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.