title: Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients.
abstract: A large proportion of adult patients with acute myeloid leukemia (AML) relapse after treatment, and some of them are resistant to primary induction chemotherapy. Sixty-one patients from seven hematological centers with poor-risk AML, primary refractory (n = 16), or relapsed (n = 45) were treated with a salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a sequential continuous infusion, associated with liposomal daunorubicin (3 days) (FLAD). Complete response rate was 44% and 56% for refractory and relapsed patients, respectively, with an overall response rate of 52% (32 of 61). Twenty-two patients (36%) were resistant to the salvage therapy. Seven patients (12%) died early during chemotherapy, four of them because of sepsis. Nineteen patients in complete remission (CR) underwent a stem-cell transplant (SCT) procedure: five autologous, nine from a HL-A identical sibling, and five from HL-A matched unrelated donors. Post-treatment aplasia and mucositis were major toxicities. Twenty patients (62.5%) relapsed after this treatment in a median of 7.3 months; ten patients relapsed after a SCT procedure. Nine patients are alive and disease free; three of them were rescued after a further cytotoxic treatment. The FLAD regimen proved to be an effective and well-tolerated treatment, with acceptable toxicity in this group of high-risk patients. A better response rate was obtained in the subgroup of relapsed patients, compared to patients treated for refractory disease. More then half (five of nine) of long-surviving patients are those who were submitted to a transplant procedure; thus, the main indication for FLAD seems to be to try to induce a rapid CR with minimum toxicity in order to perform a transplant as soon as possible.
authors: Hematology, Università Federico II, Naples, Italy.
authors: Andrea
authors: A
authors: Camera
authors: Ciro R
authors: CR
authors: Rinaldi
authors: Salvatore
authors: S
authors: Palmieri
authors: Nicola
authors: N
authors: Cantore
authors: Giuseppina
authors: G
authors: Mele
authors: Vincenzo
authors: V
authors: Mettivier
authors: Eustachio
authors: E
authors: Miraglia
authors: Lucia
authors: L
authors: Mastrullo
authors: Francesco
authors: F
authors: Grimaldi
authors: Luigia
authors: L
authors: Luciano
authors: Anna
authors: A
authors: Guerriero
authors: Bruno
authors: B
authors: Rotoli
authors: Felicetto
authors: F
authors: Ferrara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003630:Daunorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000601:surgery; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013997:Time Factors; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D008081:Liposomes; D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine; D003630:Daunorubicin