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      Primary plasma cell leukemia: consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage

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          Abstract

          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.

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          Most cited references35

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          Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group.

          (2003)
          The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is /= 30 g/l and/or bone marrow clonal cells >/= 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.
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            Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group.

            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 × 10(9)/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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              Genetic aberrations and survival in plasma cell leukemia.

              Plasma cell leukemia (PCL) is an aggressive and rare hematological malignancy that originates either as primary disease (pPCL) or as a secondary leukemic transformation (sPCL) of multiple myeloma (MM). We report here the genetic aberrations and survival of 80 patients with pPCL or sPCL and make comparisons with 439 cases of MM. pPCL presents a decade earlier than sPCL (54.7 vs 65.3 years) and is associated with longer median overall survival (11.1 vs 1.3 months; P<0.001). 14q32 (IgH) translocations are highly prevalent in both sPCL and pPCL (82-87%); in pPCL IgH translocations almost exclusively involve 11q13 (CCND1), supporting a central etiological role, while in sPCL multiple partner oncogenes are involved, including 11q13, 4p16 (FGFR3/MMSET) and 16q23 (MAF), recapitulating MM. Both show ubiquitous inactivation of TP53 (pPCL 56%; sPCL 83%) by coding mutation or 17p13 deletion; complemented by p14ARF epigenetic silencing in sPCL (29%). Both show frequent N-RAS or K-RAS mutation. Poor survival in pPCL was predicted by MYC translocation (P=0.006). Survival in sPCL was consistently short. Overall pPCL and sPCL are different disorders with distinct natural histories, genetics and survival.
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                Author and article information

                Contributors
                cfernan1@clinic.cat
                Journal
                Blood Cancer J
                Blood Cancer J
                Blood Cancer Journal
                Nature Publishing Group UK (London )
                2044-5385
                2 December 2021
                2 December 2021
                December 2021
                : 11
                : 12
                : 192
                Affiliations
                [1 ]GRID grid.10403.36, Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Clínic of Barcelona, , Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), ; Barcelona, Spain
                [2 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Internal Medicine, Division of Hematology, Mayo Clinic, ; Rochester, MN USA
                [3 ]GRID grid.411730.0, ISNI 0000 0001 2191 685X, Centro de Investigacion Medica Aplicada Instituto de Investigacion Sanitaria de Navarra, , Clínica Universidad de Navarra, ; Pamplona, Spain
                [4 ]GRID grid.7708.8, ISNI 0000 0000 9428 7911, Medical Department, Hematology, Oncology & Stem Cell Transplantation, , University Medical Center Freiburg, ; Freiburg, Germany
                [5 ]GRID grid.468189.a, Hematogic Oncology and Blood Disorders, Levine Cancer Institute, ; Charlotte, NC USA
                [6 ]GRID grid.411374.4, ISNI 0000 0000 8607 6858, Department of Hematology, , CHU de Liège, ; Liège, Belgium
                [7 ]GRID grid.55325.34, ISNI 0000 0004 0389 8485, Oslo Myeloma Centre, Department of Hematology, , Oslo University Hospital, ; Oslo, Norway
                [8 ]GRID grid.8982.b, ISNI 0000 0004 1762 5736, Department of Molecular Medicine, , University of Pavia, ; Pavia, Italy
                [9 ]GRID grid.21729.3f, ISNI 0000000419368729, Department of Medicine, , Columbia University, ; New York, NY USA
                [10 ]GRID grid.411258.b, Department of Hematology, , Hospital Universitario de Salamanca-IBSAL, IBMCC (USAL-CSIC), ; Salamanca, Spain
                [11 ]GRID grid.412370.3, ISNI 0000 0004 1937 1100, Service d’Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, ; Paris, France
                [12 ]GRID grid.277151.7, ISNI 0000 0004 0472 0371, Department of Hematology, , University Hospital Nantes, ; Nantes, France
                [13 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Hematology, , Erasmus Medical Center, ; ZuidHolland, The Netherlands
                [14 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, Greenebaum Cancer Center, , University of Maryland, ; Baltimore, MD USA
                [15 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Department of Medicine, , Karolinska Institutet, ; Stockholm, Sweden
                [16 ]GRID grid.5253.1, ISNI 0000 0001 0328 4908, Internal Medicine V, , University Hospital Heidelberg, ; Heidelberg, Germany
                [17 ]GRID grid.410711.2, ISNI 0000 0001 1034 1720, Lineberger Comprehensive Cancer Center, , University of North Carolina, ; Chapel Hill, NC USA
                [18 ]GRID grid.411760.5, ISNI 0000 0001 1378 7891, Department of Internal Medicine II, , University Hospital Würzburg, ; Würzburg, Germany
                [19 ]GRID grid.50956.3f, ISNI 0000 0001 2152 9905, Hematology/Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai 2 Medical Center, ; Los Angeles, CA USA
                [20 ]GRID grid.29857.31, ISNI 0000 0001 2097 4281, Bone Marrow Transplant Program, Penn State Cancer Institute, ; Hershey, PA USA
                [21 ]IRCCS-CROB, Referral Cancer Center of Basilicata, Vulture, Italy
                [22 ]GRID grid.416409.e, ISNI 0000 0004 0617 8280, Department of Haematology, , St. James’s Hospital, ; Dublin, Ireland
                [23 ]GRID grid.18886.3f, Myeloma Molecular Therapy Group, The Institute of Cancer Research, ; London, UK
                Author information
                http://orcid.org/0000-0003-4930-9255
                http://orcid.org/0000-0002-2534-9239
                http://orcid.org/0000-0003-1977-3815
                http://orcid.org/0000-0003-0405-1676
                http://orcid.org/0000-0002-5484-8731
                http://orcid.org/0000-0002-3175-1195
                http://orcid.org/0000-0003-1096-0569
                http://orcid.org/0000-0001-7680-3254
                http://orcid.org/0000-0003-1708-7344
                http://orcid.org/0000-0002-0808-2237
                http://orcid.org/0000-0003-0961-0035
                http://orcid.org/0000-0003-2109-1573
                http://orcid.org/0000-0002-7680-0819
                http://orcid.org/0000-0002-2804-2531
                http://orcid.org/0000-0002-3677-4804
                http://orcid.org/0000-0002-9183-4857
                http://orcid.org/0000-0002-5862-1833
                http://orcid.org/0000-0003-2390-1218
                Article
                587
                10.1038/s41408-021-00587-0
                8640034
                34857730
                d6be4a85-3645-4b3c-9277-6618b7de9138
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 August 2021
                : 10 November 2021
                : 15 November 2021
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                cell biology,myeloma,cancer genetics
                Oncology & Radiotherapy
                cell biology, myeloma, cancer genetics

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