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Stem Cell Procurement

Intermediate-dose Ara-C plus G-CSF for stem cell mobilization in patients with lymphoid malignancies, including predicted poor mobilizers

Bone Marrow Transplantation volume 48, pages 915–921 (2013)Cite this article

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Abstract

The optimal protocol for mobilization of hematopoietic stem cells in patients with lymphoid malignancies has not been determined so far. We retrospectively analyzed the efficacy and safety of Ara-C at a dose of 1.6 g/m2 compared with CY at a dose of 4.0 g/m2, both combined with filgrastim. Seventy and forty-five patients, respectively, were included, among whom 60% were defined as ‘predicted poor mobilizers’. The use of Ara-C was associated with significantly higher peak number of circulating CD34+ cells compared with CY (P<0.0001). In the Ara-C group, 95% of patients with multiple myeloma (MM) collected at least 5 × 106 CD34+ cells/kg required for tandem transplantation, and 97% of lymphoma patients collected at least 2 × 106 CD34+ cells/kg, needed for a single autologous hematopoietic SCT (autoHSCT), which was achieved with a single leukapheresis in 91% of cases. Results for the CY group were significantly inferior (P<0.0001). No patient mobilized with Ara-C experienced febrile neutropenia, whereas 35% required platelet transfusions. Among patients who proceeded to autoHSCT, the time of both neutrophil and platelet recovery was significantly shorter for those mobilized with Ara-C than CY. We conclude that intermediate-dose Ara-C+filgrastim is a very effective and relatively safe mobilization protocol for patients with lymphoid malignancies.

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References

  1. Baldomero H, Gratwohl M, Gratwohl A, Tichelli A, Niederwieser D, Madrigal A et al. The EBMT activity survey 2009: trends over the past 5 years. Bone Marrow Transplant 2011; 46: 485–501.

    Article  CAS  PubMed  Google Scholar 

  2. 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: 1360–1377.

    Article  CAS  PubMed  Google Scholar 

  3. Sola C, Maroto P, Salazar R, Mesia R, Mendoza L, Brunet J et al. Bone marrow transplantation: prognostic factors of peripheral blood stem cell mobilization with cyclophosphamide and filgrastim (r-metHuG-CSF): the CD34+ cell dose positively affects the time to hematopoietic recovery and supportive requirements after high-dose chemotherapy. Hematology 1999; 4: 195–209.

    Article  CAS  PubMed  Google Scholar 

  4. Jantunen E, Fruehauf S . Importance of blood graft characteristics in auto-SCT: implications for optimizing mobilization regimens. Bone Marrow Transplant 2011; 46: 627–635.

    Article  CAS  PubMed  Google Scholar 

  5. O’Shea D, Giles C, Terpos E, Perz J, Politou M, Sana V et al. Predictive factors for survival in myeloma patients who undergo autologous stem cell transplantation: a single-centre experience in 211 patients. Bone Marrow Transplant 2006; 37: 731–737.

    Article  PubMed  Google Scholar 

  6. Pavone V, Gaudio F, Console G, Vitolo U, Iacopino P, Guarini A 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.

    Article  CAS  PubMed  Google Scholar 

  7. Bolwell BJ, Pohlman B, Rybicki L, Sobecks R, Dean R, Curtis J et al. Patients mobilizing large numbers of CD34+ cells ('super mobilizers') have improved survival in autologous stem cell transplantation for lymphoid malignancies. Bone Marrow Transplant 2007; 40: 437–441.

    Article  CAS  PubMed  Google Scholar 

  8. Goterris R, Hernández-Boluda JC, Teruel A, Gómez C, Lis MJ, Terol MJ et al. Impact of different strategies of second-line stem cell harvest on the outcome of autologous transplantation in poor peripheral blood stem cell mobilizers. Bone Marrow Transplant 2005; 36: 847–853.

    Article  CAS  PubMed  Google Scholar 

  9. Weaver CH, Hazelton B, Birch R, Palmer P, Allen C, Schwartzberg L et al. An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy. Blood 1995; 86: 3961–3969.

    CAS  PubMed  Google Scholar 

  10. Fu S, Liesveld J . Mobilization of hematopoietic stem cells. Blood Rev 2000; 14: 205–218.

    Article  CAS  PubMed  Google Scholar 

  11. Narayanasami U, Kanteti R, Morelli J, Klekar A, Al-Olama A, Keating C 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.

    Article  CAS  PubMed  Google Scholar 

  12. Gertz MA . Current status of stem cell mobilization. Br J Haematol 2010; 150: 647–662.

    Article  CAS  PubMed  Google Scholar 

  13. Demirer T, Buckner CD, Gooley T, Appelbaum FR, Rowley S, Chauncey T et al. Factors influencing collection of peripheral blood stem cells in patients with multiple myeloma. Bone Marrow Transplant 1996; 17: 937–941.

    CAS  PubMed  Google Scholar 

  14. Perea G, Sureda A, Martino R, Altés A, Martínez C, Cabezudo E et al. Predictive factors for a successful mobilization of peripheral blood CD34+ cells in multiple myeloma. Ann Hematol 2001; 80: 592–597.

    Article  CAS  PubMed  Google Scholar 

  15. Kuittinen T, Nousiainen T, Halonen P, Mahlamäki E, Jantunen E . Prediction of mobilisation failure in patients with non-Hodgkin’s lymphoma. Bone Marrow Transplant 2004; 33: 907–912.

    Article  CAS  PubMed  Google Scholar 

  16. Fietz T, Rieger K, Dimeo F, Blau IW, Thiel E, Knauf WU . Stem cell mobilization in multiple myeloma patients: do we need an age-adjusted regimen for the elderly? J Clin Apher 2004; 19: 202–207.

    Article  CAS  PubMed  Google Scholar 

  17. Hosing C, Saliba RM, Ahlawat S, Körbling M, Kebriaei P, Alousi A et al. Poor hematopoietic stem cell mobilizers: a single institution study of incidence and risk factors in patients with recurrent or relapsed lymphoma. Am J Hematol 2009; 84: 335–337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Boccadoro M, Palumbo A, Bringhen S, Merletti F, Ciccone G, Richiardi L et al. Oral melphalan at diagnosis hampers adequate collection of peripheral blood progenitor cells in multiple myeloma. Haematologica 2002; 87: 846–850.

    CAS  PubMed  Google Scholar 

  19. Laszlo D, Galieni P, Raspadori D, Tozzi M, Lauria F, Martinelli G . Fludarabine combination regimen severely affected peripheral blood stem cell mobilization. Acta Haematol 2004; 111: 228–229.

    Article  PubMed  Google Scholar 

  20. Ford CD, Green W, Warenski S, Petersen FB . Effect of prior chemotherapy on hematopoietic stem cell mobilization. Bone Marrow Transplant 2004; 33: 901–905.

    Article  CAS  PubMed  Google Scholar 

  21. Ghobrial IM, Dispenzieri A, Bundy KL, Gastineau DA, Rajkumar SV, Therneau TM et al. Effect of thalidomide on stem cell collection and engraftment in patients with multiple myeloma. Bone Marrow Transplant 2003; 32: 587–592.

    Article  CAS  PubMed  Google Scholar 

  22. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Gastineau DA 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: 2035–2042.

    Article  CAS  PubMed  Google Scholar 

  23. Hübel K, Fresen MM, Apperley JF, Basak GW, Douglas KW, Gabriel IH et al. European data on stem cell mobilization with plerixafor in non-Hodgkin's lymphoma, Hodgkin's lymphoma and multiple myeloma patients. A subgroup analysis of the European Consortium of stem cell mobilization. Bone Marrow Transplant 2012; 47: 1046–1050.

    Article  PubMed  Google Scholar 

  24. Basak GW, Jaksic O, Koristek Z, Mikala G, Basic-Kinda S, Mayer J et al. Haematopoietic stem cell mobilization with plerixafor and G-CSF in patients with multiple myeloma transplanted with autologous stem cells. Eur J Haematol 2011; 86: 488–495.

    Article  CAS  PubMed  Google Scholar 

  25. Montillo M, Tedeschi A, Rossi V, Cairoli R, Pungolino E, Intropido L et al. Successful CD34+ cell mobilization by intermediate-dose Ara-C in chronic lymphocytic leukemia patients treated with sequential fludarabine and Campath-1H. Leukemia 2004; 18: 57–62.

    Article  CAS  PubMed  Google Scholar 

  26. Kruzel T, Sadus-Wojciechowska M, Najda J, Czerw T, Glowala-Kosinska M, Holowiecki J et al. Very high efficacy of intermediate-dose cytarabine in combination with G-CSF as a second-line mobilization of hematopoietic stem cells. Int J Hematol 2012; 96: 287–289.

    Article  PubMed  Google Scholar 

  27. Olivieri A, Marchetti M, Lemoli R, Tarella C, Iacone A, Lanza F 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: 342–351.

    Article  CAS  PubMed  Google Scholar 

  28. Smagur A, Mitrus I, Giebel S, Sadus-Wojciechowska M, Najda J, Kruzel T et al. Impact of different dimethyl sulfoxide concentrations on cell recovery, viability and clonogenic potential of cryopreserved peripheral blood hematopoietic stem and progenitor cells. Vox Sang, (e-pub ahead of print 9 October 2012; doi:10.1111/j.1423-0410.2012.01657.x).

    Article  PubMed  Google Scholar 

  29. Sheppard D, Bredeson C, Allan D, Tay J . Systematic review of randomized controlled trials of hematopoietic stem cell mobilization strategies for autologous transplantation for hematologic malignancies. Biol Blood Marrow Transplant 2012; 18: 1191–1203.

    Article  PubMed  Google Scholar 

  30. Bensinger W, DiPersio JF, McCarty JM . Improving stem cell mobilization strategies: future directions. Bone Marrow Transplant 2009; 43: 181–195.

    Article  CAS  PubMed  Google Scholar 

  31. Dingli D, Nowakowski GS, Dispenzieri A, Lacy MQ, Hayman S, Litzow MR et al. Cyclophosphamide mobilization does not improve outcome in patients receiving stem cell transplantation for multiple myeloma. Clin Lymphoma Myeloma 2006; 6: 384–388.

    Article  CAS  PubMed  Google Scholar 

  32. Bourhis JH, Bouko Y, Koscielny S, Bakkus M, Greinix H, Derigs G et al. Relapse risk after autologous transplantation in patients with newly diagnosed myeloma is not related with infused tumor cell load and the outcome is not improved by CD34+ cell selection: long term follow-up of an EBMT phase III randomized study. Haematologica 2007; 92: 1083–1090.

    Article  PubMed  Google Scholar 

  33. Ahn JS, Park S, IM S-A, Yoon S-S, Lee J-S, Kim BK et al. High-dose versus low-dose cyclophosphamide in combination with G-CFS for peripheral blood progenitor cell mobilization. Korean J Int Med 2005; 20: 224–231.

    Article  CAS  Google Scholar 

  34. Pavone V, Gaudio F, Guarini A, Perrone T, Zonno A, Curci P 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.

    Article  CAS  PubMed  Google Scholar 

  35. Facon T, Harousseau JL, Maloisel F, Attal M, Odriozola J, Alegre A et al. Stem cell factor in combination with filgrastim after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: a randomized, controlled trial. Blood 1999; 94: 1218–1225.

    CAS  PubMed  Google Scholar 

  36. Gazitt Y, Callander N, Freytes CO, Shaughnessy P, Liu Q, Tsai TW et al. Peripheral blood stem cell mobilization with cyclophosphamide in combination with G-CSF, GM-CSF, or sequential GM-CSF/G-CSF in non-Hodgkin’s lymphoma patients: a randomized prospective study. J Hematother Stem Cell Res 2000; 9: 737–748.

    Article  CAS  PubMed  Google Scholar 

  37. Quittet P, Ceballos P, Lopez E, Lu ZY, Latry P, Becht C et al. Low doses of GM-CSF (molgramostim) and G-CSF (filgrastim) after cyclophosphamide (4 g/m2) enhance the peripheral blood progenitor cell harvest: results of two randomized studies including 120 patients. Bone Marrow Transplant 2006; 38: 275–284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Fitoussi O, Perreau V, Boiron JM, Bouzigon E, Cony-Makhoul P, Pigneux A et al. A comparison of toxicity following two different doses of cyclophosphamide for mobilization of peripheral blood progenitor cells in 116 multiple myeloma patients. Bone Marrow Transplant 2001; 27: 837–842.

    Article  CAS  PubMed  Google Scholar 

  39. Jantunen E, Putkonen M, Nousiainen T, Pelliniemi TT, Mahlamäki E, Remes K . Low-dose or intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor for progenitor cell mobilisation in patients with multiple myeloma. Bone Marrow Transplant 2003; 31: 347–351.

    Article  CAS  PubMed  Google Scholar 

  40. Dao MA, Arevalo J, Nolta JA . Reversibility of CD34 expression on human hematopoietic stem cells that retain the capacity for secondary reconstitution. Blood 2003; 101: 112–118.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Bone Marrow Transplantation, Maria Sklodowska–Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland

    S Giebel, T Kruzel, T Czerw, M Sadus-Wojciechowska, J Najda, M Glowala-Kosinka, A Chwieduk, I Mitrus, A Smagur & J Holowiecki

  2. Department of Brachytherapy and Clinical Oncology, Mikolaj Kopernik Medical University, Torun, Poland

    E Chmielowska

  3. Department of Chemotherapy, Oncology Center, Bydgoszcz, Poland

    E Chmielowska

  4. Department of Hematology, Municipal Hospital, Chorzow, Poland

    S Grosicki

  5. Department of Hematology, University Hospital, Krakow, Poland

    A Jurczyszyn

  6. Department of Hematology, Holycross Cancer Center, Kielce, Poland

    M Pasiarski

  7. Department of Clinical and Experimental Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland

    E Nowara

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Giebel, S., Kruzel, T., Czerw, T. et al. Intermediate-dose Ara-C plus G-CSF for stem cell mobilization in patients with lymphoid malignancies, including predicted poor mobilizers. Bone Marrow Transplant 48, 915–921 (2013). https://doi.org/10.1038/bmt.2012.269

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