[Algorithm for examination of bone marrow trephine biopsy specimens in myelodysplastic syndromes].

Based on the analysis of more than 1000 bone marrow trephine biopsy specimens from patients with myelodysplastic syndromes before starting any specific therapy, the authors propose histological criteria for their evaluation (an examination algorithm), an optimal panel of immunohistochemical examination, and histological criteria for predicting the course of the disease.

[Morphological evaluation of dysmyelopoiesis in decitabine-treated patients with myelodysplastic syndromes].

AIM: To estimate a change in myelodysplasia in decitabine-treated patients with myelodysplastic syndromes (MDS). SUBJECTS AND METHODS: Thirteen MDS patients from a high-risk group were examined; 75 bone marrow puncture specimens and 67 bone marrow trepanobiopsy specimens from these patients were analyzed before and after decitabine treatment. Dysplastic changes in the hematopoietic cells were monitored during the treatment. RESULTS: The dysplastic changes in the hematopoietic cells are a morphological portrayal of the ineffective hematopoiesis in patients with MDS. The study has indicated that the use of the hypomethylating agent decitabine promotes the restoration of cell differentiation to mature forms, causing hematopoiesis to be more effective. The incidence of myelodysplasias (including mixed double- and triple-lineage ones) was statistically significantly reduced by decitabine treatment, which was associated with a positive response to treatment as a whole. The count of cells with dysplastic features remained unchanged in patients with therapy resistance or further disease progression. CONCLUSION: Analysis of myelodysplastic manifestations in different hematopoietic lineages in patients with MDS should be based on the comprehensive dynamic assessment of cytological and histological parameters at both the primary diagnosis of the disease and different stages of treatment. With a response to decitabine therapy (as shown by the results of aspiration and trepanobiopsy), all cell lines displayed reduced myelodysplastic changes, indirectly indicating a decrease of the abnormal clone itself in high-risk MDS patients.

[Crystalline histiocytosis].

The paper describes a case of diagnosis of the rare monoclonal secretion-associated disease crystalline histiocytosis with kidney and bone marrow involvement. The female patient with multiple myeloma (MM) was found to have intralysosomal crystals in the cells of the bone marrow (histiocytes, plasmocytes), kidneys proper (mesangiocytes, podocytes), and subsequently in those of a kidney graft. Lower secreted monoclonal IgG and ceased Bence-Jones protein secretion after MM chemotherapy were accompanied by improved and stabilized kidney graft function. However, a repeat morphological study of a renal biopsy specimen showed that the crystalline inclusions were preserved in the podocytes. By comparing the immunological and renal responses, it is reasonable to suggest that monoclonal IgG rather than Bence-Jones protein is of value in the pathogenesis of crystal formation.

[Parenchymatous-stromal factors in hemoblastoses].

The data available in the literature data on the role of neoangiogenesis and extracellular matrix factors in the pathogenesis of acute and chronic leukemias and lymphoproliferative diseases are presented. Hematopoiesis and endothelial cells have a common pluripotential progenitor. Angiogenic and fibroblast growth factors are involved chronic leukemia. The phenotype of lymphoid cells determines the type of the cellular and extracellular factors.

[Transplantations of allogenic and autologous hemopoietic stem cells in acute leukemia (results of 20-year experience)].

AIM: To analyse results of transplantation of allogenic and autologous hemopoietic stem cells (allo-THSC and auto-THSC) with myeloablation preconditioning in patients with acute leukemia (AL) performed in 1987-2006. MATERIAL AND METHODS: A total of 71 allogenic and 45 autologous THSC were performed in 116 patients with different AL variants. Conditioning in all allo-THSC included busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). This regimen was used in 29 recipients of auto-HSC. Cyclophosphamide in a dose 120 mg/kg and total radiation of the body in a dose 12 Gy were given to 16 recipients. Overall, relapse-free and event-free survival of patients after THSC were analysed as well as early (first 100 days) and overall lethality. Auto-THSC in 15 patients was for the first time followed by immunomodulating therapy aimed at prevention of AL relapses: in acute myeloid leukemia ATRA in combination with alpha-interferon, in acute lymphoblastic leukemia (ALL)--ronkoleukin, interleukin-2 preparation. RESULTS: Overall survival of AL patients after allo-THSC for the observation period increased from 31 to 58%, early lethality fell from 44 to 4%. Results of allo-THSC conducted in the first complete remission were much better than in patients with other AL stages at the time of THSC. After auto-THSC 5-year survival rose from 22 to 60% while early lethality reduced from 33 to 4%. Administration of immunomodulating therapy after auto-THSC increases 5-year survival from 35 to 80%. CONCLUSION: Outcomes of THSC in AL has improved for the last 20 years. Outcomes of allo-THSC performed in the first complete remission are much higher. Immunomodulating therapy after auto-THSC promoted better results.

[Diagnosis of lymphoproliferative diseases by bone marrow trepanobiopsy specimens].

Based on the study of 2000 bone marrow trepanobiopsy specimens from patients with different types of lymphoproliferative diseases, the authors present the incidence and specific features of specific bone marrow lesion and the state of normal hemopoiesis and stroma. They also give data of bone marrow immunohistochemical studies using a many mono- and polyclonal antibody panels. The criteria for the differential diagnosis of reactive polyclonal lymphoid proliferation in the bone marrow that may accompany many hematological and non-hematological diseases with specific bone marrow lesion in lymphoproliferative diseases are outlined. The high diagnostic value of a study of bone marrow trepanobiopsy specimens is shown in the diagnosis of lymphoproliferative diseases.

[Diagnosis of early manifestations of myocardial dysfunction at early stages of antitumor treatment in patients with lymphogranulomatosis and lymphosarcomas].

AIM: To comparatively assess the capabilities of currently available instrumental studies in the diagnosis of early cardiac performance changes in patients with lymph tumors at different stages of treatment and to study the myocardial histomorphological pattern in relation to the intensity of the therapy performed (as evidenced by sectional studies). MATERIALS AND METHODS: 44 patients, including 26 with various types of lymphogranulomatosis (LGM) and 18 with lymphosarcomas were examined at different stages of antitumor treatment. Radionuclide equilibrium ventriculography (REVG), echocardiography (EchoCG), and electrocardiography (ECG) were used. Postmortem studies of the myocardial histological pattern were conducted in 20 patients (archive data). RESULTS: No significant pathological REVG, EchoCG, and ECG changes were found in 10 patients examined prior to treatment. In a group of 17 patients receiving a total dose of doxorubicine of 240 +/- 30 mg/m2, there was a significant decrease in diastolic duration, a reduction in diastolic volume, end systolic volume, stroke volume, stroke index, filling fraction over 1/3 diastole. In a group of 17 patients receiving a total dose of doxorubicine of 250 +/- 30 mg/m2 and radiotherapy applied to the mediastinum, the above changes were more marked. There were myocardial histomorphological changes whose magnitude progressed as therapy became more intensive. CONCLUSION. The findings have indicated that by using relatively small cumulative dose of anthracyclines, cardiovascular dysfunction can occur at the early stages of programmed treatment for LGM and lymphosarcomas. REVG has the greatest advantage in their detection.

[A case of the long course of acute intermittent porphyria].

A case of acute intermittent porphyria is described in a 37-year-old female patient treated with normasang, a drug that regulates porphyrin metabolism at the last stages of the disease. Chronic renal failure with the hypertensive syndrome, severe neurological symptoms, and vascular sclerotic changes in all organs were the symptoms of the underlying disease. Infectious complications were the cause of sepsis and favoured deteriorated multiple organ dysfunction that determined lethal exitus.

[Chromosomal aberrations in myelodysplastic syndrome].

AIM: To analyse incidence rate of chromosomal aberrations in myelodysplastic syndromes (MDS), specification of clinicomorphological features of some cytogenetic variants. MATERIAL AND METHODS: Chromosomal analysis by the method of G-differential staining of chromosomes was made in 209 patients with different variants of MDS. RESULTS; Clonal chromosomal aberrations occured in 60.8%. The following aberrations were found most frequently: deletion of the long arm of the chromosome 5 (del(5q)) - 34.6%, trisomy of chromosome 8 (14.1%), monosomy of chromosome 7 (13.4%), aberrations 3q21q26 (12.6%), aberrations of a long arm of X-chromosome (4.7%), the absence of Y-chromosome (3.1%). Complex aberrations of karyotype were found in 13.5% cases. Chromosomal aberrations determined not only clinical and morphological features but also the prognosis of the disease. CONCLUSION: Cytogenetic examination is an essential component of MDS patients examination. It allows more precise classification of MDS variant and prognostification of the disease course.

[Lung biopsy in the diagnosis of causes of lung involvement in hemoblastosis]. / Biopsiia legkogo v diagnostike prichin porazheniia legkikh u bol'nykh gemoblastozami.

AIM: To ascertain the role of lung biopsy in diagnosis of lung lesions in hemoblastosis (HB) patients. MATERIAL AND METHODS: The results of diagnostic biopsies of the lungs obtained from 22 HB patients are presented. Ten patients had no respiratory insufficiency (RI), twelve patients had RI. The biopsy was transbronchial in 1 case, thoracoscopic in 10 and open in 11 cases. RESULTS: In RI-free patients lung biopsy was informative in all the cases. The biopsy provided information which allowed therapy modification resulting in improvement of the patient condition. In RI patients biopsy was informative in 8 of 12 patients. Nonspecific changes in the lungs were identified histologically in 2 of 12 patients. In 2 RI patients lung biopsy confirmed the diagnosis made after examination of the bronchoalveolar lavage. Modification of therapy after the biopsy was conducted in 58.3% HB patients with RI. Improvement was seen in 2 of them. 10 of 12 patients with RI died within 1-2 weeks after biopsy. CONCLUSION: Lung biopsy in HB patients should be obtained only after examination with noninvasive methods and before development of RI as prognosis after lung biopsy in the presence of RI is unfavourable. The histological material should be examined for all expected pathogens.

[Bone marrow alterations in sarcoidosis]. / Izmenenie kostnogo mozga pri sarkoidoze.

Trepanobiopsy of the bone marrow followed by a histological study was performed in 3 patients with sarcoidosis diagnosed in peripheral lymph node (LN) biopsies. Granulemas revealed in trepanobiopsies were identical to those found in LN. Trepanobiopsy is advisable in patients with sarcoidosis having some changes in hemogram.

[Clinical manifestations, diagnosis and course of Pneumocystis carinii pneumonia in patients with hematologic diseases]. / Klinicheskie proiavleniia, diagnostika i techenie pnevmotsistnoi pnevmonii u bol'nykh s zabolevaniiami sistemy krovi.

AIM: To characterize clinical, diagnostic and course features of pneumonia caused by Pneumocystis carinii (PC) in hematologic inpatients. MATERIALS AND METHODS: 27 patients with blood diseases were studied. 22 of them had acute respiratory insufficiency and 5 had unclear lung affection. The data from bronchoalveolar lavage (BAL), lung biopsy, serum tests for IgG, IgM anti-PC-antibodies were used for diagnosis of PC-pneumonia. RESULTS: PC-pneumonia was diagnosed in 8 of 27 patients. Clinical manifestations characteristic for PC-pneumonia were not found. In 5 patients the diagnosis was made on the evidence provided by BAL. Lymphocyte count in BAL was elevated to 27.7 +/- 8.7%. Open biopsy of the lung and transbronchial biopsy diagnosed PC-pneumonia in 2 and 1 patients, respectively. Previous BAL examinations failed to detect PC-pneumonia in 2 of them. In all the patients PC-pneumonia was associated with another infection (bacterial, cytomegaloviral). Histologically, the picture of the disease was determined by the severity of the lung affection or its complications. 5 of 8 patients failed treatment with trimethoprim-sulphamethoxazole and died. Marked respiratory insufficiency was registered at PC-pneumonia diagnosis in all the lethal cases. CONCLUSION: Clinical and x-ray pictures of PC-pneumonia in hemoblastosis patients are not specific. All such patients with symptoms of lung infection resistant to antibacterial and antifungal therapy should be examined for PC-pneumonia.

[The prognostic criteria in the primary myelodysplastic syndrome]. / Prognosticheskie kriterii pri pervichnom mielodisplasticheskom sindrome.

Basing on computer processing of 126 primary clinical and laboratory parameters obtained from 92 patients with myelodysplasia and using multifactorial regression analysis, the authors have developed prognostic models of life span and probability of transformation into acute leukemia. The model of life span enabled recognition of 3 prognostic groups of myelodysplasia patients: of high (median 10 months), moderate (median 22 months) and low (median 35 months) risk. This makes it possible to prognosticate the disease and assume optimal therapeutic policy.

[Restoration of hematopoiesis following allo- and automyelotransplantation in patients with hemoblastosis]. / Osobennosti vosstanovleniia gemopoéza posle allo- i automielotransplantatsii u bol'nykh gemoblastozami.

The early stages of hemopoiesis repair as indicated by histologic examinations of trephine biopsy specimens (visual assessment and morphometry) are characterized in 39 patients with hemoblastoses, 33 of these with acute leukemia, 4 with chronic myeloleukemia, and 2 with lymphoblastic lymphosarcoma, following transplantation of allogeneic (n = 19), syngeneic (n = 5), and autologous (n = 15) bone marrow after conditioning with cyclophosphamide plus total radiation exposure in 27 patients and myelosan with cyclophosphamide in 12 ones. Hemopoiesis repair was found to be slower after autologous transplantation of bone marrow than after allogeneic transplantation and in patients following conditioning with cyclophosphamide and total irradiation in comparison with those pretreated with myelosan and cyclophosphamide. Patients' age over 25, diagnosis of the disease more than 12 months before transplantation, and variant of leukemia (nonlymphoblastic) were the factors exerting negative influence on the rate of hemopoiesis recovery.

[Cytopenic syndromes in chronic hepatitis]. / Tsitopenicheskie sindromy pri khornicheskom gepatite.

The course of chronic hepatitis complicated by cytopenia has been analyzed for 31 patients. Clinical manifestations, early and differential diagnosis, treatment policy have been specified. It is advisable that such patients be observed both by hematologists and hepatologists.