Necessity of flow cytometry assessment of circulating plasma cells and its connection with clinical characteristics of primary and secondary plasma cell leukaemia.

Plasma cell leukaemia (PCL) is a rare and very aggressive plasma cell disorder. Preventing a dismal outcome of PCL requires early diagnosis with appropriate analytical tools. Therefore, the investigation of 33 patients with primary and secondary PCL was done when the quantity of circulating plasma cells (PCs) using flow cytometry (FC) and morphology assessment was evaluated. The phenotypic profile of the PCs was also analysed to determine if there is an association with clinical outcomes and to evaluate the prognostic value of analysed markers. Our results revealed that FC is an excellent method for identifying circulating PCs as a significantly higher number was identified by FC than by morphology (26·7% vs. 13·5%, P = 0·02). None of secondary PCL cases expressed CD19 or CD20. A low level of expression with similar positivity of CD27, CD28, CD81 and CD117 was found in both PCL groups. A decrease of CD44 expression was detected only in secondary PCL. Expression of CD56 was present in more than half of PCL cases as well as cytoplasmic nestin. A decreased level of platelets, Eastern Cooperative Oncology Group score of 2-3 and lack of CD20+ PC were associated with a higher risk of death. FC could be incorporated in PCL diagnostics not only to determine the number of circulating PCs, but also to assess their phenotype profile and this information should be useful in patients' diagnosis and possible prognosis.

Utilizing multiparametric flow cytometry in the diagnosis of patients with primary plasma cell leukemia.

The diagnosis of primary plasma cell leukemia (pPCL) has been made by quantifying circulating plasma cells (cPCs) morphologically on a peripheral blood (PB) smear. However, this technique is not sufficiently sensitive. Multiparametric flow cytometry (MFC) provides a readily available and highly sensitive method to identify and quantify cPCs that could complement PB smear assessment. However, an optimal quantitative cutoff for cPCs by MFC to identify pPCL has not been established. Thus, a total of 591 patients newly diagnosed multiple myeloma (NDMM) patients who had their PB samples evaluated morphologically by PB smear, and immunophenotypically by MFC prior to beginning therapy were evaluated. The presence of ≥200 cPCs/µL by MFC (N = 25 or 5% of the total population) was chosen to identify patients with ≥5% cPCs by PB smear with a specificity of 99% and a sensitivity of 77%. For patients with ≥200 cPCs/µL by MFC compared to the remainder of the cohort, the median Time to next therapy (TTNT) was 18 vs 30 months and the median OS was 38 vs 70 months respectively. Thus, MFC assessment of PB can be utilized in conjunction with the morphological assessment of a PB smear to aid in improving the identification of pPCL among NDMM patients.

[A primitive plasma cell leukemia with immunoglobulin (Ig) E]. / À propos d'un cas de leucémie plasmocytaire primitive à IgE.

We report here a case of primitive plasma cell leukemia with immunoglobulin (Ig) E. IgE myeloma is an exceptional variant of multiple myeloma, with a very poor prognosis. Its biological diagnosis requires specific analyzes in order to detect IgE gammopathy. Plasma cell leukemia (PCL) is also a very rare and very severe form of multiple myeloma. There are two variants: primitive PCL (pPCL) occurring de novo and secondary PCL (sPCL), evolution of a preexisting myeloma. Its diagnosis is essentially biological since it is defined by a blood plasmocytosis greater than 2 G/L or 20% of the leucocytes.

Primary Nonsecretory Plasma Cell Leukemia With Multiple Chromosomal Abnormalities: A Case Report.

Primary nonsecretory plasma cell leukemia (PCL) is an extremely rare type of multiple myeloma. Here, we report a case of nonsecretory PCL with no previous history of multiple myeloma. The case exhibited extremely low levels of serum immunoglobulin and light chain, no detectable serum M-protein or free light chain restriction, no urine BJP, and no cytoplasmic light chain expression in flow cytometry. In fluorescence in situ hybridization, tumor cells exhibited fusion genes for IgH/BCL1 and IgH/cMyc, disappearance of the p53 signal, and a split signal for IgK(2p11), but no split signal for IgL (22q11). Therefore, we diagnosed primary nonsecretory PCL with multiple chromosomal abnormalities.

Circulating Plasma Cells in Monoclonal Gammopathies.

BACKGROUND: Monoclonal gammopathies are characterized by presence of clonal plasma cells in the bone marrow, although peripheral blood circulating plasma cells can be found in a significant proportion of patients. The number of circulating plasma cells is an independent prognostic marker associated with shorter survival, but it can also help to predict early relapse. The reason and mechanism of plasma cell expansion from the bone marrow to enter peripheral blood is still not entirely clear, but possible changes in the expression of adhesion molecules are probably involved. Multiparametric flow cytometry allows simple and exact enumeration of circulating plasma cells in different types of cell suspensions, even in their low quantity. The phenotype profile and confirmation of clonality regarding to their bone marrow clonal counterparts should be verified as well. There is no uniform method used in clinical laboratories for circulating plasma cells analyses at this moment. AIM: Review is focused on use of multiparametric flow cytometry for circulating plasma cells analysis in peripheral blood. It is comparing possibilities of their detection by different methods and on clinical relevance of that assessment. The standardization of analyses is the main goal. CONCLUSION: Multiparametric flow cytometry is a very sensitive method for detection of circulating plasma cells, so using a standardized approach can lead to determination and implementation of the flow cytometry diagnostic threshold in plasma cell leukemia suspicious cases as well as in prognostication of monoclonal gammopathies patients. Moreover, analysis of plasma cells phenotypic profile could probably clarify their future behaviour.Key words: monoclonal gammopathies - circulating plasma cells - plasma cell leukemia - flow cytometry.

Multiple myeloma and secondary plasma cell leukemia.

Plasma cell leukemia is very rare condition characterized by malignant proliferation of plasma cells in blood and bone marrow, which is aggressive and has a short survival even with conventional treatment. This ominous entity may be primary, or develops secondarily during the course of multiple myeloma. A 53-year-old Brazilian woman with multiple myeloma is described with bone marrow evaluation revealing 25% plasma cells. The quantification of plasma cell infiltration in bone marrow aspirate and immunohistochemistry study revealed consistent features of myeloma and plasma cell leukemia, and lambda light chain expression. Worthy of note was the absence of CD56 expression and the expression of CD20; moreover, 23% of circulating plasma cells were detected in peripheral blood smears. Therefore, the diagnosis of plasma cell leukemia was characterized and therapeutic schedules with dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide were utilized. With significant clinical improvement, the patient is currently waiting for bone marrow transplant.

Extended high cut-off haemodialysis for myeloma cast nephropathy in Auckland, 2008-2012.

Myeloma cast nephropathy contributes to high morbidity and early mortality associated with the development of end-stage renal disease. Treatment with extended high cut-off haemodialysis coupled with novel anti-myeloma therapies enables significant reduction of serum-free light chains and has been shown to improve renal outcomes. In this case series, medical records of 6 patients who received high cut-off haemodialysis for biopsy-proven cast nephropathy were retrospectively reviewed. Patients received a total of 344 hours of high cut-off haemodialysis and concurrent chemotherapy. Only 50% became dialysis independent following treatment. One patient who achieved sustained remission remained dialysis dependent. The added benefit of high cut-off haemodialysis in the light of novel anti-myeloma therapies requires further evaluation.

Secondary plasma cell leukemia.

Plasma cell leukemia (PCL) is a rare disease and is the least common variant of multiple myeloma accounting for 2-3% of all plasma cell dyscrasias. We report a patient who was diagnosed with multiple myeloma, 12 months earlier; he was treated with VBCMP, VCMP regime, and after 12 months he presented of high grade fever, weakness, palpitations, loss of appetite, bone pains, dyspnea. Initial evaluation revealed plasmacytosis with blood plasma cell count of 13 860/mm³. His hemoglobin (Hb) was 8.4 mg/dL, platelets were 45 000/mm³ and total leukocyte count (TLC) was 23 100/mm³ (60% plasma cells). Bone marrow examination revealed 90% plasmablastic cells. Serum LDH was high at 3117 U/L and serum calcium was also elevated at 9.1 mg/dL. A diagnosis of PCL was made and the patient was started on treatment with VAD regime along with supportive care. Patient condition deteriorated very quickly, despite treatment and he died on the third day. A detailed report of this case and a review of PCL is presented here.