Outcome and Toxicities of Modified Augmented Berlin-Frankfurt-Muenster (ABFM) Therapy Used in the Treatment of Acute Lymphoblastic Leukemia in Adolescent and Young Adult Patients, Single Center Experience From Saudi Arabia

Acute lymphoblastic leukemia (ALL) is a neoplasm of precursor lymphoid cells known as lymphoblasts. ALL is the most common cancer in children. The prognosis among Adolescents and young adults (AYA) is intermediate between children, who have a very good prognosis with a 5-year survival rate of 80%, and adults, who have a worse prognosis with an overall survival of about 30–50%. We found no studies in Saudi Arabia which assessed the use of a Berlin-Frankfurt-Muenster (BFM) to treat patients in the AYA group. The purpose of this study is to measure the outcome and toxicities of the BFM protocol used in treatment of ALL patients in the AYA population seeking treatment at Princess Noorah Oncology Center (PNOC), at the National Guard Hospital, Jeddah, Saudi Arabia. PNOC is a tertiary referral center for the Western region of the Kingdom of Saudi Arabia. Patients referred between the ages of 14 to 25 were treated according to an augmented modified version of the Berlin-Frankfurt-Muenster (BFM) protocol. Patients' treatments were based on risk factor stratification. High risk category was identified based on the presence of one of following factors: phenotype of the leukemia (i.e. T-cell ALL is considered high risk), lack of response to therapy on day 29 of induction, cytogenetics, presence of extramedullary disease e.g. testicular or CNS disease and whether they have received steroid treatment prior to the first diagnostic marrow. High risk group was treated with doubled blocks of interim maintenance, delayed intensification the first of delayed intensification blocks included a high dose methotrexate at the dose of 5g/m² which was first started at our center in 2008.

This study is a retrospective chart review. Patients who met the inclusion criteria within the last five years were included. The inclusion criteria were those with confirmed ALL (excluding mature B cell phenotype) aged between 14 to 25 years, and were treated with the Modified Augmented Berlin-Frankfurt-Muenster (ABFM) therapy protocol. 45 patients were indentified who fulfilled the above criteria 4 were excluded due to the lack of data and loss to follow up. Data were analyzed using SPSS version 19.

The mean age of 41 patients treated was 16.4 years (range; 14 – 25 years). Of 41 patients treated, 23 (56%) were males. Only one patient (2%) had CNS involvement at presentation. B cell ALL compromised 61% of the patients while 39% were T cell ALL. All 41 (100%) patients achieved complete remission after induction therapy however two patients (5%) required extended induction to achieve a complete remission status. Five (12.2%) patients relapsed at a median follow up of 30 months. Two (4.9%) patients died while in complete remission from treatment related causes. The probability of Overall Survival (OS) is 95.1% and 87.8% at 2 and 3 years, respectively. The probability of Event-free Survival (EFS) of our 41 patients is 90.2% and 82.9% at 2 and 3 years respectively. Thirty three (81%) patients developed febrile neutropenia with a total of 50 documented episodes. Thirty two (64%) of the febrile neutropenia episodes occurred during induction and re-intensification phases those two blocks were associated with a statistically significant increased risk of neutropenia (P < 0.001)compared to other blocks. Five (12%) of patients developed fungal infections there is one patient who developed two separate episodes of fungal infection. Four fungal infection episodes occurred during induction and re-intensification phases which constituted the highest risk phases for the development of fungal infections. In 38% of febrile neutropenic episodes an infectious agent was identified in 8% of episodes the isolate was a fungus. Eight patients (20%) developed Venous Thromboembolism (VTE) with a total of 9 episodes.

In our study population the OS & EFS were comparable to other reported groups despite the relatively increased numbers of T cell ALL (39%) patients compared to the reported average of 15–25%. The reported incidence of VTE is similar to the incidence reported by other groups while the incidence of fungal infections is relatively more than we would have expected. Complete remissions, survival, relapse and death rates are comparable to international studies. However new measures are required to lower the increased rates of fungal infections & VTE for future patients.

No relevant conflicts of interest to declare.