Journal article
Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant
JAMA oncology, Vol.7(7), pp.993-1003
07/01/2021
DOI: 10.1001/jamaoncol.2021.1074
PMCID: PMC8283558
PMID: 33956047
Abstract
Question What are the outcomes associated with autologous hematopoietic cell transplant based on conditioning regimen used in patients with primary central nervous system lymphoma (PCNSL)? Findings In this cohort study of registry data from 603 adult patients with PCNSL undergoing autologous hematopoietic cell transplant, the thiotepa-containing conditioning regimens were associated with higher survival rates compared with carmustine/etoposide/cytarabine/melphalan. Although thiotepa-containing conditioning regimens were associated with a lower relapse risk compared with thiotepa/carmustine, there was comparable survival owing to a higher nonrelapse mortality risk. Meaning In this study, thiotepa-based conditioning regimens were associated with favorable outcomes, suggesting that the use of carmustine/etoposide/cytarabine/melphalan should be avoided in patients with PCNSL.
Importance Primary central nervous system lymphoma (PCNSL) requires induction and consolidation to achieve potential cure. High-dose therapy and autologous hematopoietic cell transplant (AHCT) is an accepted and effective consolidation strategy for PCNSL, but no consensus exists on the optimal conditioning regimens. Objective To assess the outcomes in patients with PCNSL undergoing AHCT with the 3 most commonly used conditioning regimens: thiotepa/busulfan/cyclophosphamide (TBC), thiotepa/carmustine (TT-BCNU), and carmustine/etoposide/cytarabine/melphalan (BEAM). Design, Setting, and Participants This observational cohort study used registry data from the Center for International Blood and Marrow Transplant Research registry. The Center is a working group of more than 380 transplantation centers worldwide that contributed detailed data on HCT to a statistical center at the Medical College of Wisconsin, Milwaukee. The participant data were from 603 adult patients with PCNSL who underwent AHCT as initial, or subsequent, consolidation between January 2010 and December 2018. Patients were excluded if they had a non-Hodgkin lymphoma subtype other than diffuse large B-cell lymphoma, systemic non-Hodgkin lymphoma, or HIV; received an uncommon conditioning regimen; or were not in partial remission or complete remission prior to AHCT. Statistical analysis was performed from July 5, 2020, to March 1, 2021. Interventions Patients received 1 of 3 conditioning regimens: TBC (n = 263), TT-BCNU (n = 275), and BEAM (n = 65). Main Outcomes and Measures The primary outcome was progression-free survival. Secondary outcomes included hematopoietic recovery, incidence of relapse, nonrelapse mortality, and overall survival. Results Of 603 patients, the mean age was 57 (range, 19-77) years and 318 (53%) were male. The 3-year adjusted progression-free survival rates were higher in the TBC cohort (75%) and TT-BCNU cohort (76%) compared with the BEAM cohort (58%) (P = .03) owing to a higher relapse risk in the BEAM cohort (hazard ratio [HR], 4.34; 95% CI, 2.45-7.70; P < .001). In a multivariable regression analysis, compared with the TBC cohort, patients who received TT-BCNU had a higher relapse risk (HR, 1.79; 95% CI, 1.07-2.98; P = .03), lower risk of nonrelapse mortality (NRM) (HR, 0.50; 95% CI, 0.29-0.87; P = .01), and similar risk of all-cause mortality more than 6 months after HCT (HR, 1.54; 95% CI, 0.93-2.55; P = .10). Age of 60 years or older, Karnofsky performance status less than 90, and an HCT-comorbidity index greater than or equal to 3 were associated with lower rates of survival across all 3 cohorts. Subgroup analyses demonstrated that patients aged 60 years and older had considerably higher NRM with TBC. Conclusions and Relevance In this cohort study, thiotepa-based conditioning regimen was associated with higher rates of survival compared with BEAM, despite higher rates of early toxic effects and NRM; these findings may assist clinicians in choosing between TBC or TT-BCNU based on patient and disease characteristics.
This cohort study used registry data to assess outcomes in patients with primary central nervous system lymphoma undergoing autologous hematopoietic cell transplant with commonly used conditioning regimens.
Details
- Title: Subtitle
- Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant
- Creators
- Michael Scordo - Cornell UniversityTrent P. Wang - University of MiamiKwang W. Ahn - Medical College of WisconsinYue Chen - Medical College of WisconsinSairah Ahmed - Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USAFarrukh T. Awan - The University of Texas Southwestern Medical CenterAmer Beitinjaneh - University of MiamiAndy Chen - Oregon Health & Science UniversityVictor A. Chow - Fred Hutch Cancer CenterBhagirathbhai Dholaria - Vanderbilt University Medical CenterNarendranath Epperla - The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteUmar Farooq - University of Iowa Hospitals and ClinicsNilanjan Ghosh - Levine Cancer InstituteNatalie Grover - University of North Carolina HospitalsNada Hamad - St Vincent's Hospital SydneyGerhard C. Hildebrandt - Markey Cancer CenterLeona Holmberg - Fred Hutch Cancer CenterSanghee Hong - Cleveland ClinicDavid J. Inwards - Mayo ClinicAntonio Jimenez-Jimenez - University of MiamiReem Karmali - Northwestern UniversityVaishalee P. Kenkre - University of Wisconsin–MadisonFarhad Khimani - Moffitt Cancer CenterEvgeny Klyuchnikov - University Cancer Center HamburgMaxwell M. Krem - Markey Cancer CenterPashna N. Munshi - Georgetown UniversityYago Nieto - The University of Texas MD Anderson Cancer CenterTim Prestidge - Starship Children's HealthPraveen Ramakrishnan Geethakumari - The University of Texas Southwestern Medical CenterAndrew R. Rezvani - Stanford UniversityPeter A. Riedell - University of ChicagoSachiko Seo - Dokkyo Medical UniversityNirav N. Shah - Medical College of WisconsinMelhem Solh - Northside HospitalJean A. Yared - University of Maryland, BaltimoreMohamed A. Kharfan-Dabaja - Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, Florida.Alex Herrera - City Of Hope National Medical CenterMehdi Hamadani - Medical College of WisconsinCraig S. Sauter - Cornell University
- Resource Type
- Journal article
- Publication Details
- JAMA oncology, Vol.7(7), pp.993-1003
- Publisher
- Amer Medical Assoc
- DOI
- 10.1001/jamaoncol.2021.1074
- PMID
- 33956047
- PMCID
- PMC8283558
- ISSN
- 2374-2437
- eISSN
- 2374-2445
- Number of pages
- 11
- Grant note
- U24CA076518 / Public Health Service from the National Cancer Institute (NCI) National Institute of Allergy and Infectious Diseases (NIAID); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) National Heart, Lung and Blood Institute (NHLBI); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) HHSH250201700006C / Health Resources and Services Administration (HRSA); United States Department of Health & Human Services; United States Health Resources & Service Administration (HRSA) National Marrow Donor Program N00014-20-1-2705; N00014-20-1-2832 / Office of Naval Research Medical College of Wisconsin; General Electric Be the Match Foundation
- Language
- English
- Date published
- 07/01/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359692602771
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