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Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group

Leukemia volume 27, pages 780–791 (2013)Cite this article

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Abstract

Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (⩾20%) and absolute number (⩾2 × 109/l) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be re-examined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL.

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Acknowledgements

This work has been supported in part by ‘Josep Font’ Grant from Hospital Clínic de Barcelona and RD12/0036/0046 from Instituto de Salud Carlos III, Spain. Meeting on Plasma Cell Leukemia was supported by the International Myeloma Foundation.

Author Contributions

The first drafts were written by CFdL and JJS and were reviewed by JB. The first mature draft, including tables and treatment algorithm, was circulated among the authors on May 2012 and was presented and deeply discussed, particularly the response criteria and treatment approach, at the International Myeloma Foundation Summit Meeting on 12th and 13th June 2012 in Amsterdam, at the general sessions and at the ‘Workshop 5’. The suggestions were incorporated and the draft was circulated among all the members of the International Myeloma Working Group, for further comments and suggestions which were incorporated when possible. All the authors approved the final version of the manuscript.

Author information

Author notes

  1. See Appendix for the complete list of all authors part of International Myeloma Working Group.

Authors and Affiliations

  1. Department of Hematology, Amyloidosis and Myeloma Unit, IDIBAPS, Hospital Clinic de Barcelona, Barcelona, Spain

    C Fernández de Larrea & J Bladé

  2. Department of Hematology, Mayo Clinic, Rochester, MN, USA

    R A Kyle & S K Kumar

  3. Southwest Oncology Group, International Myeloma Foundation, Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA

    B G M Durie

  4. Department of Medicine, Center for Oncology and Hematology, Wilhelminenspital, Vienna, Austria

    H Ludwig

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

    S Usmani

  6. John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA

    D H Vesole

  7. Department of Haemato-Oncology, University Hospital Ostrava and School of Medicina University, Ostrava, Czech Republic

    R Hajek

  8. Servicio de Hematologia, Hospital Universitario de Salamanca, CIC, IBMCC (USAL-CSIC), Salamanca, Spain

    J F San Miguel

  9. University of Hamburg, University Medical Center, Hamburg, Germany

    O Sezer

  10. Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands

    P Sonneveld

  11. Massachusetts General Hospital Cancer Center, Boston, MA, USA

    A Mahindra

  12. Tufts Medical Center, Boston, MA, USA

    R Comenzo

  13. Division of Hematology, Myeloma Unit, University of Torino, Torino, Italy

    A Palumbo

  14. NYU Comprehensive Cancer Center, New York, NY, USA

    A Mazumber

  15. Dana-Farber Cancer Institute, Medical Oncology, Boston, MA, USA

    K C Anderson & P G Richardson

  16. Department of BMT, Hematology/Oncology, University of Maryland, Baltimore Campus, Baltimore, MD, USA

    A Z Badros

  17. Department of Hematology, Centre Hospitalier Universitaire de Liege, Liege, Belgium

    J Caers

  18. Seragnoli Institute of Haematology, Bologna School of Medicine, S. Orsola’s University Hospital, Bologna, Italy

    M Cavo

  19. Department of Hematology, Hospital Claude Huriez, Lille, France

    X LeLeu

  20. Department of Clinical Therapeutics, University of Athens, School of Medicine, Athens, Greece

    M A Dimopoulos

  21. Division of Haematology & Medical Oncology, Queen Mary Hospital, Hong Kong

    C S Chim

  22. Department of Clinical Hematology, University Ziekenhuis Brussels, Brussels, Belgium

    R Schots

  23. Hospital Ruiz y Paez, Bolivar, Venezuela

    A Noeul

  24. Hospital Italiano De Buenos Aires, Caba, Argentina

    D Fantl

  25. Department of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden

    U-H Mellqvist

  26. Metabolism Branch, National Cancer Institute, NIH, Bethesda, MD, USA

    O Landgren

  27. Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL, USA

    A Chanan-Khan

  28. Department of Clinical Hematology, University Hospital, Nantes, France

    P Moreau

  29. Division of Hematology-Oncology, Mayo Clinic Scottsdale, Scottsdale, AZ, USA

    R Fonseca

  30. Department of Biochemistry, University of Pavia, Pavia, Italy

    G Merlini

  31. Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain

    J J Lahuerta

  32. Department of Lymphoma/Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    R Z Orlowski & J J Shah

Authors
  1. C Fernández de Larrea
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  2. R A Kyle
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  3. B G M Durie
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  4. H Ludwig
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  22. M A Dimopoulos
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  31. R Fonseca
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  32. G Merlini
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  33. J J Lahuerta
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  34. J Bladé
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  35. R Z Orlowski
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  36. J J Shah
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Consortia

on behalf of the International Myeloma Working Group

Corresponding authors

Correspondence to C Fernández de Larrea or J J Shah.

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Competing interests

The authors declare no conflict of interest.

Appendix

Appendix

International Myeloma Working Group

  1. 1

    N Abildgaard, Syddansk Universitet, Odense, Denmark

  2. 2

    R Abonour, Indiana University School of Medicine, Indianapolis, Indiana, USA

  3. 3

    R Alexanian, MD Anderson, Houston, TX, USA

  4. 4

    M Alsina, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

  5. 5

    KC Anderson, DFCI, Boston, MA, USA

  6. 6

    M Attal, Purpan Hospital, Toulouse, France

  7. 7

    H Avet-Loiseau, Institute de Biologie, Nantes, France

  8. 8

    A Badros, University of Maryland, Baltimore, MD, USA

  9. 9

    D Baris, National Cancer Institute, Bethesda, MD, USA

  10. 10

    B Barlogie, M.I.R.T. UAMS Little Rock, AR, USA

  11. 11

    R Bataille, Institute de Biologie, Nantes, France

  12. 12

    M Beksaç, Ankara University, Ankara, Turkey

  13. 13

    A Belch, Cross Cancer Institute, Alberta, Canada

  14. 14

    D Ben-Yehuda, Hadassah University Hospital, Hadassah, Israel

  15. 15

    B Bensinger, Fred Hutchinson Cancer Center, Seattle, WA, USA

  16. 16

    PL Bergsagel, Mayo Clinic Scottsdale, Scottsdale, AZ, USA

  17. 17

    J Bird, Bristol Haematology and Oncology Center, Bristol, UK

  18. 18

    J Bladé, Hospital Clínic de Barcelona, Barcelona, Spain

  19. 19

    M Boccadoro, University of Torino, Torino, Italy

  20. 20

    J Caers, Centre Hospitalier Universitaire de Liège, Liège, Belgium

  21. 21

    M Cavo, Universita di Bologna, Bologna, Italy

  22. 22

    A Chanan-Khan, Mayo Clinic, Jacksonville, FL, USA

  23. 23

    W Ming Chen, MM Research Center of Beijing, Beijing, China

  24. 24

    M Chesi, Mayo Clinic Scottsdale, Scottsdale, AZ, USA

  25. 25

    T Child, Leeds General Hospital, Leeds, UK

  26. 26

    J Chim, Department of Medicine, Queen Mary Hospital, Hong Kong

  27. 27

    W-J Chng, National University Health System, Singapore

  28. 28

    R Comenzo, Tufts Medical School, Boston, MA, USA

  29. 29

    J Crowley, Cancer Research and Biostatistics, Seattle, WA, USA

  30. 30

    W Dalton, H. Lee Moffitt, Tampa, FL, USA

  31. 31

    F Davies, Royal Marsden Hospital, London, England

  32. 32

    J de la Rubia, Hospital Universitario La Fe, Valencia, Spain

  33. 33

    C de Souza, Univeridade de Campinas, Caminas, Brazil

  34. 34

    M Delforge, University Hospital Gasthuisberg, Leuven, Belgium

  35. 35

    M Dimopoulos, University of Athens School of Medicine, Athens, Greece

  36. 36

    A Dispenzieri, Mayo Clinic, Rochester, MN, USA

  37. 37

    J Drach, University of Vienna, Vienna, Austria

  38. 38

    M Drake, Mayo Clinic Rochester, Rochester, MN, USA

  39. 39

    BGM Durie, Cedars-Sinai Samuel Oschin Cancer Center, Los Angeles, CA, USA

  40. 40

    H Einsele, Universitätsklinik Würzburg, Würzburg, Germany

  41. 41

    T Facon, Centre Hospitalier Regional Universitaire de Lille, Lille, France

  42. 42

    D Fantl, Socieded Argentina de Hematología, Buenos Aires, Argentina

  43. 43

    J-P Fermand, Hopitaux de Paris, Paris, France

  44. 44

    C Fernández de Larrea, Hospital Clínic de Barcelona, Barcelona, Spain

  45. 45

    R Fonseca, Mayo Clinic Arizona, Scottsdale, AZ, USA

  46. 46

    G Gahrton, Karolinska Institute for Medicine, Huddinge, Sweden

  47. 47

    R García-Sanz, University Hospital of Salamanca, Salamanca, Spain

  48. 48

    C Gasparetto, Duke University Medical Center, Durham, NC, USA

  49. 49

    M Gertz, Mayo Clinic, Rochester, MN, USA

  50. 50

    I Ghobrial, Dana-Farber Cancer Institute, Boston, MA, USA

  51. 51

    J Gibson, Royal Prince Alfred Hospital, Sydney, Australia

  52. 52

    P Gimsing, University of Copenhagen, Copenhagen, Denmark

  53. 53

    S Giralt, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

  54. 54

    H Goldschmidt, University Hospital Heidelberg, Heidelberg, Germany

  55. 55

    P Greipp, Mayo Clinic, Rochester, MN, USA

  56. 56

    R Hajek, University Hospital Ostrava and School of Medicine, University Ostrava, Czech Republic

  57. 57

    I Hardan, Tel Aviv University, Tel Aviv, Israel

  58. 58

    P Hari, Medical College of Wisconsin, Milwaukee, WI, USA

  59. 59

    H Hata, Kumamoto University Hospital, Kumamoto, Japan

  60. 60

    Y Hattori, Keio University School of Medicine, Tokyo, Japan

  61. 61

    T Heffner, Emory University, Atlanta, GA, USA

  62. 62

    J Ho, Royal Prince Alfred Hospital, Sydney, Australia

  63. 63

    A Hoering, Cancer Research and Biostatistics, Seattle, WA, USA

  64. 64

    J Hou, Shanghai Chang Zheng Hospital, Shanghai, China

  65. 65

    V Hungria, Clinica San Germano, Sao Paolo, Brazil

  66. 66

    S Ida, Nagoya City University Medical School, Nagoya, Japan

  67. 67

    P Jacobs, Constantiaberg Medi-Clinic, Plumstead, South Africa

  68. 68

    S Jagannath, Mt. Sinai Cancer Institute, New York, NY, USA

  69. 69

    H Johnsen, Aalborg Hospital Science and Innovation Center, Aalborg, Denmark

  70. 70

    D Joshua, Royal Prince Alfred Hospital, Sydney, Australia

  71. 71

    A Jurczyszyn, The Myeloma Treatment Foundation, Poland

  72. 72

    J Kaufman, Emory Clinic, Atlanta, GA, USA

  73. 73

    M Kawano, Yamaguchi University, Ube, Japan

  74. 74

    E Kovacs, Cancer Immunology Research-Life, Birsfelden, Switzerland

  75. 75

    A Krishnan, City of Hope, Duarte, CA, USA

  76. 76

    S Kristinsson, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden

  77. 77

    N Kröger, University Hospital Hamburg, Hamburg, Germany

  78. 78

    S Kumar, Department of Hematology, Mayo Clinic, MN, USA

  79. 79

    RA Kyle, Department of Laboratory Med. and Pathology, Mayo Clinic, MN, USA

  80. 80

    C Kyriacou, Northwick Park Hospital, London, UK

  81. 81

    M Lacy, Mayo Clinic Rochester, Rochester, MN, USA

  82. 82

    J José Lahuerta, Grupo Español de Mieloma, Hospital Universitario 12 de Octubre, Madrid, Spain

  83. 83

    O Landgren, National Cancer Institute, Bethesda, MD, USA

  84. 84

    J Laubach, Dana-Farber Cancer Institute, Boston, MA, USA

  85. 85

    G Laurent, Hôpital Saint Antoine, Paris, France

  86. 86

    F Leal da Costa, Instituto Portugues De Oncologia, Lisbon, Portugal

  87. 87

    J Hoon Lee, Gachon University Gil Hospital, Incheon, Korea

  88. 88

    M Leiba, Sheba Medical Center, Tel Hashomer, Israel

  89. 89

    X LeLeu, Hospital Huriez, CHRU Lille, France

  90. 90

    S Lentzsch, University of Pittsburgh, Pittsburgh, PA, USA

  91. 91

    H Lokhorst, University Medical CenterUtrecht, Utrecht, The Netherlands

  92. 92

    S Lonial, Emory University Medical School, Atlanta, GA, USA

  93. 93

    H Ludwig, Wilhelminenspital Der Stat Wien, Vienna, Austria

  94. 94

    A Mahindra, Dana-Farber Cancer Institute, Massachusetts General Hospital, Boston, MA, USA

  95. 95

    A Maiolino, Rua fonte da Saudade, Rio de Janeiro, Brazil

  96. 96

    M Mateos, University of Salamanca, Salamanca, Spain

  97. 97

    A Mazumder, NYU Comprehensive Cancer Center, New York, NY, USA

  98. 98

    P McCarthy, Roswell Park Cancer Center, Buffalo, NY, USA

  99. 99

    J Mehta, Northwestern University, Chicago, IL, USA

  100. 100

    U-H Mellqvist, Sahlgrenska University Hospital, Gothenburg, Sweden

  101. 101

    GP Merlini, University of Pavia, Pavia, Italy

  102. 102

    J Mikhael, Mayo Clinic Arizona, Scottsdale, AZ, USA

  103. 103

    P Moreau, University Hospital, Nantes, France

  104. 104

    G Morgan, Royal Marsden Hospital, London, England

  105. 105

    N Munshi, Diane Farber Cancer Institute, Boston, MA, USA

  106. 106

    H Nahi, Karolinska University Hospital, Stockholm, Sweden

  107. 107

    R Niesvizky, Weill Cornell Medical College, New York, NY, USA

  108. 108

    A Nouel, Hospital Ruíz y Paez, Bolivar, Venezuela

  109. 109

    Y Novis, Hospital Sírio Libanês, Bela Vista, Brazil

  110. 110

    E Ocio, Salamanca, Spain

  111. 111

    R Orlowski, MD Anderson Cancer Center, Houston, TX, USA

  112. 112

    A Palumbo, Cathedra Ematologia, Torino, Italy

  113. 113

    S Pavlovsky, Fundaleu, Buenos Aires, Argentina

  114. 114

    L Pilarski, University of Alberta, Alberta, Canada

  115. 115

    R Powles, Leukemia & Myeloma, Wimbledon, England

  116. 116

    N Raje, Massachusetts General Hospital, Boston, MA, USA

  117. 117

    S Vincent Rajkumar, Mayo Clinic, Rochester, MN, USA

  118. 118

    D Reece, Princess Margaret Hospital, Toronto, Canada

  119. 119

    T Reiman, Saint John Regional Hospital, Saint John, New Brunswick, Canada

  120. 120

    PG Richardson, Dana Farber Cancer Institute, Boston, MA, USA

  121. 121

    A Rodríguez Morales, Banco Metropolitano de Sangre, Caracas, Venezuela

  122. 122

    KR Romeril, Wellington Hospital, Wellington, New Zealand

  123. 123

    D Roodman, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

  124. 124

    L Rosiñol, Hospital Clinic, Barcelona, Spain

  125. 125

    S Russell, Mayo Clinic, Rochester, MN, USA

  126. 126

    JS Miguel, University of Salamanca, Salamanca, Spain

  127. 127

    R Schots, Universitair Ziekenhuis Brussel, Brussels, Belgium

  128. 128

    S Sevcikova, Masaryk University, Brno, Czech Republic

  129. 129

    O Sezer, Universität Hamburg, Hamburg, Germany

  130. 130

    JJ Shah, MD Anderson Cancer Institute, Houston, TX, USA

  131. 131

    J Shaughnessy, M.I.R.T. UAMS, Little Rock, AR, USA

  132. 132

    K Shimizu, Nagoya City Midori General Hospital, Nagoya, Japan

  133. 133

    C Shustik, McGill University, Montreal, Canada

  134. 134

    D Siegel, Hackensack, Cancer Center, Hackensack, NJ, USA

  135. 135

    S Singhal, Northwestern University, Chicago, IL, USA

  136. 136

    P Sonneveld, Erasmus MC, Rotterdam, The Netherlands

  137. 137

    A Spencer, The Alfred Hospital, Melbourne, Australia

  138. 138

    E Stadtmauer, University of Pennsylvania, Philadelphia, PA, USA

  139. 139

    K Stewart, Mayo Clinic Arizona, Scottsdale, AZ, USA

  140. 140

    E Terpos, University of Athens School of Medicine, Athens, Greece

  141. 141

    P Tosi, Italian Cooperative Group, Istituto di Ematologia Seragnoli, Bologna, Italy

  142. 142

    G Tricot, Huntsman Cancer Institute, Salt Lake City, UT, USA

  143. 143

    I Turesson, SKANE University Hospital, Malmo, Sweden

  144. 144

    S Usmani, M.I.R.T UAMS, Little Rock, AR, USA

  145. 145

    B Van Camp, Vrije Universiteit Brussels, Brussels, Belgium

  146. 146

    B Van Ness, University of Minnesota, Minneapolis, MN, USA

  147. 147

    I Van Riet, Brussels Vrija University, Brussels, Belgium

  148. 148

    I Vande Broek, Vrije Universiteit Brussels, Brussels, Belgium

  149. 149

    K Vanderkerken, Vrije University Brussels VUB, Brussels, Belgium

  150. 150

    R Vescio, Cedars-Sinai Cancer Center, Los Angeles, CA, USA

  151. 151

    D Vesole, Hackensack Cancer Center, Hackensack, NJ, USA

  152. 152

    P Voorhees, University of North Carolina, Chapel Hill, NC, USA

  153. 153

    A Waage, University Hospital, Trondheim, Norway NSMG

  154. 154

    M Wang, MD Anderson, Houston, TX, USA

  155. 155

    D Weber, MD Anderson, Houston, TX, USA

  156. 156

    J Westin, Sahlgrenska University Hospital, Gothenburg, Sweden

  157. 157

    K Wheatley, University of Birmingham, Birmingham, UK

  158. 158

    E Zamagni, University of Bologna, Bologna, Italy

  159. 159

    J Zonder, Karmanos Cancer Institute, Detroit, MI, USA

  160. 160

    S Zweegman, VU University Medical Center, Amsterdam, The Netherlands

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Fernández de Larrea, C., Kyle, R., Durie, B. et al. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group. Leukemia 27, 780–791 (2013). https://doi.org/10.1038/leu.2012.336

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