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Myeloma

Hematopoietic progenitor cell collection after autologous transplant for multiple myeloma: low platelet count predicts for poor collection and sole use of resulting graft enhances risk of myelodysplasia

Leukemia volume 28, pages 888–893 (2014)Cite this article

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Abstract

Collection of hematopoietic progenitor cells (HPC) after previous autologous hematopoietic progenitor cell transplant (aHCT) was studied in 221 patients with multiple myeloma (MM). With a total of 333 collections, the median number of CD34+ cells collected was 4.7 × 106 CD34+ cells/kg, and 74% of the patients collected ⩾2.5 × 106 CD34+ cells/kg. Among 26 variables examined, the strongest predictor for poor collection was a platelet count <100 × 106/l before mobilization (P<0.001). A subsequent aHCT was performed in 154 of the 221 patients. Sole use of HPC procured after aHCT in 86 patients was associated with delayed platelet recovery (P<0.001) and linked to development of myelodysplastic syndrome (MDS)-associated cytogenetic abnormalities (MDS-CA; P=0.027, odds ratio (OR) 10.34) and a tendency towards clinical MDS/acute myeloid leukemia (AML; P=0.091, OR 3.57). However, treatment-related mortality (P=0.766) and time to absolute neutrophil count recovery ⩾0.5 × 109/l (P=0.879) were similar to when a pre-aHCT graft was used. Indeed, adding HPC collected before any aHCT neutralized the risk of MDS-CA or MDS/AML. Therefore, we advise generous initial HPC collection to broaden the salvage armamentarium for patients with MM.

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References

  1. Kyle RA, Rajkumar SV . Multiple myeloma. N Engl J Med 2004; 351: 1860–1873.

    Article  CAS  Google Scholar 

  2. Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354: 1021–1030.

    Article  CAS  Google Scholar 

  3. Nair B, van Rhee F, Shaughnessy JD Jr, Anaissie E, Szymonifka J, Hoering A et al. Superior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance. Blood 2010; 115: 4168–4173.

    Article  CAS  Google Scholar 

  4. Cook G, Liakopoulou E, Pearce R, Cavet J, Morgan GJ, Kirkland K et al. Factors influencing the outcome of a second autologous stem cell transplant (ASCT) in relapsed multiple myeloma: a study from the British Society of Blood and Marrow Transplantation Registry. Biol Blood Marrow Transplant 2011; 17: 1638–1645.

    Article  Google Scholar 

  5. Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 2012; 366: 1759–1769.

    Article  CAS  Google Scholar 

  6. Barlogie B, Tricot G, Haessler J, van Rhee F, Cottler-Fox M, Anaissie E et al. Cytogenetically defined myelodysplasia after melphalan-based autotransplantation for multiple myeloma linked to poor hematopoietic stem-cell mobilization: the Arkansas experience in more than 3,000 patients treated since 1989. Blood 2008; 111: 94–100.

    Article  CAS  Google Scholar 

  7. McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012; 366: 1770–1781.

    Article  CAS  Google Scholar 

  8. Debes-Marun CS, Dewald GW, Bryant S, Picken E, Santana-Davila R, Gonzalez-Paz N et al. Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma. Leukemia 2003; 17: 427–436.

    Article  CAS  Google Scholar 

  9. Schoch C, Kern W, Schnittger S, Hiddemann W, Haferlach T . Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML. Leukemia 2004; 18: 120–125.

    Article  CAS  Google Scholar 

  10. Usmani SZ, Sawyer J, Rosenthal A, Cottler-Fox M, Epstein J, Yaccoby S et al. Risk factors for MDS and acute leukemia following total therapy 2 and 3 for multiple myeloma. Blood 2013; 121: 4753–4757.

    Article  CAS  Google Scholar 

  11. Rosenbaum ER, O’Connell B, Cottler-Fox M . Validation of a formula for predicting daily CD+34(+) cell collection by leukapheresis. Cytotherapy 2012; 14: 461–466.

    Article  CAS  Google Scholar 

  12. Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR . Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry 1998; 34: 61–70.

    Article  CAS  Google Scholar 

  13. Bensinger W, Appelbaum F, Rowley S, Storb R, Sanders J, Lilleby K et al. Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Oncol 1995; 13: 2547–2555.

    Article  CAS  Google Scholar 

  14. 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  Google Scholar 

  15. Singhal S, Mehta J, Desikan K, Siegel D, Singh J, Munshi N et al. Collection of peripheral blood stem cells after a preceding autograft: unfavorable effect of prior interferon-alpha therapy. Bone Marrow Transplant 1999; 24: 13–17.

    Article  CAS  Google Scholar 

  16. Morris CL, Siegel E, Barlogie B, Cottler-Fox M, Lin P, Fassas A et al. Mobilization of CD34+ cells in elderly patients (&gt;/=70 years) with multiple myeloma: influence of age, prior therapy, platelet count and mobilization regimen. Br J Haematol 2003; 120: 413–423.

    Article  Google Scholar 

  17. Zhu J, Emerson SG . Hematopoietic cytokines, transcription factors and lineage commitment. Oncogene 2002; 21: 3295–3313.

    Article  CAS  Google Scholar 

  18. Bautz F, Rafii S, Kanz L, Mohle R . Expression and secretion of vascular endothelial growth factor-A by cytokine-stimulated hematopoietic progenitor cells. Possible role in the hematopoietic microenvironment. Exp Hematol 2000; 28: 700–706.

    Article  CAS  Google Scholar 

  19. Wickenhauser C, Lorenzen J, Thiele J, Hillienhof A, Jungheim K, Schmitz B et al. Secretion of cytokines (interleukins-1 alpha, -3, and -6 and granulocyte-macrophage colony-stimulating factor) by normal human bone marrow megakaryocytes. Blood 1995; 85: 685–691.

    CAS  PubMed  Google Scholar 

  20. Winter O, Moser K, Mohr E, Zotos D, Kaminski H, Szyska M et al. Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow. Blood 2010; 116: 1867–1875.

    Article  CAS  Google Scholar 

  21. Kaser A, Brandacher G, Steurer W, Kaser S, Offner FA, Zoller H et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood 2001; 98: 2720–2725.

    Article  CAS  Google Scholar 

  22. Barlogie B, Shaughnessy J, Tricot G, Jacobson J, Zangari M, Anaissie E et al. Treatment of multiple myeloma. Blood 2004; 103: 20–32.

    Article  CAS  Google Scholar 

  23. Shaughnessy J, Jacobson J, Sawyer J, McCoy J, Fassas A, Zhan F et al. Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression. Blood 2003; 101: 3849–3856.

    Article  CAS  Google Scholar 

  24. Noll JE, Williams SA, Purton LE, Zannettino AC . Tug of war in the haematopoietic stem cell niche: do myeloma plasma cells compete for the HSC niche? Blood Cancer J 2012; 2: e91.

    Article  CAS  Google Scholar 

  25. Dar A, Schajnovitz A, Lapid K, Kalinkovich A, Itkin T, Ludin A et al. Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells. Leukemia 2011; 25: 1286–1296.

    Article  CAS  Google Scholar 

  26. Joles JA, Willekes-Koolschijn N, Koomans HA . Hypoalbuminemia causes high blood viscosity by increasing red cell lysophosphatidylcholine. Kidney Int 1997; 52: 761–770.

    Article  CAS  Google Scholar 

  27. Ford CD, Pace N, Lehman C . Factors affecting the efficiency of collection of CD34-positive peripheral blood cells by a blood cell separator. Transfusion 1998; 38: 1046–1050.

    Article  CAS  Google Scholar 

  28. Vasu S, Leitman SF, Tisdale JF, Hsieh MM, Childs RW, Barrett AJ et al. Donor demographic and laboratory predictors of allogeneic peripheral blood stem cell mobilization in an ethnically diverse population. Blood 2008; 112: 2092–2100.

    Article  CAS  Google Scholar 

  29. Zhang C, Chen X, Zhang X, Gao L, Kong P, Wang Q et al. Mobilization of peripheral blood stem cells for autologous transplantation patients with hematological malignancies: influence of disease, mobilization method, age and sex. Transfusion Apheresis Sci 2008; 39: 21–28.

    Article  Google Scholar 

  30. Pelus LM, Fukuda S . Chemokine-mobilized adult stem cells; defining a better hematopoietic graft. Leukemia 2008; 22: 466–473.

    Article  CAS  Google Scholar 

  31. Deol A, Abrams J, Masood A, Al-Kadhimi Z, Abidi MH, Ayash L et al. Long-term follow up of patients proceeding to transplant using plerixafor mobilized stem cells and incidence of secondary myelodysplastic syndrome/AML. Bone Marrow Transplantation 2013; e-pub ahead of print 11 March 2013; PMID: 23474805.

  32. Hubel 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  CAS  Google Scholar 

  33. Landgren O, Ma W, Kyle RA, Rajkumar SV, Korde N, Albitar M . Polymorphism of the erythropoietin gene promotor and the development of myelodysplastic syndromes subsequent to multiple myeloma. Leukemia 2012; 26: 844–845.

    Article  CAS  Google Scholar 

  34. Barlogie B, Anaissie E, van Rhee F, Pineda-Roman M, Zangari M, Shaughnessy J et al. The Arkansas approach to therapy of patients with multiple myeloma. Best practice & research. Clin Haematol 2007; 20: 761–781.

    CAS  Google Scholar 

  35. Shah N, Ahmed F, Bashir Q, Qureshi S, Dinh Y, Rondon G et al. Durable remission with salvage second autotransplants in patients with multiple myeloma. Cancer 2012; 118: 3549–3555.

    Article  Google Scholar 

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Acknowledgements

This research was presented in part at the American Society of Hematology Annual meeting, December 2012, Atlanta, GA, USA.

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Authors and Affiliations

  1. Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    X Papanikolaou, J Sawyer, C J Heuck & B Barlogie

  2. Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    E R Rosenbaum, L N Tyler, J Sawyer & M Cottler-Fox

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  1. X Papanikolaou
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  2. E R Rosenbaum
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  4. J Sawyer
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  5. C J Heuck
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  6. B Barlogie
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  7. M Cottler-Fox
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Corresponding author

Correspondence to M Cottler-Fox.

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Competing interests

BB received research funding from Celgene Corp. and Millennium Pharmaceuticals, Inc. and is a consultant for Celgene Corp., Millennium Pharmaceuticals, Inc., Onyx Pharmaceuticals, Inc. and Amgen, Inc. He is a co-inventor on patents and patent applications related to use of gene expression profiling in cancer medicine that have been licensed to Myeloma Health, LLC, but has no financial interests in this company. The remaining authors declare no conflict of interest.

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Author contributions

Conception and design: MCF, BB and XP. Administrative support: MCF and BB. Provision of study material or patients: MCF, ER, LNT, BB, JS and CJH. Collection and assembly of data: XP and LNT. Data analysis and interpretation: XP, ER, MCF and BB.

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Papanikolaou, X., Rosenbaum, E., Tyler, L. et al. Hematopoietic progenitor cell collection after autologous transplant for multiple myeloma: low platelet count predicts for poor collection and sole use of resulting graft enhances risk of myelodysplasia. Leukemia 28, 888–893 (2014). https://doi.org/10.1038/leu.2013.214

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