the L-ASP to Peg-ASP (3,750 unit/m2) and switched Vincristine to Vinorelbine (20mg/m2).

Five patients were eligible for the study. Among the 82 evaluated patients, 68 achieved CR (83%) in induction. There was no treatment related mortality during the induction. Major complications during the induction were myelosupression related neutropenia, fever and infection. Early treatment response parameters, or minimal residual disease (MRD) levels, served as the most important prognostic factor in the ALL treatment. Good prednisone response was reported among 66 patients (80%). The day 33 MRD detection by flow cytometry for those in CR indicated 65 (79%) reached ≤5 *10^-2 and five achieved 10^-3. The MRD detection at month three and six suggested that 55 (67%) vs 48 (60%) patients were within the level of ≤5 *10^-2 and eight (10%) vs 13 (16%) achieved 10^-3, respectively. Relapse-related death occurred in 27 of 82 patients (33%), and 10 of 82 patients (12%) experienced treatment-related mortality. Grade 3-4 adverse events were observed among 40% of all the cases. Five-year probability of event-free survival (pEFS) was found to be 54.8%. Those who went with hematopoietic stem cell transplantation (HSCT) after chemotherapy achieved significantly better pEFS than only chemotherapy (60.3% vs 48.6%, p=0.04). The pEFS for B-cell precursor and T-cell ALL was 58.5% and 52.1%, respectively(P=0.72)

ALL-BFM 95 protocol can be used as an effective treatment option to improve the outcome of middle aged adults with ALL. The main toxicities include GI adverse events and coagulation abnormality which can both be solved by close monitoring and multi-disciplinary care.