etoposide

Organ Lesions in Adults with Secondary Hemophagocytic Syndrome

AUTOIMMUNE THROMBOCYTOPENIA

VG Potapenko1,2, AV Klimovich1, DD Avdoshina3, VV Baikov2, NV Vinogradova3, OV Goloshchapov2, EV Doguzhieva3, EE Zinina4, GV Kachenya3, YuA Krivolapov5, EV Karyagina6, TG Kulibaba7, SV Lapin2, EE Leenman5, ES Pavlyuchenko5, NA Potikhonova8, MYu Pervakova2, NB Popova4, AV Rysev9, VV Ryabchikova1, EA Surkova2, IP Fedunyak3, 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 SP Botkin Clinical Hospital for Infectious Diseases, 3 Mirgorodskaya str., Saint Petersburg, Russian Federation, 191167

4 Surgut District Clinical Hospital, 24 bld. 2 Energetikov str., Surgut, Russian Federation, 628408

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

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

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

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

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

For correspondence: Vsevolod Gennadevich Potapenko, MD, PhD, 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, Klimovich AV, Avdoshina DD, et al. Organ Lesions in Adults with Secondary Hemophagocytic Syndrome. Clinical oncohematology. 2021;14(1):91–102. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-91-102

ABSTRACT

Background. Secondary hemophagocytic syndrome (SHPS) is a reaction of systemic hyperinflammation triggered by infectious, tumor, or autoimmune processes. With no immunosuppressive (modulating) therapy most patients die from multiple organ failure.

Aim. To describe organ lesions characteristic of SHPS patients.

Materials & Methods. The retrospective study included patients treated from June 2009 to June 2019. SHPS was diagnosed using HLH-2004 criteria and H-Score. The analysis focused on the incidence and character of lesions in lungs, central nervous system, liver, skin, and cardiovascular system. All patients with persistent fever received anti-infective treatment with broad-spectrum antibiotics in line with local hospital practice. Patients with collagenosis and tumors, which caused SHPS, received standard immunosuppressive and antitumor therapy, respectively.

Results. The analysis covered the data of 91 patients (41 man and 50 women), median age was 58 years (range 2–90 years). SHPS was caused by hematological malignancies (n = 52; 57 %), infections (n = 11; 12 %), autoimmune diseases (n = 5; 6 %), and allogeneic hematopoietic stem cell transplantation (n = 13; 14 %). In 10 (11 %) patients no cause was identified. Immunosuppressive therapy was administered to 71 (78 %) patients. Overall survival was 27 % (median 15 days) with median follow-up for alive of 540 days (range from 7 days to 10 years). Clinically significant organ lesions were identified in 76 (83 %) patients. Most commonly SHPS was reported together with polyserositis, respiratory and hepatic disorders, and neurological symptoms from focal deficit to seizure status. Less often skin lesions (from macular rash to epidermolysis bullosa) and such cardiovascular disorders as arrhythmia and/or arterial hypotension were observed. The effective SHPS therapy resulted in restoration of organ functions.

Conclusion. SHPS can cause respiratory disorders, polyserositis, different neurological disorders, cytopenia in patients with unexplained fever and cytolytic and/or cholestatic syndrome. Primary organ lesions as well as clinical and laboratory manifestations of SHPS may vary in different patients.

Keywords: hemophagocytic syndrome, ferritin, inflammation, cytokine storm, etoposide, Epstein-Barr virus infection.

Received: August 2, 2020

Accepted: November 29, 2020

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Secondary Hemophagocytic Syndrome in the Adult Patients. Literature Review and Authors’ Experience

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , , ,

VG Potapenko1,2, NA Potikhonova4, VV Baikov2, MB Belogurova1, IA Lisukov3, AV Klimovich1, SV Lapin2, MO Ivanova2, VM Kravtsova2, EI Podol’tseva1, NV Medvedeva1, BV Afanas’ev2

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

2 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

3 I.I. Mechnikov North-Western State Medical University, 41 Kirochnaya str., Saint Petersburg, Russian Federation, 197022

4 Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Vsevolod Gennad’evich Potapenko, Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110; Tel.: +7(812)230-19-33; e-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko V.G., Potikhonova N.A., Baikov V.V., Belogurova M.B., Lisukov I.A., Klimovich A.V., Lapin S.V., Ivanova M.O., Kravtsova V.M., Podol’tseva E.I., Medvedeva N.V., Afanas’ev B.V. Secondary Hemophagocytic Syndrome in the Adult Patients. Literature Review and Authors’ Experience. Klin. Onkogematol. 2015;8(2):169–84. (In Russ.).

ABSTRACT

Background & Aims. The hemophagocytic syndrome is a dangerous hyperinflammatory syndrome usually caused by an infection. It is a result of excessive cell activation in the mononuclear phagocyte system which is manifested itself through cytopenia, systemic inflammatory reaction, liver and spleen impairment. Since the disease is rare and its diagnosing is very complicated, this syndrome has not been studied thoroughly and is overlooked very often. The aim of this work is to describe authors’ experience in dealing with the secondary hemophagocytic syndrome (HPS) and to present a literature review.

Methods. Clinical and laboratory data of 15 patients aged 16 to 64 (median age 48 years) with secondary HPS observed over the period from 2009 till 2013 were analyzed. Secondary HPS was diagnosed in patients with malignant lymphoproliferative and infectious diseases. HPS signs were found in lymphoproliferative disorders (n = 5), chronic active EBV-infection (n = 3), allogeneic hematopoietic stem cell transplantation (n = 3), acute leukemia (n = 1), multiple myeloma (n = 1), pneumonia (n = 1), and glomerulonephritis (n = 1). 8 patients underwent treatment for HPS: etoposide (n = 1), glucocorticoids (n = 1), intravenous immunoglobulin (n = 2), combination of rituximab + glucocorticoids (n = 2), etoposide + cyclosporine A (n = 1), as well as combined HLH-2004 chemotherapy (n = 1). The median observation period was 42 months.

Results. Among 15 adult patients enrolled into the retrospective analysis, malignant lymphoproliferative disorders and chronic EBV-infection were most common underlying disorders in case of secondary HPS. Early diagnosing is very complicated, because diagnostic criteria accepted at present are typical for the late-phase HPS. The above factors require development of more sensitive and universal diagnostic criteria.

Conclusion. In oncohematological practice, the secondary HPS is a severe complication requiring differential diagnosing with other critical conditions and intensive care. In case of HPS associated with oncohematological disorders, patients require close monitoring throughout the antitumor treatment period and after it.

Keywords: secondary hemophagocytic syndrome, lymphoma, Epstein-Barr virus, etoposide, hematopoietic stem cells transplantation.

Received: December 9, 2014

Accepted: February 7, 2015

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