The Prophylactic Use of G-CSF During Induction and Consolidation of Adults with Acute Lymphoblastic Leukemia Is Associated with Reduced Risk of Relapse and Improved Leukemia-Free Survival. A Joint Analysis of Five Randomized Trials on Behalf of the European Working Group for Adult ALL (EWALL)

Abstract 2130

The use of granulocyte colony stimulating factor (G-CSF), either filgrastim or lenograstim, along with induction and consolidation of adults with acute lymphoblastic leukemia (ALL) was a subject of several trials documenting significant shortening of neutropenia, reduced rate of infections and better adherence to chemotherapy protocol. The above studies, however, were not powered to detect differences with regard to long-term outcome.

We performed a joint analysis of follow-up data from five multicenter prospective, randomized trials performed in France, Poland, Sweden, Austria and Australia. Among 347 adults with ALL (median age 33 years), 185 were assigned to receive prophylactically G-CSF while 162 patients were treated without G-CSF support. G-CSF was administered either in parallel to chemotherapy or in a sequential mode.

With the median follow-up of 3.2 years, the remission duration was significantly longer for patients receiving G-CSF compared to controls (33 vs. 17 months, p=0.007). The difference was particularly pronounced for T-ALL (median not reached vs. 13 m., p=0.01) and a trend was observed for B-ALL (22 vs. 17 m., p=0.11). The 5-years probability of leukemia-free survival (LFS) was 38% for patients assigned to the G-CSF arm and 23% for the remaining subjects (p=0.01). There was also a tendency to increased overall survival (OS) rate in favor of patients receiving G-CSF (45% vs. 39%, p=0.17), which reached statistical significance in a subgroup of T-ALL (54% vs. 33%, p=0.03). In a multivariate analysis adjusted to age, initial WBC and the presence of Ph chromosome the prophylactic use of G-CSF was associated with reduced risk of relapse (HR=0.65, p=0.01) and treatment failure (HR=0.7, p=0.02). The differences remained significant when the observations were censored at the time of alloHSCT.

We conclude that the prophylactic use of G-CSF during induction and consolidation of adults with ALL is associated with reduced risk of relapse and improved LFS. The possible explanation could be better adherence to chemotherapy schedules, as demonstrated in previous studies. Patients with T-ALL appear to particularly benefit from the use of G-CSF.