MA Kucher1, МS Motalkina2, ОU Klimova1, ЕV Kondakova1, ОB Kalashnikova1, SМ Alekseev2, DV Motorin3, DV Babenetskaya3, EI Podol’tseva4, NB Mikhailova1, МА Estrina1, ЕV Babenko1, AYu Zaritskii3, BV Afanas’ev1
1 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022
2 N.N. Petrov Scientific Research Institute of Oncology, 68 Leningradskaya str., settlement Pesochnyi, Saint Petersburg, Russian Federation, 197758
3 V.A. Almazov Federal North-West Medical Research Centre, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341
4 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110
For correspondence: Maksim Anatol’evich Kucher, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)338-62-60; e-mail: doctorkucher@yandex.ru
For citation: Kucher MA, Motalkina MS, Klimova OU, et al. Plerixafor in Patients with Decreased Mobilizing Ability of Autologous Hematopoietic Stem Cells. Clinical oncohematology. 2016;9(2):155–61 (In Russ).
DOI: 10.21320/2500-2139-2016-9-2-155-161
ABSTRACT
Background & Aims. Autologous hematopoietic stem cell transplantation (autoHSCT) is an effective treatment for patients with malignant lymphoproliferative disorders, multiple myelomas and solid tumors sensitive to chemotherapy. Harvesting of hematopoietic stem cells (HSC) prior autoHSCT may be ineffective in up to 40 % of cases, if aggravating factors are present. One of methods to overcome the reduced mobilization ability is to include a CXCR4-inhibitor (plerixafor) to the mobilization strategies. The aim was to evaluate the efficacy and safety of different autologous HSC mobilization regimens containing plerixafor.
Methods. 63 patients with solid and hematological malignancies were included into the study. 2 mobilization regimens were used: filgrastim + plerixafor (n = 47) and pegfilgrastim + plerixafor (n = 16). Filgrastim was prescribed at a dose 5 mg/kg twice a day subcutaneously on days 1–4; on day 4, at 12.00 am, plerixafor was prescribed at a dose of 0.24 mg/kg subcutaneously; on day 5, filgrastim 5 mg/kg was administered subcutaneously, and then a cytapheresis session was performed at 10.00 am. Pegfilgrastim was administered subcutaneously at a dose of 6 mg on day 1; on day 4, plerixafor was administered subcutaneously at a dose of 0.24 mg/kg at 06.00 am; then, 11 hours later, cytapheresis was performed. The cytapheresis was performed at a level of CD34+ cells ³ 20 ´ 106/mL.
Results. In 73.7 % of cases (n = 42), patients had an advanced stage disease and underwent more than one chemotherapy line prior to mobilization of autologous HSC. After mobilization with G-CSF (filgrastim or pegfilgrastim), the CD34+ cell count in peripheral blood was 0–17 ´ 106/mL (median 9.8 ´ 106/mL). Further injection of plerixafor increased the CD34+ cell count to 2–89 ´ 106/mL (median 31.6 ´ 106/mL) (p = 0.0001). In 85.7 % of cases (n = 54), the sufficient amount of CD34+ cells (³ 2 ´ 106/kg; median 5.1 ´ 106/kg) was harvested for transplantation. The effectiveness of mobilization in two groups was comparable 90.2 % for the filgrastim + plerixafor regimen and 68.7 % for pegfilgrastim + plerixafor (p = 0.08). The use of the filgrastim + plerixafor combination in patients with low baseline CD34+ cell counts increased the number of hematopoietic stem cells up to 6.6–63 ´ 106/mL (median 27.1 ´ 106/mL), thus allowing to harvest a good quality graft in 83.3 % of cases (p = 0.0001). When the level of CD34+ cell counts was in the «grey zone», successful graft harvesting was performed in 90 % of cases: 1.74–4.6 ´ 106/kg; median 3.1 ´ 106/kg (p = 0.0001). Complications associated with plerixafor were observed in 2 cases: diarrhea (n = 1) and hypocalcaemia (n = 1).
Conclusion. In patients who are poor mobilizers, the use of plerixafor-containing regimens increased the chance of successful graft harvesting with good tolerability.
Keywords: hematopoietic stem cell mobilization, G-CSF, pegfilgrastim, plerixafor.
Received: February 17, 2016
Accepted: February 18, 2016
REFERENCES
- Ljungman P, Bregni M, Brune M, et al. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant. 2010;45(2):219–34. doi: 10.1038/bmt.2009.141.
- Gratwohl A, Baldomero H, Schwendener A, et al. The EBMT activity survey 2008: impact of team size, team density and new trends. Bone Marrow Transplant. 2011;46(2):174–91. doi: 10.1038/bmt.2010.69.
- Baldomero H, Gratwohl M, Gratwohl A, et al. The EBMT activity survey 2009: trends over the past 5 years. Bone Marrow Transplant. 2011;46(4):485–501. doi: 10.1038/bmt.2011.11.
- Duong HK, Savani BN, Copelan E, et al. Peripheral blood progenitor cell mobilization for autologous and allogeneic hematopoietic cell transplantation: Guidelines from the American Society for blood and marrow transplantation. Biol Blood Marrow Transplant. 2014;20(9):1262–73. doi: 10.1016/j.bbmt.2014.05.003.
- 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(4):490–9. doi: 10.1016/j.bbmt.2009.11.012.
- Han X, Ma L, Zhao L, et al. Predictive factors for inadequate stem cell mobilization in Chinese patients with NHL and HL: 14-year experience of a single-center study. J Clin Apher. 2012;27(2):64–74. doi: 10.1002/jca.21204.
- Sancho JM, Morgades M, Grifols JR, et al. Predictive factors for poor peripheral blood stem cell mobilization and peak CD34(+) cell count to guide pre-emptive or immediate rescue mobilization. Cytotherapy. 2012;14(7):823–9. doi: 10.3109/14653249.2012.681042.
- Olivieri A, Marchetti M, Lemoli R et al. Proposed definition of ‘poor mobilizer’ in lymphoma and multiple myeloma: an analytic hierarchy process by ad hoc working group Gruppo ItalianoTrapianto di Midollo Osseo. Bone Marrow Transplant. 2012;47(3):342–51. doi: 10.1038/bmt.2011.82.
- Mohty M, Hubel K, Kroger N, et al. Autologous haematopoietic stem cell mobilization in multiple myeloma and lymphoma patients: a position statement from the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2013;49(7):1–5. doi: 10.1038/bmt.2014.39.
- Jantunen E, Kvalheim G. Mobilization strategies in hard-to-mobilize patients with lymphoid malignancies. Eur J Haematol. 2010;85(6):463–71. doi: 10.1111/j.1600-0609.2010.01520.x.
- Fricker SP. Physiology and Pharmacology of Plerixafor. Transfus Med Hemother. 2013;40(4):237–45. doi: 10.1159/000354132.
- Hartmann T, Hubel K, Monsef I, et al. Additional plerixafor to granulocyte colony-stimulating factors for haematopoietic stem cell mobilisation for autologous transplantation in people with malignant lymphoma or multiple myeloma. Cochrane Database Syst Rev – Article in press, 2015. doi: 10.1002/14651858.CD010615.pub2.
- DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009;113:5720–6. doi: 10.1182/blood-2008-08-174946.
- DiPersio JF, Micallef IN, Stiff PJ, et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin’s lymphoma. J Clin Oncol. 2009;27(28):4767–73. doi: 10.1200/JCO.2008.20.7209.
- Saraceni F, Shem-Tov N, Olivieri A, Nagler A. Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective. Bone Marrow Transplant. 2015;50(7):886–91. doi: 10.1038/bmt.2014.330.
- Flomenberg N, Devine SM, DiPersio JF, et al. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood. 2005;106(5):1867–74. doi: 10.1182/blood-2005-02-0468.
- Fruehauf S. Current Clinical Indications for Plerixafor. Transfus Med Hemother. 2013;40(4):246–50. doi: 10.1159/000354229.
- Veeraputhiran M, Jain T, Cronin S, et al. Successful hematopoietic stem cell collection in patients who fail initial plerixafor mobilization for autologous stem cell transplant. J Clin Apheresis. 2014;26(6):293–8. doi: 10.1002/jca.21321.
- Herbert KE, Demosthenous L, Wiesner G, et al. Plerixafor plus pegfilgrastim is a safe, effective mobilization regimen for poor or adequate mobilizers of hematopoietic stem and progenitor cells: a phase I clinical trial. Bone Marrow Transplant. 2014;49(8):1056–62. doi: 10.1038/bmt.2014.112.
- Maschan AA, Balashov DN, Kurnikova EE, et al. Efficacy of plerixafor in children with malignant tumors failing to mobilize a sufficient number of hematopoietic progenitors with G-CSF. Bone Marrow Transplant. 2015;50(8):1089–91. doi: 10.1038/bmt.2015.71.