title: Myeloablative intravenous pharmacokinetically targeted busulfan plus fludarabine as conditioning for allogeneic hematopoietic cell transplantation in patients with non-Hodgkin lymphoma.
abstract: BACKGROUND
  Mortality associated with allogeneic hematopoietic cell transplantation (allo-HCT) has limited its broader application in patients with non-Hodgkin lymphoma (NHL). Pharmacokinetic treatment with targeted intravenous busulfan combined with fludarabine (BuFlu) was developed as a preparative regimen for acute leukemia and myelodysplasia. Data from this regimen in lymphoid malignancies are limited.
  
  
  METHODS
  We assessed outcomes in 60 consecutive patients with various subtypes of NHL and a median age of 54 years (range, 27-68 years) who received allo-HCT with targeted intravenous BuFlu between December 2004 and August 2010. The median number of previous therapies was 3 (range, 1-8) and median time from diagnosis to HCT was 32 months (range, 4.5-177.5 months).
  
  
  RESULTS
  At conditioning, 28 (47%) patients had a complete response (CR). Graft versus host disease (GVHD) prophylaxis consisted of tacrolimus plus methotrexate in 65% of cases. Donors were matched/related (n = 32 [53%]), matched/unrelated (n = 21 [35%]), or mismatched/unrelated (n = 7 [12%]). All patients underwent grafting. The cumulative incidence of grade II/IV acute GVHD was 74% (grade III/IV was 20%). The 2-year cumulative incidence of moderate to severe chronic GVHD was 62%. Nonrelapse mortality (NRM) at 100 days and 3 years was 10% and 25%, respectively. The cumulative incidence of relapse was 27%. Three-year progression-free and overall survival for all patients was 47.8% and 55%, respectively.
  
  
  CONCLUSIONS
  Targeted intravenous BuFlu is a relatively well tolerated regimen and offers an alternative option when myeloablation is deemed necessary in patients with NHL.
authors: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL; Department of Oncologic Sciences, University of South Florida College of Medicine, Tampa, FL. Electronic address: ernesto.ayala@moffitt.org.
authors: Ernesto
authors: E
authors: Ayala
authors: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL.
authors: Javier
authors: J
authors: Figueroa
authors: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL.
authors: Janelle
authors: J
authors: Perkins
authors: Department of Biostatistics, Moffitt Cancer Center, Tampa, FL.
authors: Jongphil
authors: J
authors: Kim
authors: Department of Biostatistics, Moffitt Cancer Center, Tampa, FL.
authors: Binglin
authors: B
authors: Yue
authors: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL; Department of Oncologic Sciences, University of South Florida College of Medicine, Tampa, FL.
authors: Marcie
authors: M
authors: Riches
authors: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL; Department of Oncologic Sciences, University of South Florida College of Medicine, Tampa, FL.
authors: Taiga
authors: T
authors: Nishihori
authors: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL; Department of Oncologic Sciences, University of South Florida College of Medicine, Tampa, FL.
authors: Frederick
authors: F
authors: Locke
authors: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL; Department of Oncologic Sciences, University of South Florida College of Medicine, Tampa, FL.
authors: Claudio
authors: C
authors: Anasetti
authors: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL; Department of Oncologic Sciences, University of South Florida College of Medicine, Tampa, FL.
authors: Mohamed A
authors: MA
authors: Kharfan-Dabaja
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D016559:Tacrolimus; D008727:Methotrexate
keywords: Allogeneic hematopoietic cell transplantation; Intravenous fludarabine and busulfan; Myeloablative conditioning; Non-hodgkin lymphoma; Non-relapse mortality