Haemophagocytic lymphohistiocytosis: case series. Serum ferritin level as an indicator of treatment effectiveness

Introduction: Haemophagocytic lymphohistiocytosis (HLH) is a medical condition associated with over-activation of the immune system. HLH results from the inactivity of NK cells and uncontrolled activity of cytotoxic T lymphocytes and macrophages with the massive cytokine response.[1] Cytohistological examinations might show hemophagocytes in different tissues (e.g., bone marrow). Exceptionally high level of ferritin is often observed in the laboratory findings. Due to aggressive course of the disease mortality rate is extremely high. Material and methods: We presented three patients with acquired form of HLH treated successfully in Heaematooncology Department of Medical University of Lublin from September 2018 to April 2021. Results: In the first patient, HLH developed during pregnancy. Patient 2 was first hospitalized in the Intensive Care Unit (ICU) and 10 therapeutic plasma exchanges (TPE) were carried out. In both patients, stabilization -of ferritin levels and remission of the disease were achieved soon after the application of the treatment according to the HLH-2004 protocol. Case 3 presents a patient in whom HLH was induced by EBV and SARS CoV-2 infections. In the first stage of the treatment, the patient received drugs according to the HLH-2004 protocol, but the serum ferritin did not normalize. The reinfection with SARS CoV-2 virus occurred again in the course of the treatment. Due to the disease resistance and inability to continue the HLH-2004 protocol, it was decided to start ruxolitinib therapy, which resulted in stabilization of the serum ferritin and improvement of the general condition. The patient was qualified for allogeneic bone marrow transplantation. Conclusions: HLH is a difficult and interdisciplinary diagnostic and therapeutic problem. It is essential to popularize knowledge about fast and targeted diagnostics. Among laboratory finding, the ferritin concentration seemed to be particularly helpful as a predictor of treatment effectiveness. Proper diagnosis and treatment implemented as early as possible could save patients’ lives.Introduction: Haemophagocytic lymphohistiocytosis (HLH) is a medical condition associated with the over-activation of the immune system. HLH results from the inactivity of natural killer cells and uncontrolled activity of cytotoxic T lymphocytes and macrophages, with a massive cytokine response. Cytohistological examinations might show haemophagocytes in different tissues (e.g., bone marrow). Among laboratory findings especially(particularly) high ferritin level is often seen. Due to the aggressive course of the disease mortality rate is extremely high. Case reports: The study presented three patients with an acquired form of HLH treated successfully in the Haemato-Oncology Department Medical University of Lublin from September 2018 to April 2021. In case 1 HLH developed during pregnancy. Patient 2 was first hospitalized in the Intensive Care Unit and 10 therapeutic plasma exchanges were carried out. In both patients, stabilization of ferritin levels and remission of the disease were achieved soon after the application of treatment according to the HLH-2004 protocol. Case 3 presents a patient in whom HLH was induced by Epstein-Bárr virus and severe acute respiratory syndrome coronavirus type SARS-CoV-2 infections. In the first stage of treatment, the patient received drugs according to the HLH-2004 protocol, but the serum ferritin did not normalize. The reinfection with (SARS-CoV-2) virus occurred again during the treatment. Due to the disease resistance and the inability to continue the HLH-2004 protocol, it was decided to start ruxolitinib therapy, which resulted in the stabilization of the serum ferritin and improvement of the general condition. The patient was qualified for allogeneic bone marrow transplantation. Conclusions: HLH is a difficult and interdisciplinary diagnostic and treatment problem. It is necessary to popularize knowledge about fast and targeted diagnostics. Among laboratory finding the ferritin concentration seemed to be especially helpful as a predictor of treatment effectiveness. Proper diagnosis and treatment introduced as early as possible could save patients’ life

Limfohistiocytoza hemofagocytarna — opis serii przypadków. Stężenie ferrytyny w surowicy jako wskaźnik skuteczności leczenia

Introduction: Haemophagocytic lymphohistiocytosis (HLH) is a medical condition associated with the over-activation of the immune system. HLH results from the inactivity of natural killer cells and uncontrolled activity of cytotoxic T lymphocytes and macrophages, with a massive cytokine response. Cytohistological examinations might show haemophagocytes in different tissues (e.g., bone marrow). Among laboratory findings especially(particularly) high ferritin level is often seen. Due to the aggressive course of the disease mortality rate is extremely high. Case report: The study presented three patients with an acquired form of HLH treated successfully in the Haemato-Oncology Department from September 2018 to April 2021. In case 1 HLH developed during pregnancy. Patient 2 was first hospitalized in the Intensive Care Unit and 10 therapeutic plasma exchanges were carried out. In both patients, stabilization of ferritin levels and remission of the disease were achieved soon after the application of treatment according to the HLH-2004 protocol. Case 3 presents a patient in whom HLH was induced by Epstein-Bárr virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. In the first stage of treatment, the patient received drugs according to the HLH-2004 protocol, but the serum ferritin did not normalize. The reinfection with SARS CoV-2 occurred again during the treatment. Due to the disease resistance and the inability to continue the HLH-2004 protocol, it was decided to start ruxolitinib therapy, which resulted in the stabilization of the serum ferritin and improvement of the general condition. The patient was qualified for allogeneic bone marrow transplantation. Conclusions: HLH is a difficult and interdisciplinary diagnostic and treatment problem. It is necessary to popularize knowledge about fast and targeted diagnostics. Among laboratory finding the ferritin concentration seemed to be especially helpful as a predictor of treatment effectiveness. Proper diagnosis and treatment introduced as early as possible could save patients’ life.Wprowadzenie: Limfohistiocytoza hemofagocytarna (HLH) jest chorobą związaną z nadmierną aktywacją układu odpornościowego. Charakteryzuje się brakiem aktywności komórek naturalnej toksyczności i niekontrolowaną aktywnością cytotoksycznych limfocytów T i makrofagów, z masywną odpowiedzią cytokinową. Badanie cytologiczne może wykazać obecność hemofagocytów w różnych tkankach (np. szpiku). W badaniach laboratoryjnych często obserwuje się wyjątkowo duże stężenie ferrytyny. Ze względu na agresywny przebieg choroby śmiertelność jest niezwykle wysoka. Opis przypadku: Przedstawiono opis 3 pacjentów z nabytą postacią HLH leczonych z powodzeniem w klinice hematoonkologii i transplantacji szpiku od września 2018 do kwietnia 2021 roku. W 1 przypadku HLH rozwinęła się w czasie ciąży. Pacjenta 2. początkowo hospitalizowano na oddziale intensywnej terapii, gdzie przeprowadzono 10 zabiegów plazmaferezy. U obojga chorych wkrótce po zastosowaniu leczenia według protokołu HLH-2004 uzyskano stabilizację stężenia ferrytyny i remisję choroby. U 3. pacjenta HLH wywołało zakażenie wirusem Epsteina-Bárr i zespołu ostrej niewydolności oddechowej 2 (SARS-CoV-2). W pierwszym etapie leczenia pacjent otrzymywał leki zgodnie z protokołem HLH-2004, ale stężenie ferrytyny w surowicy nie ulegało normalizacji. W trakcie leczenia doszło do ponownego zakażenia SARS-CoV-2. Ze względu na oporność na leczenie i brak możliwości kontynuacji terapii według protokołu HLH-2004 zdecydowano o rozpoczęciu leczenia ruksolitynibem, co spowodowało stabilizację stężenia ferrytyny w surowicy i poprawę stanu ogólnego. Pacjenta zakwalifikowano do allogenicznego przeszczepienia szpiku. Podsumowanie: Limfohistiocytoza hemofagocytarna to trudny i interdyscyplinarny problem diagnostyczno-leczniczy. Konieczne jest poszerzanie wiedzy dotyczącej konieczności szybkiej i ukierunkowanej diagnostyki. Stężenie ferrytyny wydawało się szczególnie pomocnym parametrem laboratoryjnym, będącym czynnikiem predykcyjnym skuteczności leczenia. Właściwa diagnostyka i jak najwcześniejsze leczenie może uratować życie pacjenta