Overview of Plasma Cell Leukemia (PCL)
Plasma cell leukemia (PCL) was first reported by Foa in 1904, and according to incomplete statistics, more than 200 cases have been reported in foreign literature and more than 100 cases in China. The disease is often diagnosed when the peripheral blood plasma cell count is >20% at the onset of the disease, or when the absolute value of plasma cells is >2.0×109/L, and when there are morphological abnormalities. Data show that this disease accounts for 1% to 2% of acute leukemia, with a short course, similar to other acute leukemias.PCL is currently unsatisfactory in overall treatment, difficult to treat, poor efficacy, and there are no good treatment options, and there is no standard treatment regimen or optimal chemotherapy regimen.
Clinically, plasma cell leukemia is divided into primary plasma cell leukemia (PPCL) and secondary plasma cell leukemia (SPCL), and about 60% to 70% are primary plasma cell leukemia. Primary plasma cell leukemia (PPCL) is a separate type of leukemia with clinical manifestations similar to acute leukemia. The majority of secondary plasma cell leukemia is secondary to multiple myeloma (MM), and the clinicopathology is basically similar to that of MM, which is an end-stage manifestation of MM. The incidence accounts for 1.6% to 2% of MM, and is reported to account for 8% of MM in China. There are also a few secondary to macroglobulinemia, lymphoma, chronic leukemia and amyloidosis.
Etiology
The etiology is unknown, and secondary PCL is most often the end stage of MM.
Symptoms
The clinicopathology of SPCL secondary to MM is basically similar to that of MM, and it is an end-stage manifestation of MM, which is characterized by a marked increase in peripheral blood plasma cells and extensive infiltration of the bone marrow and extramedullary organs.The clinical features of PPCL are as follows: ① the age of onset is small, with the youngest being 9 months, the median being 45.2 years old, and the proportion of those who are <40 years old accounting for 34.1%, whereas the age of onset of MM is larger, with the median being 53 years old; ② the onset of disease is acute, the symptoms are obvious, and most of them occur in 2 years of age. The onset of the disease is acute, with obvious symptoms, most of which can be diagnosed within 2 months, rarely more than half a year; (3) There are symptoms such as high fever, hemorrhage, enlargement of the liver, spleen, lymph nodes and sternal tenderness, which are similar to those of acute leukemia; there is often infiltration of multiple organs, and hepatosplenomegaly is more common than MM; (4) Anemia and thrombocytopenia are more frequent than in MM, and there is a significant increase in the number of peripheral blood leukocytes, and there is a significant increase in the number of myeloproliferative cells and plasma cell proliferation in PPCL, which is more significant than that in MM. The bone damage is relatively mild.
Examination
Pathologic examination: compared with multiple myeloma, PCL plasma cells mostly express CD20 (50% vs. 17%) and mostly do not express CD56, while MM cells mostly express CD56, which is a poor prognostic indicator. Secondary PCL mostly expressed CD28, which was associated with high proliferation rates and disease progression. Deletion 13q and monosomy of chromosome 13 can be detected in more than 80% of PCL patients by applying the Fish technique. Chromosome 16 deletions are present in approximately 80% of patients. In addition, PCL patients also tend to have 2q and 6p deletions.PRAD1/CyclinD1, which plays an important role in controlling the cell cycle, is also present in PCL plasma cells.
Diagnosis
Plasma cell leukemia is a malignant proliferative disease of plasma cells. The domestic diagnostic criteria are as follows:
1. clinical presentation of clinical manifestations of leukemia or MM.
2. peripheral blood leukocyte classification of plasma cells is greater than 20% or absolute value ≥2.0×109/L.
3. bone marrow image with marked proliferation of plasma cells and marked increase of primitive and naïve plasma cells with abnormal morphology.
Differential diagnosis
PCL should be differentiated from multiple myeloma, lymphoma, reactive plasmacytosis and other diseases.
Differential Disease Names
Differential history/signs/symptoms
Differences in ancillary tests
Multiple myeloma
Onset of disease is often characterized by bone pain that is significant. Extensive osteoporotic or osteolytic lesions
Presence of malignant plasma cells in the bone marrow and significant elevation of monoclonal heavy and light chains on serum protein electrophoresis
Lymphoma
Most of them are in the young and middle-aged, with a variety of clinical manifestations, often with painless enlargement of lymph nodes as the first symptom, and liver and spleen enlargement are common.
The diagnosis mainly depends on the pathologic diagnosis of biopsy tissue.
Reactive plasmacytosis
The disease itself does not cause clinical symptoms, and its clinical manifestations depend on the primary disease.
There is a limited increase in plasma cells in the bone marrow, usually ≥3% but less than 10%, and they are all normal mature plasma cells. The immunoglobulins secreted are normal polyclonal and the level of elevation is limited.
Other acute leukemias
Clinical signs of infection, hemorrhage, and systemic infiltration
Bone marrow ≥20% primitive cells
Treatment
The overall treatment of plasma cell leukemia (PCL) is currently unsatisfactory, difficult to treat, with poor efficacy, poor prognosis, and short survival, with a median survival of 2 to 7 months. Primary plasma cell leukemia (PPCL) currently has no good treatment options, and there is no standard treatment protocol or optimal chemotherapy regimen. In principle, the treatment used to be mostly for multiple myeloma (MM), and COAP, CCOP, VCP, CP, CONP and MP regimens have been used, with some patients in remission.
Plasma cells are prone to multidrug resistance and regenerative resistance in chemotherapy, which is the main reason for PCL relapse, refractory and poor prognosis. Application of combination chemotherapy regimens containing anthracyclines can overcome the drug resistance phenomenon and increase the efficacy.
In recent years, the use of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation has been reported to be effective in the treatment of PPCL.
Prognosis
Studies on the prognostic factors of patients with primary plasma cell leukemia have pointed out that there are two factors affecting the prognosis: the first is the response to chemotherapy, if the chemotherapy is effective, the survival period will be longer; if there is no response, the survival period will be very short; the second is the chromosomal karyotype, primary plasma cell leukemia is similar to multiple myeloma in that there are a variety of chromosomal abnormalities and oncogenic gene mutations, of which the subdiploid karyotype and chromosome 13 monosomy or 13q- are more closely related to poor prognosis.