Review Articles
Vol. 17 No. 1 (2025): Review Articles, Original Article, Scientific Letter, Case Reports Letter to the Editor
PLASMA CELL LEUKEMIA UPDATE ON IMMUNOPHENOTYPE, MOLECULAR CHARACTERISTICS, AND THERAPY. The second part of plasma cell neoplasms with spreading in the blood and tissues
Plasma Cell Leukemia
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: October 31, 2025
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Plasma cell leukemia (PCL) is a rare and aggressive form of multiple myeloma (MM), characterized by the presence of malignant plasma cells in the peripheral blood. Until 2021, PCL was defined by having plasmacytosis making up at least 20% of the differential white blood cell count . PCL was found in 2-4% of newly diagnosed MM cases (primary PCL). It can also develop from a preexisting, usually end-stage, MM, known as secondary PCL (sPCL), which exhibits distinct biological and clinical features. Both primary plasma cell leukemia (pPCL) and secondary plasma cell leukemia (sPCL) are very rare presentations of MM. However, the rate of MM transforming into sPCL is increasing as patients are living longer. According to the International Myeloma Working Group, plasma cell leukemia is generally diagnosed when the percentage of CPCs in peripheral blood exceeds 5%. PCL has a more aggressive clinical presentation than MM, involving more severe cytopenia, hypercalcemia, and renal failure. Higher tumor burden and proliferation activity in PCL are reflected by elevated levels of B2-microglobulin and lactate dehydrogenase (LDH). Extramedullary localization at diagnosis is more common in pPCL and sPCL than in MM. Conversely, osteolytic lesions are less frequent in pPCL. The immunophenotype of PCL expresses the common MM markers, CD38 and CD138. Still, it exhibits a more immature phenotype than MM. Molecularly, PCL lacks a specific marker but shows a markedly lower frequency of hyperploidy, gains of chromosome 1, and translocations t(14;16) or t(14;20). The recent therapy of PCL is similar to that of other high-grade myelomas, taking advantage of anti-proteasome, like bortezomib, an immunomodulator, like lenalidomide, and dexamethasone triplet + anti-CD38 antibody and/or cyclophosphamide, and hematopoietic stem cell transplantation. However, the results are not as good as in the other forms of myeloma.
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Kyle RA, Maldonado JE, Bayrd ED. Plasma cell leukemia. Report on 17 cases. Arch Intern Med. 1974 May;133(5):813-8. doi: 10.1001/archinte.133.5.813.
de Larrea CF, 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;27:780–9
Gertz MA, Buadi FK. Plasma cell leukemia. Haematologica. 2010; 95:705–707. doi:10.3324/haematol.2009.021618
Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010;116:3724–3734. doi:10.1182/blood-2010-0528263
de Larrea CF, Kyle R, Rosiñol L, et al. Primary plasma cell leukemia: consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage. Blood Cancer J. 2021;11:192. doi:10.1038/s41408-021-00587-0.
Musto P, Engelhardt M, van de Donk NWCJ, Gay F, Terpos E, Einsele H, Fernández de Larrea C, Sgherza N, Bolli N, Katodritou E, Gentile M, Royer B, Derudas D, Jelinek T, Zamagni E, Rosiñol L, Paiva B, Caers J, Kaiser M, Beksac M, Hájek R, Spencer A, Ludwig H, Cavo M, Bladé J, Moreau P, Mateos MV, San-Miguel JF, Dimopoulos MA, Boccadoro M, Sonneveld P. European Myeloma Network Group review and consensus statement on primary plasma cell leukemia. Ann Oncol. 2025 Apr;36(4):361-374. doi: 10.1016/j.annonc.2025.01.022.
Bohra A, Hassan R, Zanwar S, Jevremovic D, Olteanu H, Gonsalves WI, Otteson G, Horna P, Rajkumar SV, Kumar S. Peripheral Blood Flow Cytometry-based Definition of Plasma Cell Leukemia. Leukemia. 2025 May 26. doi: 10.1038/s41375-025-02653-z
Bruinink DH, Kuiper R, van Duin M, Cupedo T, van der Velden V, Hoogenboezem R, van der Holt B, Berveloo O, Valent ET, Vermeulen M, et al. Identification of high-risk multiple myeloma with a plasma cell leukemia-like transcriptomic profile. J Clin Oncol 2022; 40: 3132-3150
Liang D, Yan Y, Bai S, Xu W, Wang Q, Feng D, Bu Y, Zeng M, Nie X, Feng Y,
Chen X, Xia Z, Liang Y, Jin F, Wang H. Clinical outcome of ≥2% circulating tumor
cells in newly diagnosed multiple myeloma: insights from a multicenter study.
Ann Med. 2025 Dec;57(1):2496796. doi: 10.1080/07853890.2025.2496796
Jin X, Jiang X, Li H, Shen K, Liu S, Chen M, Yang C, Han B, Zhuang J. Prognostic Implications of Circulating Plasma Cell Percentage in Multiple Myeloma and Primary Plasma Cell Leukemia Defined by New Criteria. Acta Haematol. 2025;148(1):48-57. doi: 10.1159/000538658. Epub 2024 Apr 1
Jelinek T, Bezdekova R, Zihala D, Seccikova T, Sithara AA, Pospisilova L, Sevcikova S, Pothakova P, Stork M, Knecktova Z, et al. More than 2% of circulating tumor plasma cell leukemia-like multiple myeloma. J Clin Oncol 2023; 41: 13831392
Deng J, Qin X, Ma G, Shen X, Sun J, Zhao Y, Zhang Z, Sun Y, Jie G, Su L, Ma
J, Tian W, Yang L, Wang Q, Huang H, Shi M, Ma Y, Gao W, Chen W. Development of a clinical prognostic model for primary plasma cell leukemia patients treated with
novel agents: a multicenter retrospective cohort study. Ann Hematol. 2024 July 19
Sep;103(9):3691-3699. doi: 10.1007/s00277-024-05862-1. Epub 2024
Cazaubiel T, Leleu X, Perrot A, Manier S, Buisson L, Maheo S, Do Souto Ferreira L, Lannes R, Pavageau L, Hulin C, et al. Primary plasma cell leukemias displaying t(11;14) have specific genomic, transcriptional and clinical features. Blood 2022; 139 (17): 2666- 2672.
Gonzalez-Paz NC, Van Wier S, Santana-Davila R, Ahmann G, Price-Troska T, Henderson K, Gertz M, Kyle R, Greipp P, et al. Plasma cells from secondary plasma cell leukemia display different cytogenetics pattern when compared with primary plasma cell leukemia. Blood 2005; 106: 3267.
Tessier C, LeBlanc R, Roy J, Trudel S, Côté J, Lalancette M, Boudreault JS, Lemieux-Blanchard É, Kaedbey R, Pavic M. Poor outcome despite modern treatments: A retrospective study of 99 patients with primary and secondary plasma cell leukemia. Cancer Med. 2024; 13(17):e70192. doi: 10.1002/cam4.70192.
Manimaran P, Rai V, Ranka R, Sawhney J. Plasma Cell Leukemia-Clinicopathological Profile from a Tertiary Care Center in Western India. South Asian J Cancer. 2023 Jun 9;12(3):280-285. doi: 10.1055/s-0043-57231.
Valentini CG, Bozzoli V, Fianchi L, Voso MT, Di Paolantonio G, Criscuolo M, Leone G, Larocca LM, Pagano L. Primary plasma cell leukemia followed by testicular
plasmacytoma. Int J Hematol. 2011 Feb;93(2):224-227. doi: 10.1007/s12185-010-0745-z.
Ca Vela-Ojeda J, Ramirez-Alvarado A, Sanchez-Rodriguez AS, Garcia-Chavez J,
Montiel-Cervantes LA. Extraosseous Plasmacytoma Confers Poor Outcomes in Primary
Plasma Cell Leukemia. Arch Med Res. 2025 Mar 24;56(5):103207. doi:10.1016/j.arcmed.2025.103207
Rasillo A, Tabernero MD, Sánchez ML, Pérez de Andrés M, Martín Ayuso M, Hernández J, Moro MJ, Fernández-Calvo J, Sayagués JM, Bortoluci A, San Miguel JF, Orfao A. Fluorescence in situ hybridization analysis of aneuploidization patterns in monoclonal gammopathy of undetermined significance versus multiple myeloma and plasma cell leukemia. Cancer. 2003 Feb 1;97(3):601-9. doi: 10.1002/cncr.11100.
García-Sanz R, Orfão A, González M, Tabernero MD, Bladé J, Moro MJ, Fernández-Calvo J, Sanz MA, Pérez-Simón JA, Rasillo A, Miguel JF. Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. Blood. 1999 Feb 1;93(3):1032-7
Evans LA, Jevremovic D, Nandakumar B, Dispenzieri A, Buadi FK, Dingli D, Lacy MQ, Hayman SR, Kapoor P, Leung N, Fonder A, Hobbs M, Hwa YL, Muchtar E, Warsame R, Kourelis TV, Go R, Russell S, Lust JA, Lin Y, Siddiqui M, Kyle RA, Gertz MA, Rajkumar SV, Kumar SK, Gonsalves WI. Utilizing multiparametric flow cytometry in the diagnosis of patients with primary plasma cell leukemia. Am J Hematol. 2020 Jun;95(6):637-642. doi: 10.1002/ajh.25773.
Bezdekova R, Jelinek T, Kralova R, Stork M, Polackova P, Vsianska P, Brozova L, Jarkovsky J, Almasi M, Boichuk I, Knechtova Z, Penka M, Pour L, Sevcikova S, Hajek R, Rihova L. Necessity of flow cytometry assessment of circulating plasma cells and its connection with clinical characteristics of primary and secondary plasma cell leukaemia. Br J Haematol. 2021 Oct;195(1):95-107. doi: 10.1111/bjh.17713
Cazuabiel T, Buisson L, Maheo S, Do Souto Ferreira L, Lannes R, Perrot A, Hulin C, Avet- Loiuseau H, Corre J. The genomic and transcriptomic landscape of plasma cell leukemia. Blood 2020; 136 (suppl.1): 48-49.
Chu B, Wang Y, Shi L, Sun K, Bao L. Combination of circulating plasma cells enhances the efficacy of R2-ISS stage system for risk classification of newly diagnosed multiple myeloma: a single-center real-world study. Blood 2023; 142 (suppl.1): 4740.
Schinke C, Boyle EM, Ashby C. Wang Y, Lyzogubov V, Wandell C, Qu P, Hoering A, Deshpande S, Ryank K, et al. Genomic analysis of primary plasma cell leukemia reveals complex structural alterations and high-risk mutational patterns. Blood Cancer J 2020; 10:70
Cazaubiel T, Leleu X, Perrot A, Manier S, Buisson L, Maheo S, Do Souto Ferreira L, Lannes R, Pavageau L, Hulin C, et al. Primary plasma cell leukemias displaying t(11;14) have specific genomic, transcriptional and clinical features. Blood 2022; 109: 2666-2672
Van de Donk N, Minnema MC, van der Holt B, Schjesvold F, Wu KL, Broijl A, Roeloffzen W, Gradisseur A, Pietrantuono G, et al. Treatment of primary plasma cell leukemia with carfilzomib and lenalidomide-based therapy (EMN12/HOVON-129): final analysis of a non-randomised, multicentre, phase 2 study. Lancet Oncol 2023, 24: 1119-1133
Papadhimitriou SI, Terpos E, Liapis K, Pavlidis D, Marinakis T, Kastritis E, Dimopoulos MA, Tsitsilonis QE, Kostopoulos IV. The cytogenetic profile of primary and secondary plasma cell leukemia: etiopathogenetic perspectives, prognostic impact and clinical relevance to newly diagnosed multiple myeloma with differential circulating clonal plasma cells. Biomedicines 2022; 10: 209.
Skerget S, Penaherrera D, Chari A, et Al. Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes. Nat Genet. 2024 Sep;56(9):1878-1889
Skerget S, Peneherrera D, Mikhael J, Keats JJ. High-risk gene expression subtype provides molecular basis for different clinical presentation of primary and secondary plasma cell leukemia. Blood 2021; 138(suppl.1): 726.
Lee Y, Lee N, Yoon SS, Yoon SH, Lee DS. Distinct genetic features in peripheral blood represent the characteristics of circulating plasma cells in primary plasma cell leukemia. Blood 2023; 142( suppl.1): 3349.
Rojas EA, Gutiérrez NC. Genomics of Plasma Cell Leukemia. Cancers (Basel). 2022 Mar 21;14(6):1594. doi: 10.3390/cancers14061594.
D'Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, Zamagni E, Mateos MV, Dall'Olio D, van de Donk NWCJ, Jackson G, Rocchi S, Salwender H, Bladé Creixenti J, van der Holt B, Castellani G, Bonello F, Capra A, Mai EK, Dürig J, Gay F, Zweegman S, Cavo M, Kaiser MF, Goldschmidt H, Hernández Rivas JM, Larocca A, Cook G, San-Miguel JF, Boccadoro M, Sonneveld P. Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project. J Clin Oncol. 2022 Oct 10;40(29):3406-3418. doi: 10.1200/JCO.21.02614. Epub 2022 May 23. Erratum in: J Clin Oncol. 2022 Dec 1;40(34):4032. doi: 10.1200/JCO.22.02228.
Jurczyszyn A, Olszewska-Szopa M, Vesole DH. The Current State of Knowledge About Evolution of Multiple Myeloma to Plasma Cell Leukemia. Clin Lymphoma Myeloma Leuk. 2023 Mar;23(3):188-193. doi: 10.1016/j.clml.2022.12.002.
Granell M, Calvo X, Garcia-Guiñón A, Escoda L, Abella E, Martínez CM, Teixidó M, Gimenez MT, Senín A, Sanz P, Campoy D, Vicent A, Arenillas L, Rosiñol L, Sierra J, Bladé J, de Larrea CF; GEMMAC (Grup per l’estudi del mieloma i l’amiloïdosi de Catalunya). Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition. Haematologica. 2017 Jun;102(6):1099-1104. doi: 10.3324/haematol.2016.158303
Jurczyszyn A, Radocha J, Davila J, Fiala MA, Gozzetti A, Grząśko N, Robak P, Hus I, Waszczuk-Gajda A, Guzicka-Kazimierczak R, Atilla E, Mele G, Sawicki W, Jayabalan DS, Charliński G, Szabo AG, Hajek R, Delforge M, Kopacz A, Fantl D, Waage A, Avivi I, Rodzaj M, Leleu X, Richez V, Knopińska-Posłuszny W, Masternak A, Yee AJ, Barchnicka A, Druzd-Sitek A, Guerrero-Garcia T, Liu J, Vesole DH, Castillo JJ. Prognostic indicators in primary plasma cell leukaemia: a multicentre retrospective study of 117 patients. Br J Haematol. 2018 Mar;180(6):831-839. doi: 10.1111/bjh.15092.
Katodritou E, Terpos E, Delimpasi S, Kotsopoulou M, Michalis E, Vadikolia C, Kyrtsonis MC, Symeonidis A, Giannakoulas N, Vadikolia C, Michael M, Kalpadakis C, Gougopoulou T, Prokopiou C, Kaiafa G, Christoulas D, Gavriatopoulou M, Giannopoulou E, Labropoulou V, Verrou E, Kastritis E, Konstantinidou P, Anagnostopoulos A, Dimopoulos MA. Real-world data on prognosis and outcome of primary plasma cell leukemia in the era of novel agents: a multicenter national study by the Greek Myeloma Study Group. Blood Cancer J. 2018 Mar 9;8(3):31. doi: 10.1038/s41408-018-0059-6.
Tian M, An G, Fu W, Yan W, Li L, Sun C, Li Z, Chen L, Liao A, Gao G, Qin X, Li M, Li C, Xue H, Gao L, Wang Y, He A, Zhou F, Guo D, Dong Y, Fang Z, Chu X, Mi J, Fu C, Zeng H, Hou S, Wang X, Wang H, Wei Y, Liang X, Yi X, Sun Y, Qiu L, Dai Y, Jin F. Development and validation of a prognostic staging system for primary plasma cell leukemia. J Hematol Oncol. 2025 Jul 15;18(1):72. doi: 10.1186/s13045-025-01723-0
Saba L, Landau KS, Liang H, Fu CL, Chaulagain CP. Real world analysis on the determinants of survival in primary plasma cell leukemia in the United States. Leukemia. 2024 Feb;38(2):435-437. doi: 10.1038/s41375-023-02100-x.
Dimopoulos MA, Palumbo A, Delasalle KB, Alexanian R. Primary plasma cell leukaemia. Br J Haematol. 1994 Dec;88(4):754-9. doi: 10.1111/j.1365-2141.1994.tb05114.x
Sica S, Chiusolo P, Salutari P, Piccirillo N, Laurenti L, Ortu La Barbera E, Serra FG, Leone G. Long-lasting complete remission in plasma cell leukemia after aggressive chemotherapy and CD34-selected autologous peripheral blood progenitor cell transplant: molecular follow-up of minimal residual disease. Bone Marrow Transplant. 1998 Oct;22(8):823-5. doi: 10.1038/sj.bmt.1701420.
Usmani SZ, Nair B, Qu P, Hansen E, Zhang Q, Petty N, Waheed S, Shaughnessy JD Jr, Alsayed Y, Heuck CJ, van Rhee F, Milner T, Hoering A, Szymonifka J, Sexton R, Sawyer J, Singh Z, Crowley J, Barlogie B. Primary plasma cell leukemia: clinical and laboratory presentation, gene-expression profiling and clinical outcome with Total Therapy protocols. Leukemia. 2012 Nov;26(11):2398-405. doi: 10.1038/leu.2012.107
Pagano L, Valentini CG, De Stefano V, Venditti A, Visani G, Petrucci MT, Candoni A, Specchia G, Visco C, Pogliani EM, Ferrara F, Galieni P, Gozzetti A, Fianchi L, De Muro M, Leone G, Musto P, Pulsoni A; for GIMEMA-ALWP (Gruppo Italiano Malattie EMatologiche dell'Adulto, Acute Leukemia Working Party: coordinator Sergio Amadori). Primary plasma cell leukemia: a retrospective multicenter study of 73 patients. Ann Oncol. 2011 Jul;22(7):1628-1635. doi: 10.1093/annonc/mdq646.
Musto P, Rossini F, Gay F, et al: Efficacy and safety of bortezomib in patients with plasma cell leukemia. Cancer 2007; 109:2285-2290.
Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet. 2009 Jul 25;374(9686):324-39. doi: 10.1016/S0140-6736(09)60221-X.
D'Arena G, Valentini CG, Pietrantuono G, Guariglia R, Martorelli MC, Mansueto G, Villani O, Onofrillo D, Falcone A, Specchia G, Semenzato G, Di Renzo N, Mastrullo L, Venditti A, Ferrara F, Palumbo A, Pagano L, Musto P. 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 Jun;23(6):1499-502. doi: 10.1093/annonc/mdr480.
Musto P, Simeon V, Todoerti K, Neri A. Primary Plasma Cell Leukemia: Identity Card 2016. Curr Treat Options Oncol. 2016 Apr;17(4):19. doi: 10.1007/s11864-016-0392-6
Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, Brechignac S, Belhadj K, Chretien ML, Wetterwald M, Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP. 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 Myélome. J Clin Oncol. 2016 Jun 20;34(18):2125-32. doi: 10.1200/JCO.2015.63.1929.
Pagano L, Maraglino AME, Fianchi L, Criscuolo M, Rossi E, Za T, Chiusolo P, Bonanni M, Dragonetti G, Bacigalupo A, Sica S, De Stefano V. Treatment of primary plasma cell leukemia with high doses of cyclophosphamide, bortezomib, and dexamethasone followed by double autologous HSCT. Ann Hematol. 2020 Jan;99(1):207-209. doi: 10.1007/s00277-019-03885-7.
Houbaida Y., Del Giudice M.L., Galimberti S., Buda G. How first-line therapy is changing in transplant-eligible multiple myeloma patients. Mediterr J Hematol Infect Dis 2025, 17(1): e2025026, DOI: http://dx.doi.org/10.4084/MJHID.2025.026
Mina R, Joseph NS, Kaufman JL, Gupta VA, Heffner LT, Hofmeister CC, Boise LH, Dhodapkar MV, Gleason C, Nooka AK, Lonial S. Survival outcomes of patients with primary plasma cell leukemia (pPCL) treated with novel agents. Cancer 2019; 125: 416-
Singh S, Peshin S, Wertheim BC, Larsen A, Chineke I, Sborov DW, Green D, Liedtke M, Okoniewski M, Wazir M, Nadeem O, Schachter LG, DeGraaff D, Vardell VA, Coffey DG, Gowin K. Outcomes and treatment patterns in primary and secondary plasma cell leukemia: insights from a large US cohort study. Haematologica. 2025 Sep 1;110(9):2129-2138. doi: 10.3324/haematol.2024.287158.
Parrondo RD, Moustafa MA, Reeder C, Sher T, Roy V, Muchtar E, Warsame R, Alegria V, Gonsalves W, Dingli D, Hayman S, Kapoor P, Chanan-Khan AA, Ailawadhi S. Efficacy of Daratumumab-Based Regimens for the Treatment of Plasma Cell Leukemia. Clin Lymphoma Myeloma Leuk. 2021 May;21(5):355-360. doi: 10.1016/j.clml.2021.01.002.
Cotte C, Hartley-Brown M. Plasma cell leukemia: Retrospective review of cases at Monter Cancer Center/Northwell Health Cancer Institute, 2014-2019. Curr Probl Cancer. 2022 Jun;46(3):100831. doi: 10.1016/j.currproblcancer.2021.100831.
Li AY, Kamangar F, Holtzman NG, Rapoport AP, Kocoglu MH, Atanackovic D, Badros AZ. A Clinical Perspective on Plasma Cell Leukemia: A Single-Center Experience. Cancers (Basel). 2024 Jun 5;16(11):2149. doi: 10.3390/cancers16112149.
Katodritou E, Kastritis E, Dalampira D, Delimpasi S, Spanoudakis E, Labropoulou V, Ntanasis-Stathopoulos I, Gkioka AI, Giannakoulas N, Kanellias N, Papadopoulou T, Sevastoudi A, Michalis E, Papathanasiou M, Kotsopoulou M, Sioni A, Triantafyllou T, Daiou A, Papadatou M, Kyrtsonis MC, Pouli A, Kostopoulos I, Verrou E, Dimopoulos MA, Terpos E. Improved survival of patients with primary plasma cell leukemia with VRd or daratumumab-based quadruplets: A multicenter study by the Greek myeloma study group. Am J Hematol. 2023 May;98(5):730-738. doi: 10.1002/ajh.26891.
Shalaby K, Azad F, Parker S, Wang C, Yu H, Attwood K, Hillengass J. Clinical Characteristics and Survival Outcomes of Patients With Primary and Secondary Plasma Cell Leukemia According to the 2021 Definition: A Single Center Retrospective Study. Clin Lymphoma Myeloma Leuk. 2025 Jan;25(1):67-75
Rees MJ, D'Agostino M, Leypoldt LB, Kumar S, Weisel KC, Gay F. Navigating High-Risk and Ultrahigh-Risk Multiple Myeloma: Challenges and Emerging Strategies. Am Soc Clin Oncol Educ Book. 2024 Jun;44(3):e433520. doi: 10.1200/EDBK_433520.
Usmani SZ, Hoering A, Ailawadhi S, Sexton R, Lipe B, Hita SF, Valent J, Rosenzweig M,, Zonder JA, Dhodapkar M, Callander N, Zimmerman T, Voorhees PM, Durie B, Rajkumar SV, Richardson PG, Orlowski RZ; SWOG1211 Trial Investigators. Bortezomib, lenalidomide, and dexamethasone with or without elotuzumab in patients with untreated, high-risk multiple myeloma (SWOG-1211): primary analysis of a randomised, phase 2 trial. Lancet Haematol. 2021 Jan;8(1):e45-e54. doi: 10.1016/S2352-3026(20)30354-9.
Kaiser MF, Hall A, Walker K, Sherborne A, De Tute RM, Newnham N, Roberts S, Ingleson E, Bowles K, Garg M, Lokare A, Messiou C, Houlston RS, Jackson G, Cook G, Pratt G, Owen RG, Drayson MT, Brown SR, Jenner MW. Daratumumab, Cyclophosphamide, Bortezomib, Lenalidomide, and Dexamethasone as Induction and Extended Consolidation Improves Outcome in Ultra-High-Risk Multiple Myeloma. J Clin Oncol. 2023 Aug 10;41(23):3945-3955. doi: 10.1200/JCO.22.02567.
Leypoldt LB, Tichy D, Besemer B, Hänel M, Raab MS, Mann C, Munder M, Reinhardt HC, Nogai A, Görner M, Ko YD, de Wit M, Salwender H, Scheid C, Graeven U, Peceny R, Staib P, Dieing A, Einsele H, Jauch A, Hundemer M, Zago M, Požek E, Benner A, Bokemeyer C, Goldschmidt H, Weisel KC.) Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2024 Jan 1;42(1):26-37. doi: 10.1200/JCO.23.01696.
Dhakal B, Patel S, Girnius S, Bachegowda L, Fraser R, Davila O, Kanate AS, Assal A, Hanbali A, Bashey A, Pawarode A, Freytes CO, Lee C, Vesole D, Cornell RF, Hildebrandt GC, Murthy HS, Lazarus HM, Cerny J, Yared JA, Schriber J, Berdeja J, Stockerl-Goldstein K, Meehan K, Holmberg L, Solh M, Diaz MA, Kharfan-Dabaja MA, Farhadfar N, Bashir Q, Munker R, Olsson RF, Gale RP, Bayer RL, Seo S, Chhabra S, Hashmi S, Badawy SM, Nishihori T, Gonsalves W, Nieto Y, Efebera Y, Kumar S, Shah N, Qazilbash M, Hari P, D'Souza A. Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era. Leukemia. 2020 Dec;34(12):3338-3347. doi: 10.1038/s41375-020-0830-0. Epub 2020 Apr 20. Erratum in: Leukemia. 2021 Jun;35(6):1828. doi: 10.1038/s41375-021-01233-1. Erratum in: Leukemia. 2021 Jul;35(7):2141. doi: 10.1038/s41375-021-01304-3.
Lawless S, Iacobelli S, Knelange NS, Chevallier P, Blaise D, Milpied N, Foà R, Cornelissen JJ, Lioure B, Benjamin R, Poiré X, Minnema MC, Collin M, Lenhoff S, Snowden JA, Santarone S, Wilson KMO, Trigo F, Dreger P, Böhmer LH, Putter H, Garderet L, Kröger N, Yaukoub-Agha I, Schönland S, Morris C. Comparison of autologous and allogeneic hematopoietic cell transplantation strategies in patients with primary plasma cell leukemia, with dynamic prediction modeling. Haematologica. 2023 Apr 1;108(4):1105-1114. doi: 10.3324/haematol.2021.280568.
Maegaki M, Takahashi T, Suzuki K, Minakata D, Terao T, Satake A, Akira H, Oyake T, Kanda Y, Aotsuka N, Tsukada N, Tabayashi T, Kobayashi H, Nawa Y, Ichinohe T, Ohbiki M, Atsuta Y, Kawamura K. Comparison of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation for Primary Plasma Cell Leukemia in Japan. Transplant Cell Ther. 2025 Sep 8:S2666-6367(25)01402-2. doi: 10.1016/j.jtct.2025.08.026.
Rees MJ, Kumar S. High-risk multiple myeloma: Redefining genetic, clinical, and functional high-risk disease in the era of molecular medicine and immunotherapy. Am J Hematol. 2024 Aug;99(8):1560-1575. doi: 10.1002/ajh.27327
Szita VR, Mikala G, Kozma A, Fábián J, Hardi A, Alizadeh H, Rajnics P, Rejtő L, Szendrei T, Váróczy L, Nagy Z, Illés Á, Vályi-Nagy I, Masszi T, Varga G. Targeted Venetoclax Therapy in t(11;14) Multiple Myeloma: Real World Data From Seven Hungarian Centers. Pathol Oncol Res. 2022 Feb 28;28:1610276. doi: 10.3389/pore.2022.1610276
Usmani SZ, Hoering A, Ailawadhi S, Sexton R, Lipe B, Hita SF, Valent J, Rosenzweig MAlvanidis G, Kotsos D, Frouzaki C, Fola A, Hatjiharissi E. The potential role of BCL-2 inhibition in amyloidosis and plasma cell leukemia. Front Oncol. 2025 Mar 21;15:1549891. doi: 10.3389/fonc.2025.1549891
Gonsalves WI, Buadi FK, Kumar SK. Combination therapy incorporating Bcl-2 inhibition with Venetoclax for the treatment of refractory primary plasma cell leukemia with t (11;14). Eur J Haematol. (2018) 100:215–7. doi: 10.1111/ejh.2018.100.issue-2
Nalghranyan S, Singh AP, Schinke C. The combination of venetoclax,
daratumumab and dexamethasone for the treatment of refractory primary plasma
cell leukemia. Am J Hematol. (2020) 95:E34–5. doi: 10.1002/ajh.25676
Valliani S, Ali M, Mahmoo O, Hinduja S, Chen CK, Damon L, et al. Efficacy of
venetoclax and dexamethasone in refractory IgM primary plasma cell leukemia with t
(11;14) and TP53 mutation: A case report and literature review. Case Rep Hematol.
(2020) 2020:8823877. doi: 10.1155/2020/882387735.
Tang ASO, Ahmad Asnawi AW, Koh AZY, Chong SL, Liew PK, Selvaratnam V,
et al. Plasma cell leukemia with successful upfront venetoclax in combination with
allogeneic transplantation. Am J Case Rep. (2023) 24:e938868. doi: 10.12659/AJCR.938868
Charalampous C, Doucette K, Chappell A, Vesole DH. Venetoclax-based induction therapy for primary plasma cell leukemia with high BCL-2 expression.
Leuk Lymphoma. (2024) 65(12):1901–4. doi: 10.1080/10428194.2024.2381647
Vo K, Guan T, Banerjee R, Lo M, Young R, Shah N. Complete response following
treatment of plasma cell leukemia with venetoclax and dexamethasone: A case report. J
Oncol Pharm Pract. (2022) 28:1244–8. doi: 10.1177/10781552221074269
Roy T, An JB, Doucette K, Chappell AM, Vesole DH. Venetoclax in upfront
induction therapy for primary plasma cell leukemia with t(11;14) or BCL2 expression.
Leuk Lymphoma. (2022) 63:759–61. doi: 10.1080/10428194.2021.2010065
Yang Y, Fu LJ, Chen CM, HuMW. Venetoclax in combination with chidamide and dexamethasone in relapsed/refractory primary plasma cell leukemia without t(11;14): A case report. World J Clin Cases. (2021) 9:1175–83. doi: 10.12998/wjcc.v9.i5.117540.
Kupsh A, Arnall J, Voorhees P. A successful case of venetoclax-based therapy in
relapsed/refractory secondary plasma cell leukemia. J Oncol Pharm Pract. (2020)
:1274–8. doi: 10.1177/1078155219895072
Glavey SV, Flanagan L, Bleach R, Kelly C, Quinn J, Nı́ Chonghaile T, et al. Secondary plasma cell leukaemia treated with single agent venetoclax. Br J Haematol. (2020) 190:e242–5. doi: 10.1111/bjh.v190.4
Elsabah H, Ghasoub R, El Omri H, Benkhadra M, Cherif H, Taha RY. Venetoclax in the treatment of secondary plasma cell leukemia with translocation t(11;14): a case report and literature review. Front Oncol. (2024) 14:1390747. doi: 10.3389/fonc.2024.1390747
Morgan HT, Derman BA, Ma H, Kumar SK. Changing lanes: extending CAR T-cell therapy to high-risk plasma cell dyscrasias. Front Immunol. 2025 Apr 8;16:1558275. doi: 10.3389/fimmu.2025.1558275
Fortuna GMG, Sidana S, Hovanky V, Khouri J, Dima D, Kocoglu MH, et al. Idecabtagene vicleucel (ide-cel) chimeric antigen receptor T-cell for plasma cell leukemia (PCL): A multicenter experience. Transplant Cell Ther Off Publ Am Soc Transplant Cell Ther. (2024) 30:S381–S2. doi: 10.1016/j.jtct.2023.12.534 121.
Guo Y, Hu K, Ke X, Yang F, Ma L, Xu T, et al. PB2101: A prospective investigation into the timing and status of BCMA-CART in secondary plasma cell leukemia. HemaSphere. (2023) 7:e640168c. doi: 10.1097/01.HS9.0000975188.64016.8c
Li C, Cao W, Que Y, Wang Q, Xiao Y, Gu C, et al. A phase I study of anti-BCMA
CAR T cell therapy in relapsed/refractory multiple myeloma and plasma cell leukemia.
Clin Transl Med. (2021) 11:e346. doi: 10.1002/ctm2.v11.333.
Deng J, Lin Y, Zhao D, Tong C, Chang AH, Chen W, et al. Case report: Plasma
cell leukemia secondary to multiple myeloma successfully treated with anti-BCMA CAR-T cell therapy. Front Oncol. (2022) 12:901266. doi: 10.3389/fonc.2022.901266
Li C, Wang Q, Zhu H, Mao X, Wang Y, Zhang Y, et al. T cells expressing anti-BCMA chimeric antigen receptors for plasma cell Malignancies. Blood. (2018) 132:1013–. doi: 10.1182/blood-2018-99-116898
Li C, Cao W, Que Y, Wang Q, Xiao Y, Gu C, Wang D, Wang J, Jiang L, Xu H, Xu J, Zhou X, Hong Z, Wang N, Huang L, Zhang S, Chen L, Mao X, Xiao M, Zhang W, Meng L, Cao Y, Zhang T, Li J, Zhou J. A phase I study of anti-BCMA CAR T cell therapy in relapsed/refractory multiple myeloma and plasma cell leukemia. Clin Transl Med. 2021 Mar;11(3):e346. doi: 10.1002/ctm2.346.
(1): e2025045, DOI: http://dx.doi.org/10.4084/MJHID.2025.045
Han W, Wang S, Zhang M, Fu S, Wu W, Zhao H, Wong KW, Yip SF, Cui J, Chang AH, Wei G, Huang H, Hu Y. Sequential intrathoracic injection and intravenous infusion of BCMA CAR-T cells in a patient with relapsed/refractory primary plasma cell leukemia. Int J Hematol. 2025 Sep 10. doi: 10.1007/s12185-025-04064-3
Kasap C, Izgutdina A, Patiño-Escobar B, Kang AS, Chilakapati N, Akagi N, Manoj A, Johnson H, Rashid T, Werner J, Barpanda A, Geng H, Lin YT, Rampersaud S, Gil-Alós D, Sobh A, Dupéré-Richer D, Aleman A, Wicaksono G, Kelii KMK, Dalal R, Ramos E, Vijayanarayanan A, Lakhani K, Salangsang F, Phojanakong P, Camara Serrano JA, Zakraoui O, Tariq I, Chari A, Chung A, Kumar AD, Martin TG 3rd, Wolf J, Wong SW, Steri V, Shanmugam M, Boise LH, Kortemme T, Parekh S, Stieglitz E, Licht JD, Karlon WJ, Barwick BG, Wiita AP. Targeting high-risk multiple myeloma genotypes with optimized anti-CD70 CAR T cells. Blood. 2025 Aug 14;146(7):819-833. doi: 10.1182/blood.2024025536
Puppi M., Sacchetti I., Mancuso K., Tacchetti P., Pantani L., Rizzello I., Iezza M., Talarico M., Manzato E., Masci S., Restuccia R., Barbato S., Armuzzi S., Taurisano B., Vigliotta I., Zamagni E. Bispecific antibodies and CART in multiple myeloma: appropriate selection of patients and sequencing. Mediterr J Hematol Infect Dis 2025,
Bernardi, C.; Beauverd, Y.; Tran, T.A.; Maulini, M.; Mappoura, M.; Morin, S.; Simonetta, F.; Cairoli, A.; Auner, H.W.; Samii, K.; et al. Anti-BCMA and GPRC5D bispecific antibodies in relapsed/refractory primary plasma cell leukemia: A case report. Front. Immunol. 2024, 15, 1495233.
How to Cite
“PLASMA CELL LEUKEMIA UPDATE ON IMMUNOPHENOTYPE, MOLECULAR CHARACTERISTICS, AND THERAPY. The second part of plasma cell neoplasms with spreading in the blood and tissues: Plasma Cell Leukemia” (2025) Mediterranean Journal of Hematology and Infectious Diseases, 17(1), p. e2025080. doi:10.4084/MJHID.2025.080.
Copyright (c) 2025 Giuseppe G.M. Leone, Ugo Testa
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