Plasma cell leukemia
- S Vincent Rajkumar, MD
S Vincent Rajkumar, MD
- Edward W. and Betty Knight Scripps Professor of Medicine
- Mayo Clinic
Plasma cell leukemia (PCL) is a rare, yet aggressive form of multiple myeloma characterized by high levels of plasma cells circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of multiple myeloma (secondary PCL).
The epidemiology, clinical presentation, diagnosis, prognosis, and treatment of plasma cell leukemia are discussed here. The related disorders of multiple myeloma and plasmacytoma are presented separately. (See "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma" and "Diagnosis and management of solitary extramedullary plasmacytoma" and "Diagnosis and management of solitary plasmacytoma of bone".)
Plasma cell leukemia (PCL) is a rare variant of multiple myeloma that presents either as a progression of previously diagnosed multiple myeloma (ie, secondary PCL) or as the initial manifestation of disease (ie, primary PCL). Historically, the majority of cases have been primary PCL (60 to 70 percent), although the incidence of secondary PCL may be increasing, perhaps due to the longer survival of myeloma patients, such that the distribution of disease is more evenly split [1,2]
The most extensive data on the epidemiology of PCL come from a series of 291 patients identified in the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2004 . During this period, approximately 49,000 patients with multiple myeloma were identified, for a relative incidence of 0.6 percent. In this series there were no significant differences based upon gender, age, or race when compared with patients with multiple myeloma. This SEER study did not distinguish between primary and secondary PCL.
PCL occurs in all races and all geographic locations. The incidence of PCL in Europe is approximately 4 cases per 10,000,000 persons per year . As with multiple myeloma, PCL is more common in African Americans and blacks from Africa than in whites .
Subscribers log in hereLiterature review current through: May 2017. | This topic last updated: Aug 08, 2016.References
- Tiedemann RE, Gonzalez-Paz N, Kyle RA, et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia 2008; 22:1044.
- Fernández de Larrea C, Kyle RA, Durie BG, 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.
- Ramsingh G, Mehan P, Luo J, et al. Primary plasma cell leukemia: a Surveillance, Epidemiology, and End Results database analysis between 1973 and 2004. Cancer 2009; 115:5734.
- 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.
- Bladé J, Kyle RA. Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia. Hematol Oncol Clin North Am 1999; 13:1259.
- Gertz MA. Managing plasma cell leukemia. Leuk Lymphoma 2007; 48:5.
- Pagano L, Valentini CG, De Stefano V, et al. Primary plasma cell leukemia: a retrospective multicenter study of 73 patients. Ann Oncol 2011; 22:1628.
- Craig FE, Foon KA. Flow cytometric immunophenotyping for hematologic neoplasms. Blood 2008; 111:3941.
- Ioannou MG, Stathakis E, Lazaris AC, et al. Immunohistochemical evaluation of 95 bone marrow reactive plasmacytoses. Pathol Oncol Res 2009; 15:25.
- Noel P, Kyle RA. Plasma cell leukemia: an evaluation of response to therapy. Am J Med 1987; 83:1062.
- Grogan TM, Van Camp B, Kyle RA. Plasma cell neoplasms. In: World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds), IARC Press, Lyon 2001. p.142.
- Kyle RA, Maldonado JE, Bayrd ED. Plasma cell leukemia. Report on 17 cases. Arch Intern Med 1974; 133:813.
- Avet-Loiseau H, Daviet A, Brigaudeau C, et al. Cytogenetic, interphase, and multicolor fluorescence in situ hybridization analyses in primary plasma cell leukemia: a study of 40 patients at diagnosis, on behalf of the Intergroupe Francophone du Myélome and the Groupe Français de Cytogénétique Hématologique. Blood 2001; 97:822.
- Gonsalves WI, Rajkumar SV, Go RS, et al. Trends in survival of patients with primary plasma cell leukemia: a population-based analysis. Blood 2014; 124:907.
- Rajkumar SV. Multiple myeloma: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol 2012; 87:78.
- García-Sanz R, Orfão A, González M, et al. Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. Blood 1999; 93:1032.
- Dimopoulos MA, Palumbo A, Delasalle KB, Alexanian R. Primary plasma cell leukaemia. Br J Haematol 1994; 88:754.
- Musto P, Pietrantuono G, Guariglia R, et al. Salvage therapy with lenalidomide and dexamethasone in relapsed primary plasma cell leukemia. Leuk Res 2008; 32:1637.
- Benson DM Jr, Smith MK. Effectiveness of lenalidomide (Revlimid) for the treatment of plasma cell leukemia. Leuk Lymphoma 2007; 48:1423.
- Royer B, Minvielle S, Diouf M, 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 Myélome. J Clin Oncol 2016; 34:2125.
- Musto P, Simeon V, Martorelli MC, et al. Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia. Leukemia 2014; 28:222.
- Pineda-Roman M, Zangari M, Haessler J, et al. Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2. Br J Haematol 2008; 140:625.
- Santamaría CM, Chillón MC, García-Sanz R, et al. Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia. Blood 2009; 114:148.
- Katodritou E, Terpos E, Kelaidi C, 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; 89:145.
- Esparís-Ogando A, Alegre A, Aguado B, et al. Bortezomib is an efficient agent in plasma cell leukemias. Int J Cancer 2005; 114:665.
- Jaskiewicz AD, Herrington JD, Wong L. Tumor lysis syndrome after bortezomib therapy for plasma cell leukemia. Pharmacotherapy 2005; 25:1820.
- Grassinger J, Südhoff T, Andreesen R, Hennemann B. Complete remission and successful stem cell mobilization after treatment of refractory plasma cell leukemia with bortezomib. Ann Hematol 2006; 85:132.
- Ataergin S, Arpaci F, Kaya A, et al. VAD combination chemotherapy followed by bortezomib may be an effective treatment in secondary plasma cell leukemia. Am J Hematol 2006; 81:987.
- Finnegan DP, Kettle P, Drake M, et al. Bortezomib is effective in primary plasma cell leukemia. Leuk Lymphoma 2006; 47:1670.
- Ali R, Beksac M, Ozkalemkas F, et al. Efficacy of bortezomib in combination chemotherapy on secondary plasma cell leukemia. Leuk Lymphoma 2007; 48:1426.
- Katodritou E, Verrou E, Gastari V, et al. Response of primary plasma cell leukemia to the combination of bortezomib and dexamethasone: do specific cytogenetic and immunophenotypic characteristics influence treatment outcome? Leuk Res 2008; 32:1153.
- Musto P, Rossini F, Gay F, et al. Efficacy and safety of bortezomib in patients with plasma cell leukemia. Cancer 2007; 109:2285.
- Gozzetti A, Musto P, Defina M, et al. Efficacy of bortezomib, lenalidomide and dexamethasone (VRD) in secondary plasma cell leukaemia. Br J Haematol 2012; 157:497.
- D'Arena G, Valentini CG, Pietrantuono 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; 23:1499.
- Saccaro S, Fonseca R, Veillon DM, et al. Primary plasma cell leukemia: report of 17 new cases treated with autologous or allogeneic stem-cell transplantation and review of the literature. Am J Hematol 2005; 78:288.
- Hovenga S, de Wolf JT, Klip H, Vellenga E. Consolidation therapy with autologous stem cell transplantation in plasma cell leukemia after VAD, high-dose cyclophosphamide and EDAP courses: a report of three cases and a review of the literature. Bone Marrow Transplant 1997; 20:901.
- Mahindra A, Kalaycio ME, Vela-Ojeda J, et al. Hematopoietic cell transplantation for primary plasma cell leukemia: results from the Center for International Blood and Marrow Transplant Research. Leukemia 2012; 26:1091.
- Nishihori T, Abu Kar SM, Baz R, et al. Therapeutic advances in the treatment of primary plasma cell leukemia: a focus on hematopoietic cell transplantation. Biol Blood Marrow Transplant 2013; 19:1144.
- Drake MB, Iacobelli S, van Biezen A, et al. Primary plasma cell leukemia and autologous stem cell transplantation. Haematologica 2010; 95:804.
- CLINICAL PRESENTATION
- PATHOLOGIC FEATURES
- Peripheral blood
- - Morphology
- - Immunophenotype
- - Genetic features
- Bone marrow aspiration and biopsy
- Protein electrophoresis and immunofixation
- DIAGNOSTIC EVALUATION
- DIFFERENTIAL DIAGNOSIS
- Pretreatment evaluation
- Initial treatment
- - Induction therapy
- - Transplantation
- - Maintenance
- Response assessment
- Treatment of recurrent or refractory disease
- SUMMARY AND RECOMMENDATIONS