title: A single high dose of idarubicin combined with high-dose ABA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University La Sapienza of Rome.
abstract: OBJECTIVE
  The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance.
  
  
  METHODS
  In a clinical phase II study the combination of a single high dose (HD) idarubicin and HD cytosine-arabinoside (ARA-C), as designed at the Memorial Sloan Kettering Cancer Center, was applied to 70 adults and children with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL). Therapy consisted of HD-ARA-C 3 g/m2/d on days 1-5, idarubicin 40 mg/m2 on day 3, prophylactic intrathecal methotrexate on days 1 and 4, and G-CSF 5 mg/kg/d s.c. from day 7 to hematopoietic reconstitution (PMN > 0.5 x 10(9)/L).
  
  
  RESULTS
  Fifty-five of the 70 patients (78%) achieved complete remission (CR), four died in aplasia due to infection and 11 were non-responders. Recovery of blood counts occurred at a median of 21 days from the start of treatment. Non-hematologic side effects were extremely limited and consisted predominantly of infections.
  
  
  CONCLUSIONS
  In view of the highly unfavorable series of patients selected, this study confirms the feasibility and antileukemic activity of the HD-idarubicin + HD- ARA-C combination in patients with refractory and early relapse ALL and NHL. The excellent tolerance to this regimen does not preclude bone marrow transplantation as post-remission treatment.
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Rome, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Testi
authors.forename: M L
authors.initials: ML
authors.lastname: Moleti
authors.forename: F
authors.initials: F
authors.lastname: Giona
authors.forename: L
authors.initials: L
authors.lastname: Annino
authors.forename: S
authors.initials: S
authors.lastname: Chiaretti
authors.forename: I
authors.initials: I
authors.lastname: Del Giudice
authors.forename: E
authors.initials: E
authors.lastname: Todisco
authors.forename: G
authors.initials: G
authors.lastname: D'Elia
authors.forename: A
authors.initials: A
authors.lastname: Ferrari
authors.forename: W
authors.initials: W
authors.lastname: Arcese
authors.forename: F
authors.initials: F
authors.lastname: Mandelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012384:Rome; D014495:Universities
chemical_list: D000903:Antibiotics, Antineoplastic; D003561:Cytarabine; D015255:Idarubicin