Mixed phenotype acute leukemia – how to diagnose, how to treat?

In 2009, the World Health Organization has published an updated classification of proliferative diseases, whereby biphenotypic acute leukemia and acute bilineal leukemia, which previously were two separate diseases, were replaced by a single name, mixed phenotype acute leukemia (MPAL). Incidence of MPAL is not exactly known and varies in different publications from 0.5 to 5% of all leukemias in children. In these patients genetic disorders are particularly important for both diagnosis and prognosis. However, due to the still unsatisfactory outcome, the main problem remains optimal therapeutic strategy of patients with MPAL. The majority of research points to better outcomes of MPAL treatment with usage of therapeutic programs for the treatment of acute lymphoblastic leukemia (ALL), although the results are worse than in patients with ALL. An attempt to standardize the therapeutic approach and further improve is the project iBFM AMBI2012

Prognostic impact of combined fludarabine, treosulfan and mitoxantrone resistance profile in childhood acute myeloid leukemia

Background: The role of cellular drug resistance in childhood acute myeloid leukemia (AML) has not yet been established. The aim of the study was the analysis of the clinical value of ex vivo drug resistance in pediatric AML. Patients and Methods: A cohort of 90 children with de novo AML were assayed for drug resistance profile by the 3-4,5- dimethylthiazol-2-yl-2,5-difenyl tetrazolium bromide (MTT) assay and prognostic model of in vitro drug sensitivity was analyzed. Results: Children who relapsed during follow-up showed higher in vitro resistance of leukemic blasts to most of the drugs tested, except for cytarabine, cladribine, vincristine, mercaptopurine and thioguanine. A combined in vitro drug resistance profile to fludarabine, treosulfan and mitoxantrone (FTM score) was defined and it had an independent prognostic significance for disease free survival in pediatric AML. Conclusion: The combined fludarabine, treosulfan and mitoxantrone resistance profile to possibly may be used for better stratification of children with AML or indicate the necessity for additional therapy

Chronic Disseminated Candidiasis Complicated by Immune Reconstitution Inflammatory Syndrome in Child with Acute Lymphoblastic Leukemia

Hepatosplenic candidiasis also known as chronic disseminated candidiasis is a rare manifestation of invasive fungal infection typically observed in patients with acute leukemia in prolonged, deep neutropenia. Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory disorder triggered by rapid resolution of neutropenia. Diagnosis and treatment of IRIS are still challenging due to a variety of clinical symptoms, lack of certain diagnostic criteria, and no standards of treatment. The diagnosis of IRIS is even more difficult in patients with hematological malignancies complicated by “probable” invasive fungal infection, when fungal pathogen is still uncertain. We report a case of probable hepatic candidiasis in 4-year-old boy with acute lymphoblastic leukemia. Despite proper antifungal therapy, there was no clinical and radiological improvement, so diagnosis of Candida-related IRIS was made and corticosteroid therapy was added to antifungal treatment achieving prompt resolution of infection symptoms

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