title: Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma.
abstract: OBJECTIVE
  Cladribine (2-CdA) is a purine analogue that exhibits activity against a variety of hematological malignancies and has a potent immunosuppressive effect. We therefore performed a pilot study to evaluate the feasibility of a novel 2-CdA-based reduced-intensity stem cell transplantation (RIST) regimen.
  
  
  METHODS
  A total of 16 scheduled patients with hematological malignancies were enrolled for comparison of their data with conventional stem cell transplantation (n = 19). The regimen for RIST consisted of 2-CdA (0.11 mg/kg/day for 6 days), busulfan (4 mg/kg/day for 2 days), and rabbit antithymocyte globulin (2.5 mg/kg/day for 4, 2, or 0 days). The underlying diseases included acute myelogenous leukemia (n = 6), chronic myelogenous leukemia (n = 2), myelodysplastic syndrome (n = 6), and non-Hodgkin's lymphoma (n = 2).
  
  
  RESULTS
  After RIST, four patients died before day 100 as a result of acute graft-versus-host disease (n = 1), bacteremia (n = 1), disseminated candidasis (n = 1) and congestive heart failure (n = 1). Another patient died of cerebral infarction on day 140. Thus, acute-phase regimen-related toxicities >grade III were observed in only one patient. Engraftment and complete donor chimerism were achieved by day 28 in 14 evaluable patients, and 6 of them (43%) experienced grade II-IV acute graft-versus-host disease. With a median follow-up of 328 days (range, 231-633 days), the actuarial 1-year overall and disease-free survival rates were 69% and 50%, respectively. Notably, among seven high-risk patients (five patients had been in complete remission two or more times and two not in complete remission with refractory disease at transplant), only two patients developed leukemia relapse after RIST. Although the recovery of CD4+ cells was significantly slower (P = 0.02) in RIST than in conventional stem cell transplantation, the incidence of clinically documented infections was not significantly different between the two groups.
  
  
  CONCLUSIONS
  The results suggest that this novel regimen containing 2-CdA is well tolerated and induces early complete donor chimerism. The unexpected durable remission achieved in patients with advanced disease at transplant suggests the presence of an acceptable antileukemia/lymphoma effect, which would warrant a further clinical trial.
authors.affiliation: Hematopoietic Stem Cell Transplantation and Hematology Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kami
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kato
authors.forename: Nahoko
authors.initials: N
authors.lastname: Shoji
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Kanai
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kawano
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Nakai
authors.forename: Toshie
authors.initials: T
authors.lastname: Ogasawara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsubara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Makimoto
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tanosaki
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Hiro
authors.initials: H
authors.lastname: Wakasugi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takaue
authors.forename: Shin
authors.initials: S
authors.lastname: Mineishi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use; D002066:Busulfan / Q000009:adverse effects / Q000627:therapeutic use; D017338:Cladribine / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D010865:Pilot Projects; D013203:Staphylococcal Infections / Q000209:etiology; D016019:Survival Analysis; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D017338:Cladribine; D002066:Busulfan