What Is Plasma Cell Leukemia?

Plasma cell leukemia is clinically divided into primary plasma cell leukemia (PPCL) and secondary plasma cell leukemia (SPCL). About 60% -70% are primary plasma cell leukemia. Primary plasma cell leukemia (PPCL) is an independent type of leukemia, and its clinical manifestations are similar to acute leukemia. The majority of secondary plasma cell leukemias are secondary to multiple myeloma (MM). The clinical pathology is similar to that of MM, and it is an end-stage manifestation of MM. The incidence accounts for 1.6% to 2% of MM, and domestic reports account for 8% of MM. There are also a few secondary to macroglobulinemia, lymphoma, chronic leukemia and amyloidosis. ^[1]

Li Xin

(Deputy Chief Physician)

Department of Hematology and Oncology, West District, Beijing Chaoyang Hospital, Capital Medical University

Plasma cell leukemia (PCL) was first reported by Foa in 1904, with incomplete statistics. There are more than 200 cases reported in foreign literature and more than a hundred cases reported in China. At the time of onset, the number of peripheral plasma cells is> 20%, or the absolute value of plasma cells is> 2.0 × 109 / L, and there are morphological abnormalities, and PC is often diagnosed. Data show that this disease accounts for 1% -2% of acute leukemia, and the course is short, similar to other acute leukemias. At present, the overall treatment effect of PCL is unsatisfactory, difficult to treat, and poor in efficacy. At present, there is no good treatment option, and there is no standard treatment plan or optimal chemotherapy plan.

Western Medicine Name: Plasma cell leukemia
English name: Plasma cell leukemia
Affiliated Department: Internal Medicine-Hematology

The main symptoms: High fever, bleeding
Main cause: Etiology unknown
Contagious: Non-contagious

Classification of Plasma Cell Leukemia Diseases

Causes of plasma cell leukemia

The etiology is unknown, and secondary PCL is mostly the end stage of MM.

Plasma cell leukemia pathophysiology

Compared with multiple myeloma, PCL plasma cells expressed more CD20 (50% vs 17%), but did not express CD56, while MM cells expressed C56, and CD56 is a poor prognostic indicator. Secondary PCL mostly expresses CD28, which is associated with high proliferation rate and disease progression. Using the Fish technique, 13q deletions and chromosome 13 monomers were detected in more than 80% of PCL patients. Approximately 80% of patients have a chromosome 16 deletion. In addition, patients with PCL also tend to have 2q and 6p deletions. PRAD1 / CyclinD1 plays an important role in controlling the cell cycle and is also present in PCL plasma cells. ^[2]

Clinical manifestations of plasma cell leukemia

The clinical pathology of SPCL secondary to MM is basically similar to that of MM. It is an end-stage manifestation of MM, manifested by a marked increase in peripheral plasma cells, and extensive infiltration of bone marrow and extramedullary organs. The clinical characteristics of PPCL are as follows: the age of onset is light, the minimum is 9 months, the median is 45.2 years old, and 34.1% are <40 years old, and the age of MM is older, the median is 53 years old; Most are diagnosed within 2 months, rarely more than six months; often have symptoms such as high fever, bleeding, liver, spleen, lymphadenopathy, and sternal tenderness, which are similar to acute leukemia; often have multiple organ infiltration and hepatosplenomegaly It is more common than MM; Anemia and thrombocytopenia, peripheral blood leukocytes are significantly increased, bone marrow hyperplasia of PPCL is significantly active, plasma cell system is significantly proliferated, both are significantly more than MM, and deformed plasma cells are significantly increased; and bone damage is relatively light. ^[3]

Diagnosis and differential diagnosis of plasma cell leukemia

Plasma cell leukemia diagnostic criteria

It is a plasma cell malignant proliferative disease. Domestic diagnostic criteria

(1) Clinical manifestations of leukemia or MM.

(2) In the classification of peripheral blood leukocytes, plasma cells are greater than 20% or the absolute value is 2.0 × 109 / L.

(3) The bone marrow-like plasma cells proliferated significantly, and the number of primitive and immature plasma cells increased significantly, with abnormal morphology.

Differential diagnosis of plasma cell leukemia

PCL should be distinguished from multiple myeloma, lymphoma, reactive plasmacytosis and other diseases.

Identify the disease name	Identification of medical history / signs / symptoms	Identification of auxiliary examinations
Multiple myeloma	Bone pain is the main symptom when the disease starts, and the pain is obvious. Extensive osteoporosis or osteolytic disease.	Malignant plasma cells appeared in the bone marrow. Monoclonal heavy and light chains were significantly increased in serum protein electrophoresis.
Lymphoma	Most of them are young and mature, with various clinical manifestations. Painless enlargement of the lymph nodes is the first symptom, and liver and splenomegaly are common.	The diagnosis is mainly based on the pathological diagnosis of the biopsy tissue.
Reactive plasmacytosis	The disease itself does not cause clinical symptoms, and its clinical manifestations depend on the primary disease.	The increase of plasma cells in bone marrow is limited, generally 3% but less than 10%, and all are normal mature plasma cells. The secreted immunoglobulins are normal polyclonal and have limited elevation.
Other acute leukemias	Clinical manifestations are symptoms of infection, bleeding, and systemic infiltration.	The blast cells in bone marrow are 20%.

Plasma Cell Leukemia Treatment

The overall treatment effect of PCL is currently unsatisfactory, difficult to treat, poor curative effect, poor prognosis, short survival time, and median survival time is 2-7 months. There are currently no good treatment options for PPCL, and there is no standard or optimal chemotherapy regimen. In principle, the treatment of MM has been used in the past. COAP, CCOP, VCP, CP, CONP and MP have been used. Some patients can be relieved. Dimopoulos MA and other clinical investigations found that the overall response rate of PCL was 37%. Failure to reduce plasma cells by 50% within the first 10 days of treatment is indicative of a final response to treatment. The short survival of patients with PPCL is mainly due to complications (22%) in some patients during the first 2 months of treatment. Chen Shaohua et al. Used modified VCMP protocol to treat 9 cases of PCL. The specific protocol is as follows: vincristine 2mg plus saline 40ml intravenous injection (day 1); melphalan 6mg / d, orally divided into 3 times (days 2-11, sharing 10 days) (Some patients take it to the 13th day); Cyclophosphamide 0.4g plus 40ml saline (intravenous injection) (2nd, 4th, 6th, 8th days, 4 times for sharing. Some patients use it to the 10th day, 5 times) 40-90mg / d of pine, taken orally in 3 times (days 2-11, 10 days). Results There were 6 cases of complete remission, and the number of courses of complete remission was 2-3 courses; 1 case of partial remission; 1 case of no remission; and 1 case of death. The average survival time was 2.2 years. One patient survived 4 years and 1 patient survived 11 years. It is currently the case of PCL with good efficacy reported in China.

Plasma cells are prone to multidrug resistance and regenerative resistance during chemotherapy, which are the main reasons for PCL recurrence, refractory and poor prognosis. The application of anthracycline-containing combined chemotherapy regimen and the replacement of daunorubicin with demethoxy daunorubicin (IDA) can overcome the phenomenon of drug resistance and increase the efficacy.

MM is a proliferative disease of malignant B lymphocytes. Considering the close relationship between MM and PCL in pathogenesis, Gemmel C et al. Tried to use anti-CD20 antibody in combination with high-dose chemotherapy and autologous stem cell transplantation in 1 PCL patient ( Rituximab) for consolidation therapy. Rituximab (375mg / m2) was used for 4 weeks. The results showed that Rituximab completely cleared CD20 + cells in peripheral blood and bone marrow. Plasma cells in peripheral blood and bone marrow at 40 days after treatment were unchanged from plasma cells in peripheral blood at 70 days (0.037% in peripheral blood, 0.026% in bone marrow). Peripheral plasma cells increased to 0.066% 90 days after treatment. The patient relapsed at 120 days, with 0.65% of CD38 ++ / CD138 + / CD20-plasma cells in peripheral blood, but no CD20 + B cells. The results suggest that the patient's disease progression was not caused by the proliferation of CD20 + monoclonal B cells.

In recent years, it has been reported that autologous hematopoietic stem cell transplantation is effective in the treatment of PPCL after high-dose chemotherapy. Hovenga et al. Reported that three patients with PPCL first received various combined chemotherapy, including VAD, high-dose cyclophosphamide, EDAP (etoposide, cisplatin, dexamethasone, and cytarabine), and then treated with high-dose melphalan. Autologous peripheral blood stem cell transplantation. All patients received CR after transplantation, one patient relapsed 3 months after transplantation, and the other patients continued to respond for 14-26 months.

In short, the treatment regimen of alkylate plus prednisone alone is not suitable for patients with PPCL. Combined use of VAD, cyclophosphamide, etoposide, or alternate use of vincristine, cyclophosphamide, melphalan, prednisone / vincristine, nitrosyl-uracil mustard, doxorubicin, prednisone ( VCMP / VBAP) chemotherapy regimen may be the better treatment option initially. With the emergence of new drugs such as bortezomib and lenalidomide, new options and attempts have been provided for the treatment of plasma cell leukemia. ^[4-6]

Prognosis of plasma cell leukemia

Studies on the prognostic factors of patients with primary plasma cell leukemia have pointed out that there are two factors that affect the prognosis: first, the response to chemotherapy, if chemotherapy is effective, the survival time is longer, if there is no response, the survival time is short; Chromosome karyotype, primary plasma cell leukemia and multiple myeloma are similar, with multiple chromosomal abnormalities and oncogene mutations, of which the subdiploid karyotype and chromosome 13 monomer or 13q- are closely related to poor prognosis Relationship.