Plasma Cell Leukemia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate-Editor-in-Chief: Azeezat Ariwoola, MBChB
Overview
Plasma cell leukemia (PCL) is an uncommon and aggressive form of leukemia and plasma cell dyscrasias. It occurs when there is a monoclonal proliferation of immunoglobulin-secreting plasma cells with a resultant increase in serum levels of a single homogenous immunoglobulin or its fragments. It could be primary or secondary.
Epidemiology
Patients with PCL represent a unique subset of patients with multiple myeloma. It represents about 0.6% of all cases of multiple myeloma. It is not commonly seen in children, and it is rarely seen in adults under 30. The median age of diagnosis is ~70 years. It occurs twice as frequently in African-Americans than in Caucasians. About 60–70% of cases are primary while ~40% are secondary.
Etiology
The exact cause of PCL is unknown. It develops due to a series of genetic mutations whose presence can lead to the emergence of abnormal cells that grow and divide out of control. Some cases of translocations have been reported involving t(11;14), t(14;16), t(14;20), and t(4;14). Translocation occurring at the cell regulator genes MYC and MAF, located on chromosomes 8 and 16, respectively have also been reported; MAF translocations [t(14;16) and t(14;20)]. Some mutations in the KRAS genes and TP53 genes were also reported.
Clinical Features
• Anemia; pallor, dizziness, syncope
•Thrombocytopenia; bleeding, bruises
• Recurrent infections due to neutropenia
• Renal failure, due to deposition of free light chain in renal tubules
• Hypercalcemia; polyuria, constipation, fatigue
•Bone pain, due to increased osteoclastic activity
•Symptoms of hyper-viscosity (rarely) due to paraprotein secretion; blurry vision, deafness
Patients can be asymptomatic, with the diagnosis being suspected by abnormal ‘routine’ blood tests.
Diagnosis
•The diagnostic criteria of plasma cell leukemia (PCL) were established in 1974 by Kyle requiring both;
•more than 20% of circulating plasma cells; and
•an absolute count greater than 2 × 109/l plasma cells in peripheral blood
•As of now, the International Myeloma Working Group (IMWG) and WHO both suggest that either one of the two criteria is sufficient for the PCL diagnosis.
•Bone marrow biopsy; increased blast cells, plasmacytosis with nuclear atypia.
•Peripheral blood film; elevated plasma cells, monoclonal gammopathy in serum
•Plasmacytoma
• Immunoglobulin free-light chain assay.
Investigations
•Complete Blood Count- anemia, neutropenia, and/or thrombocytopenia
•Comprehensive Metabolic Panel
•Elevated creatinine, Hyperuricemia, Hypercalcemia, elevated LDH
•Elevated Total protein, hypoalbuminemia, elevated β2-microglobulin
•Quantitative Immunoglobulins (monoclonal/polyclonal).
•Bone marrow Biopsy – to evaluate % plasma cells
•Serum protein electrophoresis with immunofixation; M-spike
•Free serum light chain assay
•24-hr urine protein electrophoresis with immunofixation – shows the presence of Bence Jones protein
•PET/CT scan – osteolytic bone destruction
•Flow cytometry and cytogenetics – to identify circulating plasma cells and check for genetic mutations.
Treatment
Characterized by the induction and maintenance phase involving the combination of;
•Proteasome inhibitors – Bortezomib
•Immune modulatory drugs - Thalidomide and Lenalidomide
•Steroids – Dexamethasone
•Bortezomib – 1.3mg/sqm given IV or sub cute once a week on days 1,8,15 and a weekly rest in a 4-week cycle
•Tabs Dexamethasone 12 mg weekly
•Tabs Lenalidomide 25 mg daily for 21 days and 7 days off
Other treatment options include;
•Autologous Stem Cell Transplantation (ASCT)
•Allogeneic Stem Cell Transplantation (AlloSCT)
New and Upcoming Treatments and Studies
•BCL-2 inhibitor – Venetoclax has demonstrated remarkable efficacy in hematological diseases harboring the (11;14) translocation
•Immunomodulatory Imide Drug (third-generation) - Pomalidomide has shown good response and survival benefits in refractory MM
•Proteasome Inhibitor (second-generation) - Ixazomib is used in combination with lenalidomide and dexamethasone in cases of relapsed or refractory MM and plasma cell leukemia
•Anti-CD38 antibody - Daratumumab
Prognosis
•The prognosis of PCL is poor, with a median survival of 7–11 months and 2–7 months for primary and secondary plasma cell leukemia respectively.
•The best survival data for PCL is in patients who received salvage autologous stem cell transplantation (ASCT) following an aggressive chemotherapeutic regimen
•Unfavorable prognostic factors include elevated β2-microglobulin, low serum albumin, hypercalcemia, elevated serum lactate-dehydrogenase, poor performance status, and advanced age.
Conclusion
•PCL is a very aggressive disease with adverse prognoses
•Secondary PCL is often treatment-resistant, whereas early responses are common in primary PCL, but early relapses and development of resistance are typical.
•Treatment should start promptly with an effective proteasome inhibitor-containing regimen, followed by high-dose chemotherapy and ASCT in eligible patients.
References