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Immune profiling in diffuse large B-cell lymphoma and mantle cell lymphoma patients treated with autologous hematopoietic cell transplant

A Correction to this article was published on 30 August 2019

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Abstract

This is the first longitudinal study of immune profiles and autologous hematopoietic cell transplant (AHCT) survival in B-cell non-Hodgkin lymphoma (B-NHL) patients and the effect of plerixafor mobilization on immune reconstitution in this population. A comprehensive immunophenotyping panel was performed in 104 consecutive adult B-NHL patients (58% diffuse large B cell and 42% mantle cell) who received AHCT (1/2008–11/2014), at a median of 28 days pre-AHCT (N = 104) and Day +100 (N = 83) post-AHCT. Median follow-up post-AHCT was 61 months (range: 8–120 months). Compared to patients mobilized with filgrastim and plerixafor, patients mobilized with filgrastim alone had a higher proportion of CD4+ naïve (p = 0.006) and CD8+ central memory T-cells (p = 0.006) pre-AHCT. For patients transplanted in complete remission (CR), a higher proportion of CD8+ effector memory T-cells pre-AHCT was associated with worse progression-free survival (PFS; p < 0.01) and overall survival (OS; p < 0.01). A higher ratio of CD8:CD4+ central memory T-cells pre-AHCT was associated with worse PFS (p < 0.0001) and OS (p = 0.0034). This same ratio measured post-AHCT among patients in CR on Day +100 was associated with worse and OS (p = 0.008) but not PFS (p = not significant). These immune subsets are complementary biomarkers which identify patients transplanted in CR who have poor survival prognoses and may warrant further clinical interventions.

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References

  1. D’Souza A, Fretham C. Current uses and outcomes of hematopoietic cell transplantation (HCT): CIBMTR Summary Slides. 2017. https://www.cibmtr.org/ReferenceCenter/SlidesReports/SummarySlides/pages/index.aspx.

  2. Lazarus HM, Carreras J, Boudreau C, Loberiza FR Jr., Armitage JO, Bolwell BJ, et al. Influence of age and histology on outcome in adult non-Hodgkin lymphoma patients undergoing autologous hematopoietic cell transplantation (HCT): a report from the Center For International Blood & Marrow Transplant Research (CIBMTR). Biol Blood Marrow Transplant. 2008;14:1323–33.

    Article  Google Scholar 

  3. Wildes TM, Augustin KM, Sempek D, Zhang QJ, Vij R, Dipersio JF, et al. Comorbidities, not age, impact outcomes in autologous stem cell transplant for relapsed non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008;14:840–6.

    Article  CAS  Google Scholar 

  4. Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, De Vivo A, Ricci P, et al. High-dose therapy with autologous transplantation for aggressive non-Hodgkin’s lymphoma: the Bologna experience. Leuk Lymphoma. 2004;45:321–6.

    Article  Google Scholar 

  5. Lerner RE, Thomas W, Defor TE, Weisdorf DJ, Burns LJ. The International Prognostic Index assessed at relapse predicts outcomes of autologous transplantation for diffuse large-cell non-Hodgkin’s lymphoma in second complete or partial remission. Biol Blood Marrow Transplant. 2007;13:486–92.

    Article  Google Scholar 

  6. Chen YB, Lane AA, Logan BR, Zhu X, Akpek G, Aljurf MD, et al. Impact of conditioning regimen on outcomes for patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015;21:1046–53.

    Article  Google Scholar 

  7. Dean R, Masci P, Pohlman B, Andresen S, Serafino S, Sobecks R, et al. Dendritic cells in autologous hematopoietic stem cell transplantation for diffuse large B-cell lymphoma: graft content and post transplant recovery predict survival. Bone Marrow Transplant. 2005;36:1049–52.

    Article  CAS  Google Scholar 

  8. Porrata LF, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Hogan WJ, et al. Infused autograft lymphocyte to monocyte ratio and survival in diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2014;20:1804–12.

    Article  Google Scholar 

  9. Steingrimsdottir H, Gruber A, Bjorkholm M, Svensson A, Hansson M. Immune reconstitution after autologous hematopoietic stem cell transplantation in relation to underlying disease, type of high-dose therapy and infectious complications. Haematologica . 2000;85:832–8.

    CAS  PubMed  Google Scholar 

  10. Valtola J, Varmavuo V, Ropponen A, Nihtinen A, Partanen A, Vasala K, et al. Blood graft cellular composition and posttransplant recovery in non-Hodgkin’s lymphoma patients mobilized with or without plerixafor: a prospective comparison. Transfusion. 2015;55:2358–68.

    Article  CAS  Google Scholar 

  11. Varmavuo V, Mantymaa P, Silvennoinen R, Nousiainen T, Kuittinen T, Jantunen E. CD34+ cell subclasses and lymphocyte subsets in blood grafts collected after various mobilization methods in myeloma patients. Transfusion. 2013;53:1024–32.

    Article  CAS  Google Scholar 

  12. Siena S, Schiavo R, Pedrazzoli P, Carlo-Stella C. Therapeutic relevance of CD34 cell dose in blood cell transplantation for cancer therapy. J Clin Oncol. 2000;18:1360–77.

    Article  CAS  Google Scholar 

  13. Stiff PJ, Micallef I, Nademanee AP, Stadtmauer EA, Maziarz RT, Bolwell BJ, et al. Transplanted CD34(+) cell dose is associated with long-term platelet count recovery following autologous peripheral blood stem cell transplant in patients with non-Hodgkin lymphoma or multiple myeloma. Biol Blood Marrow Transplant. 2011;17:1146–53.

    Article  CAS  Google Scholar 

  14. Benekli M, Smiley SL, Younis T, Czuczman MS, Hernandez-Ilizaliturri F, Bambach B, et al. Intensive conditioning regimen of etoposide (VP-16), cyclophosphamide and carmustine (VCB) followed by autologous hematopoietic stem cell transplantation for relapsed and refractory Hodgkin's lymphoma. Bone Marrow Transplant. 2008;41:613–19.

  15. Ho CM, McCarthy PL, Wallace PK, Zhang Y, Fora A, Mellors P, et al. Immune signatures associated with improved progression-free and overall survival for myeloma patients treated with AHSCT. Blood Adv. 2017;1:1056–66.

    Article  CAS  Google Scholar 

  16. Reshef R, Huffman AP, Gao A, Luskin MR, Frey NV, Gill SI, et al. High graft CD8 cell dose predicts improved survival and enables better donor selection in allogeneic stem-cell transplantation with reduced-intensity conditioning. J Clin Oncol. 2015;33:2392–8.

    Article  CAS  Google Scholar 

  17. Mehlhop-Williams ER, Bevan MJ. Memory CD8+T cells exhibit increased antigen threshold requirements for recall proliferation. J Exp Med. 2014;211:345–56.

    Article  CAS  Google Scholar 

  18. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 2005;102:18538–43.

    Article  CAS  Google Scholar 

  19. Preston CC, Maurer MJ, Oberg AL, Visscher DW, Kalli KR, Hartmann LC, et al. The ratios of CD8+ T cells to CD4+ CD25+ FOXP3+ and FOXP3- T cells correlate with poor clinical outcome in human serous ovarian cancer. PLoS ONE. 2013;8:e80063.

    Article  Google Scholar 

  20. Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12:492–9.

    Article  CAS  Google Scholar 

  21. Zajac AJ, Blattman JN, Murali-Krishna K, Sourdive DJD, Suresh M, Altman JD, et al. Viral immune evasion due to persistence of activated T Cells without effector function. J Exp Med. 1998;188:2205–13.

    Article  CAS  Google Scholar 

  22. Reiser J, Banerjee A. Effector, memory, and dysfunctional CD8+ T cell fates in the antitumor immune response. J Immunol Res. 2016;2016:1–14.

  23. Kenderian SS, Porter DL, Gill S. Chimeric antigen receptor T cells and hematopoietic cell transplantation: How not to put the CART before the horse. Biol Blood Marrow Transplant. 2017;23:235–46.

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Acknowledgements

We acknowledge our patients and the nurses and staff who participated in their care. We also thank the BMT data managers, Dr Lin Mei and Mr Benjamin McCarthy who assisted with data collection. This work was partially supported by National Cancer Institute (NCI) grant P30 CA016056 involving the use of the Roswell Park Comprehensive Cancer Center Flow and Imaging Cytometry Shared Resource.

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PLM, PKW and TH designed the research; PT, PLM, and TH performed research and collected data; PT, YZ, PKW, MMH and TH analyzed data; PT, PLM, YZ, PKW, GLC, CMH, SRB, BP, MR, FJH, EAR, MMH and TH interpreted results; PT, PLM, YZ, PKW, GLC, CMH, SRB, BP, MR, FJH, EAR, JDT, MMH and TH wrote the paper. All authors gave final approval of the paper.

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Correspondence to Theresa Hahn.

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Herr, M.M., Torka, P., Zhang, Y. et al. Immune profiling in diffuse large B-cell lymphoma and mantle cell lymphoma patients treated with autologous hematopoietic cell transplant. Bone Marrow Transplant 55, 77–85 (2020). https://doi.org/10.1038/s41409-019-0591-4

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