HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CARE
Significant mortality due to oncological diseases as a whole, and oncohematological diseases in particular, motivates scientific and medical community to develop new treatment methods. One of the newest methods is adoptive cell therapy using patient’s own T-cells modified to express chimeric antigen receptors (CAR) to tumor-specific antigens. Despite high cost and side effects of treatment, promising clinical trials even in patients with advanced disease allow to anticipate successful use of this method in clinical practice.
The article includes a review of the main principles of this technique, published results of clinical studies of CAR T-cells with a focus on CD19 gene targeting, complications of this therapy, mechanisms of tumor resistance to CAR T-cells, and potential ways to overcome it.
Kidney involvement in the onset of lymphoproliferative diseases (LPD) detected rarely, observed mainly at tumor progression or relapse.
Objective: to determine the clinical and morphological features of kidney damage in the initial manifestation of LPD.
Materials and methods: 19 patients with LPD and kidney damage were included in the study. The diagnosis of non-Hodgkin’s lymphomas was established according to 2008 WHO classification. Histological and immunohistochemical, immunofluorescent and electron microscopic studies of nephrobiopsy have been performed.
Results. Patients were aged 46-83 years (median 63 years), of which 13 were men and 6 women. Chronic lymphocytic leukemia / small cell lymphocytic lymphoma was established in 12 patients, marginal zone lymphoma – in 4 pts, follicular lymphoma – in 1 patient, Waldenstrom's macroglobulinemia – in 1 patient and diffuse large B-cell lymphoma (DLBCL) in 1 patient. Proteinuria was observed in 18 patients, microhematuria – in 6 pts, arterial hypertension – in 8 pts, nephrotic syndrome – in 3 pts and renal failure in 18 patients. The mean creatinine level was 330.9 ± 52.3 µmol/L, the average glomerular filtration rate was 25.7 ± 12.9 ml/min. Monoclonal IgMκ secretion was detected in 6 patients, BJκ protein – in 9 pts, increased free light chain level – in 4 pts, cryoglobulin – in 4 pts (type II cryoglobulin in 3 of them, type I – in 1 patient).
Morphological study of nephrobiopsy revealed tumor lymphoid infiltration of kidney interstitium in 10 (52.6 %) cases. Diffuse small cell lymphoid proliferation was detected in 1 patient, local infiltration – in 9 pts, in 3 of them in combination with glomerulonephritis, and in 4 cases with kidney carcinoma. Local large cell lymphoid proliferation was found in 1 patient with DLBCL. Amyloidosis was detected in 2 pts and thrombotic microangiopathy – in 2 patients. Glomerulopathy was revealed in 10 patients (52.6 %): mesangioproliferative glomerulonephritis (MPGN) – in 4, mesangiocapillary glomerulonephritis – in 3, fibrillar glomerulonephritis (FGN) – in 1, immunotactoid glomerulonephritis – in 1, and glomerulonephritis with minimal changes – in 1 patient.
Conclusion. Kidney damage in the onset of lymphatic tumor does not always manifest with proteinuria, hematuria, nephrotic syndrome and renal failure. In most cases, secretion of BJ protein, free light chains, monoclonal immunoglobulin and cryoglobulin are detected. Morphological changes are heterogeneous, including lymphoid proliferation, various types of glomerulopathies, amyloidosis and thrombotic microangiopathy.
BASIC RESEARCH
We have studied the morphology and immunophenotype of circulating tumor cells isolated from peripheral blood of 22 patients with splenic marginal zone lymphoma and show that both of them are highly heterogeneous. Using a cell-binding microarray we have demonstrated that the circulating lymphoma cells are positive for CD19 (100 %), CD20 (100 %), CD22 (100 %), surface IgM (73 %), CD38 (23 %), CD5 (9 %), CD11c (36 %), CD103 (5 %), CD25 (32 %), CD23 (23 %) and these immunophenotypes are confirmed in all cases by flow cytometry.
Higher surface density of lymphocyte binding onto anti-CD antibody microarray spots compared to blood smears permits to find circulating lymphoma cells even in leukopenic patients.
RARE DISEASES: DIFFERENTIAL DIAGNOSIS
The article presents a systematic diagnostic approach for thrombocytopenia, as well as the results of practical implementation of thrombocytopenia diagnostic protocol in adult patients. Among 183 patients first admitted to HRC with unspecified origin thrombocytopenia, primary immune thrombocytopenia (ITP) was established only in 48 % of patients, while in 52 % of cases it was a symptom of another pathology (the ratio was 1 : 1). As a result of re-examination of 118 relapse patients with long-term history of ITP diagnosis was confirmed in 85 % of cases, in 15 % the diagnosis has been changed to a different nosology.
The results show that to establish the true causes of thrombocytopenia is necessary to conduct an extensive diagnostic search according to presented protocol.
Differential diagnosis between primary immune and secondary thrombocytopenia should be carried out not only in the onset of the disease, but also in the relapse of an earlier established ITP.
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