The Effect of Anticoagulant Therapy on Survival and Outcome of Venous Thrombosis in Children, Teenagers, and Young Adults with Acute Lymphoblastic Leukemia Treated According to ALL-MB-2008 and ALL-MB-2015 Protocols

VV Dmitriev, NV Migal, OI Bydanov, NV Lipai, EV Dmitriev

Republican National Applied Research Center of Pediatric Oncology, Hematology and Immunology, 43 Frunzenskaya, Borovlyany, Minskii district, Republic of Belarus, 223053

For correspondence: Vyacheslav Vasil’evich Dmitriev, MD, PhD, 43 Frunzenskaya str., Borovlyany, Minskii district, Republic of Belarus, 223053; Tel.: +375(17)265-42-22; e-mail: dmitrievhaematol@mail.ru

For citation: Dmitriev VV, Migal NV, Bydanov OI, et al. The Effect of Anticoagulant Therapy on Survival and Outcome of Venous Thrombosis in Children, Teenagers, and Young Adults with Acute Lymphoblastic Leukemia Treated According to ALL-MB-2008 and ALL-MB-2015 Protocols. Clinical oncohematology. 2019;12(3):338–43 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-338-343


ABSTRACT

Aim. To assess the effect of anticoagulant therapy on survival and outcome of venous thrombosis in children, teenagers, and young adults with acute lymphoblastic leukemia (ALL).

Materials & Methods. Venous thrombosis was diagnosed in 42 out of 592 ALL patients treated according to ALL-MB-2008 and ALL-MB-2015 protocols from 2008 to 2017.

Results. A daily dose of 150–200 IU/kg low molecular weight heparin (LMWH) was administered to 30 patients. Duration of anticoagulant treatment was up to 1 month in 4 patients, 2–3 months in 8 patients, 4–6 months in 12 patients, and 7–12 months in 4 patients. To 2 patients anticoagulants were administered for more than 24 months. Complete recanalization of thrombosed vessel was achieved in 19 patients, partial recanalization was achieved in 6 patients, obliteration of predominantly internal jugular vein was found in 5 patients. During thrombocytopenia (100 to 35 × 109/L) 12 patients received reduced doses of LMWH for 1–4 weeks. In the period of chemotherapy-induced thrombocytopenia the daily LMWH dose was reduced in proportion to thrombocyte level. After thrombocyte recovery up to more than 100 × 109/L antithrombotic treatment was continued with LMWH daily dose of 150–200 anti-Xa IU/kg. The duration of anticoagulant treatment among 12 patients who received reduced doses of LMWH was up to 1 month in 3 patients, 2–3 months in 4 patients, 4–6 months in 3 patients, and 7–12 months in 2 patients. Complete recanalization of thrombosed vessel was achieved in 8 patients, partial recanalization was achieved in 2 patients, vein obliteration was found in 2 patients. No correlation between LMWH dosage and thrombosis outcome was observed (χ2 = 0.494; = 0.78). Maintenance (accompanying) therapy was completed in 38 out of 42 ALL patients with venous thrombosis. Event-free survival was 83 ± 8 %, that was similar to the one (81 ± 2 %) in patients without thrombosis (= 0.654).

Conclusion. Anticoagulant treatment of venous thrombosis complicating ALL in children, teenagers, and young adults did not yield a decrease of either overall or event-free survival. Reduction of LMWH doses in the period of chemotherapy-induced thrombocytopenia did not affect the outcome of venous thrombosis.

Keywords: venous thrombosis, coagulation, acute lymphoblastic leukemia, children, teenagers, young adults, anticoagulant therapy, low molecular weight heparin.

Received: October 30, 2018

Accepted: June 5, 2019

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REFERENCES

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Clinical and Laboratory Characteristics and Differential Diagnosis between Secondary Hemophagocytic Syndrome and Sepsis

VG Potapenko1,2, MYu Pervakova2, AV Titov1, OV Goloshchapov2, SV Lapin2, EA Surkova2, AV Klimovich1, OP Mironova1, NN Petrova1, NYu Chernookaya1, EV Karyagina3, NV Skorobogatova1, ES Pavlyuchenko4, EA Karev4, NA Potikhonova5, VA Dubkova6, AYu Kaskov7, AV Rysev7, TG Kulibaba6, NV Medvedeva1

1 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

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

3 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

4 II Mechnikov North-Western State Medical University, 41 Kirochnaya str., Saint Petersburg, Russian Federation, 191015

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

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

7 II Dzhanelidze Saint Petersburg Research Institute of Emergency Medicine, 3 Budapeshtskaya str., Saint Petersburg, Russian Federation, 192242

For correspondence: Vsevolod Gennad’evich Potapenko, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110; Tel.: +7(905)284-51-38; e-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Pervakova MYu, Titov AV, et al. Clinical and Laboratory Characteristics and Differential Diagnosis between Secondary Hemophagocytic Syndrome and Sepsis. Clinical oncohematology. 2019;12(3):329–37 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-329-337


ABSTRACT

Background. Secondary hemophagocytic syndrome (SHPS) and sepsis, although very similar in their clinical manifestations and laboratory parameters, essentially differ in terms of methods of their treatment. SHPS therapy is aimed at immunosuppression, whereas in sepsis anti-infectious treatment is required. To choose the correct therapy a rapid differential diagnosis is necessary.

Aim. Search and analysis of criteria of differential diagnosis between SHPS and sepsis.

Materials & Methods. The data of 102 patients were analyzed: 55 SHPS patients (median age 60 and range 18–81 years) and 47 sepsis patients (median age 60 and range 18–89 years). SHPS was diagnosed on the basis of HLH-2004 and H-Score criteria. Sepsis was confirmed by documented inflammatory lesions and systemic inflammatory reactions. Microbiologically confirmed sepsis was reported in 10 (21 %) patients. In all sepsis patients multiple organ failure was identified.

Results. The study of SHPS and sepsis groups revealed significant differences (< 0.05) in the levels of C-reactive protein, procalcitonin, creatinine, albumin, and sodium. It was also found out that splenomegaly rate and the levels of triglycerides, ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in SHPS were significantly higher than in sepsis, but the levels of glycosylated ferritin (%GF), fibrinogen, leukocytes, neutrophils, and thrombocytes were lower. The following medians (quartiles 1–3) were reported in SHPS and sepsis, respectively: triglycerides (mmol/L) were 3.1 (2.3–3.8) and 1.5 (0.8–2.7), total ferritin (ng/mL) was 7,170 (3,159.2–12,551.0) and 1,274 (559.0–3,041.5), %GF was 26.5 (16.7–37.3) and 54.5 (37.7–71.8), fibrinogen (g/L) was 2.8 (1.4–4.4) and 5.3 (2.8–6.8), ALT (IU/L) was 50 (20–102) and 30 (15.3–55.5), AST (IU/L) was 66 (40.0–105.6) and 36 (24.6–78.0), leukocytes (×109/L) were 3.7 (2.1–5.5) and 8.9 (6.5–14.5), thrombocytes (×109/L) were 56 (25.2–93.5) and 157 (97–308). According to ROC analysis the areas under the curve were as follows: 0.88 for neutrophil level, 0.85 for total ferritin, %GF, leukocytes, and thrombocytes, 0.74 for triglycerides, 0.71 for fibrinogen, 0.65 for sodium, and 0.61 for ALT and AST.

Conclusion. In differential diagnosis between SHPS and sepsis most important are the levels of total ferritin, its glycosylated fraction, and triglycerides; less important are fibrinogen, neutrophils, thrombocytes and spleen size. As diagnosis and differential diagnosis between SHPS and sepsis are based on the sum total of clinical and laboratory markers, none of the specified characteristics can serve as a reliable parameter if taken separately.

Keywords: secondary hemophagocytic syndrome, sepsis, ferritin, glycosylated ferritin, triglycerides, hyperferritinemia.

Received: November 20, 2018

Accepted: May 15, 2019

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Cardiovascular Toxicity of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia

IL Davydkin1,2, KV Naumova1, AM Osadchuk1, IA Zolotovskaya1, OE Danilova1, TYu Stepanova1, OV Tereshina1, LV Limareva3, AS Shpigel’1, TP Kuz’mina1

1 Samara State Medical University, 89 Chapaevskaya str., Samara, Russian Federation, 443099

2 SamGMU Research Institute of Hematology, Transfusiology and Intensive Care, 89 Chapaevskaya str., Samara, Russian Federation, 443099

3 SamGMU Institute of Experimental Medicine and Biotechnology, 89 Chapaevskaya str., Samara, Russian Federation, 443099

For correspondence: Kseniya Viktorovna Naumova, 89 Chapaevskaya str., Samara, Russian Federation, 443099; Tel.: +7(905)303-12-08; e-mail: senechka.naumova@rambler.ru

For citation: Davydkin IL, Naumova KV, Osadchuk AM, et al. Cardiovascular Toxicity of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia. Clinical oncohematology. 2018;11(4):378–87.

DOI: 10.21320/2500-2139-2018-11-4-378-387


ABSTRACT

In the present review the cardiovascular complications in patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitors (TKI) are discussed. It covers current views on pathogenesis of TKI cardiovascular toxicity. The pathophysiology of cardiovascular diseases (CVD) is considered as a part of the so-called pathophysiological continuum, i.e. a complex of processes developing at the molecular and cellular levels before clinical symptoms of the above diseases occur. Cardiovascular toxicity of certain TKIs can contribute to progression of pathophysiological processes in CML patients. The study of mechanisms underlying cardiovascular complications of TKI-based therapy is essential for evaluating the risks of their development in each patient. Identification of CVD predictors during TKI-based therapy can allow to elaborate a scheme for cardiovascular monitoring and safe patient management under consideration of individual risks and to avoid severe life-threatening complications.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, adverse effects, cardiotoxicity, cardiovascular events.

Received: May 14, 2018

Accepted: August 29, 2018

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Dermatological Toxicity of Hydroxycarbamide

IN Subortseva, AL Melikyan, EA Gilyazitdinova, TI Kolosheinova, EI Pustovaya, EK Egorova, AM Kovrigina, AB Sudarikov, AO Abdullaev

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

For correspondence: Irina Nikolaevna Subortseva, MD, PhD, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: soubortseva@yandex.ru.

For citation: Subortseva IN, Melikyan AL, Gilyazitdinova EA, et al. Dermatological Toxicity of Hydroxycarbamide. Clinical oncohematology. 2018;11(3):252–58.

DOI: 10.21320/2500-2139-2018-11-3-252-258


ABSTRACT

Hydroxycarbamide is an antitumor agent mainly used for treatment of Ph-negative myeloproliferative disorders and sickle cell disease. The development of skin ulcers is a rare but serious adverse event in long-term antitumor therapy. Hydroxycarbamide-induced ulcers are often multiple and bilateral, and usually occur in the lower legs, although they can occur in other regions of the body. The ulcers are small-sized and shallow with sharp margins and yellow fibrine-covered base. They cause constant severe, difficult to treat pain which is a characteristic sign. The drug withdrawal usually leads to spontaneous healing of ulcers. Regular dermatologic screening must be obligatory for all the patients receiving hydroxycarbamide. The present paper provides a literature review on dermatological toxicity of hydroxycarbamide and a clinical case description.

Keywords: hydroxycarbamide, adverse events, dermatologic screening, Ph-negative chronic myeloproliferative disorders.

Received: February 7, 2018

Accepted: May 4, 2018

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Stevens-Johnson Syndrome after Treatment of Female Patient with Small Lymphocytic B-Cell Lymphoma, Autoimmune Hemolytic Anemia and Antiphospholipid Antibody Syndrome with Rituximab

AL Melikyan, IN Subortseva, AM Kovrigina, TI Kolosheinova, EK Egorova, EI Pustovaya

Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Irina Nikolaevna Subortseva, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-44-71; e-mail: soubortseva@yandex.ru

For citation: Melikyan AL, Subortseva IN, Kovrigina AM, et al. Stevens-Johnson Syndrome after Treatment of Female Patient with Small Lymphocytic B-Cell Lymphoma, Autoimmune Hemolytic Anemia and Antiphospholipid Antibody Syndrome with Rituximab Clinical oncohematology. 2017;10(1): 120–7 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-120-127


ABSTRACT

Stevens-Johnson syndrome is a severe delayed type systemic allergic reaction which affects the skin and mucous membranes. In adults, Stevens-Johnson syndrome is usually caused by the administration of drugs or a malignant process. The paper presents a case of Stevens-Johnson syndrome after the treatment of a female patient with small lymphocytic B-cell lymphoma, autoimmune hemolytic anemia and antiphospholipid antibody syndrome with rituximab. A rare combination of Stevens-Johnson syndrome and small lymphocytic B-cell lymphoma of small lymphocytes, as well as the development of severe delayed type systemic allergic reaction to introduction of rituximab are of special interest. A detailed medical history and the clinical manifestations of the disease allowed to diagnose Stevens-Johnson syndrome at early stages and prescribe an adequate therapy. As a result of the treatment, the patient’s condition has improved considerably. Symptoms of general toxicity were arrested completely; there was a complete epithelization of erosive defects. Therefore, the presented clinical observation shows that timely diagnosis, complex drug therapy, and comprehensive care can cure the diseases as soon as possible and prevent complications.

Keywords: Stevens-Johnson syndrome, pathogenesis, clinical manifestations, diagnosis, treatment, rituximab.

Received: July 28, 2016

Accepted: December 6, 2016

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Diagnostic and Prognostic Value of Biochemical Markers of Infectious Complications of High-Dose Therapy with Autologous Hematopoietic Stem Cell Transplantation in Malignant Lymphoproliferative Diseases

VO Sarzhevskii, YuN Dubinina, VYa Mel’nichenko

NI Pirogov National Medical and Surgical Center under the Ministry of Health of the Russian Federation, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Vladislav Olegovich Sarzhevskii, PhD, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203; Tel: +7(495)603-72-18; e-mail: vladsar@pochta.ru

For citation: Sarzhevskii VO, Dubinina YuN, Mel’nichenko VYa. Diagnostic and Prognostic Value of Biochemical Markers of Infectious Complications of High-Dose Therapy with Autologous Hematopoietic Stem Cell Transplantation in Malignant Lymphoproliferative Diseases. Clinical oncohematology. 2017;10(1):113–9 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-113-119


ABSTRACT

Aim. To evaluate diagnostic and prognostic value of C-reactive protein (CRP), procalcitonin (PCT) and presepsin (PSP) in patients with malignant lymphoproliferative disorders after a high-dose chemotherapy and auto-HSCT.

Methods. 28 patients were included in the study (20 women and 8 men; 12 of them with Hodgkin’s lymphoma, 6 with non-Hodgkin’s lymphomas, and 10 with multiple myeloma). The median age was 40 years (23–66 years). The conditioning regimens were CBV, BEAM or melphalan 200 mg/m2. PSP, PCT and CRP levels were evaluated on the day of admission (DA), D+1, D+3, D+7 and on the day of discharge (DD). Depending on the presence of infectious complications, the patients were divided into 2 groups: group 1 — patients without complications (n = 12), group 2 — patients with complications (n = 16). In group 2 there were 15 patients with febrile neutropenia (FN) and 1 with sepsis.

Results. The median (range) of FN development was 5.5 days. Median CRP level on the DA and the DD in group 1 was 2.25 mg/l (0.6–20.4) and 14.85 mg/l (3.7–50), respectively (= 0.001), while in group 2 it was 3.2 mg/l (0.2–53) and 19.7 mg/l (5.1–152.2), respectively (= 0.025). However, CRP did not significantly differ between groups 1 and 2 at any point of analysis. The study also demonstrated a significant increase in the PCT levels in both groups after allo-HSCT. Median PCT level on the DA and the DD in group 1 was 0.023 ng/ml (0.02–0.112) and 0.07 ng/mL (0.02–0.356), respectively (= 0.04), and in group 2 — 0.039 ng/ml (0.02–0.158) and 0.106 ng/mL (0.045–3.67), respectively (= 0.001). Comparison of PCT levels on study days demonstrated no significant difference between groups. On the DA the median PSP level in group 1 was 166.5 pg/ml (77.2–476), on the DD it was 199 pg/ml (90–298) (= 0.78). Median PSP levels in group 2 on the DA (129 pg/ml, range 84.2–501) and also on the DD (288.5 pg/ml, range 83.4–1345) were significantly different (= 0.03). In the comparative analysis of PSP in groups 1 and 2, there were no significant differences on the DA and on the D+1. Significant difference in PSP levels between the analyzed groups was on the D+3, D+7 and on the DA.

Conclusion. The preliminary data showed that PSP is the most sensitive marker of infectious complications in patients with lymphoproliferative diseases after auto-HSCT.

Keywords: high-dose chemotherapy, autologous hematopoietic stem cells transplantation, infection, presepsin, procalcitonin, C-reactive protein.

Received: July 28, 2016

Accepted: December 10, 2016

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Arterial Events in Patients with Chronic Myeloid Leukemia Receiving Treatment with Second Generation Tyrosine Kinase Inhibitors

GA Gusarova, AG Turkina

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

For correspondence: Galina Anatol’evna Gusarova, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel: +7(495)612-16-36; e-mail: galina1966@bk.ru

For citation: Gusarova GA, Turkina AG. Arterial Events in Patients with Chronic Myeloid Leukemia Receiving Treatment with Second Generation Tyrosine Kinase Inhibitors. Clinical oncohematology. 2016;9(4):474–84 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-474-484


ABSTRACT

Target therapy of chronic myeloid leukemia (CML) by tyrosine kinase inhibitors (TKI) allows to achieve high rates of the overall survival in CML. The choice of TKI treatment in every particular case should be based on individual CML patient’s characteristics, including comorbidities and the risk of adverse events (AE). Every TKI has a particular toxicity profile depending on off-target action spectrum. A probability of arterial AEs on TKI therapy is comparatively low but they may be life threatening. It is highly important to evaluate this kind of AEs during a long period of vascular TKI exposure. The age-specific increased incidence of cardiovascular and respiratory diseases is an additional factor in these patients with high overall survival on TKI therapy. The article is devoted to the analysis of frequency, mechanisms, particular features, methods of diagnostics and treatment of arterial AEs emerging on second generation TKI (nilotinib and dasatinib) therapy. The detailed characteristics of arterial occlusive events on nilotinib therapy and pulmonary arterial hypertension on dasatinib are presented. Special attention is paid to the analysis of risk factors of vascular AEs and the ways to correct modified risk factors. Timely assessment of clinical symptoms of cardiopulmonary, ischemic diseases/complications, and metabolic disorders helps to find specialized medical care (by a cardiologist, pulmonologist, endocrinologist), to prescribe an adequate therapy, provide prevention of complications and make decision about TKI dose adjustment/switching to alternative TKI being a true foundation of safe personalized treatment in CML patients.


Keywords: tyrosine kinase inhibitors, artery occlusion, atherosclerosis, pulmonary hypertension.

Received: May 24, 2016

Accepted: June 16, 2016

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Biochemical Markers of Cardiotoxicity of High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation in Patients with Malignant Lymphoproliferative Disorders

VO Sarzhevskii, DS Kolesnikova, VYa Mel’nichenko

NI Pirogov National Medical and Surgical Center, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Vladislav Olegovich Sarzhevskii, PhD, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203; Tel: +7(495)603-72-18; e-mail: vladsar@pochta.ru

For citation: Sarzhevskii VO, Kolesnikova DS, Mel’nichenko VYa. Biochemical Markers of Cardiotoxicity of High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation in Patients with Malignant Lymphoproliferative Disorders. Clinical oncohematology. 2016;9(4):465–73 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-465-473


ABSTRACT

Background. High-dose chemotherapy (HDCT) with autologous hematopoietic stem cells transplantation (auto-HSCT) is an effective therapeutic option for patients with Hodgkin’s lymphoma and aggressive non-Hodgkin’s lymphomas in those cases, when the standard chemotherapy combined with the radiation therapy proves to be ineffective. The HDCT and auto-HSCT are also basic treatment options for multiple myeloma. However, toxic effects of the transplantation, including cardiotoxicity, may significantly worsen the prognosis of patients who receive this treatment.

Aim. To evaluate changes in biochemical markers of cardiotoxicity (troponin and N-terminal prohormone of brain natriuretic peptide (NT-proBNP)) in patients with malignant lymphomas (receiving HDCT and auto-HSCT).

Materials & Methods. 157 patients were enrolled in the study. The sensitivity threshold of the troponin T test was 0.1 ng/mL and troponin I 0.001 ng/mL (highly sensitive troponin). Troponin T (conventional troponin) was measured in 56 patients, troponin I was assessed in 101 patients. Serum troponin levels were evaluated before the conditioning, on D0, D+7, and D+12. The level of NT-proBNP was assessed before the conditioning, on D0 and D+12.

Results. Increased troponin T level was observed in 2 of 56 patients (3.6 %), increased troponin I level — in 27 of 101 patients (26.7 %) (< 0.01). Troponin levels were within normal limits in all patients at admission. Troponin T levels increased only on D+7. Troponin I level increased in 4 patients (4 %) on D0, in 17 patients (16.8 %) on D+7 and in 11 patients (10.9 %) on D+12. The median concentration of troponin I was 0.215 ng/mL after HDCT completion, 0.74 ng/mL on D+7 and 0.21 ng/mL on D+12. No cases of myocardial infarction were observed. NT-proBNP levels in most patients were within normal limits at admission (median level 79.2 pg/mL). The situation changed significantly after conditioning: in most patients the level was almost twice as high as the upper normal limit (medial 240.6 pg/mL). Significant differences in levels of NT-proBNP (< 0.05) were observed at comparison of data before conditioning and D0, and before conditioning and D+12.

Conclusion. The data obtained confirm a significant impact of HDCT and auto-HSCT on the cardiovascular system of patients with malignant lymphomas. Further studies and observation of the patients are needed to clarify the prognostic significance of the findings related to cardiotoxicity (in particular, congestive heart failure).


Keywords: high-dose chemotherapy, autologous hematopoietic stem cells transplantation, cardiotoxicity, troponin, NT-proBNP.

Received: June 13, 2016

Accepted: June 14, 2016

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Single-Photon Emission Computed Tomography Synchronized with ECG as Method for Evaluation of Cardiotoxicity of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation for Malignant Lymphoproliferative Disorders

VO Sarzhevskii, DS Kolesnikova, MN Vakhromeeva, VYa Melnichenko

N.I. Pirogov National Medical and Surgical Center under the Ministry of Health of the Russian Federation, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Vladislav Olegovich Sarzhevskii, PhD, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203; Tel.: +7(495)603-72-18; e-mail: vladsar@pochta.ru

For citation: Sarzhevskii VO, Kolesnikova DS, Vakhromeeva MN, Mel’nichenko VYa. Single-Photon Emission Computed Tomography Synchronized with ECG as Method for Evaluation of Cardiotoxicity of High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation for Malignant Lymphoproliferative Disorders. Clinical oncohematology. 2015;8(1):84–90 (In Russ).


ABSTRACT

Background. High-dose chemotherapy (HDC) with autologous hematopoietic stem cells transplantation (auto-HSCT) is currently widely used for the treatment of relapsed and refractory to standard chemotherapy cases of malignant lymphoproliferative disorders. Cardiac monitoring of patients treated with HDC with subsequent auto-HSCT is performed by means of ECG and Echo-CG in most cases. The method of single-photon emission computed tomography of the left ventricle (LV) synchronized with ECG (gated-SPECT) is rarely used to assess cardiotoxic effect of HDC and auto-HSCT.

Objective. To evaluate perfusion and regional myocardial function of the left ventricle (LV) in patients with malignant lymphomas receiving HDC and auto-HSCT.

Methods. The study included 69 patients (37 with Hodgkin’s lymphoma, 19 with non-Hodgkin’s lymphoma, and 13 with multiple myeloma). The median age was 36 year (range from 19 to 66 years); 40 females, 29 males. Perfusion and regional LV function at rest before the HDC and auto-HSCT (point 1) and at discharge (point 2) were assessed. Each study was performed on a double-headed rotating gamma camera Forte (Philips, USA). 740 MBq of technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) was used as a radiopharmaceutical. Semiquantitative assessment of tomoscintigrams was performed using polar diagrams (20-segment model); they were used for complex analysis of perfusion and LF myocardium function parameters.

Results. The total area of hypoperfusion, expressed as a percentage of the area of the LV myocardium, did not change significantly during treatment (> 0.05). However, the segmental analysis demonstrated a statistically significant decrease in the median uptake level of the radiopharmaceutical in 1, 2, 4, 7, 8, 10, 13, 16, 17, and 19 segments (< 0.05). The total ejection fraction (TEF) did not change (median TEF was 59.5 % at point 1 and 58 % at point 2). But it showed a statistically significant decrease in median of local systolic thickening in 2, 3, 5, 7, 8, 9, 10, 11, 12, 15, 17, 18, 19, and 20 segments of the left ventricle (< 0.05).

Conclusions. HDC and auto-HSCT significantly change perfusion and regional LV myocardial function in patients with malignant lymphomas. The changes demonstrate diffuse myocardial damage. Gated-SPECT can be considered a promising method for assessing cardiotoxicity of HDC and auto-HSCT.


Keywords: high-dose chemotherapy, autologous hematopoietic stem cells transplantation, cardiotoxicity, gated-SPECT.

Received: July 23, 2014

Accepted: November 5, 2014

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Gastrointestinal Complications after High-Dose Chemotherapy and Autologous Bone Marrow Transplantation in Oncohematological Patients

V.O. Sarzhevskiy, E.G. Smirnova, V.Yа. Melnichenko

N.I. Pirogov National Medical and Surgical Centre of RF MH, Moscow, Russian Federation

For citation: Sarzhevskiy V.O., Smirnova E.G., Mel’nichenko V.Ya. Gastrointestinal Complications after High-Dose Chemotherapy and Autologous Bone Marrow Transplantation in Oncohematological Patients. Klin. onkogematol. 2014; 7(3): 343–53 (In Russ.).

ABSTRACT

Different gastrointestinal disorders with different degrees of severity are diagnosed in almost all oncohematological patients receiving the high-dose chemotherapy (HDC) with autologous bone marrow transplantation (transplantation of peripheral hematopoietic stem cells). The mentioned disorders (mucositis) significantly impair the quality of life, promote the development of infectious complications, and, in some cases, can cause a lethal outcome. Authors emphasize the importance of GIT disorders due to HDC with autologous bone marrow transplantation, present etiological and pathogenetic factors of mucosites and give a detailed description of the clinical evaluation, test methods, prevention and treatment of such transplantation complications in oncohematological patients.


Keywords: high dose chemotherapy, autologous bone marrow transplantation, mucositis.

Address correspondence to: vladsar@pochta.ru

Accepted: May 26, 2014

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