A Rationale for a New Operational Integrated Quality and Efficiency Index for Assessing the Performance of Hematological Services in Constituent Entities of the Russian Federation

EN Parovichnikova1, TTs Garmaeva1, OV Lazareva1, KA Lukina1, YuA Chabaeva1, SM Kulikov1, VV Troitskaya1, TV Gaponova1, LI Menshikova2, VG Savchenko1

1 National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 Federal Research Institute for Health Organization and Informatics, 11 Dobrolyubova str., Moscow, Russian Federation, 127254

For correspondence: Elena Nikolaevna Parovichnikova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: parovichnikova@gmail.com

For citation: Parovichnikova EN, Garmaeva TTs, Lazareva OV, et al. A Rationale for a New Operational Integrated Quality and Efficiency Index for Assessing the Performance of Hematological Services in Constituent Entities of the Russian Federation. Clinical oncohematology. 2022;15(1):1–15. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-1-15


Background. Since 2018 a widespread national project “Healthcare” has been implemented in the Russian Federation (RF) to improve the quality, efficiency, availability, and affordability of medical care in the profiles of specialties in constituent entities of the RF. Modern hematology as a medical field of high technology and crucial solutions is notable for its multi- and interdisciplinarity of most nosological forms, complexity of diagnostic process, multi-structuredness and diversity of related physician teams in different structural units and subdivisions. One of the key issues in federal projects is to determine the indicators for assessing the efficiency of regional hematological services in constituent entities of the RF.

Aim. To elaborate and substantiate a new integrated operational efficiency index for hematological services in constituent entities of the RF.

Materials & Methods. The analysis of data and assessment of feasibility of a new integrated operational index “early mortality in acute leukemia” (AL) were based on the results of 5 multi-center trials, including an epidemiological one.

Results. Multi-center clinical studies on AL are the only objective tools for assessing the treatment efficacy, its improvement, and further training of hematologists taking part in the trials. AL treatment requires well-developed infrastructure of hematological services involving not only staff matters and organization of hematologists’ activities, but also management of many highly important related subdivisions and laboratories, logistics of their interaction, time specifications, meeting clinical guidelines, and lastly, and most importantly, financial support.

Conclusion. The Unified State Information System “Hematology” is the only platform providing the objective information on patients’ vital status and enabling the use of the suggested integrated index for assessing the quality and efficiency of hematological services in the regions of the RF. This indicator of early mortality in AL patients less than 60 years of age is 15 % for acute myeloid leukemias and 10 % for acute lymphoblastic leukemias. Its low values would demonstrate that this or that constituent entity of the RF is provided with sufficient infrastructure, technologies, and a professional team to keep those patients alive who have severe but curable hematological diseases. The indicator of long-term survival or “life years gained” should become the main strategic criterion for the therapy efficacy in hematological diseases.

Keywords: hematological services, assessment of the medical care quality, early mortality, overall survival, acute leukemia, acute myeloid leukemia, acute lymphoblastic leukemia.

Received: September 27, 2021

Accepted: December 15, 2021

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Hemostasis Disorders in Patients with De Novo Acute Leukemias

OA Polevodova, GM Galstyan, VV Troitskaya, EB Orel, MYu Drokov, EN Parovichnikova

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Gennadii Martinovich Galstyan, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: 8(495)612-48-59; e-mail: gengalst@gmail.com

For citation: Polevodova OA, Galstyan GM, Troitskaya VV, et al. Hemostasis Disorders in Patients with De Novo Acute Leukemias. Clinical oncohematology. 2021;14(2):231–8. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-231-238


Aim. To study hemostasis disorders in patients with de novo acute leukemias (AL) prior to chemotherapy.

Materials & Methods. The study enrolled 107 patients with newly diagnosed AL, aged 18–80 years and treated at the National Research Center for Hematology. Acute lymphoblastic leukemia (ALL) was identified in 37 patients, acute myeloid leukemia (AML) was diagnosed in 46 patients, and acute promyelocytic leukemia (APL) was reported in 24 patients. Hemorrhagic and thrombotic complications were analyzed; platelet count, APPT, prothrombin and fibrinogen concentration were determined; thromboelastography (TEG; native tests, functional fibrinogen tests) and rotation thromboelastometry (ROTEM; EXTEM, INTEM, FIBTEM, APTEM) were performed. The data were statistically processed using SAS 9.4 software.

Results. At AL onset hemorrhagic syndrome was detected in 34 (32 %) out of 107 patients. It was manifested by petechia (n = 16), subcutaneous hematomas (n = 12), gingival (n = 10) and nose (n = 6) bleeding, uterine bleeding (n = 2), hematuria (n = 2), gastrointestinal bleeding (n = 1), brain hemorrhage (n = 6), and periorbital hematoma (n = 1). According to TEG and ROTEM hypocoagulation was more common in APL patients. Hyperfibrinolysis could be detected using only ROTEM in 54 % of APL patients, in 8 % of ALL and 4 % of AML patients. Compared to other AL patients those with APL showed different parameters of fibrinogen concentration of < 1.75 g/L (sensitivity 83.3 %, specificity 83.13 %), D-dimer concentration of > 2686 µg/L (sensitivity 72.73 %, specificity 64.79 %), MCFFIBTEM < 12.5 mm (sensitivity 80 %, specificity 80 %), and МАFF < 9.7 mm (sensitivity 86.96 %, specificity 90.12 %).

Conclusion. The parameters that distinguish APL from other categories of AL patients are hypofibrinogenemia, higher D-dimer concentration, ROTEM changes, and hyperfibrinolysis.

Keywords: hemostatic system, acute leukemia, hemorrhagic syndrome, thrombosis, integral tests, thromboelastometry, thromboelastography.

Received: December 2, 2020

Accepted: March 5, 2021

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Статистика Plumx английский


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Antibiotic Treatment of Febrile Neutropenia in Patients with Acute Leukemia

VA Okhmat, GA Klyasova, EN Parovichnikova, VV Troitskaya, EO Gribanova, VG Savchenko

National Medical Hematology Research Center, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Vladimir Aleksandrovich Okhmat, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)614-92-72; e-mail: okhmatvladimir@mail.ru

For citation: Okhmat VA, Klyasova GA, Parovichnikova EN, et al. Antibiotic Treatment of Febrile Neutropenia in Patients with Acute Leukemia. Clinical oncohematology. 2018;11(1):100-9.

DOI: 10.21320/2500-2139-2018-11-1-100-109


Aim. To estimate the efficacy of antibiotic treatment of febrile neutropenia in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Materials & Methods. The prospective study (2013 to 2015) included 66 AML and 44 ALL patients receiving 480 chemotherapy cycles within the period of 6 months.

Results. Febrile neutropenia was registered during 242 (50 %) chemotherapy cycles occurring more frequently in AML than in ALL patients (93 % vs. 18 %, p < 0.0001). In AML patients infections were more common during induction and consolidation (98 and 89 %) phases compared to ALL patients who most commonly had infection during induction phase (55 %). Compared to ALL patients, AML patients had lower recovery rates after first-line antibiotic monotherapy (24 % vs. 57 %, < 0.0001), compared to combination therapy (37 % vs. 18 %, = 0.01). The use of beta-lactam antibiotics in ALL patients was associated with lower recovery rates during the induction phase compared to consolidation phase (47 % vs. 72 %, = 0.0004). In cases of granulocytopaenia longer that 14 days the clinical recovery rate with administration of the first-line antibiotics and carbapenems accounted for 23–24 % compared to 47 % with other antimicrobials, more commonly with antifungal (21 %) administration. In patients with fever of unknown origin the monotherapy with first-line antibiotics proved to be successful (45 %). In patients with clinically and microbiologically defined infections the best results were achieved by the combined treatment with the beta-lactam antibiotics and other drugs (43 %).

Conclusion. Antibiotic escalation has proved to be the optimal strategy in treatment of ALL patients and in cases of fever of unknown origin. The efficacy of the beta-lactam antibiotic monotherapy was lower in AML patients during the induction phase as well as in cases of continuous neutropenia (> 14 days) and clinically and microbiologically diagnosed infections. The adding of other antimicrobial administration resulted in the recovery in 37–48 % of cases.

Keywords: acute leukemia, AML, ALL, febrile neutropenia, fever of unknown origin, clinically and microbiologically defined infections, antibiotics.

Received: July 2, 2017

Accepted: October 20, 2017

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Efficacy of Chemotherapy in Acute Leukemia Patients Resistant to Previous Standard Treatment According to the Series Measurement of WT1 Gene Expression

NN Mamaev, YaV Gudozhnikova, TL Gindina, IM Barkhatov, AI Shakirova, VA Katerina, MV Gubina, ES Nikolaeva, EV Semenova, OV Paina, EI Darskaya, OV Pirogova, VV Porunova, IS Moiseev, IA Mikhailova, BI Ayubova, VM Kravtsova, SN Bondarenko, LS Zubarovskaya, BV Afanas’ev

IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Nikolai Nikolaevich Mamaev, PhD, Professor, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: nikmamaev524@gmail.com

For citation: Mamaev NN, Gudozhnikova YaV, Gindina TL, et al. Efficacy of Chemotherapy in Acute Leukemia Patients Resistant to Previous Standard Treatment According to the Series Measurement of WT1 Gene Expression. Clinical oncohematology. 2018;11(1):78-88.

DOI: 10.21320/2500-2139-2018-11-1-78-88


Aim. To estimate the efficacy of chemotherapy in acute leukemia patients resistant to previous standard treatment according to the series measurement of WT1 expression.

Materials & Methods. The series measurement of WT1 expression formed the basis of the efficacy estimation of induction chemotherapy in 31 patients (15 men and 16 women aged from 3 months to 68 years; the median age was 28 years) with prognostically unfavourable variants of acute myeloid (AML) and lymphoblastic leukemia (ALL) (23 AML and 8 ALL patients). The WT1 gene expression was measured at baseline and 2–3 weeks after the treatment by the quantitative real-time PCR. The threshold level for detection was 250 copies of WT1/104 copies of ABL. The cytogenetic profile of leukemia cells was assessed by standard cytogenetics and FISH.

Results. The baseline expression level of WT1 varied from 305 to 58,569 copies/104 copies of ABL. The expected reduction of WT1 expression after the first induction chemotherapy treatment was reported in 22/23 (96 %) AML patients and in 6/8 (75 %) ALL patients. According to our results WT1 expression reached the threshold in 13/31 (42 %) patients, including 9 AML patients and 4 ALL patients. After 11/31 (35 %) patients received the second course of treatment, WT1 expression level became normal in 8 cases (5 ALL and 3 AML patients). Despite high dose chemotherapy, HSCT and such agents as blinatumomab and gemtuzumab, an unfavourable outcome was observed in 18/31 (58 %) patients including 6 patients with complex karyotype (CK+) and 2 patients with monosomal karyotype (MK+). Once the MK+ and CK+ combination was observed, in another case the MK+ was combined with the prognostically unfavourable inv(3)(q21q26) inversion.

Conclusion. Our results show that the molecular monitoring should be included as part of treatment of the prognostically unfavourable acute leukemia. The WT1 gene was shown to be the most appropriate marker. WT1 expression was shown to correlate with the common fusion genes allowing to estimate the blast cell count at the molecular level.

Keywords: acute leukemia, induction chemotherapy, molecular monitoring, WT1.

Received: August 18, 2017

Accepted: November 12, 2017

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Classification of Conditioning Regimens for Bone Marrow Transplantation: Historical Background and Current Perspectives

KN Melkova, GD Petrova, NV Gorbunova, TZ Chernyavskaya, OP Trofimova

NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Kapitolina Nikolaevna Melkova, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: frolov63@bk.ru

For citation: Melkova KN, Petrova GD, Gorbunova NV, et al. Classification of Conditioning Regimens for Bone Marrow Transplantation: Historical Background and Current Perspectives. Clinical oncohematology. 2017;10(4):494–500 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-494-500


Hematopoietic stem cells transplantation is a current standard treatment for many oncohematological diseases. The milestone of any type of transplantation is the choice of conditioning regimen. This article presents the principles of classification of conditioning regimens in terms of myeloablativity and discusses the concepts of “autologous transplantation”, “high-dose chemotherapy supported by hematopoietic stem cells”, “allogeneic transplantation” and “immunotherapy”. Up-to-date uniform classification of conditioning regimens may serve an important prognostic component in assessing both the risks and efficacy of hematopoietic stem cells transplantation.

Keywords: conditioning regimens, allogeneic hematopoietic stem cell transplantation, autologous hematopoietic stem cell transplantation, total therapeutic exposure, acute leukemia, Hodgkin’s lymphoma, multiple myeloma.

Received: March 29, 2017

Accepted: July 8, 2017

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Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia

GA Tsaur1,2,3, C Meyer4, TO Riger1,2, AM Kustanovich5, EV Fleischman6, YuV Ol’shanskaya7, AM Popov7, OI Sokova6, EA Matveeva7, OV Nikulina1,2, AE Drui1,2, OR Arakaev1,2, OV Streneva1,2, SA Rumyantsev7, EV Shorikov1,2, AG Solodovnikov2, LI Savel’ev1,2, R Marschalek4, LG Fechina1

 1 Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149

2 Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026

3 First President of Russia B.N. Yeltsin Ural Federal University , 19 Mira str., Ekaterinburg, Russian Federation, 620002

4 Diagnostic Center of Acute Leukemia, Institute of Pharmaceutical Biology/ZAFES, Goethe-University of Frankfurt, N230, Max-von-Laue Str. 9, Frankfurt am Main Deutschland, 60438

5 Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, 43 Frunzenskaya str., Borovlyany, Minsk District, Belarus, 223053

6 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

7 Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117198

For correspondence: Grigorii Anatol’evich Tsaur, PhD, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149; Tel.: +7(343)216-25-17; e-mail: tsaur@mail.ru

For citation: Tsaur GA, Meyer C, Riger TO, et al. Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia. Clinical oncohematology. 2016;9(1):22–9 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-22-29


Aim. To evaluate the relation between genomic DNA breakpoints in MLL and translocation partner genes (TPG) and clinical parameters of infant AL.

Methods. 68 infants (29 boys and 39 girls with median age of 4.8 mo) with MLL-rearranged acute lymphoblastic leukemia (ALL) (n = 46), acute myeloid leukemia (AML) (n = 20) and mixed phenotype acute leukemia (MPAL) (n = 2) were included in the current study.

Results. 5-year EFS was significantly lower in patients with breakpoints in intron 11 (n = 29) in comparison to patients with breakpoint localized from intron 7 to exon 11 (n = 17) (0.16 ± 0.07 vs 0.38 ± 0.14, = 0.039). While cumulative incidence of relapse was remarkably higher in the first group of patients (0.74 ± 0.09 vs 0.52 ± 0.17, = 0.045). Although in Cox regression model including breakpoint location in intron 11 together with age, immunophenotype, initial white blood cell count, initial CNS involvement, type of MLL rearrangements, absolute blast number at day 8 of dexamethasone profase, minimal residual disease (MRD) at time point 4 (TP4) of MLL-Baby protocol, the only significant covariate was the presence of MRD at TP4 (HR 5.994, 95% CI 2.209–16.263, < 0.001). In 22 AML patients there was not any correlation between breakpoint location and treatment outcome.

Conclusion. Breakpoints in intron 11 of MLL gene led to significantly worse outcome in infants with ALL, treated by MLL-Baby protocol, although this parameter was overcome by MRD-positivity at TP4. The latter was the only independent covariate in multivariate analysis. Our data provide additional information of molecular genetic features of MLL-rearranged infant AL.

Keywords: acute leukemia, infants, 11q23/MLL rearrangements, MLL-Baby, treatment outcome.

Received: September 14, 2015

Accepted: October 20, 2015

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Selection of patients for iron-chelating therapy

S.V. Gritsaev, B. Davaasambuu, N.A. Romanenko, and K.M. Abdulkadyrov

Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation


Emergence of iron aggressive forms in patients with hematological or oncohematological diseases is potentially life-threatening. This can be caused by several situations: multiple allogeneic RBC transfusions, increased intestinal absorption of iron, or damaging effects of chemotherapeutic agents. The objective of the study was to identify candidates for iron-chelating therapy. The data on 727 patients with screening blood tests were analyzed. The highest serum ferritin level was revealed in patients with thalassemia, PMF, or MDS. They received 80, 37, or 35 RBC transfusions, respectively. The lowest serum ferritin levels were found in patients with CLL or hemolytic anemia that received lesser number of RBC transfusions, namely, 18.5 and 16.5, respectively. The correlation between serum ferritin level and the total number of RBC transfusions was revealed: r = 0.462; p = 0.000. We concluded that iron-chelating therapy is primarily indicated to the patients with MDS or PMF in whom the high serum ferritin level is due to excessive post-transfusion iron.

Keywords: myelodysplastic syndromes, primary myelofibrosis, thalassemia, acute leukemia, multiple myeloma, serum ferritin, allogeneic RBC transfusions.

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