title: A Comprehensive Assessment of Toxicities in Patients with Central Nervous System Lymphoma Undergoing Autologous Stem Cell Transplantation Using Thiotepa, Busulfan, and Cyclophosphamide Conditioning.
abstract: High-dose therapy and autologous stem cell transplantation (ASCT) with thiotepa, busulfan, and cyclophosphamide (TBC) conditioning has emerged as an effective postinduction treatment strategy for patients with primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL), but it is associated with considerable toxicity and transplantation-related mortality (TRM) in the modern era. Forty-three adult patients with chemosensitive PCNSL or SCNSL underwent TBC-conditioned ASCT between 2006 and 2015. Twenty-eight of these patients received pharmacokinetically (PK)-targeted busulfan dosing. The median number of clinically relevant individual grade ≥3 nonhematologic toxicities per patient was 5. We found no association between pretransplantation patient characteristics and the presence of more than 5 grade ≥3 nonhematologic toxicities. Patients with elevated first-dose busulfan area under the curve values did not experience more toxicity. Paradoxically, patients treated with more than 2 regimens before undergoing ASCT had lower first-dose busulfan AUC values. With a median follow-up among survivors of 20 months, 1-year progression-free survival (PFS) and overall survival (OS) from the time of ASCT were 83% and 87%, respectively. Although this study reaffirms the favorable PFS and OS associated with TBC-conditioned ASCT for PCNSL or SCNSL, this treatment strategy carries a large toxicity burden.
authors.affiliation: Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: scordom@mskcc.org.
authors.forename: Michael
authors.initials: M
authors.lastname: Scordo
authors.affiliation: Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Valkal
authors.initials: V
authors.lastname: Bhatt
authors.affiliation: Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Meier
authors.initials: M
authors.lastname: Hsu
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Neurology, Weill Cornell Medical College, New York, New York.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Omuro
authors.affiliation: Department of Medicine, Lymphoma Service, Adult BMT Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Matasar
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Neurology, Weill Cornell Medical College, New York, New York.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DeAngelis
authors.affiliation: Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Parastoo B
authors.initials: PB
authors.lastname: Dahi
authors.affiliation: Department of Medicine, Lymphoma Service, Adult BMT Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Craig H
authors.initials: CH
authors.lastname: Moskowitz
authors.affiliation: Department of Medicine, Adult Bone Marrow Transplant Service, 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: Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Sauter
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity*; D002066:Busulfan / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D008223:Lymphoma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D013852:Thiotepa; D002066:Busulfan
keywords: Autologous stem cell transplantation; Central nervous system lymphoma; High-dose therapy; Regimen-related toxicity; Toxicity