[Five year experience in ibrutinib therapy for relapsed and refractory mantle cell lymphoma in real world Russian clinical practice].

BACKGROUND: Mantle cell lymphoma (MCL) is a rare and clinically aggressive lymphoma subtype. Current approaches have greatly improved patients outcomes, but relapse is inevitable. In phase IIIII clinical trials, ibrutinib has shown significant activity in patients with relapsed or refractory (R/R) MCL. AIM: To assess efficacy and toxicity of ibrutinib monotherapy in patients with R/R MCL in routine practice outside of clinical trials. MATERIALS AND METHODS: The study enrolled patients with confirmed R/R MCL who had received at least one line of previous chemotherapy. ECOG 24, cytopenia, infectious complications, hemorrhagic syndrome were not exclusion criteria. Patients received daily oral ibrutinib 560 mg until progression or unacceptable toxicity. RESULTS: From May 2015 to September 2020 ibrutinib therapy was started in 106 patients with R/R MCL in 16 regions of Russia. The median age was 66 years; ECOG2 18%, blastoid variant (or Ki6740% or WBC50109/l) 43%. The median number of previous treatment lines was 2 (111). The ORR was 78.4% (CRR 27.4%). The median PFS was 13.6 months and OS 23.2 months. In the blastoid group the median PFS was 4.4 months vs 36.5 months in the alternative group (p0.001), the median OS 9.0 vs 41.0 (p=0.001). The median OS of patients after progression on ibrutinib was 3.2 months. The common complications are hemorrhages (63%), diarrhea (62%), myalgia and muscle cramps (60%), infections (31%), skin and nail toxicity 15%, arrhythmia 8%. None of recipients had to completely discontinue ibrutinib therapy due to complications. CONCLUSION: Ibrutinib is effective and well tolerated in routine practice of R/R MCL treatment and our results are consistent with international clinical trials. The favorable toxicity profile and the high response rate made it possible to prescribe ibrutinib in severe somatic status, cytopenia, and even in the presence of infectious complications.

[The experience in non-relative allogenic transplantation of stem hemopoietic cells in the Clinic of Bone Marrow Transplantation at I.P. Pavlov St-Petersburg Medical Academy].

AIM: To evaluate efficacy of allogenic transplantation of hemopoietic stem cells (allo-THSC) from non-relative donor in patients with hematological diseases in the Clinic of Bone Marrow Transplantation at L.P. Pavlov St-Petersburg Medical Academy for the period 2000-2006. MATERIAL AND METHODS: A total of 84 allo-THSC from non-relative donor to patients aged from 10 months to 65 years (median 18 months, 44 years) was carried out. RESULTS: Six-year overall survival (OS) in all the patients was 51.4%, in remission of AML--66.7%, ALL--33%, depending on the presence or absence of acute reaction graft versus host reaction (GVHR)--54 and 50.9%, chronic FVHR--75.6 and 58.2%, blood group compatibility or incompatibility in donor/recipient pairs--58.4 and 47.9%, by gender--61.4 and 40.6%, in use of HSC of the bone marrow--58.3%, peripheral blood--26.7%. OS in the dose of transplanted CD 34+ cells per 1 kg body mass < 5.0 x 10(6)/kg--173%, in the dose 5.0--8.0 x 10(6)/kg--38.8%, > 8.0 x 10(6)/kg--35.5%. Acute GVHR developed in 56% patients, chronic--in 20%, hemorrhagic cystitis--in 27.7%, bacterial, cytomegalovirus and fungal infection--in 10, 70 and 30%, respectively. The causes of death were acute GVHR (20%), infection 99%), polyorganic failure (4%), transplant rejection (5.3%), recurrence (18.7%). CONCLUSION: Bone marrow transplantation clinics in the Russian Federation must develop all kinds of allo-THSC--relative, non-relative and haploidentical using bone marrow, peripheral blood, umbilical blood as the source of HSC. It is necessary to create a national register of non-relative donors.

[Use of dexamethasone in treatment of high- and low-grade non-Hodgkin's lymphoma]. / Primenenie deksametazona pri nekhodzhinskikh limfomakh vysokoi i nizkoi stepeni zlokachestvennosti.

Since it exerts a stronger antitumor action than predinisolone, dexamethasone was used for therapy of patients with non-Hodgkin's lymphoma refractory to CHOP. All patients (66), resistant to CHOP, suffered bone marrow involvement. Dexamethasone pulsed therapy was given to 45 patients, with 21 COP-BLAM or ASHAP, MAD, Dexa-BEAM treated in control. Median response duration in high- and low-grade non-Hodgkin's lymphoma groups was 2 and 12 months, respectively.

[Effectiveness of dose-intensive polychemotherapy with autologous hemopoietic cell transplantation for high-grade non-Hodgkin lymphoma]. / Effektivnost' intensifikatsii polikhimioterapii, vkliuchaia autologichnuiu transplantatsiiu gemopoéticheskikh kletok, u bol'nykh nekhodzhkinskimi limfomami vysokoi stepeni zlokachestvennosti.

The study included 29 patients with high-grade non-Hodgkin's lymphoma. Nine patients (group 1) received 6-8 cycles of CHOP, another 20-6 cycles of CHOP and Dexa-BEAM followed by autologous hemopoietic cell transplantation with CBV or BEAM conditioning regimen (bone marrow or peripheral stem cells) (group 2). The groups were comparable as far as gender and age are concerned. Overall 5-year survival was in 24.1 and 71.4%, respectively. Double CHOP-Dexa-BEAM plus autologous hemopoietic cell transplantation proved superior to standard CHOP-therapy.

[Effectiveness of high-dose polychemotherapy and autologous hemopoietic cell transplantation in patients with low-grade non-Hodgkin lymphoma]. / Effektivnost' intensifikatsii polikhimioterapii i autologicheskoi transplantatsii gemopoéticheskikh kletok u bol'nykh nekhodzhkinskimi limfomami nizkoi stepeni zlokachestvennosti.

The study included 70 patients with high-grade malignant non-Hodgkin's lymphoma (Kiel) who received the following treatment: group 1(24)--6-8 cycles of CHOP; group 2 (relapse or tumor progression after standard chemotherapy--13)--6 cycles of CHOP and Dexa-BEAM, and group 3 (relapse or tumor progression after standard chemotherapy--8)--6 cycles of CHOP plus Dexa-BEAM plus autologous hemopoietic cell transplantation with CBV or BEAM conditioning regimen (bone marrow or peripheral stem cells). The groups were comparable as far as gender and age are concerned. Overall 5-year survival rates were 81, 20 and 48%, respectively. CHOP-Dexa-BEAM plus autologous hemopoietic cell transplantation proved superior to CHOP-Dexa-BEAM alone.

[The transplantation of hemopoietic cells in patients with solid tumors]. / Transplantatsiia gemopoéticheskikh kletok u bol'nykh s solidnymi opukholiami.

AIM: Evaluation of efficiency of bone marrow and peripheral stem cells transplantation in patients with solid tumors. MATERIALS AND METHODS: A total of 38 patients aged 30-40 years with stage III or IV solid tumors (15 cases of breast cancer, 5 cases of Ewing's sarcoma, 4 cases of osteogenic sarcoma, ovarian or testicular tumors, 3 cases of soft tissue sarcoma) underwent high-dose polychemotherapy with autologous hematopoietic rescue. All the patients were resistant to the first line chemotherapy or were in relapse of the disease. 21, 11 and 6 patients were transplanted bone marrow, peripheral blood stem cells and both bone marrow and peripheral blood stem cells, respectively. RESULTS: The only factor which influenced overall survival of the patients was the stage of the disease at the moment of the transplantation. 66% of patients in complete or partial remission survived 3 years versus 16.6% of those in progression or relapse of the disease. Other parameters such as the patients' age, the source of hemopoietic cells, number of chemotherapy courses were not essential for the survival. 2 patients died after transplantation. The main cause of death was relapse or progression of the disease after the transplantation. CONCLUSION: Transplantation of hemopoietic cells is a promising therapy of patients with solid tumors sensitive to chemotherapy.

[Distribution of viruses from the Californian encephalitis serogroup (Bunyaviridae, Bunyavirus) in the northern expanses of Russia]. / Rasprostranenie virusov serogruppy Kaliforniiskogo éntsefalita (Bunyaviridae, Bunyavirus) v severnykh shirotakh Rossii.

The study was carried out in 1983-1991 and covered a territory of about 10 x 10(6) km2 in various physico-geographic areas (East Fennoscandia, Northern Russian Plain, West Siberia, Central Siberia, North-Eastern Siberia, and Northern Pacific Region) in the Arctic, Subarctic, Northern-Central-Southern taiga, forest-steppe, and steppe in Northern Russia. A total of 251 strains were isolated from 1391,900 mosquitoes, identified as the California group snowshoe hare (83), Inkoo (44), and Tahyna (2) viruses; 122 strains were not completely identified. Some of the strains with uncommon antigenic composition can be natural reassortants. Fifty-two percent of strains were isolated from Aedes communis and the associate species of mosquitoes, other hosts were A. excrucians (8%), A. cantans (6.25%), A. flavescens (6.25%), A. ciprius (6.25%), A. punctor (4.5%), A. vexans (4.5%), A. cataphylla (3.6%), A. nigripes (3.6%), and A. hexodontus (2.6%). The infection rate of mosquitoes was 0.009% in the tundra, 0.012% in forest-tundra, 0.01% in Northern taiga, 0.02% in Central taiga, 0.017% in Southern taiga, 0.026% in forest-steppe, and 0.097% in steppe. The epidemic season is one month in the tundra (from the beginning of July till the beginning of August), two months in Northern taiga (July-August), and three months in Central taiga (from the second half of June till the beginning of September). The highest infection rate of mosquitoes was observed at the end of the epidemic season in all regions. SSH strains prevailed to the East from the Enisei river, whereas to the West and in the Subarctic regions INK virus predominated, SSH being rare; in the taiga the distribution was quite the opposite. TAH virus was virtually absent. Human morbidity was observed in all territories studied. The immune stratum of adult population is about 30% in the tundra and forest-tundra and about 50% in Northern and Central taiga.

[Intracellular interactions in the hematopoietic system after massive radiation exposure]. / Mezhkletochnye vzaimodeistviia v sisteme gemopoéza posle massivnogo radiatsionnogo vozdeistviia.

The review article deals with acute radiation damage to the bone marrow spatial structure, disturbances of cell-cell interactions, and stromal cytokine(s) production, hence representing limiting factors for effective postradiation recovery of blood system. The evidence for radiation-induced stromal functional activation is discussed, along with opportunity of local growth factors deficiency, thus requiring a replacement therapy with exogenous cytokines.

[The target cells of serotoninergic innervation in the locus coeruleus]. / Kletki-misheni serotoninergicheskoi innervatsii v golubovatom meste.

Method of selective chemical injury of locus ceruleus (LC) has revealed the following serotonergic structures: axonal varicosities, terminals and synapses. Serotonergic structures in LC are numerous. Small neurons with peculiar structures are described which are the targets of serotonergic innervation in LC and are responsible for interrelation with the proper noradrenergic cells and for intermediate interactions.

[The determination of hepatitis A antibodies in epidemiological practice]. / Opredelenie antitel k gepatitu A v épidemiologicheskoi praktike.

Epidemiological analysis of hepatitis A morbidity in a city with the population of 500,000 persons in 1960-1987 was carried out. Three periods of morbidity rises among children aged 3-6 years and 7-14 years and living at the same areas (microdistricts) were established. Blood sera from healthy children were tested for the presence of antibodies to hepatitis A in enzyme immunoassay. The data on the sanitary and bacteriological study of tap water were analyzed. Unsatisfactory results of water analysis in different microdistricts correlated with the presence of antibodies in the population of these microregions and with the average morbidity indices for many years.

[Specific prevention of diphtheria in adults in foci of this infection]. / Spetsificheskaia profilaktika difterii u vzroslykh v ochagakh étoi infektsii.

The studies demonstrated the immunological and epidemiological effectiveness of a single injection of adsorbed diphtheria-tetanus toxoid with reduced antigen content for adults: intense antidiphtheria immunity in 92.3% of the vaccinees 1-3 months and in 94.5% of the vaccinees 1 year after the injection. This immunity remained sufficiently intense for 3 years (the term of observation). The geometric mean of antitoxic titers was 0.84 I. U./ml. The highest intensity of immunity appearing after the injection was observed in persons aged 18-20 years who showed the highest antitoxic titers (exceeding 0.5 I. U./ml) in 100% of cases, the lowest intensity was registered in the age group of 30-39 years; in 14.2% of these vaccinees antitoxic titers were below the protective level. In other age groups (40-49 years, 50 years and over) the intensity of immunity was high. The geometric mean of the titers of diphtheria antitoxin were 1.2 I. U./ml and 2.1 I. U./ml respectively. In none of the foci under study the spread of the manifest forms of the disease was observed.

[Experience in dividing Tyumen Province into districts according to typhoid morbidity based on sanitary demographic factors]. / Opyt raionirovaniia Tiumenskoi oblasti po zabolevaemosti briushnym tifom na osnove sanitarno-demograficheskikh faktorov.

For the first time the territory of Tyumen Province has been zoned according to situation in typhoid fever morbidity by means of a complex of methods for computerized statistical data processing in combination with extensive epidemiological analysis. As a result, 43 administrative districts have been grouped in 5 zones having similar epidemiological, sanitary, hygienic, and demographic characteristics. For these zones territorially differentiated measures for decreasing typhoid fever morbidity have been worked out.