title: Second Allogeneic Stem Cell Transplantation for Acute Leukemia Using a Chemotherapy-Only Cytoreduction with Clofarabine, Melphalan, and Thiotepa.
abstract: Relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains one of the leading causes of mortality in patients with leukemia. Treatment options in this population remain limited, with concern for both increased toxicity and further relapse. We treated 18 patients with acute leukemia for marrow ± extramedullary relapse after a previous alloHSCT with a myeloablative cytoreductive regimen including clofarabine, melphalan, and thiotepa followed by a second or third transplantation from the same or a different donor. All patients were in remission at the time of the second or third transplantation. All evaluable patients engrafted. The most common toxicity was reversible transaminitis associated with clofarabine. Two patients died from transplantation-related causes. Seven patients relapsed after their second or third transplanation and died of disease. Nine of 18 patients are alive and disease free, with a 3-year 49% probability of overall survival (OS). Patients whose remission duration after initial alloHSCT was >6 months achieved superior outcomes (3-year OS, 74%, 95% confidence interval, 53% to 100%), compared with those relapsing within 6 months (0%) (P < .001). This new cytoreductive regimen has yielded promising results with acceptable toxicity for second or third transplantations in patients with high-risk acute leukemia who relapsed after a prior transplantation, using various graft and donor options. This approach merits further evaluation in collaborative group studies.
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: spitzerb@mskcc.org.
authors.forename: Barbara
authors.initials: B
authors.lastname: Spitzer
authors.affiliation: Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pediatrics, Weill Cornell Medical College, New York, New York.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pediatrics, Weill Cornell Medical College, New York, New York.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Prockop
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Zabor
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Webb
authors.affiliation: Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Hugo
authors.initials: H
authors.lastname: Castro-Malaspina
authors.affiliation: Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Esperanza B
authors.initials: EB
authors.lastname: Papadopoulos
authors.affiliation: Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: James W
authors.initials: JW
authors.lastname: Young
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Andromachi
authors.initials: A
authors.lastname: Scaradavou
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kobos
authors.affiliation: Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Giralt
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pediatrics, Weill Cornell Medical College, New York, New York.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.affiliation: Bone Marrow Transplant Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pediatrics, Weill Cornell Medical College, New York, New York.
authors.forename: Farid
authors.initials: F
authors.lastname: Boulad
mesh_terms: D000208:Acute Disease; D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000633:toxicity; D000293:Adolescent; D000328:Adult; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D000077866:Clofarabine; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D007938:Leukemia / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008558:Melphalan / Q000008:administration & dosage; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012074:Remission Induction / Q000379:methods*; D016879:Salvage Therapy / Q000379:methods* / Q000401:mortality; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D019653:Myeloablative Agonists; D000077866:Clofarabine; D013852:Thiotepa; D008558:Melphalan
keywords: Clofarabine; Leukemia; Second; Transplantation