TI Ionova^1,2, OYu Vinogradova^3,4,5, TV Shelekhova⁶, DG Sherstnev⁶, AV Proidakov⁷, EV Lyyurova⁷, MM Pankrashkina³, LA Mukha³, EE Markova³, NV Novitskaya³, TI Pospelova⁸, TN Babaeva⁸, NB Bulieva⁹, GB Kuchma¹⁰, EA Andreevskaya¹¹, EE Zinina¹², MV Frolova¹³, KB Trizna¹⁴, IL Shestopalova¹⁵, TV Shneider¹⁶, SA Volkova¹⁷, SG Zakharov¹⁸, II Mulina¹⁹, IE Solov’eva¹⁹, AA Myasnikov²⁰, AA Kuchin²⁰, LB Khvorostenko²¹, NM Porfirieva¹, TP Nikitina^1,2, VV Ptushkin^3,4,5, SV Gritsaev²²

¹ Multinational Center for Quality of Life Research, 1 Artilleriiskaya ul., Saint Petersburg, Russian Federation, 191014

² NI Pirogov Clinic for High Medical Technology, Saint Petersburg State University, 154 Fontanki nab., Saint Petersburg, Russian Federation, 198103

³ Moscow Municipal Center of Hematology, SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

⁴ NI Pirogov Russian National Research Medical University, 1 Ostrovityanova ul., Moscow, Russian Federation, 117997

⁵ Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela ul., Moscow, Russian Federation, 117997

⁶ VI Razumovskii Saratov State Medical University, 112 Bol’shaya Kazach’ya ul., Saratov, Russian Federation, 410012

⁷ Komi Republican Oncology Dispensary, 46 Nyuvchimskoe sh., Syktyvkar, Republic of Komi, Russian Federation, 167904

⁸ Novosibirsk State Medical University, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091

⁹ I Kant Baltic Federal University, 14 Aleksandra Nevskogo ul., Kaliningrad, Russian Federation, 236041

¹⁰ Orenburg State Medical University, 6 Sovetskaya ul., Orenburg, Russian Federation, 460000

¹¹ Krai Clinical Hospital No. 1, 7 Kokhanskogo ul., Chita, Russian Federation, 672038

¹² Clinical and Diagnostic Center (Hematology), Surgut District Clinical Hospital, 14 Energetikov ul., Surgut, Russian Federation, 628408

¹³ Vologda Regional Clinical Hospital, 17 Lechebnaya ul., Vologda, Russian Federation, 160002

¹⁴ Tomsk Regional Clinical Hospital, 96 I. Chernykh ul., Tomsk, Russian Federation, 634063

¹⁵ SI Sergeev Krai Clinical Hospital No. 1, 9 Krasnodarskaya ul., Khabarovsk, Russian Federation, 680009

¹⁶ Leningrad Regional Clinical Hospital, 45 korp. 1 lit. A Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

¹⁷ Privolzhsky Research Medical University, 10/1 Minina i Pozharskogo pl., Nizhny Novgorod, Russian Federation, 603005

¹⁸ MF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina ul., Moscow, Russian Federation, 129110

¹⁹ Republican Hospital No. 1, National Medical Center, 4 Sergelyakhskoe sh., Yakutsk, Republic of Sakha (Yakutiya), Russian Federation, 677008

²⁰ VA Baranov Republican Clinical Hospital, 3 Pirogova ul., Petrozavodsk, Republic of Karelia, Russian Federation, 185002

²¹ Regional Clinical Hospital No. 1, 55 Kotovskogo ul., Tyumen, Russian Federation, 625023

²² Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

For correspondence: Tatyana Pavlovna Nikitina, MD, PhD, 1 Artilleriiskaya ul., Saint Petersburg, Russian Federation, 191014; Tel.: +7(962)710-17-12; e-mail: tnikitina_74@mail.ru

For citation: Ionova TI, Vinogradova OYu, Shelekhova TV, et al. Quality of Life Changes in Patients with Chronic Immune Thrombocytopenia in the Process of Romiplostim Therapy, its Efficacy and Safety in the Real-World Setting: Results of a Multi-Center Observational Study. Clinical oncohematology. 2023;16(2):154–65. (In Russ).

DOI: 10.21320/2500-2139-2023-16-2-154-165

ABSTRACT

Aim. To study the quality of life in patients with chronic immune thrombocytopenia (ITP) in the process of romiplostim therapy and to assess the efficacy and safety of this drug in real-world setting.

Materials & Methods. The study enrolled adult patients with the confirmed chronic ITP diagnosis and indications for romiplostim therapy. Clinical parameters, RAND SF-36 and FACT-Th6 quality of life as well as FACIT-Fatigue scores were evaluated prior to romiplostim administration vs. 3, 6, and 12 months after the treatment onset. Patient satisfaction checklist was also administered at all study points after the start of therapy. The clinical efficacy of romiplostim was analyzed along with assessing response and time to response. To study the quality of life and fatigue changes, the Generalized Estimating Equation (GEE) method was used during the observation period. Significant fatigue changes were determined and compared in terms of the perception differences from patient’s and physician’s perspective.

Results. The study enrolled 60 chronic ITP patients treated with romiplostim in the real-world setting (mean age 51.9 years, 70 % women). The median thrombocyte count prior to romiplostim therapy was 18.5 × 10⁹/L (interquartile range 10.8–22.3 × 10⁹/л). On the enrollment date, 90 % of patients showed hemorrhagic syndrome. Overall response to romiplostim therapy was 98.3 % (complete response was achieved in 93.3 % of patients). After 6 months of therapy, 89.5 % of patients preserved response. After 3 months of therapy, hemorrhagic syndrome was eliminated in 81 % of patients, after 6 months the same was achieved in 93 % of patients. The median time to response was 4.4 weeks (95% confidence interval 3.6–5.3 weeks). Adverse events of grades 1/2 associated with romiplostim were reported in 6.7 % of patients. On romiplostim therapy, pronounced positive changes in quality of life were shown by all scales of the general questionnaire SF-36 and the targeted questionnaire FACT-Th6 (p < 0.001). The clearest improvements were observed in role-physical and role-emotional functioning. Already after 3 months of therapy, a considerable fatigue reduction was observed and sustained for the next 6 and 12 months of romiplostim administration (p < 0.001). During the therapy, the proportion of patients with fatigue impacting various aspects of functioning became considerably smaller. The vast majority of patients (85 %) were satisfied with the treatment. Discrepancies between patients’ and physicians’ evaluations of fatigue were also identified during the treatment.

Conclusion. The results of the present multi-center observational study demonstrate high efficacy and safety of romiplostim for chronic ITP patients in the real-world setting. Romiplostim therapy yields considerable quality of life improvement and fatigue reduction. To optimize the patient monitoring system and patient-centered ITP treatment in the real-world setting, it is advisable to use the standardized questionnaires assessing quality of life and fatigue.

Keywords: chronic immune thrombocytopenia, quality of life, romiplostim, efficacy, safety, data in the real-world setting.

Received: October 21, 2022

Accepted: March 1, 2023

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AL Melikyan¹, IN Subortseva¹, SM Kulikov¹, YuA Chabaeva¹, EA Gilyazitdinova¹, KP Novoselov², EA Knyazeva², AS Egorova², IS Stepochkin², EV Koroleva³, TM Sycheva⁴, VP Belgesova⁴, AYu Putintseva⁵, OM Senderova⁶, IV Vasil’eva⁷, EYu Komartseva⁸, AA Kaplina⁸, VI Bakhtina⁹, MA Mikhalev⁹, YuB Chernykh¹⁰, EN Parovichnikova¹

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

² Novgorod Regional Clinical Hospital, 14 Pavla Levitta ul., Velikiy Novgorod, Russian Federation, 173008

³ Regional Clinical Hospital, 105 Peterburgskoe sh., Tver, Russian Federation, 170036

⁴ Aleksandro-Mariinskaya Astrakhan Regional Clinical Hospital, 2 Tatishcheva ul., Astrakhan, Russian Federation, 414056

⁵ AN Kabanov Municipal Clinical Hospital No. 1, 7 Pereleta ul., Omsk, Russian Federation, 644112

⁶ Irkutsk Regional Clinical Hospital, 100 Yubileinyi mikroraion, Irkutsk, Russian Federation, 664049

⁷ Central Municipal Hospital No. 7, 33 Vilonova ul., Ekaterinburg, Russian Federation, 620137

⁸ Rostov Regional Clinical Hospital, Zapadnyi zhiloi massiv, 170 Blagodatnaya ul., Rostov-on-Don, Russian Federation, 344015

⁹ VF Voino-Yasenetskii Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka ul., Krasnoyarsk, Russian Federation, 660022

¹⁰ MF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina ul., Moscow, Russian Federation, 129110

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, Subortseva IN, Kulikov SM, et al. Approaches to the Treatment of Patients with Myelofibrosis and Polycythemia Vera with Constitutional Symptoms in Real-World Clinical Practice in the Russian Federation: Intermediate Results of a Multi-Center Observational Prospective Clinical Study. Clinical oncohematology. 2023;16(2):146–53. (In Russ).

DOI: 10.21320/2500-2139-2023-16-2-146-153

ABSTRACT

Aim. To describe the methods of drug therapy implemented for the disease control in patients with polycythemia vera (PV) and myelofibrosis (MF) as well as to analyze manifestations and severity of the disease symptoms in real-world clinical practice.

Materials & Methods. The analysis focused on the data of 1229 patients. In 629 (51.18 %) patients, PV was diagnosed, MF was identified in 521 (42.39 %) patients. The diagnosis of 79 (6.43 %) patients was not reported. Early stage of primary MF (PMF) was detected in 182 (34.93 %) patients, PMF fibrosis stage was identified in 251 (48.18 %) patients, post-polycythemic MF was registered in 61 (11.71 %) patients, and 13 (2.5 %) patients showed post-thrombocythemic MF. In 14 (2.69 %) patients, MF type was not reported. By the time of diagnosis, the median age of PV patients was 56 years (range 17–86 years), and that of MF patients was 55 years (range 16–83 years) (p = 0.022). The proportion of women among PV patients was 57 %, among MF patients it was 65 % (p = 0.0065).

Results. The assessment of thrombotic complication risk in PV showed that 51.01 % (n = 302) of patients belong to the low-risk, 39.86 % (n = 236) belong to the intermediate-risk, and only 9.12 % (n = 54) of patients belong to the high-risk groups. Distribution of MF patients between risk groups demonstrates favorable prognosis for most patients. The group of low and intermediate-1 risks includes 56.43 % (n = 294) patients according to the prognostic scoring system IPSS and 68.52 % (n = 357) according to the prognostic scoring system DIPSS. In the vast majority of cases, patients received hydroxycarbamide therapy: 81.81 % (n = 832) in the total cohort, 83.33 % (n = 465) in the PV group, and 79.96 % (n = 367) in the MF group. Interferon-α was administered to 19.71 % (n = 110) of PV patients and 29.85 % (n = 137) of MF patients. Ruxolitinib was assigned to 3.14 % (n = 19) of PV patients and 21.35 % (n = 98) of MF patients.

Conclusion. Regular monitoring of the PV and MF course and treatment efficacy can provide recommendations for adequate change of therapy in case of the failure of previous treatment. It should be emphasized that the timely switch to the second-line therapy results in reduced disability and mortality among PV and MF patients with myeloproliferative neoplasms.

Keywords: polycythemia vera, myelofibrosis, hydroxycarbamide, interferon-α, ruxolitinib.

Received: November 7, 2022

Accepted: March 9, 2023

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25. Ионова Т.И., Виноградова О.Ю., Ефремова Е.В. и др. Разработка и результаты апробации русской версии опросника MPN10 для оценки симптомов у пациентов с миелопролиферативными новообразованиями с учетом международных рекомендаций. Клиническая онкогематология. 2020;13(2):176–84. doi: 10.21320/2500-2139-2020-13-2-176-184.
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YuO Davydova, NM Kapranov, KA Nikiforova, OS Karavaeva, DV Kamelskikh, MYu Drokov, LA Kuzmina, TV Gaponova, IV Galtseva, EN Parovichnikova

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

For correspondence: Yuliya Olegovna Davydova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(499)612-62-21; e-mail: davydova.y@blood.ru

For citation: Davydova YuO, Kapranov NM, Nikiforova KA, et al. T-Helper Subpopulations in Acute Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2023;16(2):137–45. (In Russ).

DOI: 10.21320/2500-2139-2023-16-2-137-145

ABSTRACT

Aim. To identify the characteristics of T-helper subpopulations in healthy donors and to compare them with those reported in acute leukemia patients 6 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Materials & Methods. The study enrolled 41 blood donors and 49 patients after-HSCT. The median age of donors was 36 years (range 20–60 years), 29 of them were men and 12 were women. The median age of patients was 37 years (range 19–62 years), 18 of them were men and 31 were women. Acute myeloid leukemia was diagnosed in 27 (55 %) patients and acute lymphoblastic leukemia/lymphoma in 22 (45 %) patients. Myeloablative conditioning was administered to 4 (8 %) patients and reduced intensity conditioning to 45 (92 %) patients. T-helper subpopulations were studied in the blood of healthy donors vs. acute leukemia patients after allo-HSCT. The flow cytometry analysis was conducted to simultaneously assess the expression of markers CD3, CD4, CD8, CD25, CD45RA, CD197, CD28, CCR4, CCR6, CCR10, CXCR3, and CXCR5 in T-cells.

Results. The study demonstrated that the count of T-helpers at different stages of differentiation (regulatory, naive T-cells, memory cells, and effector cells) comprehensively distinguishes healthy donors from patients. Moreover, the functional structure of each of these populations differ in donors vs. patients even on Month +6 after allo-HSCT. Donors appeared to have more polarized cells among the central memory T-helpers. The proportion of T-helpers type 1 among the effector cells was higher is patients.

Conclusion. The results of the study indicate that the Т-cell parameter set can be analyzed to assess immunity and to describe its disorders in different pathologies or after drug chemotherapy.

Keywords: flow cytometry, Т-cells, Т-helpers, blood donors, lymphocyte subpopulations.

Received: October 26, 2022

Accepted: March 10, 2023

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OV Pirogova¹, OV Kudyasheva¹, AG Smirnova¹, VV Porunova¹, SV Tolstova¹, KR Kalimulina¹, MV Chernous¹, YuYu Vlasova¹, IS Moiseev¹, VA Dobronravov², AD Kulagin¹

¹ RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022

² Scientific Research Institute of Nephrology; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022

For correspondence: Olga Vladislavovna Pirogova, MD, PhD, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022; Tel.: +7(921)441-90-16; e-mail: bmt.myeloma@gmail.com, dr.pirogova@gmail.com

For citation: Pirogova OV, Kudyasheva OV, Smirnova AG, et al. The Role of Autologous Hematopoietic Stem Cell Transplantation in the Therapy of Systemic AL Amyloidosis. Clinical oncohematology. 2023;16(2):128–36. (In Russ).

DOI: 10.21320/2500-2139-2023-16-2-128-136

ABSTRACT

Aim. To assess the outcomes of autologous hematopoietic stem cell transplantation (auto-HSCT) in systemic AL Amyloidosis patients treated at the R.M. Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation.

Materials & Methods. In the period from 2005 to 2022, auto-HSCT was performed in 33 patients with systemic AL Amyloidosis. In 7 of them, auto-HSCT was not preceded by the induction therapy “upfront”. From 2012 all patients received induction therapy prior to transplantation. The median age of patients was 54 years (range 38–68 years); among them there were 17 women and 16 men.

Results. The 3-year follow-up period showed hematological response rate of 76 % (95% confidence interval [95% CI] 50–90 %), heart response rate of 27 % (95% CI 6–55 %), renal response rate of 76 % (95% CI 41–93 %), and hepatic response rate of 26 % (95% CI 8–50 %). The 5-year overall (OS) and progression-free (PFS) survivals were 71 % (95% CI 49–85 %) and 53 % (95% CI 32–71 %), respectively. The OS parameters in the group with delayed auto-HSCT, i.e., after induction therapy, were better than in the “upfront” group: 82 % (95% CI 60–93 %) vs. 43 % (95% CI 10–73 %) (p = 0.03). The OS parameters were affected by health status (p = 0.03), reduced left ventricular ejection fraction < 60 % (p = 0.006), stage of heart disease (p = 0.016), and stage III kidney disease (p = 0.007). The PFS parameters depended on ECOG performance status (p = 0.004) and stage of heart disease (p = 0.041).

Conclusion. The presented data confirm the results of the studies emphasizing the importance of induction therapy prior to auto-HSCT in the treatment of systemic AL Amyloidosis. More stringent parameters of renal function, left ventricular ejection fraction, and ECOG performance status can be used as criteria for auto-HSCT eligibility. Reduced melphalan doses, as conditioning regimen, can be administered to patients with pronounced comorbidity.

Keywords: systemic AL Amyloidosis, autologous hematopoietic stem cell transplantation, melphalan, bortezomib.

Received: October 24, 2022

Accepted: March 15, 2023

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EV Kuzmich¹, IE Pavlova¹, LN Bubnova^1,2, SS Bessmeltsev¹

¹ Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

² IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022

For correspondence: Elena Vital’evna Kuzmich, PhD in Biology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)912-52-07; e-mail: yelenakuzmich@gmail.com

For citation: Kuzmich EV, Pavlova IE, Bubnova LN, Bessmeltsev SS. KIR-Genetic Factors and Response to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia. Clinical oncohematology. 2023;16(2):119–27. (In Russ).

DOI: 10.21320/2500-2139-2023-16-2-119-127

ABSTRACT

The development of tyrosine kinase inhibitors (TKIs) and their introduction into clinical practice considerably improved the prognosis for chronic myeloid leukemia (CML) patients. About 50 % of patients with achieved deep molecular response are eligible for safe TKI discontinuation. Despite these advances, no reliable biomarkers are known to predict a response and sustaining treatment-free remission after TKI withdrawal. As TKIs do not destroy leukemic stem cells, which can be responsible for relapse, critical importance in CML is attached to natural killers (NK-cells) having antitumor activity. Functional activity of NK-cells is evaluated by expression level and repertoire of killer cell immunoglobulin-like receptors (KIR). Current studies demonstrate that a patient’s KIR genotype affects the probability of achieving early and deep molecular responses to first- and second-generation TKIs, progression-free and overall survivals, and sustaining treatment-free remission. On that ground, KIR-genetic factors can be regarded as promising predictors of response to TKI therapy in CML. Early clinical studies, which dealt with monoclonal antibodies blocking the inhibitory KIR in order to increase NK-cell activity, revealed an acceptable safety profile and efficacy in some hematological diseases (such as acute myeloid leukemia, multiple myeloma, Т-cell lymphoma) if used in combination with cytostatic drugs or antitumor monoclonal antibodies. KIR genotype determination can contribute to the development of effective therapies of this malignant hematological tumor.

Keywords: genes of killer cell immunoglobulin-like receptors, tyrosine kinase inhibitors, treatment-free remission, chronic myeloid leukemia.

Received: November 8, 2022

Accepted: March 1, 2023

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AA Sherstnev, AM Kovrigina

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

For correspondence: Andrei Alekseevich Sherstnev, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: sherstnevandrejj@mail.ru

For citation: Sherstnev AA, Kovrigina AM. Morpho-Immunohistochemical Characteristics of Different Mycosis Fungoides Stages: A Literature Review. Clinical oncohematology. 2023;16(2):109–18. (In Russ).

DOI: 10.21320/2500-2139-2023-16-2-109-118

ABSTRACT

Mycosis fungoides (MF) is the most ubiquitous type of cutaneous T-cell lymphoma. MF pathogenesis has not been well studied up to now. Differential diagnosis of the disease, especially at early stages, is complicated and poses a considerable challenge. The present review covers current views on MF pathogenesis and methods of its diagnosis.

Keywords: mycosis fungoides, naive T-cells, T-helper cells, reactive microenvironment.

Received: September 21, 2022

Accepted: March 3, 2023

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NA Romanenko, ER Shilova, LV Stelmashenko, EI Kaitandzhan, AV Kuleshova, NP Stizhak, VN Chebotkevich, SV Sidorkevich, SV Gritsaev, SS Bessmeltsev

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

For correspondence: Nikolai Aleksandrovich Romanenko, MD, PhD, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-58-57; e-mail: rom-nik@yandex.ru

For citation: Romanenko NA, Shilova ER, Stelmashenko LV, et al. Characteristic Features of the Novel Coronavirus Infection COVID-19 in Oncohematological Patients. Clinical oncohematology. 2023;16(1):101–8. (In Russ).

DOI: 10.21320/2500-2139-2023-16-1-101-108

ABSTRACT

Background. The novel coronavirus infection SARS-CoV-2 (COVID-19) is one of high-threat respiratory diseases, characterized by multiple organ disorders with primary respiratory failure and population mortality of 2–5 %. However, the mortality of oncohematological patients treated with chemotherapy is considerably higher.

Aim. To analyze the COVID-19 treatment outcomes in hematological malignancy patients who received drug chemotherapy.

Materials & Methods. The clinical course of COVID-19 was analyzed in 32 hematological malignancy patients aged 31–81 years (median 62 years). The disease onset was the date of the first positive COVID-19 PCR test. These patients were transferred to an infectious hospital specialized in the therapy of the novel coronavirus infection. Pneumonia was confirmed by standard radiography and CT. Blood oxygen saturation, body temperature, ECG, and respiratory rate were monitored. Moderate and severe COVID-19 was observed in 17 (53.1 %) of 32 patients. The condition of 15 (46.9 %) patients was described as good. For comparison, a control group was collected from 32- to 79-year-old (median 63 years) patients (n = 28) having hematological malignancies but no COVID-19.

Results. Nine (28.1 %) of 32 patients under analysis died upon increasing respiratory and multiple organ insufficiency on Day 3–17 (mean 8,6 ± 4,6 days) from the first positive COVID-19 PCR test. Death was predominantly reported in multiple myeloma patients (n = 5) as well as in a patient with Waldenstrom’s macroglobulinemia. In the control group (n = 28) with similar hematological tumors but without COVID-19, three (10.7 %) patients died throughout the 12-month follow-up period. The present paper contains a case report illustrating the clinical features of coronavirus infection in a patient with Waldenstrom’s macroglobulinemia, a monoclonal gammopathy with primary bone marrow lesions.

Conclusion. COVID-19 is a life-threatening viral disease with high mortality in patients with hematological malignancies, especially those with plasma cell dyscrasias.

Keywords: novel coronavirus infection, multiple myeloma, pneumonia, thrombosis, blood oxygen saturation, Waldenstrom’s macroglobulinemia.

Received: July 6, 2022

Accepted: December 3, 2022

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MV Smolnikova, EV Butina, AV Iovdii, EA Poponina, NA Zorina

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

For correspondence: Mariya Viktorovna Smolnikova, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027; e-mail: smolnikova_96@inbox.ru

For citation: Smolnikova MV, Butina EV, Iovdii A, et al. Monitoring of Red cell Donor Chimerism in Oncohematological Patients After Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2023;16(1):96–100. (In Russ).

DOI: 10.21320/2500-2139-2023-16-1-96-100

ABSTRACT

Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a definitive therapy for patients with different oncological and hematological diseases. The study of red cell chimerism is a crucial process for diagnosing transplant engraftment and functioning during the post-transplantation period.

Aim. To assess the effect of immunohematological (АВО and HLA donor–recipient matching) and medical (conditioning regimens) parameters on the onset time of post-transplantation donor chimerism which is determined by RBC antigens.

Materials & Methods. The study enrolled 54 patients at the Kirov Research Institute of Hematology and Transfusiology in Russia (25 female and 29 male patients) aged 3–60 years (median 32 years). All of them received allo-HSCT in 2013–2021. Acute leukemias were identified in 39 patients, 8 patients were reported to have malignant lymphoproliferative diseases, 3 patients had myeloproliferative neoplasms, and 4 patients were diagnosed with aplastic anemia. RBC antigens of donors and recipients were analyzed by gel hemagglutination using Bio-Rad (USA) reagents and equipment.

Results. The onset time of donor chimerism depends neither on the degree of HLA donor–recipient matching, nor on conditioning regimen. Donor chimerism in recipients with major ABO-incompatibility occurs significantly later than in patients with minor АВО-incompatibility and ABO-identity.

Conclusion. Monitoring of post-transplantation donor chimerism is an important diagnostic and prognostic tool to assess donor hematopoietic cell engraftment, hematologic recovery, graft rejection, and relapse of the disease. After allo-HSCT, first donor red cells occur in pairs with major АВО-incompatibility later than in pairs with minor АВО-incompatibility or ABO antigen compatibility. Other immunohematological and medical parameters do not affect the development rate of donor chimerism determined by RBC antigens.

Keywords: allogeneic hematopoietic stem cell transplantation, donor chimerism, HLA system, ABO system, conditioning regimen, RBC antigens.

Received: June 23, 2022

Accepted: November 29, 2022

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REFERENCES

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II Kostroma¹, AS Zhuk², ZhYu Sidorova^1,3, RR Sabitova¹, AYu Aksenova⁴, OB Belopolskaya⁴, SS Bessmeltsev¹, SV Sidorkevich¹, SV Gritsaev¹

¹ Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

² ITMO National Research University, 49 lit. A Kronverkskii pr-t, Saint Petersburg, Russian Federation, 197101

³ BP Konstantinov Petersburg Nuclear Physics Institute of National Research Center “Kurchatov Institute”, 1 Orlova roshcha microdistrict, Gatchina, Leningrad Region, Russian Federation, 188300

⁴ Saint Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024; e-mail: obex@rambler.ru

For citation: Kostroma II, Zhuk AS, Sidorova ZhYu, et al. Efficacy of Combined Drug Pre-transplant Conditioning Regimens in Multiple Myeloma Patients with Single Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2023;16(1):88–95. (In Russ).

DOI: 10.21320/2500-2139-2023-16-1-88-95

ABSTRACT

Aim. To conduct an interim outcome analysis of conditioning regimens with carfilzomib or thiotepa compared to standard melphalan 200 mg/m² regimen in multiple myeloma (MM) patients with single autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The retrospective analysis focused on outcomes of 67 single auto-HSCTs performed from 2017 to 2021. Responses as well as progression-free (PFS) and overall survival (OS) rates were compared in MM patients per IWMG criteria in pre- and post-transplant periods. Three conditioning regimens were assigned: melphalan 200 mg/m² (Mel200), melphalan/carfilzomib combination (Mel/Karfil), and melphalan/thiotepa combination (Mel/Thio). In an additional cohort of 12 MM patients, next-generation sequencing assay was used to detect inherited and somatic mutations associated with proteasome inhibitor efficacy. For this purpose, DNA of peripheral blood lymphocytes and bone marrow plasma cells were examined.

Results. PFS medians were comparable in MM patients treated with Mel200 (n = 40) and Mel/Karfil (n = 10) conditioning regimens, they were 32 and 23 months, respectively (p = 0.241). In these cohorts, OS median was not reached, and the curves showed no significant differences (p = 0.050). Out of 10 MM patients treated with Mel/Karfil, six received melphalan 140 mg/m², the remaining 4 patients received 200 mg/m². Complete response (CR) rate in the Mel200 and Mel/Karfil groups increased two-fold after auto-HSCT: from 35.5 % to 74.2 % and from 25.0 % to 50.0 %, respectively. The worst PFS and OS medians were in the Mel/Thio group, i.e., 12 and 17 months, respectively, and CR rate after auto-HSCT remained unchanged. The best PFS was associated with CR rather than very good partial or partial response after auto-HSCT, they were 48, 21, and 23 months, respectively (p = 0.001). Exome sequencing of DNA of peripheral blood lymphocytes and bone marrow plasma cells revealed polymorphic variants in the genes associated with chemotherapy response.

Conclusion. The outcomes of Mel/Karfil, the regimen containing the reduced dose of melphalan 140 mg/m², and the statistical comparability with the Mel200 regimen suggest that this combination can be effective in the treatment of MM patients with impaired renal function, which still needs to be further confirmed. No advantage of the combined conditioning regimen over the standard one can be accounted for by the loss of plasma cell sensitivity to proteasome inhibitors. The obtained data provide ground for modifying the study protocol with a particular focus on evaluating the efficacy and safety of conditioning regimen Mel/Karfil with melphalan 200 mg/m² depending on biologic phenotype of plasma cell.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, conditioning regimen, melphalan, carfilzomib, thiotepa.

Received: June 15, 2022

Accepted: December 2, 2022

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ES Nesterova, NA Severina, BV Biderman, AB Sudarikov, AM Kovrigina, TN Obukhova, YaK Mangasarova, SM Kulikov, EE Zvonkov, EN Parovichnikova, VG Savchenko

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

For correspondence: Ekaterina Sergeevna Nesterova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-23-61, +7(910)429-62-26; e-mail: nest.ek@yandex.ru

For citation: Nesterova ES, Severina NA, Biderman BV, et al. Identification of Somatic Mutations in EZH2 Gene and Assessment of Their Prognostic Value in Follicular Lymphoma Grades 1–3А. Clinical oncohematology. 2023;16(1):80–7. (In Russ).

DOI: 10.21320/2500-2139-2023-16-1-80-87

ABSTRACT

Aim. To determine the incidence and prognostic value of mutations in exon 16 of EZH2 as well as those of polymorphism с.1582-21А>G (rs2072407) in EZH2 in patients with follicular lymphoma (FL) grades 1–3А in relation to morphologic and cytogenetic tumor characteristics.

Materials & Methods. The prospective cohort study conducted by the National Research Center for Hematology from January 2017 to April 2021 enrolled 80 patients with newly diagnosed FL grades 1/2 and 3А. The median follow-up was 53 months. Molecular and cytogenetic analyses were based on biopsy samples of lymph nodes obtained before chemotherapy. The mutation status of exon 16 in EZH2 and the presence of intronic polymorphism rs2072407 in EZH2 were examined by Sanger sequencing method. Translocation t(14;18)(q32;q21) was detected by karyotyping or FISH.

Results. Mutations in exon 16 of EZH2 (mutEZH2) were identified in 10/80 (13 %) patients. All patients showed missense mutation in codon 646 of EZH2. Translocation t(14;18) was detected in 45/80 (56 %) cases. Poor outcome in the cohort with no t(14;18) was observed 3 times more often than in the group of patients with t(14;18) (p = 0.0001). The presence of t(14;18) was associated with favorable prognosis irrespective of either the mutation status of exon 16 in EZH2 or the FL grade. The analysis of the polymorphism rs2072407 status yielded the following genotypes: AA in 24 % (n = 19), AG in 42 % (n = 34), and GG in 34 % (n = 27) of cases. The variants АА and AG were associated with higher risk of death (hazard ratio 2.9; 95% confidence interval 1.2–10.6; p = 0.01), whereas the genotype GG was associated with wtEZH2 (10 % vs. 37 %) and favorable prognosis (p = 0.065).

Conclusion. Significant biological markers for favorable prognosis in FL appeared to be the presence of t(14;18)(q32;q21) and GG genotype of polymorphism rs2072407 in EZH2. The previously identified prognostic factors (grade 3А, bulky tumor lesions > 6 cm, Ki-67 > 35 %, and a short interval between symptom onset and chemotherapy start) were incorporated into a new unified personalized predictive (index PPI) FL model by supplementing it with two additional biological markers: the presence of t(14;18)(q32;q21) and GG genotype of polymorphism rs2072407. This approach may increase the prognostic value of the new personalized design which will provide the basis for risk-adapted algorithms for FL treatment.

Keywords: follicular lymphoma, prognosis, bulky, grades, Ki-67, t(14;18)(q32;q21), EZH2 gene.

Received: July 9, 2022

Accepted: November 30, 2022

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