Discussion
PCL is a rare and aggressive form of multiple myeloma characterized by the presence of circulating plasma cells in the peripheral blood. Plasma cells can be either primary( originating de novo) or secondary transformation of the MM.
Historically, primary plasma cell leukemia (PCL) has been found in approximately 60 to 70% of cases, with the remainder classified as secondary PCL. However, advancements in treatment and improved survival rates for patients with multiple myeloma (MM) have significantly altered the landscape of these conditions. Currently, it is estimated that only about 1 to 4 percent of patients with MM progress to develop secondary PCL. This change highlights the effectiveness of novel therapeutic strategies and enhanced management of MM, which may reduce the likelihood of progression to this more aggressive form of plasma cell dyscrasia2,3,4, The reported incidence of PCL in the USA and Europe is 4 cases per 10,000,000 persons per year. 5,6
The clinical presentation of PCL can include those seen in MM(i.e. kidney dysfunction, anemia, lytic bone lesion, bone pain, hypercalcemia) . It can also present as in other leukemia (i.e. hepatomegaly, splenomegaly, anemia, thrombocytopenia, infection, leukocytosis).7 there are reports of few cases with clinical presentation including pleural effusion, lymphadenopathy, and neurological deficit due to central nervous system involvement.8
In patients with PCL, the peripheral blood demonstrates the circulating plasma cells. The criteria to diagnose PCL is the presence of ≥5% of plasma cells9. The morphological features of plasma cells may be difficult to distinguish from myeloblasts. Mature plasma cells are oval with abundant basophilic cytoplasm. The nucleus of a mature plasma cell is round and eccentrically located with a marked perinuclear hof, or cytoplasmic clearing. The nucleus contains “clock-face” or “spoke wheel” chromatin without nucleoli. The immature plasma cells have dispersed nuclear chromatin, prominent nucleoli, and a high nuclear-to-cytoplasmic ratio. The cytoplasm of neoplastic plasma cells contains either kappa or lambda light chains, but not both. While both PCL and MM express the two common plasma cell markers CD38 and CD138, PCL demonstrates a more immature phenotype (i.e more frequent expression of CD20, CD23, CD28, CD44, and CD45; less frequent expression of CD9, CD56, CD71, CD117, and HLA-DR antigens).10, 11, 12 The bone marrow biopsy and aspiration findings demonstrate an increased number of monoclonal plasma cells.13 The serum protein electrophoresis usually demonstrates monoclonal immunoglobin production. Serum immune fixation reveals the production of IgG, IgA, IgD, and IgE in 33, 20, 3, and 1 percent of cases respectively. The International Myeloma Working Group( IMWG) recently revised the diagnostic criterion of primary PCL to ≥5% circulating plasma cells in peripheral blood smears. 14 The cytoplasm of the plasma cell must contain either kappa or lambda light chains, but not both, indicating that the cells are clonal. The conventional manual count of plasma cells from the peripheral blood is needed to differentiate it from the very few numbers of plasma cells in MM that are detected due to the high sensitivity of the assay.
The treatment to date is primarily targeting alleviating the symptoms, reversing the cytopenia, and decreasing end-organ damage. There have been no prospective randomized trials investigating the treatment of PCL. All the data are from small uncontrolled prospective studies, retrospective series, and case reports. The approaches so far are expert recommendations. Currently, every willing patient is recruited to an ongoing trial for the treatment (www.clinicaltrials.gov). In general, primary plasma cell leukemia (PCL) requires prompt intensive therapy with novel agents to decrease early mortality and disease-related complications. For transplantation-eligible individuals, autologous stem cell transplantation (ASCT) followed by maintenance therapy is recommended.15.
In retrospective studies, bortezomib-based regimen for primary PCL was effective; the overall response rate (ORR) was 76–80%, including at least a very good partial response (VGPR) in 28–38% of patients.16 In the EMN12/HOVON129 study, carfilzomib (a second-generation proteasome inhibitor) combined with lenalidomide and dexamethasone (KRd) has been assessed as an induction therapy for patients with newly diagnosed primary plasma cell leukemia (PCL). An interim analysis involving 14 patients who underwent four treatment cycles revealed impressive efficacy, with an overall response rate (ORR) of 93%. This included a complete response (CR) rate of 33% and a very good partial response (VGPR) rate of 55%. Therefore, combination treatment with a proteasome inhibitor and an immunomodulatory drug should be considered as induction therapy.17 High-dose chemotherapy followed by autologous HCT improves overall survival in patients with MM and has become part of the standard of care for those who are eligible. The role of allogenic HCT is not yet clear, though few eligible candidates have it. Maintenance with lenalidomide and/or bortezomib is suggested for all patients with PCL. The prognosis of PCL is poor and is worse than that of high-risk multiple myeloma(MM).
In a resource-limiting country like Ethiopia, where molecular and immunological studies are not available, patients were primarily treated based on pathological reports. Considering that the peripheral blood plasma cells might sometimes look like the blasts, the possibility that those patients would be misdiagnosed and treated as acute leukemia is very high.
The diagnosis of PCL in our patient was very challenging and late owing to the discrepancy between pathologic and flow cytometry results. The initial treatment introduction with dexamethasone has decreased the WBC count significantly and rapidly, which led to confusion and doubt. After the final diagnosis of PCL, our patient was started on the VRd regimen. He took three cycles of chemotherapy. After the third cycle of the chemotherapy, the patient passed away due to severe sepsis.