Allogeneic Hematopoietic Stem Cell
Although risk of relapse is higher, long term outcomes of reduced-intensity allogeneic hematopoietic stem cell transplant in patients who were ineligible for myeloablative transplant are promising . The results of a prospective multicenter phase II trial conduced by the Alliance for Clinical Trials in Oncology (formerly Cancer and Leukemia Group B) and the Blood and Marrow Transplant Clinical trial Network showed reduced intensity conditioning-based hematopoietic stem cell transplant (HSCT) to be an effective strategy for suitable older patients with an available matched donor with a disease-free survival and OS at two years after transplant
of 42% and 48%, respectively . Reduced intensity transplants are therefore becoming more common and clinically accepted.
7.3. Relapsed Disease
Of the patients who relapse, only a small fraction achieve successful second remission using salvage chemotherapy followed by allogeneic stem cell transplant with curative intent . Studies examining clonal evolution of relapse show that relapse can occur from expansion of major or minor clones present at diagnosis or through newly acquired mutations over time . Therefore, clinical trial is the preferred treatment approach especially in light of novel targeted therapies. Early relapse (occurring within the first six months after CR1) portends a poor overall survival. Salvage regimes include intermediate dose cytarabine (500–1500 mg/m2 intravenously every 12 h on days 1–3); MEC (Mitoxantrone 8 mg/m2 on days 1–5, Etoposide 100 mg/m2 on days 1–5, and Cytarabine 100 mg/m2 on days 1–5) or lastly, FLAG-IDA (Fludarabine 30 mg/m2, intravenously on days 1–5 (20 mg/m2 in patient >60 years old), Cytarabine 1500 mg/m2 (500–1000 mg/m2 in patients >60 year) intravenously, 4 h after fludarabine infusion, on days 1–5; Idarubicin 8 mg/m2, intravenously, on days 3–5; Granulocyte colony-stimulating factor 5 μg/kg, subcutaneously, from day 6 to white-cell count >1 g/L (FLAG-IDA) . The likelihood of achieving a second CR is best in patients with a long first remission, younger age and in those with favorable cytogenetics . In cases of APL, re-induction with ATO with or without ATRA remains the standard. CR rates with single agent ATO are good at roughly 85% .
8. Novel Targets
8.1. Fms-Like Tyrosine Kinase 3 (FLT3) Inhibitors
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