Plasma cell leukemia (PCL) is a rare malignancy characterized by abnormal proliferation of plasma cells.
Classification
Plasma cell leukemia can be classified into two major categories, primary and secondary, based on the presence or absence of a clinical history of myeloma:
- Primary plasma cell leukemia (PPCL) occurs in patients without a history of myeloma and accounts for approximately 50% to 70% of all plasma cell leukemias;
- Secondary plasma cell leukemia (PPCL) occurs in patients without a history of myeloma and accounts for approximately 50% to 70% of all plasma cell leukemias;
- Secondary plasma cell leukemia (SPCL) is the terminal leukemic stage of myeloma, accounting for 30% to 50% of plasma cell leukemia and only 1% of myeloma.
PPCL has a high degree of malignancy, a low response rate to conventional therapy, and a poor patient prognosis.
Definition
Kyle et al. first defined plasma cell leukemia as peripheral blood clonal plasma cells occupying 20% or more of the nucleated cells, or an absolute count of >2×10/L.
The world’s first case of PPCL was reported in 1904 in a 63-year-old woman who was found on autopsy to have extensive plasma cell infiltration in multiple organs throughout her body.
Symptom presentation
The clinical presentation of primary plasma cell leukemia has features of both acute leukemia and multiple myeloma, with an acute onset and nonspecific symptoms of fever, anemia, thrombocytopenia, and weight loss.
Compared to multiple myeloma, it has a rapid progression, less osteolytic damage, and less bone pain, while lymph node enlargement and hepatosplenomegaly, renal failure, hypercalcemia, and significant increases in serum lactate dehydrogenase and β2 microglobulin levels are more common.
Neoplastic plasma cells can be found in extramedullary tissues (e.g., liver, spleen, pleural fluid, peritoneal fluid, and cerebrospinal fluid) in addition to bone marrow and peripheral blood.
Treatment
There is no cure for primary plasma cell leukemia, and the goal of treatment is to prolong survival and improve quality of life. Conventional chemotherapy regimens used to treat myeloma have also been used to treat primary plasma cell leukemia, but the response to conventional chemotherapy is poor and survival is short. Combination chemotherapy that includes immunomodulatory drugs (thalidomide, lenalidomide, etc.) and proteasome inhibitors (e.g., bortezomib, isazomib, etc.) has better response rates and results in longer survival.
Based on the fact that primary plasma cell leukemia usually progresses rapidly and has a short survival, pediatric and young patients should undergo hematopoietic stem cell transplantation as soon as possible after induction of remission. Stem cell transplantation is currently the only possible cure for a small proportion of primary plasma cell leukemias, but further studies are needed.
New drugs are being investigated, such as CD38 monoclonal antibodies, spindle kinesin inhibitors (e.g., Filanesib), BCL-2 inhibitors (e.g., Venetoclax), and even chimeric antigen receptor-modified T cells (CAR-T). therapy may open up new perspectives for the treatment of plasma cell leukemia.
Primary plasma cell leukemia has a poor prognosis, with many patients dying within 1 month of diagnosis. With the development of precision therapy, it may be possible to improve overall treatment response and survival.