Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL‐class fusion

Patients with an ABL‐class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post‐induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABL‐class patients who did and did not receive a TKI in first remission to be compared. ABL‐class patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0·009)

International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

open47siDespite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Munster Study of Leukemias of Ambiguous Lineage [iBFM-AMBI2012]) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)type primary therapy (80% +/- 4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatment (36% +/- 7.2% and 50% +/- 12%, respectively). When ALL-or AML-specific gene fusions were excluded, 5-year EFS of CD19(+) leukemia was 83% +/- 5.3% on ALL-type primary treatment compared with 0% +/- 0% and 28% +/- 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19(+) ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19(-) and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with >= 5% blasts after remission induction. The results provide a basis for a prospective trial.openHrusak, Ondrej; De Haas, Valerie; Stancikova, Jitka; Vakrmanova, Barbora; Janotova, Iveta; Mejstrikova, Ester; Capek, Vaclav; Trka, Jan; Zaliova, Marketa; Luks, Ales; Bleckmann, Kirsten; Möricke, Anja; Irving, Julie; Konatkowska, Benigna; Alexander, Thomas B.; Inaba, Hiroto; Schmiegelow, Kjeld; Stokley, Simone; Zemanova, Zuzana; Moorman, Anthony V.; Rossi, Jorge Gabriel; Felice, Maria Sara; Dalla-Pozza, Luciano; Morales, Jessa; Dworzak, Michael; Buldini, Barbara; Basso, Giuseppe; Campbell, Myriam; Cabrera, Maria Elena; Marinov, Neda; Elitzur, Sarah; Izraeli, Shai; Luria, Drorit; Feuerstein, Tamar; Kolenova, Alexandra; Svec, Peter; Kreminska, Olena; Rabin, Karen R.; Polychronopoulou, Sophia; Da Costa, Elaine; Marquart, Hanne Vibeke; Kattamis, Antonis; Ratei, Richard; Reinhardt, Dirk; Choi, John K.; Schrappe, Martin; Stary, JanHrusak, Ondrej; De Haas, Valerie; Stancikova, Jitka; Vakrmanova, Barbora; Janotova, Iveta; Mejstrikova, Ester; Capek, Vaclav; Trka, Jan; Zaliova, Marketa; Luks, Ales; Bleckmann, Kirsten; Möricke, Anja; Irving, Julie; Konatkowska, Benigna; Alexander, Thomas B.; Inaba, Hiroto; Schmiegelow, Kjeld; Stokley, Simone; Zemanova, Zuzana; Moorman, Anthony V.; Rossi, Jorge Gabriel; Felice, Maria Sara; Dalla-Pozza, Luciano; Morales, Jessa; Dworzak, Michael; Buldini, Barbara; Basso, Giuseppe; Campbell, Myriam; Cabrera, Maria Elena; Marinov, Neda; Elitzur, Sarah; Izraeli, Shai; Luria, Drorit; Feuerstein, Tamar; Kolenova, Alexandra; Svec, Peter; Kreminska, Olena; Rabin, Karen R.; Polychronopoulou, Sophia; Da Costa, Elaine; Marquart, Hanne Vibeke; Kattamis, Antonis; Ratei, Richard; Reinhardt, Dirk; Choi, John K.; Schrappe, Martin; Stary, Ja