title: Idarubicin intensified BUCY2 regimen in allogeneic unmanipulated transplant for high-risk hematological malignancies.
abstract: Twenty-nine consecutive patients with high-risk hematological malignancy aged from 3 to 58 years underwent an unmanipulated graft from an HLA-identical sibling after an irradiation-free preparative regimen consisting of idarubicin (IDA), 21 mg/m2/day administered by continuous infusion on days -12 and -11, followed by busulphan (BU), 4 mg/kg/day orally from day -7 to -4, and cyclophosphamide (CY), 60 mg/kg/day intravenously on days -3 and -2 (IDA-BUCY2). Most clinically relevant extra-hematological regimen-related toxicities consisted of stomatitis observed in all subjects and hemorrhagic cystitis occurred in five cases (17%) within 100 days after transplant. Six patients (21%) developed a grade 2 acute graft-versus-host disease (GVHD) and three (10%) a grade 3 or 4; extensive chronic GVHD was assessed in nine of 22 (41%) evaluable patients. So far, 12 patients have died and 17 are alive, 16 of whom disease-free, 5-41 months after transplant (median, 15 months). The causes of death were related to GVHD in three patients, to sepsis in one and to disease recurrence in the remaining eight. At present, only one of nine relapsed patients is alive. For all patients the actuarial probability of survival (OS) at 1 and 2 years +/- standard error (s.e.) was 63 +/- 9% and 52 +/- 10%, respectively. The actuarial probabilities of disease-free survival (DFS), relapse and transplant-related mortality (TRM) at both 1 and 2 years +/- s.e. were 53 +/- 9%, 35 +/- 9% and 16 +/- 7%, respectively. These results are encouraging but not substantially different from those obtained in 28 patients with malignancy in advanced phase transplanted after the standard BUCY2 regimen, who had an actuarial probability of OS, DFS, relapse and TRM projected at 10 years +/- s.e. of 54 +/- 10%, 57 +/- 9%, 36 +/- 9% and 11 +/- 6%, respectively. Although the retrospective comparison between the two groups does not seem to show any advantage in the use of the IDA intensified regimen, only a prospective randomized trial could answer this question.
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Roma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mengarelli
authors.forename: A P
authors.initials: AP
authors.lastname: Iori
authors.forename: C
authors.initials: C
authors.lastname: Guglielmi
authors.forename: M P
authors.initials: MP
authors.lastname: Perrone
authors.forename: M
authors.initials: M
authors.lastname: Gozzer
authors.forename: C
authors.initials: C
authors.lastname: Girmenia
authors.forename: G
authors.initials: G
authors.lastname: Cimino
authors.forename: A M
authors.initials: AM
authors.lastname: Testi
authors.forename: R
authors.initials: R
authors.lastname: Ricci
authors.forename: L
authors.initials: L
authors.lastname: De Felice
authors.forename: G
authors.initials: G
authors.lastname: Girelli
authors.forename: F
authors.initials: F
authors.lastname: Mandelli
authors.forename: W
authors.initials: W
authors.lastname: Arcese
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan; D015255:Idarubicin