Analiza niespójności wyników badań wybranych parametrów białkowych surowicy krwi i klonalnych plazmocytów szpiku w ocenie odpowiedzi na leczenie u chorych ze szpiczakiem plazmocytowym (MM) poddanych autologicznej transplantacji krwiotwórczych komórek macierzystych (AHSCT)
An analysis of discrepancies between test results of the selected protein parameters and clonal bone marrow plasma cells in an assessment of treatment response in a group of patients with multiple myeloma (MM) prior to an autologous hematopoietic stem cell transplantation (AHSCT)
Department of Haematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice
Head of Department: prof. Sławomira Kyrcz-Krzemień, MD, PhD
Multiple myeloma (MM) is an incurable, B-cell malignancy. MM represents about 10% of all hematologic malignancies and is characterized by the proliferation of single clone plasma cells (1).
The first description of the disease comes from the 80’s of the Nineteenth Century and was written by Samuela Sollye, John Dalrymple and Henry Bence-Jones. In 1889 Otto Kahler and Osip Rusticki used the term myeloma multiplex for the first time (2).
The annual incidence rate is 4-7 cases per 100 000 inhabitants. It affects slightly more men and people of certain races, such as African or Afro-Caribbean. Furthermore, the average age of the diagnosis is 65 (3).
The etiology of multiple myeloma is not clear. The causes of the disease are complex, probably following various stages and then leading to gene mutations. The development of MM is closely connected to clonal plasma cells which secrete many autocrine substances and stimulating factors such as: MIPIα, MIPIβ, TNF, M-CSF, HGF, VEGF, MMP9, MMP2, IL-1, IL-3, IL-6, IL-11 (4, 5).
Major clinical manifestations are: renal failure, hypercalcemia, anemia, osteolitic bone lesion or pathological fractures. Non-specific symptoms are: weakness, weight loss, fever, susceptibility to infection, neuropathy (6).
Each case of MM is preceded by an asymptomatic malignant stage, termed MGUS – monoclonal gammopathy of undetermined significance. MGUS is characterized by the presence of the M protein in serum (< 30 g/L) and the appearance of clonal plasma cells in the bone marrow which is greater than or equal to 10% (7). The risk of progression to myeloma is 1% per year (8). The next stage in the development of MM is smoldering or asymptomatic multiple myeloma (SMM). In order to identify SMM, monoclonal protein concentration must be over 30 g/L and/or clonal plasma cells in the bone marrow must exceed 10% in the absence of end-organ damage (CRAB symptoms). The estimated risk of progression of SMM to multiple myeloma is on the level of 10% per year for the first 5 years since recognition (9).
A number of tests are used to help confirm multiple myeloma. The diagnosis require the presence of the clonal plasma cell in the bone marrow (> 10%), the presence of monoclonal proteins in the serum and/or urine and so-called CRAB symptoms.
International Myeloma Working Group has established criteria for the diagnosis and monitoring response to treatment in patients with monoclonal gammopathy. This organization recommends the following diagnostic tests performed in the serum and urine: electrophoresis (SPE), immunofixation (IFE), a serum kappa and lambda free light chains assessment along with a flow cytometry analysis (FC) of clonal bone marrow plasma cells (10-12).
An analysis of discrepancies in the test results of the selected protein parameters and clonal bone marrow plasma cells in MM patients prior to the AHSCT.
Seventy two MM patients (37 male and 35 female) with a median age of 58 years (range 38-81 years) were included in this study. All of them were treated with chemotherapy in the Department of Haematology and Bone Marrow Transplantation Silesian University in Katowice, between 2011 and 2013. The following diagnostic tests were used: electrophoresis (SPE), immunofixation (IFE), a serum kappa and lambda free light chains assessment (Freelite) and a flow cytometry analysis (FC) of clonal plasma cells in the bone marrow.
Out of 72 patients, 32 (44%) were found to have discrepancies in the diagnostic tests evaluating disease status before the transplant; in the remaining 40 patients (56%) the results were consistent.
4 types of discrepancies were detected: 1 – Freelite and FC tests were negative, but SPE/IFE was positive (n = 10) (tab. 1, item 1-10), 2 – Freelite test was negative whereas FC and SPE/IFE were positive (n = 10) (tab. 1, item 11-20), 3 – FC was negative with positive Freelite test and SPE/IFE (n = 8) (tab. 1, item 21-28) and 4 – FC and SPE/IFE were negative with positive Freelite test (n = 4) (tab. 1, item 29-32).
FLCr – FLC ratio κ/λ; IFE – serum protein immunofixation; SPE – serum protein electrophoresis
0 – negative result; 1 – positive result
The analysis of patients with MM identified two subgroups: Group A – without the presence of discrepancies in the study and Group B – with the presence of discrepancies in the study.
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