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Supportive Care in Cancer

, Volume 21, Issue 9, pp 2437–2442 | Cite as

Evaluating the effects of lenalidomide induction therapy on peripheral stem cells collection in patients undergoing autologous stem cell transplant for multiple myeloma

  • Divaya Bhutani
  • Jeffrey Zonder
  • Jason Valent
  • Nishant Tageja
  • Lois Ayash
  • Abhinav Deol
  • Zaid Al-Kadhimi
  • Judith Abrams
  • Lawrence Lum
  • Voravit Ratanatharathorn
  • Joseph Uberti
  • Muneer H. AbidiEmail author
Original Article

Abstract

Introduction

Lenalidomide (LEN) is a relatively new and very effective therapy for multiple myeloma (MM). Prior LEN therapy is associated with an increased risk of peripheral blood stem cell collection (PBSC) failure, particularly with filgrastim (G-CSF) alone. We performed a retrospective chart review of 319 consecutive MM patients who underwent apheresis to collect PBSCs for the first autologous stem cell transplant (ASCT).

Results

The median number of PBSCs collected in the LEN (+) group was significantly less than the LEN (−) group (6.34 vs. 7.52 × 106 CD34+ cells/kg; p = 0.0004). In addition, the median number of apheresis sessions required for adequate PBSCs collection were significantly more in the LEN (+) group as compared to LEN (−) group (2 vs. 1 sessions; p = 0.002). In the LEN (+) group, there was a negative correlation between PBSCs collected and prior number of cycles of LEN (p = 0.0001). Rate of PBSC collection failure was 9 % in the LEN (+) group and 5 % in the LEN (−) group (p = 0.16). Only six patients who failed PBSC collection with G-CSF were able to collect adequate PBSCs with G-CSF + plerixafor. LEN exposure had no effect on neutrophil or platelet recovery post-ASCT.

Conclusions

Up to four cycles of LEN exposure have minimal negative impact on PBSC collection. Despite prolong exposure of LEN, PBSC collection was adequate for two ASCTs in the majority of patients and post-ASCT engraftment was not longer than expected; however, clinical relevance (complication rate, quality of life, cost) of prolonged LEN exposure on both PBSC and ASCT, should be evaluated in prospective clinical trials.

Keywords

Lenalidomide Multiple myeloma Peripheral stem cells collection 

Notes

Conflict of interest

Muneer H. Abidi: Speaker for Millennium Pharmaceutical

Jeffrey Zonder: Advisory Board for Celgene Pharmaceutical

References

  1. 1.
    Zonder JA, Crowley J, Hussein MA et al (2010) Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood 116(26):5838–5841CrossRefGoogle Scholar
  2. 2.
    Rajkumar SV, Jacobus S, Callander NS et al (2010) Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 11(1):29–37CrossRefGoogle Scholar
  3. 3.
    Dimopoulos M, Spencer A, Attal M et al (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357:2123–2132CrossRefGoogle Scholar
  4. 4.
    Kumar S, Dispenzieri A, Lacy MQ et al (2007) Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia 21:2035–2042CrossRefGoogle Scholar
  5. 5.
    Popat U, Saliba R, Thandi R et al (2009) Impairment of filgrastim induced stem cell mobilization after prior lenalidomide in patients with multiple myeloma. Biol Blood Marrow Transplant 15:718–723CrossRefGoogle Scholar
  6. 6.
    Attal M, Harousseau JL, Stoppa AM et al (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 335:91–97CrossRefGoogle Scholar
  7. 7.
    Child JA, Morgan GJ, Davies FE et al (2003) High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 348(19):1875–1883CrossRefGoogle Scholar
  8. 8.
    Bensinger W, Appelbaum F, Rowley S et al (1995) Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Oncol 13(10):2547–2555CrossRefGoogle Scholar
  9. 9.
    Tricot G, Jagannath S, Vesole D et al (1995) Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients. Blood 85(2):588–596PubMedGoogle Scholar
  10. 10.
    Gianni M, Alessandro S, Siena M et al (1989) Granulocyte-macrophage colony-stimulating factor to harvest circulating haematopoietic stem cells for autotransplantation. Lancet 334(8663):580–585CrossRefGoogle Scholar
  11. 11.
    Mark T, Stern J, Furst JR et al (2008) Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma. Biol Blood Marrow Transplant 14:795–798CrossRefGoogle Scholar
  12. 12.
    DiPersio JF, Stadtmauer EA, Nademanee A et al (2009) 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 113(23):5720–5726PubMedGoogle Scholar
  13. 13.
    Malard F, Kröger N, Gabriel IH et al (2012) Plerixafor for autologous peripheral blood stem cell mobilization in patients previously treated with fludarabine or lenalidomide. Biol Blood Marrow Transplant 18(2):314–317CrossRefGoogle Scholar
  14. 14.
    Horwitz ME, Chute JP, Gasparetto C et al (2012) Preemptive dosing of plerixafor given to poor stem cell mobilizers on day 5 of G-CSF administration. Bone Marrow Transplant 47:1051–1055CrossRefGoogle Scholar
  15. 15.
    Kumar S, Giralt S, Stadtmauer EA et al (2009) International Myeloma Working Group. Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens. Blood 114(9):1729–1735CrossRefGoogle Scholar
  16. 16.
    Wu L, Adams M, Carter T et al (2008) Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab treated CD20+ tumor cells. Clin Cancer Res 14:4650–4657CrossRefGoogle Scholar
  17. 17.
    Chang DH, Liu N, Klimek V et al (2006) Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood 108:618–621CrossRefGoogle Scholar
  18. 18.
    Koh KR, Janz M, Mapara MY et al (2005) Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood 105(10):3833–3840CrossRefGoogle Scholar
  19. 19.
    Niesvizky R, Naib T, Christos PJ et al (2007) Lenalidomide-induced myelosuppression is associated with renal dysfunction: adverse events evaluation of treatment-naïve patients undergoing front-line lenalidomide and dexamethasone therapy. Br J Haematol 138(5):640–643CrossRefGoogle Scholar
  20. 20.
    Cavallo F, Bringhen S, Milone G et al (2011) Stem cell mobilization in patients with newly diagnosed multiple myeloma after lenalidomide induction therapy. Leukemia 25(10):1627–1631CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Divaya Bhutani
    • 1
    • 3
  • Jeffrey Zonder
    • 1
  • Jason Valent
    • 2
  • Nishant Tageja
    • 4
  • Lois Ayash
    • 1
    • 3
  • Abhinav Deol
    • 1
    • 3
  • Zaid Al-Kadhimi
    • 1
    • 3
  • Judith Abrams
    • 1
    • 3
  • Lawrence Lum
    • 1
    • 3
  • Voravit Ratanatharathorn
    • 1
    • 3
  • Joseph Uberti
    • 1
    • 3
  • Muneer H. Abidi
    • 1
    • 3
    Email author
  1. 1.Department of Bone Marrow TransplantationKarmanos Cancer InstituteDetroitUSA
  2. 2.Cleveland ClinicClevelandUSA
  3. 3.Wayne State UniversityDetroitUSA
  4. 4.Medical Oncology Branch, National Cancer InstituteNational Institutes of HealthBethesdaUSA

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