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Autografting

Long-term impact of prior rituximab therapy and early lymphocyte recovery on auto-SCT outcome for diffuse large B-cell lymphoma

Abstract

Early lymphocyte recovery following auto-SCT for non-Hodgkin's lymphoma (NHL) has been reported to be associated with improved outcome. The significance of early lymphocyte recovery following a stem cell transplant in NHL subtype diffuse large B-cell lymphoma (DLBCL) in the rituximab era remains unclear. Patients who underwent an auto-SCT at our institution for DLBCL during the time period 1998–2008 (n=115) were included in the study. Patient characteristics were well-balanced in both rituximab naïve and rituximab-exposed groups. Prior rituximab therapy did not affect lymphocyte recovery on day 14 or day 28. Lymphocyte recovery on day 14 and day 28 and prior rituximab had no impact on survival after auto-SCT for DLBCL, despite early benefit. Other factors such as age, stage at presentation, number of salvage regimens, mobilization procedure, conditioning regimen, pre-transplant radiation therapy and pre-transplant disease status had no impact on survival. Our data showed that the survival benefit with early lymphocyte recovery and prior rituximab seen in previous reports may be lost with longer follow-up. Prior rituximab therapy does not appear to influence the lymphocyte count at days 14 and 28 following auto-SCT. Our findings suggest that future trials should consider manipulating the immune system as a post transplant intervention to improve long-term outcome.

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References

  1. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med 1995; 333: 1540–1545.

    Article  CAS  PubMed  Google Scholar 

  2. Nademanee A, Molina A, Dagis A, Snyder DS, O’Donnell MR, Parker P et al. Autologous stem-cell transplantation for poor-risk and relapsed intermediate- and high-grade non-Hodgkin's lymphoma. Clin Lymphoma 2000; 1: 46–54.

    Article  CAS  PubMed  Google Scholar 

  3. Yoon DH, Sohn BS, Jang G, Kim EK, Kang BW, Kim C et al. Higher infused CD34+ hematopoietic stem cell dose correlates with earlier lymphocyte recovery and better clinical outcome after autologous stem cell transplantation in non-Hodgkin's lymphoma. Transfusion 2009; 49: 1890–1900.

    Article  CAS  PubMed  Google Scholar 

  4. Fenske TS, Hari PN, Carreras J, Zhang MJ, Kamble RT, Bolwell BJ et al. Impact of pre-transplant rituximab on survival after autologous hematopoietic stem cell transplantation for diffuse large B cell lymphoma. Biol Blood Marrow Transplant 2009; 15: 1455–1464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gordan LN, Sugrue MW, Lynch JW, Williams KD, Khan SA, Moreb JS . Correlation of early lymphocyte recovery and progression-free survival after autologous stem-cell transplant in patients with Hodgkin's and non-Hodgkin's Lymphoma. Bone Marrow Transplant 2003; 31: 1009–1013.

    Article  CAS  PubMed  Google Scholar 

  6. Porrata LF, Gertz MA, Inwards DJ, Litzow MR, Lacy MQ, Tefferi A et al. Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma. Blood 2001; 98: 579–585.

    Article  CAS  PubMed  Google Scholar 

  7. Porrata LF, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Gastineau DA et al. Early lymphocyte recovery predicts superior survival after autologous stem cell transplantation in non-Hodgkin lymphoma: a prospective study. Biol Blood Marrow Transplant 2008; 14: 807–816.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cheson BD, Vena DA, Barrett J, Freidlin B . Second malignancies as a consequence of nucleoside analog therapy for chronic lymphoid leukemias. J Clin Oncol 1999; 17: 2454–2460.

    Article  CAS  PubMed  Google Scholar 

  9. Kim H, Sohn HJ, Kim S, Lee JS, Kim WK, Suh C . Early lymphocyte recovery predicts longer survival after autologous peripheral blood stem cell transplantation in multiple myeloma. Bone Marrow Transplant 2006; 37: 1037–1042.

    Article  CAS  PubMed  Google Scholar 

  10. Porrata LF, Gertz MA, Litzow MR, Lacy MQ, Dispenzieri A, Inwards DJ et al. Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis. Clin Cancer Res 2005; 11: 1210–1218.

    CAS  PubMed  Google Scholar 

  11. Porrata LF, Litzow MR, Inwards DJ, Gastineau DA, Moore SB, Pineda AA et al. Infused peripheral blood autograft absolute lymphocyte count correlates with day 15 absolute lymphocyte count and clinical outcome after autologous peripheral hematopoietic stem cell transplantation in non-Hodgkin's lymphoma. Bone Marrow Transplant 2004; 33: 291–298.

    Article  CAS  PubMed  Google Scholar 

  12. Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U et al. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood 2004; 103: 4416–4423.

    Article  CAS  PubMed  Google Scholar 

  13. Joao C, Porrata LF, Inwards DJ, Ansell SM, Micallef IN, Johnston PB et al. Early lymphocyte recovery after autologous stem cell transplantation predicts superior survival in mantle-cell lymphoma. Bone Marrow Transplant 2006; 37: 865–871.

    Article  CAS  PubMed  Google Scholar 

  14. Tiwari D, Gao F, Hidalgo J, Adkins DR, Vij R, DiPersio JF et al. Prognostic significance of early lymphocyte recovery after post-autografting administration of GM-CSF in non-Hodgkin's lymphoma. Bone Marrow Transplant 2007; 40: 671–675.

    Article  CAS  PubMed  Google Scholar 

  15. Cox MC, Nofroni I, Ruco L, Amodeo R, Ferrari A, La Verde G et al. Low absolute lymphocyte count is a poor prognostic factor in diffuse-large-B-cell-lymphoma. Leuk Lymphoma 2008; 49: 1745–1751.

    Article  PubMed  Google Scholar 

  16. Porrata LF, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Hogan WJ et al. New-onset lymphopenia assessed during routine follow-up is a risk factor for relapse postautologous peripheral blood hematopoietic stem cell transplantation in patients with diffuse large B-cell lymphoma. Biol Blood Marrow Transplant 2010; 16: 376–383.

    Article  PubMed  Google Scholar 

  17. Oki Y, Yamamoto K, Kato H, Kuwatsuka Y, Taji H, Kagami Y et al. Low absolute lymphocyte count is a poor prognostic marker in patients with diffuse large B-cell lymphoma and suggests patients’ survival benefit from rituximab. Eur J Haematol 2008; 81: 448–453.

    Article  PubMed  Google Scholar 

  18. Guillaume T, Rubinstein DB, Symann M . Immune reconstitution and immunotherapy after autologous hematopoietic stem cell transplantation. Blood 1998; 92: 1471–1490.

    CAS  PubMed  Google Scholar 

  19. Horwitz SM, Negrin RS, Blume KG, Breslin S, Stuart MJ . Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma. Blood 2004; 103: 777–783.

    Article  CAS  PubMed  Google Scholar 

  20. Lim SH, Zhang Y, Wang Z, Esler WV, Beggs D . Maintenance rituximab after autologous stem cell transplant for high-risk B-cell lymphoma induces prolonged and severe hypogammaglobulinemia. Bone Marrow Transplant 2005; 35: 207–208.

    Article  CAS  PubMed  Google Scholar 

  21. Roberts RA, Wright G, Rosenwald AR, Jaramillo MA, Grogan TM . Loss of major histocompatibility class II gene and protein expression in primary mediastinal large B-cell lymphoma is highly coordinated and related to poor patient survival. Blood 2006; 108: 311–318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lee NR, Song EK, Jang KY, Choi HN, Moon WS . Prognostic impact of tumor infiltrating FOXP3 positive regulatory T cells in diffuse large B-cell lymphoma at diagnosis. Leuk Lymphoma 2008; 49: 247–256.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to acknowledge Carole Hunt for her contribution toward this manuscript. Vanderbilt CTSA Grant 1 UL1 RR024975 from NCRR/NIH, and 5K-12 CA090625-09.

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Correspondence to N Reddy.

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Stover, D., Reddy, V., Shyr, Y. et al. Long-term impact of prior rituximab therapy and early lymphocyte recovery on auto-SCT outcome for diffuse large B-cell lymphoma. Bone Marrow Transplant 47, 82–87 (2012). https://doi.org/10.1038/bmt.2011.29

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