Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT

II Kostroma, AA Zhernyakova, ZhV Chubukina, IM Zapreeva, SA Tiranova, AV Sel’tser, NYu Semenova, SS Bessmel’tsev, AV Chechetkin, SV Gritsaev

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Теl.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Kostroma II, Zhernyakova AA, Chubukina ZhV, et al. Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT. Clinical oncohematology. 2018;11(2):192–7.

DOI: 10.21320/2500-2139-2018-11-2-192-197


ABSTRACT

Background. A prompt graft acceptance is essential for positive autologous hematopoietic stem cell transplantation (auto-HSCT) outcome in multiple myeloma patients (MM). Prompt and favourable hematopoietic regeneration is associated with CD34+ cell count in a transplant. Although the indicators of low autotransplant cellularity have been defined, the practical application of new drug products and HSC mobilization regimens strengthens the relevance of determining their influence on the transplant quality.

Aim. To determine the factors that are associated with low efficacy of auto-HSCT in MM patients and to evaluate the impact of lenalidomide during induction period and of vinorelbine as a mobilization regimen on the prognosis.

Materials & Methods. The authors performed a retrospective analysis of autotransplant collection results in 68 MM patients treated with two mobilization regimens: 3 g/m2 cyclophosphamide with granulocyte colony-stimulating factor (G-CSF) and 30 mg/m2 vinorelbine with G-CSF. Mobilization was aimed at collecting not less than 2–4 × 106 CD34+ cells per kg body mass. CD34+ cell count was determined by four-color analysis on the Cytomics FC 500 laser flow cytometer.

Results. The analysis showed that age or MM immunochemical specificity were not associated with CD34+ cell count in the transplant. Prior lenalidomide treatment compared to therapy without immunomodulators (4.1 × 106/kg vs. 7.76 × 106/kg) tends to decrease CD34+ count (р = 0.066). Cyclophosphamide included into mobilization regimen compared to vinorelbine (3.96 × 106/kg vs. 6.8 × 106/kg) significantly increased CD34+ cell count (р = 0.022).

Conclusion. The decrease of CD34+ cell count in the autotransplant of the MM patients treated with lenalidomide prior to auto-HSC collection, and a lower mobilization activity of vinorelbine provide a basis for a differentiated selection of mobilization regimens. Vinorelbine may be administered to patients with a single auto-HSCT, i.e. elderly people and patients with complete response. In case of substantial lenalidomide treatment prior to auto-HSCT, intermediate-dose cyclophosphamide is preferred.

Keywords: auto-HSCT, multiple myeloma, mobilization regimen, cyclophosphamide, vinorelbine, lenalidomide, predictors.

Received: November 29, 2017

Accepted: February 9, 2018

Read in PDF 


REFERENCES

  1. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома: руководство для врачей. М.: МК, 2016. 504 с.[Bessmel’tsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma: rukovodstvo dlya vrachei. (Multiple myeloma: manual for physicians.) Moscow: MK Publ.; 2016. 504 p. (In Russ)]
  2. Менделеева Л.П., Вотякова О.М., Покровская О.С. и др. Национальные клинические рекомендации по диагностике и лечению множественной миеломы. Гематология и трансфузиология. 2016;61(1, прил. 2):1–24. doi: 10.18821/0234-5730-2016-61-1(Прил.2).[Mendeleeva OP, Votyakova OM, Pokrovskaya OS, et al. National clinical recommendations in diagnosis and treatment of multiple myeloma. Gematologiya i transfuziologiya. 2016;61(1, Suppl. 2):1–24. doi: 10.18821/0234-5730-2016-61-1(Прил.2). (In Russ)]
  3. Bender JG, To LB, Williams S, Schwartzberg LS. Defining a therapeutic dose of peripheral blood stem cells. J Hematother. 1992;1(4):329–41. doi: 10.1089/scd.1.1992.1.329.
  4. Olivieri A, Offidani M, Montanari M, et al. Factors affecting hemopoietic recovery after high-dose therapy and autologous peripheral blood progenitor cell transplantation: a single center experience. 1998;83(4):329–37.
  5. Nakasone H, Kanda Y, Ueda T, et al. Retrospective comparison of mobilization methods for autologous stem cell transplantation in multiple myeloma. Am J Hematol. 2009;84(12):809–14. doi: 1002/ajh.21552.
  6. Stiff PJ, Micalef I, Nademanee AP, et al. Transplanted CD34+ cell dose 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(8):1146–53. doi: 1016/j.bbmt.2010.11.021.
  7. Hamadani M, Kochuparambil T, Osman S, et al. Intermediate-dose versus low-dose cyclophosphamide and granulocyte colony-stimulating factor for peripheral blood stem cell mobilization in patients with multiple myeloma treated with novel induction therapies. Biol Blood Marrow Transplant. 2012;18(7):1128–35. doi: 1016/j.bbmt.2012.01.005.
  8. Грицаев С.В., Кузяева А.А., Волошин С.В. и др. Заготовка трансплантата для аутологичной трансплантации гемопоэтических стволовых клеток онкогематологическим больным: частота и причины неудачных сборов. Русский медицинский журнал. 2013;1:30–[Gritsaev SV, Kuzyaeva AA, Voloshin SV, et al. Transplant collection for autologous stem cell transplantation in patients with oncohematological diseases: frequency and reasons for poor mobilization. Russkii meditsinskii zhurnal. 2013;1:30–5. (In Russ)]
  9. Stockerl-Goldstein KE, Reddy SA, Horning SF, et al. Favorable treatment outcome in nonHodgkin’s lymphoma patients with ‘poor’ mobilization of peripheral blood progenitor cells. Biol Blood Marrow Transplant. 2000;6(5):506–12. doi: 1016/s1083-8791(00)70021-8.
  10. Watts MJ, Ings SJ, Flynn M, et al. Remobilization of patients who fail to achieve minimal progenitor thresholds at the first attempt is clinically worthwhile. Br J Haematol. 2000;111(1):287–91. doi: 1111/j.1365-2141.2000.02346.x.
  11. Sugrue MW, Williams K, Pollock BH, et al. Characterization and outcome of ‘hard to mobilize’ lymphoma patients undergoing autologous stem cell transplantation. Leuk Lymphoma. 2000;39(5–6):509–19. doi: 3109/10428190009113381.
  12. Грицаев С.В., Кузяева А.А., Бессмельцев С.С. Отдельные аспекты аутологичной трансплантации гемопоэтических стволовых клеток при множественной миеломе. Клиническая онкогематология. 2017;10(1):7–12. doi: 21320/2500-2139-2017-10-1-7-12.[Gritsaev SV, Kuzyaeva AA, Bessmel’tsev SS. Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma. Clinical oncohematology. 2017;10(1):7–12. doi: 10.21320/2500-2139-2017-10-1-7-12. (In Russ)]
  13. Down JD, Boudewijn A, Dillingh JH, et al. Relationships between ablation of distinct haematopoietic cell subsets and the development of donor bone marrow engraftment following recipient pretreatment with different alkylating drugs. Br J 1994;70(4):611–6. doi: 10.1038/bjc.1994.359.
  14. Lokhorst HM, Sonneveld P, Wijermans PW, et al. Intermediate-dose melphalan (IDM) combined with G-CSF (filgrastim) is an effective and safe induction therapy for autologous stem cells in multiple myeloma. Br J Haematol. 1996;92(1):44–8. doi: 1046/j.1365-2141.1996.00306.x.
  15. Kumar S, Dispenzieri A, Lacy MQ, et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia. 2007;21(9):2035– doi: 10.1038/sj.leu.2404801.
  16. Mazumder A, Kaufman J, Niesvizky R, et al. Effect of lenalidomide therapy on mobilization of peripheral blood stem cells in previously untreated multiple myeloma patients. Leukemia. 2008;22(6):1280–1. doi: 1038/sj.leu.2405035.
  17. Mark T, Stern J, Furst JR, et al. Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma. Biol Blood Marrow Transplant. 2008;14(7):795–8. doi: 1016/j.bbmt.2008.04.008.
  18. Popat U, Saliba R, Thandi R, et al. Impairment of filgrastim-induced stem cell mobilization after prior lenalidomide in patients with multiple myeloma. Biol Blood Marrow Transplant. 2009;15(6):718–23. doi: 10.1016/j.bbmt.2009.02.011.
  19. Nazha A, Cook R, Vogl DT, et al. Stem cell collection in patients with multiple myeloma: impact of induction therapy and mobilization regimen. Bone Marrow Transplant. 2011;46(1):59– doi: 10.1038/bmt.2010.63.
  20. Cavallo F, Bringhen S, Milone G, et al. Stem cell mobilization in patients with newly diagnosed multiple myeloma after lenalidomide induction therapy. Leukemia. 2011;25(10):1627–31. doi: 10.1038/leu.2011.131.
  21. Bhutani D, Zonder J, Valent J, et al. Evaluating the effects of lenalidomide induction therapy on peripheral stem cells collection in patients undergoing autologous stem cell transplant for multiple myeloma. Supp Care Cancer. 2013;21(9):2437–42. doi: 10.1007/s00520-013-1808-5.
  22. Elliot C, Samson DM, Armitage S, et al. When harvest peripheral blood stem cells after mobilization therapy: prediction of CD34-positive cell yield by preceding day CD34-positive concentration in peripheral blood. J Clin Oncol. 1996;14(3):970–3. doi: 1200/JCO.1996.14.3.970.
  23. Remes K, Matinlauri I, Grenman S, et al. Daily measurements of blood CD34+ cells after stem cell mobilization predict stem cell yield and post-transplant hematopoietic recovery. J Hematother. 1997;6(1):13–9. doi: 10.1089/scd.1.1997.6.13.
  24. Knudsen LM, Gaarsdal E, Jensen L, et al. Evaluation of mobilized CD34+ cell counts to guide timing and yield of large-scale collection by leukapheresis. J Hematother. 1998;7(1):45–52. doi: 10.1089/scd.1.1998.7.45.
  25. Corso A, Caberlon S, Pagnucco G, et al. Blood stem cell collections in multiple myeloma: definition of a scoring system. Bone Marrow Transplantat. 2000;26(3):283–6. doi: 1038/sj.bmt.1702514.
  26. Perea G, Sureda A, Martino R, et al. Predictive factors for a successful mobilization of peripheral blood CD34+ cells in multiple myeloma. Ann Hematol. 2001;80(10):592–7. doi: 1007/s002770100351.
  27. Gojo I, Guo C, Sarkodee-Adoo C, et al. High dose cyclophosphamide with or without etoposide for mobilization of peripheral blood progenitor cells in patients with multiple myeloma: efficacy and toxicity. Bone Marrow Transplant. 2004;34(1):69–76. doi: 1038/sj.bmt.1704529.
  28. Гальцева И.В., Давыдова Ю.О., Гапонова Т.В. и др. Абсолютное количество гемопоэтических стволовых клеток CD34+ в периферической крови перед процедурой лейкоцитафереза как параметр, прогнозирующий эффективность сбора стволовых клеток. Терапевтический архив. 2017;89(7):18–24. doi: 17116/terarkh201789718-24.[Gal’tseva IV, Davydova YuO, Gaponova TV, et al. Absolute numbers of peripheral blood CD34+ hematopoietic stem cells prior to a leukapheresis procedure as a parameter predicting the efficiency of stem cell collection. Terapevticheskii arkhiv. 2017;89(7):18–24. doi: 10.17116/terarkh201789718-24. (In Russ)]
  29. Fu P, Bagai RK, Meyerson H, et al. Pre-mobilization therapy blood CD34+ cell count predicts the likelihood of successful hematopoietic stem cell mobilization. Bone Marrow Transplant. 2006;38(3):189–96. doi: 1038/sj.bmt.1705431.
  30. 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(9):1045–56. doi: 1016/j.bbmt.2008.07.004.
  31. Ozsan GH, Micallef IN, Dispenzieri A, et al. Hematopoietic recovery kinetics predicts for poor CD34+ cell mobilization after cyclophosphamide chemotherapy in multiple myeloma. Am J Hematol. 2012;87(1):1–4. doi: 10.1002/ajh.22179.
  32. Duarte RF, Shaw BE, Marin P, et al. Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data. Bone Marrow Transplant. 2011;46(1):52–8. doi: 10.1038/bmt.2010.54.
  33. Fruehauf S, Ehninger G, Hubel K, et al. Mobilization of peripheral blood stem cells for autologous transplant in non-Hodgkin’s lymphoma and multiple myeloma patients by plerixafor and G-CSF and detection of tumor cell mobilization by PCR in multiple myeloma patients. Bone Marrow Transplant. 2010;45(2):269–75. doi: 1038/bmt.2009.142.