AUTOIMMUNE THROMBOCYTOPENIA

Obesity as a Poor Prognostic Factor in Multiple Myeloma

AUTOIMMUNE THROMBOCYTOPENIA ,

ES Mikhailov1, GN Salogub1, SS Bessmeltsev2

1 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Evgenii Sergeevich Mikhailov, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel.: +7(812)702-37-49; e-mail: mikhailov_md@bk.ru

For citation: Mikhailov ES, Salogub GN, Bessmeltsev SS. Obesity as a Poor Prognostic Factor in Multiple Myeloma. Clinical oncohematology. 2021;14(3):315–20. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-315-320

ABSTRACT

Aim. To assess the impact of obesity and overweight on the outcomes of multiple myeloma (MM) treatment.

Materials & Methods. The present retrospective study enrolled 214 patients with newly diagnosed MM. The median age was 59 years (range 29–89 years), male patients accounted for 40.2 %. The analysis focused on complication incidence, overall survival, and time to the second-line therapy depending on body mass index (BMI) at disease onset.

Results. In the groups of patients with BMI > 35 kg/m2 and BMI ≤ 35 kg/m2 the median overall survival was 42 and 95 months, respectively (hazard ratio [HR] 0.17; 95% confidence interval [95% CI] 0.08–0.37; p < 0.05). In the group of patients with obesity ≥ grade 2 the median time to the second-line therapy was 25 months, being less than in the group of patients with BMI ≤ 35 kg/m2 (43 months; HR 0.58; 95% CI 0.31–0.99; p < 0.05). As a result of therapy, the incidence of corticosteroid-associated hyperglycemia and infectious complications as well as the rate of delayed initiation of the next cycle and dose reduction of anticancer drugs were significantly higher in patients with BMI > 35 kg/m2 (p < 0.05).

Conclusion. Obesity ≥ grade 2 is a poor prognostic factor for complications and is associated with diminishing outcomes of ММ treatment. Accompanying morbid obesity leads to a higher incidence of therapy complications longer intervals between chemotherapy courses and drug dose reduction.

Keywords: multiple myeloma, obesity, prognosis, survival.

Received: March 9, 2021

Accepted: June 15, 2021

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Value of PD-L1 Protein Expression in the Combined Prognostic Model of Diffuse Large B-Cell Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA ,

SV Samarina1, NYu Semenova2, NV Minaeva1, DA Dyakonov1, VA Rosin1, EV Vaneeva1, SV Gritsaev2

1 Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Svetlana Valerevna Samarina, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(8332)25-46-88; e-mail: samarinasv2010@mail.ru

For citation: Samarina SV, Semenova NYu, Minaeva NV, et al. Value of PD-L1 Protein Expression in the Combined Prognostic Model of Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2021;14(3):308–14. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-308-314

ABSTRACT

Aim. To study the value of PD-L1 protein expression in the combined model of diffuse large B-cell lymphoma (DLBCL) after administration of R-СHOP induction immunochemotherapy.

Materials & Methods. A retrospective analysis was based on the data of 85 DLBCL patients. The median age was 59 years (Q1–Q3: 29–83). Each patient received at least 2–6 courses of R-СHOP immunochemotherapy. The median follow-up period was 17 months. The optimal cut-off threshold for assessing the proportion of tumor cells expressing PD-L1 protein was determined by the САRT (Classification and Regression Tree) method.

Results. Patients were divided into three groups depending on IPI (International Prognostic Index) risk and immunohistochemical subtype (Hans algorithm) using CART. In group 1 with immunohistochemical GCB subtype and any IPI risk, except for the high one, low PD-L1 expression measured in terms of the DLBCL expressing tumor cell count, was identified in 21 (84 %) patients, 4 (16 %) patients showed overexpression. In case of low PD-L1 expression the 2-year progression-free survival (PFS) was 76 % (median not reached). In 4 patients with protein overexpression, the life duration after DLBCL diagnosed was 4, 16, 2, and 6 months, respectively. In group 2 with immunohistochemical non-GCB subtype and any IPI risk, except for the high one, 27 (67.5 %) patients showed low, and 13 (32.5 %) patients showed high PD-L1 expression. The analysis of the 2-year PFS resulted in no significant differences in groups with different relative counts of РD-L1 expressing tumor cells, i.e., 46 % and 49 %, respectively (p = 0.803). In case of low (< 24.5 % tumor cells) PD-L1 expression, the 2-year overall survival (OS) was better than in patients with overexpression (≥ 24.5 % tumor cells), i.e., 87 % vs. 52 %, respectively (p = 0.049). In group 3 with IPI high risk irrespective of immunohistochemical subtype, the proportion of PD-L1 expressing cells was higher than cut-off threshold (≥ 24.5 %) in 9 (45 %) patients, low protein expression was identified in 11 (55 %) patients. Deaths were reported in all patients of group 3 showing PD-L1 overexpression. In case of low protein expression the proportion of patients alive was 46 % (p = 0.002). None of the patients with high PD-L1 expression lived longer than 2 years. In those with low PD-L1 expression the 2-year OS was 66 % (p = 0.008).

Conclusion. Overexpression of PD-L1 by DLBCL tumor cells together with high IPI progression risk and non-GCB tumor subtype is associated with the worst OS and PFS. It can probably be accounted for by insufficient efficacy of R-СHOP induction immunochemotherapy in patients with high IPI risk. With this presumption, the PD-L1 expressing tumor cell count can be regarded as an important additional criterion for stratification of DLBCL patients into risk groups. Adding this new parameter to already established ones would probably contribute to differentiated approach to the choice of chemotherapy strategy at the onset of this aggressive lymphoma.

Keywords: diffuse large B-cell lymphoma, PD-L1 expression, overall survival, progression-free survival.

Received: January 29, 2021

Accepted: May 15, 2021

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Efficacy, Safety, and Tolerance of Gemtuzumab Ozogamicin Combined with FLAG/FLAG-Ida or Azacitidine in Relapsed/Refractory Acute Myeloblastic Leukemia

AUTOIMMUNE THROMBOCYTOPENIA , , , , ,

IG Budaeva, DV Zaitsev, AA Shatilova, EN Tochenaya, AV Petrov, RI Vabishchevich, DV Motorin, RSh Badaev, DB Zammoeva, VV Ivanov, SV Efremova, KV Bogdanov, YuV Mirolyubova, TS Nikulina, YuA Alekseeva, AYu Zaritskey, LL Girshova

VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

For correspondence: Irina Garmaevna Budaeva, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel.: +7(931)351-07-06; e-mail: irina2005179@mail.ru

For citation: Budaeva IG, Zaitsev DV, Shatilova AA, et al. Efficacy, Safety, and Tolerance of Gemtuzumab Ozogamicin Combined with FLAG/FLAG-Ida or Azacitidine in Relapsed/Refractory Acute Myeloblastic Leukemia. Clinical oncohematology. 2021;14(3):299–307. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-299-307

ABSTRACT

Aim. To assess the efficacy, safety, and tolerance of gemtuzumab ozogamicin (GO) combined with FLAG/FLAG-Ida chemotherapy or azacitidine in patients with relapsed/refractory acute myeloblastic leukemia (AML) in clinical practice.

Materials & Methods. The study included 32 patients (16 men and 16 women). The median age was 44 years (range 23–83 years). Among them there were 15 (46.8 %) patients with refractory and 17 (53.2 %) patients with relapsed AML. GO combined with FLAG/FLAG-Ida was administered to 15 (46.8 %) patients, whereas 17 (53.2 %) patients were treated with GO and azacitidine combination. Therapy safety was assessed according to CTCAE v. 5.0.

Results. Overall response rate including complete remission (CR), CR MRD–, CR with incomplete hematologic recovery, and morphologic leukemia-free status was 59.4 % (19/32). Refractoriness was observed in 31.25 % (10/32) of patients. Early mortality was 9.4 % (3/32). Overall response was 64.7 % (11/17) in the azacitidine and 53.3 % (8/15) in the FLAG/FLAG-Ida groups. In 4 (80 %) out of 5 patients with prior to FLAG treatment refractoriness, the response was achieved after GO + azacitidine therapy. In 58.9 % (10/17) of patients who received GO + azacitidine therapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be performed. The incidence of GO infusion complications in the tested groups did not significantly differ (p = 0.72) and was 46.7 % (7/15) (40 % with grade 1/2 and 6.7 % with grade 3) in the GO + FLAG/FLAG-Ida group and 35.3 % (6/17) (29.4 % with grade 1/2 and 5.9 % with grade 4) in the GO + azacitidine group. In the GO + FLAG/FLAG-Ida group 5 (33.3 %) patients experienced serious adverse events (SAE) of sepsis. In the GO + azacitidine group SAEs were reported in 6 (35.3 %) patients: 4 (66.6 %) with sepsis, 1 (16.7 %) with acute cardiovascular failure, and 1 (16.7 %) with acute respiratory failure. The median (range) duration was 23 (10–39) days for neutropenia grade 4, 24 (11–38) days for neutropenia grade 3, 21 (11–41) days for thrombocytopenia grade 4, 26 (16–45) days for thrombocytopenia grade 3, and 25 (22–45) days for thrombocytopenia grade 1/2. Thrombocytopenia duration was longer in patients with GO + FLAG/FLAG-Ida therapy, however, no significant differences were identified. No cases of veno-occlusive liver disease were reported. Median overall survival (OS) for both groups (n = 32) was 31.4 months, median disease-free survival (n = 21) was 13.3 months. In the group of patients with effective treatment, the median OS was not reached. In non-responders, it was 18 months (p = 0.0442).

Conclusion. GO combined with FLAG/FLAG-Ida chemotherapy or azacitidine proved effective in relapsed/refractory AML patients. Remission did not appear to be associated with ELN risk, gender, age, CD33 expression, number of prior therapy lines, or number of relapses. GO + azacitidine combination showed efficacy, safety, and good tolerance in patients with prior high-dose chemotherapy refractoriness as well as low ECOG performance status. That allowed for the subsequent allo-HSCT administration to these patients. There was no significant difference between the groups of patients in the incidence of hematologic, non-hematologic toxicity, and time to hematologic recovery. Thrombocytopenia duration was longer in patients with GO + FLAG/FLAG-Ida therapy which is consistent with literature data. GO-based effective treatment in relapsed/refractory AML considerably improves OS: during 36 months of follow-up the median was not reached.

Keywords: acute myeloblastic leukemia, relapse, refractoriness, gemtuzumab ozogamicin, FLAG/FLAG-Ida regimens, azacitidine, efficacy, safety, toxicity.

Received: February 5, 2021

Accepted: May 15, 2021

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National Clinical Guidelines on Diagnosis and Treatment of Ph-Negative Myeloproliferative Neoplasms (Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis) (Edition 2020)

AUTOIMMUNE THROMBOCYTOPENIA , , , , , ,

AL Melikyan1, AM Kovrigina1, IN Subortseva1, VA Shuvaev2, EV Morozova3, EG Lomaia4, BV Afanasyev3, TA Ageeva5, VV Baikov3, OYu Vinogradova6, SV Gritsaev2, AYu Zaritskey4, TI Ionova7, KD Kaplanov6, IS Martynkevich2, TA Mitina8, ES Polushkina9, TI Pospelova5, MA Sokolova1, AB Sudarikov1, AG Turkina1, YuV Shatokhin10, RG Shmakov9, VG Savchenko1

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

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

3 RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

4 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

5 Novosibirsk State Medical University, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091

6 Moscow Municipal Center for Hematology, SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

7 NI Pirogov Clinic for High Medical Technology, Saint Petersburg State University, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

8 NF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina str., Moscow, Russian Federation, 129110

9 VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina str., Moscow, Russian Federation, 117997

10 ФГБОУ ВО «Ростовский государственный медицинский университет» Минздрава России, Нахичеванский пер., д. 29, Ростов-на-Дону, Российская Федерация, 344022

For correspondence: Anait Levonovna Melikyan, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: anoblood@ mail.ru

For citation: Melikyan AL, Kovrigina AM, Subortseva IN, et al. National Clinical Guidelines on Diagnosis and Treatment of Ph-Negative Myeloproliferative Neoplasms (Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis) (Edition 2020). Clinical oncohematology. 2021;14(2):262–98. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-262-298

ABSTRACT

The development of National clinical guidelines on diagnosis and treatment of Ph-negative myeloproliferative neoplasms comes in response to the need to standardize the approach to diagnosis and treatment. The availability of clinical guidelines can facilitate the choice of adequate treatment strategy, provides practicing physicians with exhaustive and up-to-date information on advantages and shortcomings of different treatment methods as well as lets health professionals better assess expected extents of treatment required by patients. In 2013 a working group was formed to develop and formulate clinical guidelines on the treatment of myeloproliferative neoplasms. These guidelines were first published in 2014, afterwards they were revised and republished. The dynamic development of current hematology presupposes constant updating of knowledge and implementation of new diagnosis and treatment methods in clinical practice. In this context clinical guidelines present a dynamic document to be continuously amended, expanded, and updated in accordance with scientific findings and new requirements of specialists who deal directly with this category of patients. The present edition is an upgraded version of clinical guidelines with updated information on the unification of constitutional symptoms assessment using MPN-SAF TSS questionnaire (MPN10), on applying prognostic scales in primary myelofibrosis, assessing therapy efficacy in myeloproliferative neoplasms, revising indications for prescription, on dose correction, and discontinuation of targeted drugs (ruxolitinib). The guidelines are intended for oncologists, hematologists, healthcare executives, and medical students.

Keywords: myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia, primary myelofibrosis, JAK2V617F, CALR, MPL, prognosis, hydroxyurea, interferon-α, ruxolitinib, anagrelide.

Received: November 12, 2020

Accepted: February 23, 2021

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Cardio-oncology and Oncohematology: Examination Algorithms, Prophylactic and Treatment of Cardiotoxicity, Trends in Rehabilitation

AUTOIMMUNE THROMBOCYTOPENIA ,

EI Emelina, GE Gendlin, IG Nikitin

NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

For correspondence: Elena Ivanovna Emelina, MD, PhD, 1 Ostrovityanova str., Moscow, Russian Federation, 117997; Tel.: +7(916)412-59-78; e-mail: eei1210@mail.ru

For citation: Emelina EI, Gendlin GE, Nikitin IG. Cardio-oncology and Oncohematology: Examination Algorithms, Prophylactic and Treatment of Cardiotoxicity, Trends in Rehabilitation. Clinical oncohematology. 2021;14(2):239–61. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-239-261

ABSTRACT

Successful chemotherapy in the treatment of hematological diseases is determined not only by the efficacy of antitumor drugs, but by the timely correction of adverse events, among which especially important are cardiac complications associated with both already existing cardiovascular diseases and cardiotoxicity of cytostatic drugs. Of particular importance is also a frequent lack of systemic cardiological examination of oncohematological patients. The urgency of this issue was the reason for creating cardio-oncological clinics focused on the closest co-operation of cardiologists with drug chemotherapy experts. Hematological patients are a particular group among chemotherapy recipients. Potential curability of an oncohematological disease and achieving durable MRD-negative remission raise the importance of irreversible or long-term cardiac complications directly affecting the quality of life and life expectancy. Besides, in some cases long-term or life-long administration of certain cardiotoxic antitumor drugs requires a particular cardiological follow-up. A broad variety of cardiotoxic effects of antitumor drugs and peculiarities of their clinical manifestations call for the exact algorithms of cardiological examination to be observed for the timely detection and treatment of cardiovascular complications. The now available studies and interdisciplinary work of cardiologists and oncologists (oncohematologists) can yield such algorithms for examination and the approaches to prophylactic and treatment of cardiotoxicity as well as to rehabilitation of patients.

Keywords: oncohematology, cardio-oncology, cardiotoxicity, antitumor drugs, prophylactic of cardiac adverse events, cardio-oncological rehabilitation.

Received: November 19, 2020

Accepted: February 10, 2021

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REFERENCES

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Hemostasis Disorders in Patients with De Novo Acute Leukemias

AUTOIMMUNE THROMBOCYTOPENIA ,

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

ABSTRACT

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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CAR-Т Cells for the Treatment of Chronic Lymphocytic Leukemia: Literature Review

AUTOIMMUNE THROMBOCYTOPENIA

IV Gribkova, AA Zav’yalov

Research Institute of Healthcare and Medical Management, 9 Sharikopodshipnikovskaya str., Moscow, Russian Federation, 115088

For correspondence: Irina Vladimirovna Gribkova, PhD in Biology, 9 Sharikopodshipnikovskaya str., Moscow, Russian Federation, 115088; Tel.: +7(916)078-73-90; e-mail: igribkova@yandex.ru

For citation: Gribkova IV, Zav’yalov AA. CAR-Т Cells for the Treatment of Chronic Lymphocytic Leukemia: Literature Review. Clinical oncohematology. 2021;14(2):225–30. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-225-230

ABSTRACT

Chronic lymphocytic leukemia (CLL) is the most common adult malignant lymphoid disease. Despite new highly effective targeted drugs, the prognosis of relapsed and resistant form of this disease is poor. CAR-Т cell therapy using T-lymphocytes with chimeric antigen receptor (CAR) demonstrated its efficacy in the treatment of such oncohematological diseases as В-cell non-Hodgkin’s lymphomas and acute lymphoblastic leukemia. The present literature review focuses on the experience of using CAR-Т cells for CLL therapy. It presents the advantages and drawbacks of this technique as well as the challenging issues to be solved for its implementation into broad clinical practice.

Keywords: chronic lymphocytic leukemia, CAR-Т cell therapy, chimeric antigen receptor, adoptive therapy, immunotherapy.

Received: December 15, 2020

Accepted: March 10, 2021

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Статистика Plumx английский

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COVID-19 in Patients with Oncohematological Diseases

AUTOIMMUNE THROMBOCYTOPENIA

AA Danilenko, SV Shakhtarina, NA Falaleeva

AF Tsyb Medical Radiological Research Centre, branch of the NMRC of Radiology, 4 Koroleva str., Obninsk, Kaluga Region, Russian Federation, 249036

For correspondence: Anatolii Aleksandrovich Danilenko, MD, PhD, 4 Koroleva str., Obninsk, Kaluga Region, Russian Federation, 249036; Tel.: +7(909)250-18-10; e-mail: danilenkoanatol@mail.ru

For citation: Danilenko AA, Shakhtarina SV, Falaleeva NA. COVID-19 in Patients with Oncohematological Diseases. Clinical oncohematology. 2021;14(2):220–4. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-220-224

ABSTRACT

After initially appearing in Wuhan (China), the COVID-19 epidemic rapidly escalated to pandemic level. Due to its high mortality COVID-19 belongs to the group of the most dangerous viral infectious diseases of today. While elderly people are at greatest risk of death, some comorbidities, including also malignant tumors, considerably worsen the course of COVID-19. In view of inherent immunodeficiency exacerbated by immunosuppressive chemotherapy, oncohematological diseases most greatly affect the course of COVID-19. The review presents few published data on coronavirus disease affecting the prognosis of hematopoietic and lymphoid tumors. In addition, the control of mortality risk in these patients is discussed.

Keywords: SARS-CoV-2, COVID-19, hematological diseases, mortality rate.

Received: October 13, 2020

Accepted: February 15, 2021

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Статистика Plumx английский

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Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas

AUTOIMMUNE THROMBOCYTOPENIA , , , ,

In memory of Academician A.I. Vorob’ev,
Russian Academy of Medical Sciences and Russian Academy of Sciences

KA Sychevskaya, SK Kravchenko, FE Babaeva, AE Misyurina, AM Kremenetskaya, AI Vorob’ev

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

For correspondence: Kseniya Andreevna Sychevskaya, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(910)409-79-44; e-mail: sychevskaya-ka@yandex.ru

For citation: Sychevskaya KA, Kravchenko SK, Babaeva FE, et al. Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas. Clinical oncohematology. 2021;14(2):204–19. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-204-219

ABSTRACT

Background. Chronology of granulopoiesis based on periodic hematopoiesis model has been thoroughly studied. However, the pattern of influence of chemotherapy- and immunotherapy-induced cytotoxic stress on the development rhythm of a stem cell requires further investigation. The interaction of antitumor drugs with normal hematopoietic cells is relevant for assessing the intensity of chemotherapy adverse events. Besides, there is a demand for studying hematopoiesis under cytotoxic stress to predict immunological reactivity as a condition for efficacy of immunotherapeutic agents, the effect of which is based on cell immunity.

Aim. To study the chronological pattern of leukocyte count dynamics after R(G)-DHAP immunochemotherapy in non-Hodgkin’s lymphomas.

Materials & Methods. The dynamics of leukocyte count changes after R(G)-DHAP immunochemotherapy was analyzed using the data of 39 treatment courses in 19 non-Hodgkin’s lymphomas patients. After 18 out of 39 cycles of treatment granulocyte colony-stimulating factor (G-CSF) was administered to prevent granulocytopenia, in other cases the previously planned hematopoietic stem cell mobilization was performed according to the accepted protocol.

Results. Time to activation of spontaneous granulopoiesis depends neither on G-CSF stimulation, nor on the total dose of growth-stimulating factor and corresponds on average to Day 10 or Day 11 of the break from the last day of immunochemotherapy. The tendency of shorter agranulocytosis duration on prophylactic use of G-CSF is associated with transient hyperleukocytosis at an early stage after completing immunochemotherapy. Regimens with platinum-based drugs, like R(G)-DHAP, are suggested to be combined with immunochemotherapeutic agents in patients with the failure of first-line chemotherapy. The time interval preceding myelopoiesis activation within the first days of the break between the courses is likely to contribute to the initiation of treatment with immunotherapeutic drugs after second-line chemotherapy.

Conclusion. The determination of granulopoiesis dynamics under R(G)-DHAP immunochemotherapy-induced cytotoxic stress enables to plan the optimum G-CSF regimen and to predict the optimum timing of immune antitumor effect combined with chemotherapy.

Keywords: periodic hematopoiesis, mathematical hematopoiesis model, non-Hodgkin’s lymphomas, chemotherapy, immunotherapy, G-CSF, antitumor immunity, R(G)-DHAP.

Received: November 15, 2020

Accepted: February 25, 2021

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Use of Blinatumomab in Acute Lymphoblastic Leukemia in Municipal Healthcare: A Case Report

AUTOIMMUNE THROMBOCYTOPENIA , ,

VA Shuvaev1,2, OV Ushakova1, EI Mullo1, TV Tolstykh1, NZ Triputen1

1 VV Veresaev Municipal Clinical Hospital, 10 Lobnenskaya str., Moscow, Russian Federation, 127644

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Vasilii Anatolevich Shuvaev, MD, PhD, 10 Lobnenskaya str., Moscow, Russian Federation, 127644; e-mail: shuvaev77@mail.ru

For citation: Shuvaev VA, Ushakova OV, Mullo EI, et al. Use of Blinatumomab in Acute Lymphoblastic Leukemia in Municipal Healthcare: A Case Report. Clinical oncohematology. 2021;14(2):198–203. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-198-203

ABSTRACT

Acute lymphoblastic leukemia is one of the groups of most challenging malignant neoplasms of hematopoietic tissue. Despite the success in achieving remission induction in primary patients, later, most of them develop disease relapses. Overall and disease-free survivals have to be improved, which cannot be achieved solely with chemotherapy intensification. The new target drugs and cell technologies improve the treatment options for the resistant forms and relapses of acute lymphoblastic leukemia. The effective use of new drugs presupposes their timely assignment which can be ensured by their availability in routine clinical practice. The provided case report describes the successful use of bispecific antibody blinatumomab for treating an early relapse of acute lymphoblastic leukemia in the clinical practice within the municipal healthcare system.

Keywords: acute lymphoblastic leukemia, clinical practice, target therapy, blinatumomab.

Received: September 22, 2020

Accepted: February 3, 2021

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