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Aim. To comparatively analyze the toxicity of 4 treatment protocols in patients with acute myeloid leukemia (AML), which were used in the Russian multicenter center in 1992 to 2009. Materials and methods. The information obtained in 4 Russian multicenter studies conducted in 33 hematology departments of 26 cities and towns of the Russian Federation in 1992 to 2009 was analyzed. Randomization was made in 243 patients with AML (median age 38 years) in 1992-1995, 396 patients (median age 39 years) in 1995-1999, 392 patients (median age 39 years) in 2001-2006, and 137 patients (median age 40 years) in 2006-2009. The analysis excluded patients with acute promyelocytic leukemias who were recruited in the AML-92 and AML-95 studies. These patients' statutory forms adequately filled in were 60-70% therefore toxicity was analyzed on the basis of the data of 631 patients. Results. The baseline clinical and laboratory parameters in the patients enrolled in the studies in different years slightly differ in the count of leukocytes at the onset of the disease and in the level of lactate dehydrogenase (LDH): the recent studies revealed a larger number of high-risk group patients (leukocytes more than 30109/l; LDH more than 500 units) possibly due to the later diagnosis of AML. During the studies, the number of complete remissions remained as before (55%) after the first course and increased from 65 to 78% after the second course using cytosine arabinoside in high doses. Despite treatment intensification, mortality in the induction period remained as before (19-21%). Remission mortality decreased from 18 to 10-13%. The long-term results of using the aggressive therapy did not differ from those obtained during the standard treatment protocols. The duration of leucopenia after standard induction courses during the all studies remained equal (17-19 days); the exclusion was a HAM course as the second induction course after which the duration of neutropenia was much more than that of the standard course (17 and 10 days, respectively). During the study years, there was an increase in platelet transfusion volumes (from 20 to 53 doses during the first course and from 7 to 28 doses during the second course) and a reduction in the percentage of severe hemorrhagic complications. The incidence of pneumonias remained at the same level (40-50%) during the induction courses and that of septic complications and necrotic enteropathy considerably decreased from 40-46 to 17-19%. The incidence of invasive aspergillosis during the current programs from AML treatment was 10% (two induction courses), that of invasive candidiasis was 4.7% (two induction courses). Conclusion. The long-term results of treatment for AML were virtually unchanged regardless significant therapy intensification. Mortality remained high during induction treatment and in the postremission period. Its cause is severe infectious complications developing during myelotoxic agranulocytosis. The results of the analysis provide the basis for developing a new AML treatment protocol that should take into account all the merits and demerits of the previous protocols and provide a toxicity-treatment efficiency balance.

Aim. To study efficacy of maintenance therapy of patients with acute promyelocyte leukemia (APL) in the APL treatment Russian multicenter trial. Material and methods. The trial was made with participation of 18 hematological departments of clinics in Russia. A total of 68 APL patients entered the trial. The maintenance therapy consisted of 5day courses of cytostatic drugs which alternated or did not altenate with 5-day courses of ATRA. Cytogenetic tests were made in 31 patients, t(15;17) was detected in 26 of them. Molecular examination conducted in 28 patients discovered chimeric transcript PML/RARa in 26 of them. Of 20 patients examined in Hematological Research Center, 7 (35%) had a bcr 1/2 variant of the transcript PML/RARa, 13 (657c) - bcr 3 variant. Results. 65 patients were eligible for assessment. A complete remission was achieved in 90% cases. No resistance was observed. In follow-up within 30 months the recurrence rate was similar on both treatments. The results of the induction therapy and survival in patients with different variants of the transcripts were also simitar. Overall 2.5 year survival for all the patients was 77%, recurrence-free 80%. The survival analysis in patients with leukocytosis higher and lower 10 lO9/! found no statistical differences by the survival. Patients with hyperleukocytosis had higher early lethality than patients with leukocytes under 10 Iff/I (25% vs 5.3%, p = 0.03). Conclusion. The APL 06.01 protocol showed high efficacy of the relevant maintenance which provides a complete molecular remission in the majority of patients with probable recurrence-free 2.5 year survival 80%.

Introduction. The risk of developing Hodgkin lymphoma (HL) with HIV infection is higher than in the general population, and the course of the disease itself is more aggressive. Currently, there is no unified approach to the treatment of HIV-related HL, and data on its epidemiology in the Russian Federation are limited.The objective was to study epidemiological characteristics, the used therapeutic tactics and the results of treatment for HIV-related HL.Methods and materials. The multicenter retrospective study included 46 patients with HIV- related HL treated in 9 centers of the Russian Federation. Descriptive statistics methods were used, the analysis of overall survival (OS) and progression-free survival (PFS) was performed using the Kaplan–Meier method.Results. HIV-related HL is more often represented by an advanced stage, B-symptoms, and extranodal lesions. The ABVD regimen was used as the first-line therapy in 60 % for HIV-related HL. The overall response to therapy was 81.6 %, and the 2-year OS and PFS were 85 % and 49 %, respectively. Factors that worsened OS were CD4+˂266 cells/mcL and general somatic status ECOG≥2.

Aim. To study the efficacy and safety of combined immunochemotherapy according to the DHAp protocol + nivolumab in patients with refractory/relapsed classical Hodgkin's lymphoma before autologous hematopoietic stem cell transplantation.Materials and methods. The study consisted of 2 phases: 1st - immunotherapy with nivolumab (2 injections as monotherapy at a dose of 240 mg/day with 14 days interval); 2nd - combined immunochemotherapy according to the DHAp protocol + nivolumab (14 days after the 2nd administration of nivolumab): nivolumab 480 mg/day on day 1 in combination with chemotherapy according to the DHAp protocol, 4 cycles in total. The effectiveness of therapy was evaluated after 2 injections of nivolumab, after 2 and 4 cycles of combination therapy. from March 2020 to November 2021, 32 patients were included in the study. The median age was 34 (18-55) years.Results. As of November 2021, the result was evaluated in 32 patients after the 1st stage of treatment (nivolumab monotherapy). A complete response was obtained in 4 (12.5 %) patients, a partial response in 20 (62.5 %) patients, disease stabilization was noted in 5 (16 %) patients, an indeterminate response in 3 (9 %) patients. At the 2nd phase, the efficacy after the 2nd cycle of DHAp + nivolumab was evaluated in 31 patients (complete response was obtained in 19 (61 %), partial response in 11 (36 %)); the final efficacy evaluation (after the 4th cycle of DHAp + nivolumab) was performed in 30 patients, and all patients achieved response to therapy (complete response in 25 (83 %), partial response in 5 (17 %)). 2 patients were excluded from the study.Conclusion. preliminary results of combined immuno- and chemotherapy according to the DHAp protocol showed high efficacy and relatively low toxicity in patients with refractory/relapsed classical Hodgkin's lymphoma before autologous hematopoietic stem cell transplantation.

Background. Assessment of lung injury in oncohematological patients is a relevant problem, since the spectrum of pathological changes is wide and includes pulmonary infections, tumor cell infiltration, cardiogenic and non-cardiogenic pulmonary edema, bronchiolitis obliterans, interstitial pneumonitis, post-radiation and post-inflammatory pneumofibrosis, pulmonary vasculopathy and pleural effusion. At the moment there are no approved recommendations with criteria of differential diagnosis for these conditions, in particular, with differences between the most common therapy complication represented by pulmonary infections and poorly explored drug-induced toxic lesions.Aim. Identification of criteria for pneumotoxicity, allowing for differential diagnosis with pulmonary infections developing during chemotherapy, according to data routinely obtained in real clinical practice.Materials and methods. The study group included 38 patients with cytotoxic and autoimmune lung injury caused by specific therapy (group 1); the comparison group included 38 patients with infectious lesions receiving the same antitumor drugs (group 2). The data of the anamnesis, clinical course, instrumental studies and standard laboratory tests was studied retrospectively. For statistical analysis, the Mann–Whitney, χ2, Kruskal–Wallis tests were used. ROC analysis was performed to assess the sensitivity and specificity of various factors in relation to toxic damage.Results. Patients with lymphomas predominated in group of toxic lung injury (63 %). In patients who underwent allogeneic hematopoietic stem cells transplantation, toxic complications developed in the period from 35 to 1289 days, infectious – from 4 to 43 days. Statistically significant differences were obtained in the presence of a concomitant state of an altered immune response: 32 % of patients in the toxic lesion group versus 5 % in the infectious group had a history of allergy, and, in contrast to the infectious lesion group, in the toxic lesion group autoimmune diseases were detected. The main symptom in patients of the first group was shortness of breath, which was observed in 68 % of cases, of the second – an increased body temperature, observed in 92 % of cases; cough was also a common symptom – in 19 % and 13 % of patients respectively. In 58 % of patients of the second group, concomitant mucositis was detected, while in the first group this complication did not occur in any of them. The most common radiological pattern (71 % of cases in each group) was ground-glass opacities, in patients of the second group often combined with infiltrative changes and thickening of the bronchial walls (in 53 and 42 % of cases respectively). Among laboratory results, the largest differences between groups were observed in the leukocyte levels (with an average level of 2.5 . 109 / L in the infectious group versus 6 . 109 / L in the toxic group), eosinophils (with an average of 3.6 % in the toxic group versus 1.75 % in the infectious group), C-reactive protein (with an average level of 146.7 mg / L in the infectious group versus 52.4 mg / L in the toxic group), and creatinine (with an average of 0.085 mmol / L in the toxic group versus 0.071 mmol / L in the infectious group).Conclusion. The data obtained in this research indicates the value of taking an anamnesis and the importance of performing additional studies in patients with suspected drug-induced lung injury, as well as identifies risk groups. Based on the revealed differences, a scale for the differential diagnosis of drug-induced toxic and infectious lung damage, which includes the results of publicly available research methods, with high sensitivity and specificity, was proposed. Further research for more specific, but, at the same time, universal for various drugs, criteria for toxic lung damage is relevant.

Introduction. Diffuse large B-cell lymphoma (DLBCL) is the most common (30-35%) type of B-cell lymphomas. Only about 60% of all newly diagnosed advanced-stage DLBCL can be completely treated by x6 CHOP-R only. High dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation in the first remission (upfront auto-HSCT) can serve an option to improve prognosis in these patients (pts).Aim. To improve prognosis in DLBCL IV stage, IPI ≥2 pts by upfront auto-HSCT.Materials and methods. Included 105 pts: DLBCL NOS, age 18-65, stage IV, IPI ≥2, CR/PR after x6 CHOP/EPOCH + R from 2010 to 2019 at NMRC of Oncology named after N.N. Petrov of MoH of Russia were retrospectively analyzed. HSCT group includes pts with upfront HDCT followed by auto-HSCT (n = 35). The control group includes pts with non-invasive follow-up after induction only (n = 70). Primary endpoints were overall (OS) and progression-free survival (PFS). Secondary endpoints were response rate, relapse rate and treatment toxicity.Results and discussion. The 3-yr OS (p = 0.01) and 3-yr PFS (p = 0.018) were significantly higher in HSCT group. The complete response rate was significantly increased after upfront auto-HSCT (p < 0.001). Early relapse served as an independent negative prognostic factor in OS (p < 0.001) and experienced statistically less in HDCT group (p = 0.027). Early (ER) and late relapse (LR) rate were higher in pts with DEL (ER - p < 0.001, LR - p < 0.001 in control group and ER - p < 0.001, LR -p = 0.013 in all pts). The overall relapse rate was higher if pts had >1 extranodal site with lung involvement (p < 0.004 in the control group and p = 0.021 in all pts). Prognostic models suggested DEL and presence of >1 extranodal site with lung involvement as an independent negative prognostic factors for increasing the relapse probability in two years after treatment.Conclusion. Upfront HSCT can serve as a clinical option to consolidate the first remission in IV stage DLBCL pts with DEL and/or >1 extranodal sites with lung involvement.

This article presented a review of the literature on the features of nutritional support for oncohematological patients who have undergone allogeneic (alloHSCT)/autologous hematopoietic stem cell transplantation (autoHSCT). Bone marrow transplantation associated with a high risk of developing nutritional deficiencies. Nutritional support (NP) is indicated for patients undergoing alloHSCT and autoHSCT in order to reduce the incidence of infectious complications and reduce the risk of developing severe forms of acute and chronic GVHD. Currently, there are recommendations for conducting NP in alloHSCT, while there are no recommendations for patients with autoHSCT. An important task in planning NP is the calculation of the daily energy requirement. Bone marrow transplantation accompanied by a prolonged negative nitrogen balance. The protein requirement for alloHSCT is significantly higher than for patients with chemotherapy alone – 1.5–2 g/kg per day. An effective method of controlling the needs of hematological patients during the analysis of HSCT and alloHSCT is the calculation of the nitrogen balance and the daily protein norm. In this article was analyzed the role of macronutrients and immunonutrients in the recovery of patients during alloHSCT. It has been shown that low levels of vitamin D and vitamin A increase the risk of development and the severity of the transplant versus host reaction. The addition of omega-3 fatty acids helps maintain an optimal proportion of calorie intake from lipids, as well as maintain the necessary level of triglycerides in the blood. The article presents data on reducing the risk of developing acute GVHD with systemic addition of omega-3 fatty acids. For a final assessment of the effect of the neutropenic diet on the development of infectious complications in oncohematological patients, randomized prospective multicenter studies with the development of a unified approach in choosing a diet for HSCT are needed.

Aim. To evaluate impact of different clinical features on prognosis in Diffuse Large B-cell lymphoma (DLBCL) patients and to determine potential correlation between IHC markers (double-expression of c-myc, bcl-2 and p53) on unfavorable clinical characteristics in DLBCL patients.Methods. We analyzed 215 patients with DLBCL who received treatment from 2008 to 2016. We assess impact of different clinical features, such as B-symptoms, extranodal involvement, advanced stages and refractory course on PFS. In this study we also access potentially unfavorable impact of double expression of c-myc and bcl-2 and p 53 by immunohistochemical analysis.Results. In both uni- and multivariant analysis B-symptoms, advanced stages and primary-refractory course were identified as negative prognostic factors for PFS rates. We found tendency to correlation between double expression of c-myc and bcl-2 and high International prognostic index as well as expression of p53 and advanced stages (87,5% vs 56,4% respectively, р = 0,095). Сonclusion. Patients with DLBCL aggressive course of the disease (B-symptoms, advanced stages and primary-refractory disease) have lower rates of PFS. Double-expression of c-myc and bcl-2 and p53 can be potentially associated with aggressive course of the disease.

The study included 108 patients with B-cell lymphoma which had complication with invasive aspergillosis, 57 patients with Hodgkin lymphoma (HL) and 51 patients with non-Hodgkin lymphoma (NHL). All patients in both groups received chemotherapy before the development of invasive aspergillosis, 73% of patients with HL and 67% patients with NHL received chemotherapy for induction and consolidation of remission. The main predictive factors for IA in patients with HL and NHL were: prolonged lymphocytopenia (70% vs 48%), agranulocytosis (64% vs 71%), use of glucocorticosteroids as part of treatment protocol (61% vs 85%), presence of B – symptoms (63% vs 48%), respectively. In most cases nosocomial invasive aspergillosis was diagnosed in both groups: 65% vs 83% respectively. We identified etiological agents in Hodgkin and non-Hodgkin lymphoma patients: A. fumigatus (50% vs 39%), A. niger (43% vs 33%) and A. flavus (7% vs 8%). The lungs were involved in 100% cases, in group with NHL patients 6% had combined lesions in lungs and other organs and different types of tissues. Clinical manifestation of IA was nonspecific in both groups: fever – 83% vs 76%, cough – 75% vs 59%, respiratory insufficiency – 50% vs 40%, respectively. CT-signs of IA were also nonspecific in both groups: infiltrative (75% vs 66%), focal changes (61% vs 63%), and «ground-glass opacity» (28% vs 31%), respectively. In most cases patients were treated with voriconazole in both patients (88% vs 98%). Overall 12-weeks survival in patients with Hodgkin lymphoma and invasive aspergillosis was 84%, in patients with non-Hodgkin lymphoma and invasive aspergillosis – 81%.

The clinic-rentgenological differential diagnosis is difficult especially in case of localized mediastinal disease. Just detailed histological diagnosis allows making a right tactic decision and choosing effective therapy. Furthermore, some indolent B-cell lymphomas and T-cell lymphomas can arise in mediastinum. Mediastinal tumors are frequent in young adults, and most of these neoplasms are lymphoproliferative disorders. The spectrum of mediastinal lymphoma is broad. The most often of them are large B-cell lymphomas: classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma and mediastinal grey zone lymphoma.

We present the results of a multicenter study of 445 patients with “proven” and “probable” invasive aspergillosis (EORTC/MSG, 2008). Invasive aspergillosis usually occurs in patients with hematological malignancies (88 %), main underlying diseases were acute myeloid and acute lymphoblastic leukemia. The risk factors: prolonged agranulocytosis (64 %), cytostatic chemotherapy (57 %), corticosteroid treatment (45 %), and allogeneic hematopoietic stem cells transplantation (29 %). The pathogens – A. fumigatus (42 %), A. niger (33 %), and A. flavus (21 %). The main site of infection were lungs (86 %). 12 week overall survival was 83 %. Bronchoscopy use for the early diagnosis (p = 0.01), adequatetherapy with voriconazole (p = 0.002) and secondary antifungal prophylaxis (p = 0.0003) were positive prognostic factors for survival of patients with invasive aspergillosis.