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Clinical relevance of MYC/BCL2 expression and cell of origin in patients with diffuse large b-cell lymphoma treated with autologous transplant

Bone Marrow Transplantation volume 58, pages 1000–1007 (2023)Cite this article

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Abstract

Dual expression of MYC and BCL2 proteins (double-expressor lymphoma [DEL]) as well as cell of origin (COO) are important prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) after conventional chemotherapy. We studied the prognostic impact of DEL and COO in patients with relapsed DLBCL treated with autologous stem cell transplant (ASCT). Three-hundred and three patients with stored tissue samples were identified. Classification was successful in 267 patients: 161 (60%) were DEL/non-double hit (DHL), 98 (37%) were non-DEL/non-DHL, and 8 (3%) were DEL/DHL. Compared to non-DEL/non-DHL, DEL/DHL had worse overall survival while DEL/non-DHL did not significantly differ in overall survival. On multivariable analysis, DEL/DHL, age >60 years, and >2 prior therapies, but not COO, were important prognostic factors for overall survival. When we explored the interaction of COO and BCL2 expression, patients with germinal center B-cell (GCB)/BCL2 (+) had inferior progression-free survival (PFS) compared to GCB/BCL2 (−) patients (HR, 4.97; P = 0.027). We conclude that the DEL/non-DHL and non-DEL/non-DHL subtypes of DLBCL have similar survival after ASCT. The negative impact of GCB/BCL2 (+) on PFS warrants future trials targeting BCL2 after ASCT. The inferior outcomes in DEL/DHL need to be verified in a larger number of patients.

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Fig. 1: Kaplan-Meier surval curves.
Fig. 2: Kaplan–Meier survival curves of progression-free survival stratified by conditioning regimen.
Fig. 3: Kaplan-Meier survival curves based on molecular profiling.

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Data availability

Raw data were generated at the University of Texas MD Anderson Cancer Center, Houston, TX. Derived data supporting the findings of this study are available from the corresponding author [IFK] upon request at ikhouri@mdanderson.org.

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Acknowledgements

The authors thank the patients and medical staff who participated in this study. The manuscript was edited by Sarah Bronson of the Research Medical Library at The University of Texas MD Anderson Cancer Center.

Funding

This study was supported by the National Institutes of Health under award number P30CA016672 to IFK and R01CA233490 to KHY.

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Author notes

  1. These authors contributed equally: Taha Al-Juhaishi, Yingjun Wang.

Authors and Affiliations

  1. Departments of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Taha Al-Juhaishi, May Daher, Jin S. Im, Qaiser Bashir, David Marin, Amanda L. Olson, Uday Popat, Muzaffar Qazilbash, Gabriela Rondon, Richard E. Champlin & Issa F. Khouri

  2. Departments of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Yingjun Wang & Ken H. Young

  3. Division of Hematopathology, Duke University Medical Center, Durham, NC, USA

    Yingjun Wang, Zijun Y. Xu-Monette & Ken H. Young

  4. Departments of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Denái R. Milton

  5. Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Elias Jabbour & Swaminathan P. Iyer

  6. The Departement of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Swaminathan P. Iyer

  7. Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Alison M. Gulbis

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  1. Taha Al-Juhaishi
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Contributions

Conception and design: TA, YW, ZUX, KHY, and IFK. Provision of study materials or patients: TA, YW, ZYX, EJ, MD, JSM, QB, SPI, BM, ALO, UP, MQ, GR, AMG, REC, KEY, and IFK. Data analysis and interpretation: DRM, TA, YW, ZUX, KHY, and IFK. Manuscript writing, final approval of manuscript, accountable for all aspects of the work: All authors.

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Correspondence to Issa F. Khouri.

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Al-Juhaishi, T., Wang, Y., Milton, D.R. et al. Clinical relevance of MYC/BCL2 expression and cell of origin in patients with diffuse large b-cell lymphoma treated with autologous transplant. Bone Marrow Transplant 58, 1000–1007 (2023). https://doi.org/10.1038/s41409-023-02006-3

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  • DOI: https://doi.org/10.1038/s41409-023-02006-3

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