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Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant.

Publication ,  Journal Article
Scordo, M; Wang, TP; Ahn, KW; Chen, Y; Ahmed, S; Awan, FT; Beitinjaneh, A; Chen, A; Chow, VA; Dholaria, B; Epperla, N; Farooq, U; Ghosh, N ...
Published in: JAMA Oncol
July 1, 2021

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.

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Published In

JAMA Oncol

DOI

EISSN

2374-2445

Publication Date

July 1, 2021

Volume

7

Issue

7

Start / End Page

993 / 1003

Location

United States

Related Subject Headings

  • Thiotepa
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Lymphoma, Non-Hodgkin
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Cyclophosphamide
  • Cohort Studies
  • Central Nervous System
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Scordo, M., Wang, T. P., Ahn, K. W., Chen, Y., Ahmed, S., Awan, F. T., … Sauter, C. S. (2021). Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant. JAMA Oncol, 7(7), 993–1003. https://doi.org/10.1001/jamaoncol.2021.1074
Scordo, Michael, Trent P. Wang, Kwang W. Ahn, Yue Chen, Sairah Ahmed, Farrukh T. Awan, Amer Beitinjaneh, et al. “Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant.JAMA Oncol 7, no. 7 (July 1, 2021): 993–1003. https://doi.org/10.1001/jamaoncol.2021.1074.
Scordo, Michael, et al. “Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant.JAMA Oncol, vol. 7, no. 7, July 2021, pp. 993–1003. Pubmed, doi:10.1001/jamaoncol.2021.1074.
Scordo M, Wang TP, Ahn KW, Chen Y, Ahmed S, Awan FT, Beitinjaneh A, Chen A, Chow VA, Dholaria B, Epperla N, Farooq U, Ghosh N, Grover N, Hamad N, Hildebrandt GC, Holmberg L, Hong S, Inwards DJ, Jimenez-Jimenez A, Karmali R, Kenkre VP, Khimani F, Klyuchnikov E, Krem MM, Munshi PN, Nieto Y, Prestidge T, Ramakrishnan Geethakumari P, Rezvani AR, Riedell PA, Seo S, Shah NN, Solh M, Yared JA, Kharfan-Dabaja MA, Herrera A, Hamadani M, Sauter CS. Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant. JAMA Oncol. 2021 Jul 1;7(7):993–1003.

Published In

JAMA Oncol

DOI

EISSN

2374-2445

Publication Date

July 1, 2021

Volume

7

Issue

7

Start / End Page

993 / 1003

Location

United States

Related Subject Headings

  • Thiotepa
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Lymphoma, Non-Hodgkin
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Cyclophosphamide
  • Cohort Studies
  • Central Nervous System