The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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The effect of the dexamethasone, cytarabine, and cisplatin (DHAP) regimen on stem cell mobilization and transplant outcomes of patients with non-Hodgkin's lymphoma who are candidates for up-front autologous stem cell transplantation

  • Jeon, So Yeon (Department of Internal Medicine, Chonbuk National University Medical School) ;
  • Yhim, Ho-Young (Department of Internal Medicine, Chonbuk National University Medical School) ;
  • Kim, Hee Sun (Chonbuk National University College of Nursing) ;
  • Kim, Jeong-A (Division of Hematology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Yang, Deok-Hwan (Department of Hematology-Oncology, Chonnam National University Hwasun Hospital) ;
  • Kwak, Jae-Yong (Department of Internal Medicine, Chonbuk National University Medical School)
  • Received : 2016.05.01
  • Accepted : 2017.02.04
  • Published : 2018.11.01
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Abstract

Background/Aims: Data on dexamethasone, cytarabine, and cisplatin (DHAP) as a mobilization regimen, compared to high-dose cyclophosphamide (HDC), for up-front autologous stem cell transplantation (ASCT) in non-Hodgkin's lymphoma (NHL) is limited. Methods: Consecutive patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP who underwent chemomobilization using HDC or DHAP plus granulocyte-colony stimulating factor (G-CSF) for up-front ASCT were enrolled from three institutions between 2004 and 2014. Results: Ninety-six patients (57 men) were included. Sixty-five patients (67.7%) received HDC; and 31 (32.3%), DHAP. The total CD34+ cells mobilized were significantly higher in patients receiving DHAP (16.1 vs. $6.1{\times}10^6/kg$, p = 0.001). More patients achieved successful mobilization with DHAP (CD34+ cells ${\geq}5.0{\times}10^6/kg$) compared to HDC (87.1% vs. 61.5%, respectively; p = 0.011), particularly within the first two sessions of apheresis (64.5% vs. 32.3%, respectively; p = 0.003). Mobilization failure rate (CD34+ cells < $2.0{\times}10^6/kg$) was significantly higher in patients receiving HDC (20.0% vs. 3.2%, p = 0.032). On multivariate analysis, the DHAP regimen (odds ratio, 4.12; 95% confidence interval, 1.12 to 15.17) was an independent predictor of successful mobilization. During chemomobilization, patients receiving HDC experienced more episodes of febrile neutropenia compared to patients receiving DHAP (32.3% vs. 12.9%, p = 0.043). Conclusions: The DHAP regimen was associated with a significantly higher efficacy for stem cell mobilization and lower frequency of febrile neutropenia. Therefore, DHAP plus G-CSF is an effective for mobilization in patients with aggressive NHL who were candidates for up-front ASCT.

Keywords

References

  1. Stiff PJ, Unger JM, Cook JR, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med 2013;369:1681-1690. https://doi.org/10.1056/NEJMoa1301077
  2. Villanueva ML, Vose JM. The role of hematopoietic stem cell transplantation in non-Hodgkin lymphoma. Clin Adv Hematol Oncol 2006;4:521-530.
  3. Lee HG, Choi Y, Kim SY, et al. R-CHOP chemoimmunotherapy followed by autologous transplantation for the treatment of diffuse large B-cell lymphoma. Blood Res 2014;49:107-114. https://doi.org/10.5045/br.2014.49.2.107
  4. Giralt S, Costa L, Schriber J, et al. Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Biol Blood Marrow Transplant 2014;20:295-308. https://doi.org/10.1016/j.bbmt.2013.10.013
  5. Sanchez-Ortega I, Querol S, Encuentra M, et al. Plerixafor in patients with lymphoma and multiple myeloma: effectiveness in cases with very low circulating CD34+ cell levels and preemptive intervention vs remobilization. Bone Marrow Transplant 2015;50:34-39. https://doi.org/10.1038/bmt.2014.196
  6. Wuchter P, Ran D, Bruckner T, et al. Poor mobilization of hematopoietic stem cells-definitions, incidence, risk factors, and impact on outcome of autologous transplantation. Biol Blood Marrow Transplant 2010;16:490-499. https://doi.org/10.1016/j.bbmt.2009.11.012
  7. Sung AD, Grima DT, Bernard LM, et al. Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF vs G-CSF alone. Bone Marrow Transplant 2013;48:1444-1449. https://doi.org/10.1038/bmt.2013.80
  8. Narayanasami U, Kanteti R, Morelli J, et al. Randomized trial of filgrastim versus chemotherapy and filgrastim mobilization of hematopoietic progenitor cells for rescue in autologous transplantation. Blood 2001;98:2059-2064. https://doi.org/10.1182/blood.V98.7.2059
  9. Pusic I, Jiang SY, Landua S, et al. Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation. Biol Blood Marrow Transplant 2008;14:1045-1056. https://doi.org/10.1016/j.bbmt.2008.07.004
  10. Milone G, Leotta S, Indelicato F, et al. G-CSF alone vs cyclophosphamide plus G-CSF in PBPC mobilization of patients with lymphoma: results depend on degree of previous pretreatment. Bone Marrow Transplant 2003;31:747-754. https://doi.org/10.1038/sj.bmt.1703912
  11. Dazzi C, Cariello A, Rosti G, et al. Is there any difference in PBPC mobilization between cyclophosphamide plus G-CSF and G-CSF alone in patients with non-Hodgkin's Lymphoma? Leuk Lymphoma 2000;39:301-310. https://doi.org/10.3109/10428190009065829
  12. Dingli D, Nowakowski GS, Dispenzieri A, et al. Cyclophosphamide mobilization does not improve outcome in patients receiving stem cell transplantation for multiple myeloma. Clin Lymphoma Myeloma 2006;6:384-388. https://doi.org/10.3816/CLM.2006.n.014
  13. Hyun SY, Cheong JW, Kim SJ, et al. High-dose etoposide plus granulocyte colony-stimulating factor as an effective chemomobilization regimen for autologous stem cell transplantation in patients with non-Hodgkin lymphoma previously treated with CHOP-based chemotherapy: a study from the Consortium for Improving Survival of Lymphoma. Biol Blood Marrow Transplant 2014;20:73-79. https://doi.org/10.1016/j.bbmt.2013.10.012
  14. Pavone V, Gaudio F, Guarini A, et al. Mobilization of peripheral blood stem cells with high-dose cyclophosphamide or the DHAP regimen plus G-CSF in non-Hodgkin's lymphoma. Bone Marrow Transplant 2002;29:285-290. https://doi.org/10.1038/sj.bmt.1703364
  15. Pavone V, Gaudio F, Console G, et al. Poor mobilization is an independent prognostic factor in patients with malignant lymphomas treated by peripheral blood stem cell transplantation. Bone Marrow Transplant 2006;37:719-724. https://doi.org/10.1038/sj.bmt.1705298
  16. Kwak JY. Treatment of diffuse large B cell lymphoma. Korean J Intern Med 2012;27:369-377. https://doi.org/10.3904/kjim.2012.27.4.369
  17. Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood 2015;125:22-32. https://doi.org/10.1182/blood-2014-05-577189
  18. Vose J, Armitage J, Weisenburger D; International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 2008;26:4124-4130. https://doi.org/10.1200/JCO.2008.16.4558
  19. Gertz MA. Current status of stem cell mobilization. Br J Haematol 2010;150:647-662. https://doi.org/10.1111/j.1365-2141.2010.08313.x
  20. Gisselbrecht C, Schmitz N, Mounier N, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol 2012;30:4462-4469. https://doi.org/10.1200/JCO.2012.41.9416
  21. Philip T, Guglielmi C, Hagenbeek A, 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. https://doi.org/10.1056/NEJM199512073332305
  22. Suh C, Kim S, Kim SH, et al. Initiation of peripheral blood progenitor cell harvest based on peripheral blood hematopoietic progenitor cell counts enumerated by the Sysmex SE9000. Transfusion 2004;44:1762-1768. https://doi.org/10.1111/j.0041-1132.2004.04166.x
  23. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25:579-586. https://doi.org/10.1200/JCO.2006.09.2403
  24. Ford CD, Green W, Warenski S, Petersen FB. Effect of prior chemotherapy on hematopoietic stem cell mobilization. Bone Marrow Transplant 2004;33:901-905. https://doi.org/10.1038/sj.bmt.1704455
  25. Jillella AP, Ustun C, Robach E, et al. Infectious complications in patients receiving mobilization chemotherapy for autologous peripheral blood stem cell collection. J Hematother Stem Cell Res 2003;12:155-160. https://doi.org/10.1089/152581603321628296
  26. Ahn JS, Park S, Im SA, et al. High-dose versus low-dose cyclophosphamide in combination with G-CSF for peripheral blood progenitor cell mobilization. Korean J Intern Med 2005;20:224-231. https://doi.org/10.3904/kjim.2005.20.3.224
  27. Damon L, Damon LE, Gaensler K, et al. Impact of intensive PBSC mobilization therapy on outcomes following auto-SCT for non-Hodgkin's lymphoma. Bone Marrow Transplant 2008;42:649-657. https://doi.org/10.1038/bmt.2008.236
  28. Yoon DH, Sohn BS, Jang G, 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. https://doi.org/10.1111/j.1537-2995.2009.02202.x
  29. 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. https://doi.org/10.1038/sj.bmt.1704050
  30. Sauter CS, Giralt S. The prognostic impact of peripheral blood progenitor cell dose following high-dose therapy and autologous stem cell transplant for hematologic malignancies. Leuk Lymphoma 2015;56:1619-1625. https://doi.org/10.3109/10428194.2014.970544
  31. Ketterer N, Salles G, Raba M, et al. High CD34(+) cell counts decrease hematologic toxicity of autologous peripheral blood progenitor cell transplantation. Blood 1998;91:3148-3155. https://doi.org/10.1182/blood.V91.9.3148
  32. Porrata LF, Gertz MA, Inwards DJ, 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 https://doi.org/10.1182/blood.V98.3.579