Infectious Complications after Haploidentical Hematopoietic Stem Cells Transplantation in Patients with High-Risk Tumors of Hematopoietic and Lymphoid Tissues: A Single-Center Experience

YuS Osipov1, SS Bessmeltsev2, GN Salogub1, VV Ivanov1, ES Mikhailov1, NA Zhukova1, AV Chechetkin2

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: Yurii Sergeevich Osipov, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel.: +7(812)702-37-65; e-mail: osipov_yus@almazovcentre.ru

For citation: Osipov YuS, Bessmeltsev SS, Salogub GN, et al. Infectious Complications after Haploidentical Hematopoietic Stem Cells Transplantation in Patients with High-Risk Tumors of Hematopoietic and Lymphoid Tissues: A Single-Center Experience. Clinical oncohematology. 2019;12(4):406–15 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-406-415


ABSTRACT

Aim. To determine the incidence of viral, bacterial, and fungal infections in post-transplant period and to assess the prognostic value of infections and their influence on early and long-term results of haploidentical hematopoietic stem cells transplantation (haplo-HSCT).

Materials & Methods. Retrospective study included 61 patients older than 18 years with high-risk oncohematological diseases. In the period from 2015 to 2018 all patients received haplo-HSCT. Median follow-up after haplo-HSCT was 12.5 months (376 days, range 6–1202). Patients were divided into two groups. The first group (n = 26) received haplo-HSCT as salvage therapy. It included patients with refractory tumors without remission by the start of haplo-HSCT and patients with early relapses after HLA-matched related or unrelated allo-HSCT. The second group (n = 35) received haplo-HSCT on reaching the optimal pretransplant status (“non-salvage”).

Results. The incidence of cytomegalovirus (CMV) reactivation, invasive mycosis, and bacterial infections was 70.4 %, 11.5 %, and 75.4 %, respectively. CMV reactivation and invasive mycosis did not affect either the 35- or the 100-day overall survival (OS). For the first time bacterial infections were stratified based on severity according to Sepsis 3 consensus, which allowed to identify groups of patients with unfavorable prognosis. Severe bacterial infections (sepsis and septic shock) correlated with worse early and long-term results, especially in patients without remission by the start of haplo-HSCT, whereas febrile neutropenia/bloodstream infection did not affect OS. On the whole, mortality associated with bacterial infections was 26.2 %.

Conclusion. The main factor affecting early lethality after haplo-HSCT is a severe bacterial infection. The key risk factor is lack of remission by the start of haplo-HSCT. Sepsis 3 criteria can be applied in the period of postcytostatic cytopenia to identify the group of patients with most unfavorable prognosis (septic shock). The implementation of current infection control methods (genotyping of multiple drug resistant strains and timely determining the strategy of antimicrobial chemotherapy on the basis of the results obtained) into everyday clinical practice can improve the treatment outcomes in this category of patients.

Keywords: haploidentical hematopoietic stem cells transplantation, infectious complications, sepsis, septic shock, cytomegalovirus reactivation, invasive mycosis.

Received: April 11, 2019

Accepted: September 18, 2019

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Role of Biochemical Inflammatory Markers in Patients with Chemotherapy-Induced Neutropenia

YuN Dubinina1, VO Sarzhevskii2, VYa Melnichenko2

1 Oncology and Hematology Outpatient Clinic, 2 bld. 1 Molodogvardeiskaya str., Moscow, Russian Federation, 121467

2 NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Yuliya Nikolaevna Dubinina, 2 bld. 1 Molodogvardeiskaya str., Moscow, Russian Federation, 121467; Tel.: +7(499)112-25-04; e-mail: medicinemsc@gmail.com

For citation: Dubinina YuN, Sarzhevskii VO, Melnichenko VYa. Role of Biochemical Inflammatory Markers in Patients with Chemotherapy-Induced Neutropenia. Clinical oncohematology. 2019;12(4):461–7 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-461-467


ABSTRACT

The growing number of autologous and allogeneic transplantations of bone marrow and hematopoietic stem cells as well as their technological effectiveness give rise to drug antineoplastic therapies with increased toxicity leading to development of complications. The most serious among this sort of complications are infections. Probability of infections in patients with chemotherapy-induced neutropenia reaches 90 %. In this context the search for an optimal marker of infectious complications becomes more and more important. The present review deals with basic biochemical inflammatory markers and the analysis of trials assessing diagnostic and prognostic value of C-reactive protein, procalcitonin, and presepsin.

Keywords: sepsis, autologous bone marrow transplantation, allogeneic bone marrow transplantation, chemotherapy, infection, procalcitonin, presepsin, C-reactive protein.

Received: May 7, 2019

Accepted: September 11, 2019

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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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Successful allogeneic bone marrow transplantation in patients with severe gram-negative sepsis and septic shock

G.M. Galstyan, P.M. Makarova, L.A. Kuzmina, Ye.N. Parovichnikova, G.A. Klyasova, O.S. Pokrovskaya, M.Yu. Drokov, V.A. Novikov, V.V. Troitskaya, I.E. Kostina, and V.G. Savchenko

Hematology Research Center, Ministry of Health, Moscow, Russian Federation


ABSTRACT

We present two cases of successful allogeneic bone marrow transplantation in the patients with severe gram-negative sepsis and septic shock. The features of the post-transplantation period and management of patients are described.


Keywords: allogeneic hematopoietic stem cell transplantation, conditioning, sepsis, septic shock, post-transplantation period, neutropenic enterocolitis, prolonged neutropenia, Pseudomonas aeruginosa, acute respiratory failure, invasive pulmonary aspergillosis, invasive lung ventilation, noninvasive ventilation, mesenchymal stromal cells.

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