Цель: проанализировать результаты терапии случаев с ВИЧ-ассоциированной лимфомой Беркитта и крайне тяжелым исходным соматическим статусом – ECOG 3–4 балла на момент госпитализации.Материалы и методы: с 2015 по 2019 г. среди госпитализированных ВИЧ-инфицированных пациентов с агрессивными лимфомами 14 случаев характеризовались крайне тяжелым соматическим статусом и ECOG 3–4 балла: 5 случаев были представлены лимфомой Беркитта (ЛБ) с лейкемизацией (2 мужчин и 3 женщины), 4 случая плазмобластной лимфомой и 5 случаев диффузной В-крупноклеточной лимфомой. Два случая ЛБ характеризовались поражением кроме костного мозга – матки и почек с развитием ХПН IV–V (клиренс креатинина менее 20 мл/мин) и матки и яичников у другой пациентки. У одного пациента отмечалось поражение теменной области больших полушарий, у другого – головного, спинного мозга с развитием нейролейкемии, нижним парапарезом, нарушением функции тазовых органов, поражением желудка и поджелудочной железы. Во всех случаях показатели ЛДГ превышали верхнюю границу нормы в 3 и более раз. Показатели вирусной нагрузки составляли от 21 000 до 660 000 копий/мл, количество CD4+ клеток в периферической крови в двух случаях менее 200 клеток/ мкл. Почти во всех случаях ЛБ ВААРТ терапия была начата после первого блока NHL-BFM-90 с модификацией. Модификация состояла в проведении первым блока B и введении первой дозы высоких доз метотрексата с отсрочкой к концу первого / началу второго блока. Случаи с ДВККЛ и плазмобластной лимфомой получали R-CHOP или DA-EPOCH-терапию.Результаты: наилучшие показатели ОВ отмечены в группе с ЛБ – в настоящее время живы 4 пациента из 5, общая 5-летняя выживаемость составила 80%. Гематологическая токсичность блоковой терапии была представлена нейтропениями III–IV степени по ВОЗ длительностью 4–11 дней и тромбоцитопениями II–IV степени длительностью 6–10 дней. Антибиотическаятерапия и стимуляция Г-КСФ проводилась во всех случаях и включала карбапенемы, линезолид и эхинокандины. Максимальная потребность в аппаратном тромбоконцентрате – 10 доз после одного из блоков AA.Выводы: выполнение блоковой терапии у пациентов с ВИЧ-ассоциированной ЛБ в условиях онкологического диспансера возможно, позволяет достигнуть хороших результатов, но требует участия высококвалифицированного врачебного и среднего медицинского персонала, а также адекватной сопроводительной терапии. Purpose. To analyze the treatment outcomes in patients with HIV-associated Burkitt lymphoma and extremely poor baseline physical health – ECOG 3-4 at the time of admission.Materials and Methods. Over the period from 2015 to 2019, 14 hospitalized patients with HIV- associated aggressive lymphomas were in extremely poor health and with ECOG of the grades 3–4: 5 cases were the patients with Burkitt lymphoma (BL) and leukemization (2 males and 3 females), 4 cases of plasmablastic lymphoma (PBL), and 5 cases of diffuse large B-cell lymphoma (DLBCL). In two cases of BL, in addition to bone marrow involvement, in one patient, the uterus and kidneys were affected, which resulted in chronic renal insufficiency IV–V (creatinine clearance – less than 20 ml per min), and uterine and ovarian involvement in the other patient. One patient also showed parietal involvement of both cerebral hemispheres, another patient had cerebral and spinal cord involvement resulting in meningeal leukemia and lower extremity paraparesis, impaired function of pelvic organs, gastric and pancreatic involvement. In all cases, the LDH values were 3 times or more as high as the upper normal level. The viral load values ranged from 21 000 to 660 000 copies/ml, the number of CD4+ cells in the peripheral blood was less than 200 cells/mcl in two cases. HAART therapy was initiated after the first cycle of modified NHL-BFM-90 almost in all cases of BL. The modification included starting with B-cycle and delayed administration of the initial dose of high dose methotrexate therapy, which was started at the end of the first/beginning of the second cycle. Patients with DLBCL and PBL received R-CHOP or DA-EPOCH regimens.Results. The best OS values were registered in the group with BL – 4 out of 5 patients are still alive, overall five-year survival reached 80%. The hematologic toxicity profile of the cycle therapy included the grade III–IV neutropenia, according to the WHO classification, which lasted 4–11 days, and the grade II–IV thrombocytopenia lasting 6–10 days. Antibiotic therapy and G-CSF stimulation were given to all patients and included carbapenems, linezolid, and echinocandins. The maximum demand for instrumentally-induced platelet concentrate was 10 doses after one of AA cycles.Conclusion. Administration of cycle therapy for treating patients with HIV-associated BL in conditions of oncological health centre helps to achieve good clinical outcomes, but requires both highly-qualified medical and paramedical staff, as well as appropriate accompanying therapy.

Since chemotherapy of Hodkgin’s lymphoma was introduced in early 60s, it has undergone fundamental changes that were associated with dramatic improvement in the disease prognosis. Currently, the various intensive modifications of original BEACOPP, such as BEACOPP-14 and escalate BEACOPP, are among the most widely used for treatment of advanced Hodkgin’s lymphoma. Initially, the International Prognostic Score (IPS) was developed for patients treated with MOPP and MOPP-ABVD protocols. We suggest that due to the well-known changing value of the various prognostic signs with protocols of different intensity, the significance of IPS for BEACOPP-based therapy should be reconsidered. One hundred seventy two patients with advanced Hodgkin’s lymphoma were included in our trial. All these patients were treated at the Hematology department of Volgograd Regional Oncology Clinic № 1. Treatment options were as follows: 64 (37%), 84 (49%), and 24 (14%) patients received intensive BEACOPP-based, standard BEACOPP, or ABVD therapy, respectively. The final data presented are related to the period up to June 30, 2012. We retrospectively evaluated the treatment outcomes for each IPS group. To distinguish the most significant prognostic signs from all six IPS factors, we studied the impact of each factor on treatment efficacy. The greatest difference in overall 3and 4-year survival was observed between the groups of patients with IPS 0-1 and ≥ 2; for IPS 0-1, 3and 4-year overall survival rate was 93%; for IPS ≥ 2, 3and 4-year overall survival rate was 81% and 75%, respectively (p = 0.05). 3-year overall survival was significantly negatively affected by such factors as age over 45 (70% versus 87%, relative risk (RR) = 3.95% CI: 1.7-7, p = 0.01) and albumin level < 40 g/L (79% versus 88%, RR= 2.8, 95% CI: 1.2-6.8, p = 0.02). Overall 3-year survival rate in males (n = 91) and females (n = 81) was 80% and 88%, respectively (p = 0.09). We found no effect on overall and freedom-from-treatment-failure survival (FFTF) of such factors as hemoglobin levels, lymphocyte count, leukocytes count, and IV stage disease. With respect to overall survival, multivariate analysis showed the greatest significance of age (relative risk, RR =3.6, 95% CI: 1.8-7, p = 0.001) and albumin level (OR = 2.6, 95% CI: 1.1-6, p = 0.036).

Mutation status of 36 chronic myeloid leukemia (CML) patients in chronic phase with primary and secondary imatinib resistance was analyzed. BCR-ABL mutations identified by direct DNA sequencing. BCR-ABL kinase domain mutations were detected in 30.5 % (11 of 36) of those patients. Most of identified mutations were missense mutations: Q252H, M244V, G250E, Y253F/H, E255K/V, T315I, M351T, F359V, F359C, F486S. Patients with BCR-ABL mutations have significantly lower 4-year event-free survival compared with CML patients without mutations (18 % vs. 53 %; р = 0.003). The results can be used as reference information in deciding on therapy in imatinib resistant CML patients with clinically relevant BCR-ABL mutations.

Today for the treatment of Hodgkin’s lymphoma schemes of varying intensity are used. The choice of first-line chemotherapy for Hodgkin’s lymphoma depends on the stage of the disease and risk factors. We present the results of patients with newly diagnosed Hodgkin’s lymphoma in the period from 2003 to 2008 (n = 244), treated in the Department of Hematology Volgograd Regional Clinical Cancer Dispensary No. 1. The early stages of Hodgkin’s lymphoma without risk factors were characterized by the best results with minimal adverse effects (3-year overall survival rate in this group is 95 %, free from treatment failure 90 %). In patients with early stages of Hodgkin’s lymphoma with risk factors there was no significant difference between ABVD and BEACOPP-basis schemes in terms of overall survival (3-year OS 80 % in each group) and free from treatment failure survival (3-year FFTF 76 % and 52 % respectively, p = 0,73). There is a slight tendency to improve OS and FFTF in these patients when treated with BEACOPP-escalated and BEACOPP-14, but the lack of patients can’t prove the benefit of these programs. Among patients with advanced Hodgkin’s lymphoma the greatest differences in OS were observed between those who received BEACOPP-basis and intensive variants of BEACOPP scheme (OS rate 74 % and 95 % (p < 0,01), FFTF 55 % and 72 % (p = 0,05) respectively.

Imatinib has shown the high effectiveness in chronic myeloid leukemia (CML) therapy. Recent papers have demonstrated that the achievement of complete cytogenetic response and major molecular response to imatinib therapy may be related with more than 1000 ng/ml imatinib plasma level. Trough plasma concentrations of imatinib (Ctrough) were detected in 551 samples of 442 CML patients. Blood samples were collected 24 b 3h after the last IM dose at 300 (n = 8), 400 (n = 337), 600 mg (n = 155) QD and 12 b 3h after the last IM dose at 800 mg BD(n = 51). Imatinib plasma concentration was determined by a validated LC/ MS/MS method. Rationales for imatinib blood level testing: the patient is not responding as well as the physician would expect, the physician suspects that the patient may be nonadherent to imatinib, the physician suspects that the patient may be experiencing a drug-drug interaction, the patient is experiencing unusually severe side effects. A result of nonadherence to treatment is one of the most important reason of treatment failure or suboptimal response to imatinib (n = 32; 5.8 %). The level of noncompliance increases with higher imatinib doses. Imatinib trough plasma level less than 1000 ng/ml were founded in one half of cases.

The effectiveness of the CD34-positive cell harvesting in multiple myeloma patients treated with four courses of PAD (bortezomib, adriablastin, dexametasone) was evaluated. As soon as treatment was finished patients were reevaluated. Three patients who had achieved complete or good partial remission received high-doses of cyclophosfamide. Then their bone marrow was stimulated with G-CSF and CD34-positive cells were collected. In all three cases the number of CD34-positive cells harvested was enough for transplantation and bone marrow repopulation. CD34-positive cells counting and cryopreservation were performed in National Centre for Hematology [Moscow]. The results of this work are crucial for introduction of modern programs of intensive treatment of hematooncological patients.