Introduction . Non-chemotherapy for acute promyelocytic leukaemia (APL) with a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) provides for a high patient survival rate at lesser toxicity as effectively or superior to standard chemotherapy programmes. Aim  — assessment of the ATO–ATRA risk-adapted exposure protocol in management of de novo acute promyelocytic leucaemia. Materials and methods . A prospective study included 51 primary APL patients aged 18–76 years. The program included remission induction (ATO 0.15 mg/kg intravenously, ATRA 45 mg/m2 orally) for 30–60 days in a low-risk (until remission) and 60 days — in a high-risk cohort that had idarubicin therapy added on days 2 and 4. Remission consolidation was attained with four (low-risk) or five (high-risk) courses. Minimal residual disease was monitored with real-time PCR at all phases. Results . The high-risk cohort was assigned 15 (29.4 %), the low-risk cohort — 36 (70.6 %) patients. Therapy induction till APL morphological remission was performed in 48/51 (94 %) patients. Molecular APL remission was achieved in 47 (92 %) patients, 100 % in the low-risk and 80 % in high-risk cohort. Early mortality was 6 % (n = 3), death in remission — 2 % (n = 1). Differentiation syndrome (DS) occurred in 16 (31.7 %) patients, more frequently in the high-risk vs. low-risk cohort (53.3 % and 22.2 %, respectively, p = 0.05; odds ratio 4.0 [1.1–14.4]). DS developed on days 1–20 (3 days median) of therapy. DS risk factors: a high-risk status, haemorrhagic syndrome and infection at the disease onset. A median follow-up time in survivors was 12.9 months (2.5–34.3), a six-month overall survival — 92 % (95 % CI: 85–100 %). A six-month overall survival was 100 and 73 % in the low- and high-risk cohorts, respectively (95 % CI: 54–100 %, p = 0.001). APL relapse not registered, 47 (92 %) patients survived and achieved the first molecular remission. Conclusion . A differentiated risk-adapted approach to APL therapy with cytostatic treatment added in high-risk patients only provided for a 100 % molecular remission and relapse-free survival. Therapy failures (early mortality and death in remission) affected high-risk patients due to a severe individual condition at the time of APL diagnosis.

Background. Cryoprecipitate is made from fresh-frozen plasma (FFP) and contains fibrinogen, factor VIII, factor XIII, von Willebrand factor, fibronectin and fibrinogen.Aim. To provide information on the composition and methods of production, storage, transportation and clinical use of cryoprecipitate.General findings. Cyoprecipitate is manufactured by slowly thawing FFP at 1–6°C. This precipitates out cryoproteins: factor VIII, von Willebrand factor, factor XIII, fibronectin and fibrinogen. After centrifugation, the cryoproteins are resuspended in a reduced volume of plasma. Cryoprecipitate is stored at temperatures not exceeding –25° С for 36 months. Indications for cryoprecipitate transfusion are hemophilia A, von Willebrand disease, factor XIII deficiency, congenital afibrinogenemia and hypofibrinogenemia, acquired hypofibrinogenemia. These indications can occur in obstetrics, neonatology, cardiac surgery, neurosurgery, hematology, orthopaedics, and general surgery during liver transplantation and disseminated intravascular coagulation. Введение. Криопреципитат — компонент донорской крови человека, получаемый при оттаивании свежезамороженной плазмы и содержащий факторы свертывания VIII, FXIII, фактор Виллебранда, фибронектин и фибриноген.Цель рекомендаций — предоставить сведения о производстве, составе, методах заготовки, хранения, транспортировки и клинического использования криопреципитата.Основные сведения. Криопреципитат получают при размораживании свежезамороженной плазмы при температуре от 1 до 6°С, что приводит к преципитации криопротеинов, содержащих факторы свертывания VIII, FXIII, фактор Виллебранда, фибронектин и фибриноген, ее последующем центрифугировании, ресуспендировании осажденных белков в небольшом объеме плазмы и повторном замораживании. Криопреципитат хранят при температуре не выше –25°С в течение 36 месяцев. Показания к переливанию криопреципитата: гемофилия А, болезнь Виллебранда, дефицит фактора XIII, врожденная афибриногенемия и гипофибриногенемия, приобретенная гипофибриногенемия. Эти показания могут возникнуть в акушерстве, неонатологии, кардиохирургии, нейрохирургии, гематологии, ортопедии, общей хирургии, при трансплантации печени, диссеминированном внутрисосудистом свертывании.

ISSUE The study of activating mutations (NRAS,KRAS,FLT3,JAK2,CRLF2genes) of RAS/RAF/MEK/ERK and JAK/STAT signaling pathways in B-cell acute lymphoblastic leukemia (B-ALL) in adult patients which are included in Russian multicenter clinical trials. MATERIALS AND METHODS Within the multicenter study there were 119 adult patients included withde novoB-ALL. The study was considered as prospective and retrospective. The group withBCR-ABL1-negative B-ALL consisted of up to 93 patients (45 male and 48 female, at the age of 17 to 59, the median age 31), they were treated according to the protocols ALL-2009, ALL-2016. The median follow-up lasted for 19 months (1119). The group withBCR-ABL1-positive B-ALL with up to 26 patients (10 male and 16 female, at the age of 23 to 78, the median age 34 years) was included in the study as well. The treatment was carried out according to the protocols ALL-2009 and ALL-2012 in combination with tyrosine kinase inhibitors. The median follow-up lasted for 23 months (4120). The molecular analysis of activating mutations inNRAS,KRASgenes (RAS/RAF/MEK/ERK signaling pathway) andJAK2,CRLF2genes (JAK/STAT signaling cascade) was performed via Sanger sequencing. The internal tandem duplications (ITDs) inFLT3gene were studied by fragment analysis. The evaluation of CRLF2 expression was fulfilled via flow cytometry. RESULTS Activating mutations inNRAS,KRAS,FLT3genes were found in 22 (23.6%) patients withBCR-ABL1-negative B-ALL. In total, 23 mutations were revealed in theNRAS(n=9),KRAS(n=12), andFLT3(n=2) genes, according to statistics that was significantly more frequent than withBCR-ABL1-positive B-ALL, these genes mutations were not identified in patients (p=0.007). The frequency of mutations detection inKRASandNRASgenes in patients withBCR-ABL1-negative B-ALL was comparable as 12.9% (12 of 93) to 9.7% (9 of 93), respectively (p=0.488). One patient was simultaneously revealed 2 mutations in theKRASgene (in codons 13 and 61).FLT3-ITD mutations were detected in 3.5% (2 of 57) cases ofBCR-ABL1-negative B-ALL. In patients withBCR-ABL1-positive B-ALLFLT3-ITD mutations were not assessed. Violations in the JAK/STAT signaling cascade were detected in 4 (4.3%) patients withBCR-ABL1-negative B-ALL. They were represented by the missense mutations ofJAK2gene (n=3) and the overexpression of CRLF2 (n=2); in one patient were detected the overexpression of CRLF2 and a mutation inJAK2gene simultaneously. No mutations were found inCRLF2gene. In patients withBCR-ABL1-positive B-ALL noJAK2mutations were detected. As long as analyzing demographic and clinical laboratory parameters between groups of patients with and without mutations, there were no statistically significant differences obtained. In the analyzed groups of patients, long-term therapy results did not differentiate according to the mutations presence inNRAS,KRAS,FLT3,JAK2genes. Also, substantive differences were not shown in the rate of the negative status achievement of the minimum residual disease between patients with and without activating mutations in the control points of the protocol (on the 70th, 133rd and 190th days). CONCLUSION NRAS,KRAS,FLT3,JAK2activating mutations do not affect the long-term results of the therapy and the rate of the negative status achievement of the minimum residual disease in patients withBCR-ABL1-negative B-ALL treated by the Russian multicenter clinical trials.

An interim analysis of long-term treatment results for 202 patients with acute lymphoblastic leukemia (ALL), aged 15–60 years, received therapy according protocol ALL-2009 was shown. The basic principle of ALL-2009 was non-aggressive, but continued cytostatic exposure, as well as the reproducibility in a regional hematology centers. Long-term treatment results of ALL-2009 are 2 times higher than the previously obtained in adult ALL patients within the Russian clinical multicenter studies of adult ALL. The 5‑year overall survival of patients younger than 30 years was 73.6 %, relapse-free survival (RFS) – 71.5 %, compared with 52.7 % and 61.8 % in patients aged 30 years and older, respectively. In patients with B-precursor ALL with normal karyotype of blast cells significantly higher 5‑year RFS (82.1 %) compared to patients with abnormal karyotype (58.8 %) was registered. For T-ALL cytogenetic characteristics of blast cells had no prognostic significance. For patients with T-ALL important to perform autologous stem cell transplantation as a later consolidation, as this significantly reduce relapse rate (from 33 to 0 %).

The purpose of the paper is to present Russian experts' consolidated opinion about acute myeloid leukemia (AML) treatment in adult patients aged less than 60 years. The guidelines have been elaborated having regard to foreign publications and Russian experience, on the basis of global and Russian clinical trials to treat AML and to define indications for allogeneic bone marrow transplantation in patients during first complete remission.

The purpose of the paper is to present Russian experts' consolidated opinion about acute myeloid leukemia (AML) treatment in adult patients aged less than 60 years. The guidelines have been elaborated having regard to foreign publications and Russian experience, on the basis of global and Russian clinical trials to treat AML and to define indications for allogeneic bone marrow transplantation in patients during first complete remission.