[en] Primary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. We could identify two retrospective series where the question about what number of circulating plasma cells in peripheral blood should be used for defining PCL. The presence of ≥5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL. Therefore, PCL should be defined by the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma.
Disciplines :
Hematology
Author, co-author :
Fernández de Larrea, Carlos
Kyle, Robert
Rosiñol, Laura
Paiva, Bruno
Engelhardt, Monika
Usmani, Saad
Caers, Jo ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Noel P, Kyle RA. Plasma cell leukemia: an evaluation of response to therapy. Am J Med. 1987;83(Dec):1062–8. DOI: 10.1016/0002-9343(87)90942-9
Kyle RA, Maldonado JE, Bayrd ED. Plasma cell leukemia. Report on 17 cases. Arch Intern Med. 1974;133(May):813–8. DOI: 10.1001/archinte.133.5.813
Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003;121:749–57.
Jurczyszyn A, Radocha J, Davila J, Fiala MA, Gozzetti A, Grzasko N, et al. Prognostic indicators in primary plasma cell leukaemia: a multicentre retrospective study of 117 patients. Br J Haematol. 2018;180(Mar):831–9. DOI: 10.1111/bjh.15092
Gonsalves WI, Rajkumar SV, Go RS, Dispenzieri A, Gupta V, Singh PP, et al. Trends in survival of patients with primary plasma cell leukemia: a population-based analysis. Blood. 2014;124(Aug):907–12. DOI: 10.1182/blood-2014-03-565051
Garcia-Sanz R, Orfao A, Gonzalez M, Tabernero MD, Blade J, Moro MJ, et al. Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. Blood. 1999;93(Feb):1032–7. DOI: 10.1182/blood.V93.3.1032
Dimopoulos MA, Palumbo A, Delasalle KB, Alexanian R. Primary plasma cell leukaemia. Br J Haematol. 1994;88(Dec):754–9. DOI: 10.1111/j.1365-2141.1994.tb05114.x
Blade J, Kyle RA. Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia. Hematol/Oncol Clin North Am. 1999;13(Dec):1259–72. DOI: 10.1016/S0889-8588(05)70125-8
Fernandez de Larrea C, Kyle RA, Durie BG, Ludwig H, Usmani S, Vesole DH, et al. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group. Leukemia. 2013;27(Apr):780–91. DOI: 10.1038/leu.2012.336
Mina R, Joseph NS, Kaufman JL, Gupta VA, Heffner LT, Hofmeister CC, et al. Survival outcomes of patients with primary plasma cell leukemia (pPCL) treated with novel agents. Cancer. 2019;125(Feb):416–23. DOI: 10.1002/cncr.31718
Tiedemann RE, Gonzalez-Paz N, Kyle RA, Santana-Davila R, Price-Troska T, Van Wier SA, et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia. 2008;22(May):1044–52. DOI: 10.1038/leu.2008.4
Sanoja-Flores L, Flores-Montero J, Garces JJ, Paiva B, Puig N, Garcia-Mateo A, et al. Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC). Blood Cancer J. 2018;8(Nov):117. DOI: 10.1038/s41408-018-0153-9
Billadeau D, Van Ness B, Kimlinger T, Kyle RA, Therneau TM, Greipp PR, et al. Clonal circulating cells are common in plasma cell proliferative disorders: a comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma. Blood. 1996;88(Jul):289–96. DOI: 10.1182/blood.V88.1.289.289
Gonsalves WI, Rajkumar SV, Dispenzieri A, Dingli D, Timm MM, Morice WG, et al. Quantification of circulating clonal plasma cells via multiparametric flow cytometry identifies patients with smoldering multiple myeloma at high risk of progression. Leukemia. 2017;31(Jan):130–5. DOI: 10.1038/leu.2016.205
An G, Qin X, Acharya C, Xu Y, Deng S, Shi L, et al. Multiple myeloma patients with low proportion of circulating plasma cells had similar survival with primary plasma cell leukemia patients. Ann Hematol. 2015;94(Feb):257–64. DOI: 10.1007/s00277-014-2211-0
Granell M, Calvo X, Garcia-Guinon A, Escoda L, Abella E, Martinez CM, et al. Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition. Haematologica. 2017;102(Jun):1099–104. DOI: 10.3324/haematol.2016.158303
Ravi P, Kumar SK, Roeker L, Gonsalves W, Buadi F, Lacy MQ, et al. Revised diagnostic criteria for plasma cell leukemia: results of a Mayo Clinic study with comparison of outcomes to multiple myeloma. Blood Cancer J. 2018;8(Nov):116. DOI: 10.1038/s41408-018-0140-1
Holtzman NG, Goloubeva O, Singh Z, Sawhney S, Zou Y, Yared J, et al. Plasma Cell Leukemia (PCL): clinical characteristics, outcomes, and the impact of circulating plasma cells (CPC) percentage—a single center experience. Blood. 2017;130:3035. Supplement 1.
Ge A, Huang VY, Martin T, Wolf JL, Shah N, Wong SW. Outcomes of plasma cell leukemia patients in the era of next-generation novel agents: a single-center retrospective cohort study. Blood. 2020;136:6–7. DOI: 10.1182/blood-2020-141525
Usmani SZ, Nair B, Qu P, Hansen E, Zhang Q, Petty N, et al. Primary plasma cell leukemia: clinical and laboratory presentation, gene-expression profiling and clinical outcome with Total Therapy protocols. Leukemia. 2012;26(Nov):2398–405. DOI: 10.1038/leu.2012.107
Lionetti M, Musto P, Di Martino MT, Fabris S, Agnelli L, Todoerti K, et al. Biological and clinical relevance of miRNA expression signatures in primary plasma cell leukemia. Clin Cancer Res. 2013;19(Jun):3130–42. DOI: 10.1158/1078-0432.CCR-12-2043
Todoerti K, Calice G, Trino S, Simeon V, Lionetti M, Manzoni M, et al. Global methylation patterns in primary plasma cell leukemia. Leuk Res. 2018;73(Oct):95–102. DOI: 10.1016/j.leukres.2018.09.007
van de Donk NW, Lokhorst HM, Anderson KC, Richardson PG. How I treat plasma cell leukemia. Blood. 2012;120(Sep):2376–89. DOI: 10.1182/blood-2012-05-408682
Mahindra A, Kalaycio ME, Vela-Ojeda J, Vesole DH, Zhang MJ, Li P, et al. Hematopoietic cell transplantation for primary plasma cell leukemia: results from the Center for International Blood and Marrow Transplant Research. Leukemia. 2012;26(May):1091–7. DOI: 10.1038/leu.2011.312
Katodritou E, Terpos E, Kelaidi C, Kotsopoulou M, Delimpasi S, Kyrtsonis MC, et al. Treatment with bortezomib-based regimens improves overall response and predicts for survival in patients with primary or secondary plasma cell leukemia: analysis of the Greek myeloma study group. Am J Hematol. 2014;89(Feb):145–50. DOI: 10.1002/ajh.23600
D'Arena G, Valentini CG, Pietrantuono G, Guariglia R, Martorelli MC, Mansueto G, et al. Frontline chemotherapy with bortezomib-containing combinations improves response rate and survival in primary plasma cell leukemia: a retrospective study from GIMEMA Multiple Myeloma Working Party. Ann Oncol. 2012;23(Jun):1499–502. DOI: 10.1093/annonc/mdr480
Musto P, Simeon V, Martorelli MC, Petrucci MT, Cascavilla N, Di Raimondo F, et al. Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia. Leukemia. 2014;28(Jan):222–5. DOI: 10.1038/leu.2013.241
Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, et al. Bortezomib, doxorubicin, cyclophosphamide, dexamethasone induction followed by stem cell transplantation for primary plasma cell leukemia: a Prospective Phase II Study of the Intergroupe Francophone du Myelome. J Clin Oncol. 2016;34(Jun):2125–32. DOI: 10.1200/JCO.2015.63.1929
Drake MB, Iacobelli S, van Biezen A, Morris C, Apperley JF, Niederwieser D, et al. Primary plasma cell leukemia and autologous stem cell transplantation. Haematologica. 2010;95(May):804–9. DOI: 10.3324/haematol.2009.013334
Gonsalves WI, Rajkumar SV, Gupta V, Morice WG, Timm MM, Singh PP, et al. Quantification of clonal circulating plasma cells in newly diagnosed multiple myeloma: implications for redefining high-risk myeloma. Leukemia. 2014;28(Oct):2060–5. DOI: 10.1038/leu.2014.98
Nowakowski GS, Witzig TE, Dingli D, Tracz MJ, Gertz MA, Lacy MQ, et al. Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood. 2005;106(Oct):2276–9. DOI: 10.1182/blood-2005-05-1858
Vagnoni D, Travaglini F, Pezzoni V, Ruggieri M, Bigazzi C, Dalsass A, et al. Circulating plasma cells in newly diagnosed symptomatic multiple myeloma as a possible prognostic marker for patients with standard-risk cytogenetics. Br J Haematol. 2015;170(Aug):523–31. DOI: 10.1111/bjh.13484
Sanoja-Flores L, Flores-Montero J, Garcés JJ, Paiva B, Puig N, García-Mateo A. et al. Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC). Blood Cancer J. 2018;8(Nov):117. DOI: 10.1038/s41408-018-0153-9
Touzeau C, Pellat-Deceunynck C, Gastinne T, Accard F, Jego G, Avet-Loiseau H, et al. Reactive plasmacytoses can mimick plasma cell leukemia: therapeutical implications. Leuk Lymphoma. 2007;48(Jan):207–8. DOI: 10.1080/10428190601016159
Shtalrid M, Shvidel L, Vorst E. Polyclonal reactive peripheral blood plasmacytosis mimicking plasma cell leukemia in a patient with Staphylococcal sepsis. Leuk Lymphoma. 2003;44(Feb):379–80. DOI: 10.1080/1042819021000029713