PH negative acute lymphoblastic leukemia in adolescents and young adults treated according a MRD adapted BFM ALL IC 2009 protocol: Argentine real-world data on 171 patients.

Intensified pediatric chemotherapy regimens to treat adolescents and young adults (AYA) patients with Philadelphia negative acute lymphoblastic leukemia (ALL) have been associated with better outcomes. The local BFM 2009-based scheme complements the risk stratification assessing the measurable residual disease (MRD) along the induction phase with increasing levels of sensitivity. The present retrospective multicenter analysis included 171 AYA (15-40 years) patients treated accordingly between 2013 and 2019. Ninety-one percent obtained morphological complete remission, 67% a negative (<0.1%) MRD at day 33 (TP1), and 78% a negative (<0.01%) MRD at day 78 (TP2). The overall survival (OS) and the event-free survival (EFS) at 2 years were 62%±4.1 and 55%±4.1, respectively. The OS and EFS were significant better for prednisone responders, who achieved <10% BM blast at day 15, a negative MRD at TP1 or at TP2, and for low-risk patients. Age ≤30 years and WBC <30×109/L, particularly among B-phenotype, were also associated with longer OS. In the multivariable analyses, TP1 MRD positive (OS HR 2.8, 95% CI 1.4-5.7, p=0.004; EFS HR 3.0, 95% CI 1.6-5.7, p=0.001) and at TP2 (OS HR 2.6, 95% CI 1.3-5.3, p=0.012; EFS HR 2.6, 95% CI 1.3-5.1, p=0.006) were independently associated with earlier events. Age >30 years was also associated with a shorter survival (HR 3.1, 95% CI 1.3-7.5, p=0.014). Therefore, those 68 patients ≤30 years with TP1/TP2 negative MRD depicted a longer OS (2 years 85%±4.8). Based on our real-world data, the pediatric-based scheme is feasible in Argentina associated with better outcomes for younger AYA patients who achieved negative MRD at day 33 and 78.

Clinical outcome of patients with relapsed/refractory acute leukemia treated with FLAG-IDA regimen

Background: Patients with Refractory/Relapsed (RIR) acute leukemia (AL) have a poor prognosis. Objective: We aimed to evaluate the chemotherapy regimen fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) in patients with RIR AL. Patients: We studied 33 patients with R/R AL. Distribution of the AL subtype was: myeloblastic n=17 (52%), lymphoblastic n=14 (42%),) and biphenotypic n=2 (6%). Results: Complete remission (CR) was achieved in 15 cases (45.5%) and seven patients dead resulting in a mortality of 21.1%. In patients with hematological recovery the median time to neutrophils recovery (> 0.5 x 10º/1) was 24 days (range 10-38); platelet levels of more than 20 x 1Oº/l and 50 x 10º/1 were reached in a median time of 24 (range 17-44) and 27 days (range 18-51), respectively. After CR, five patients underwent allogeneic transplan- tation and 10 patients

Clinical outcome of patients with relapsed/refractory acute leukemia treated with FLAG-IDA regimen

Background: Patients with Refractory/Relapsed (RIR) acute leukemia (AL) have a poor prognosis. Objective: We aimed to evaluate the chemotherapy regimen fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) in patients with RIR AL. Patients: We studied 33 patients with R/R AL. Distribution of the AL subtype was: myeloblastic n=17 (52%), lymphoblastic n=14 (42%),) and biphenotypic n=2 (6%). Results: Complete remission (CR) was achieved in 15 cases (45.5%) and seven patients dead resulting in a mortality of 21.1%. In patients with hematological recovery the median time to neutrophils recovery (> 0.5 x 10º/1) was 24 days (range 10-38); platelet levels of more than 20 x 1Oº/l and 50 x 10º/1 were reached in a median time of 24 (range 17-44) and 27 days (range 18-51), respectively. After CR, five patients underwent allogeneic transplan- tation and 10 patients received a second course of FLAG – IDA. Ten out of 15 patients who achieved CR with FLAG-IDA relapsed at a median of 7.7 months (95% CI 1.8 to 13.6 months). Overall survival (OS) after FLAG-IDA in the surviving cohort had a median of 4 months. We found a significantly better OS in patients who received allogeneic transplantation post-FLAG-IDA than those who did not (median 11.4 months vs. 2.7 monthsj HR 0.29; 95% CI 0.1 to 0.6; p=0.017). Conclusions: In our series, FLAG-IDA demonstrated to be an effective salvage chemotherapy regimen, however, the benefit in survival of this rescue treatment was restrained to patients who unde.rwent al1ogeneic transplantation