Plasma Cell Leukemia

# 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 6070% 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 . 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 2-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 711 months and 27 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 2-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.