title: Day 15 bone marrow driven double induction in young adult patients with acute myeloid leukemia: feasibility, toxicity, and therapeutic results.
abstract: The strategy named double induction (DI) in acute myeloid leukemia (AML) consists of two courses of chemotherapy irrespective of the degree of cytoreduction in the bone marrow (BM) after the first course, unless severe complications prohibit its application. We describe treatment results from a series of 33 patients in whom DI was adopted only after demonstration of persistence of more than 10% blast cells at day 15 (D15) examination of BM. All patients received as induction idarubicin, cytarabine, and etoposide. As second induction, we administered the combination of fludarabine, intermediate dose cytarabine, and Granulocyte colony stimulating factor (G-CSF). The median blast count at D15 was 30 (15-90). Overall, 30 of 33 patients were judged as eligible to receive DI, reasons for exclusion being in all cases active infection in the context of severe pancytopenia. Nineteen patients (63%) had unfavorable karyotype and 11 (37%) normal karyotype; seven of these had Fms-like tyrosine kinase gene internal tandem duplication (FLT3/ITD) mutation. Overall, complete remission (CR) was achieved in 20/30 patients (67%), while eight patients (27%) were refractory and two died of infectious complications. All refractory patients had unfavorable cytogenetics. All patients achieving CR were programmed to receive allogeneic stem cell transplantation (allo-SCT), which was actually performed in 11 patients. Our study suggest that D15 driven DI represents a feasible and effective therapeutic strategy in young adult AML patients, improving therapeutic results and not compromising feasibility of allo-SCT. When compared with conventional DI, it offers the potential to avoid unnecessary toxicity in a consistent proportion of patients.
authors.affiliation: Division of Hematology and Stem Cell Transplantation Unit, Cardarelli Hospital, Via Nicolò Piccinni 6, Naples, Italy. felicettoferrara@katamail.com
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.forename: Tiziana
authors.initials: T
authors.lastname: Izzo
authors.forename: Clelia
authors.initials: C
authors.lastname: Criscuolo
authors.forename: Cira
authors.initials: C
authors.lastname: Riccardi
authors.forename: Maria
authors.initials: M
authors.lastname: Celentano
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Mele
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001752:Blast Crisis / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D014740:Vidarabine; C024352:fludarabine; D015255:Idarubicin