Primary hemophagocytic lymphohistiocytosis (pHLH) is a life-threatening hyperinflammatory syndrome that develops mainly in patients with genetic disorders of lymphocyte cytotoxicity and X-linked lymphoproliferative syndromes. Previous studies with etoposide-based treatment followed by hematopoetic stem cell transplantation (HSCT) resulted in 5-year survival of 50% to 59%. Contemporary data are lacking. We evaluated 88 patients with pHLH documented in the international HLH registry from 2016-2021. In 12 of 88 patients, diagnosis was made without HLH activity, based on siblings or albinism. Major HLH-directed drugs (etoposide, antithymocyte globulin, alemtuzumab, emapalumab, ruxolitinib) were administered to 66 of 76 patients who were symptomatic (86% first-line etoposide); 16 of 57 patients treated with etoposide and 3 of 9 with other first-line treatment received salvage therapy. HSCT was performed in 75 patients; 7 patients died before HSCT. Three-year probability of survival (pSU) was 82% (confidence interval [CI], 72%-88%) for the entire cohort and 77% (CI, 64%-86%) for patients receiving first-line etoposide. Compared with the HLH-2004 study, both pre-HSCT and post-HSCT survival of patients receiving first-line etoposide improved, 83% to 91% and 70% to 88%. Differences to HLH-2004 included preferential use of reduced-toxicity conditioning and reduced time from diagnosis to HSCT (from 148 to 88 days). Three-year pSU was lower with haploidentical (4 of 9 patients [44%]) than with other donors (62 of 66 [94%]; P < .001). Importantly, early HSCT for patients who were asymptomatic resulted in 100% survival, emphasizing the potential benefit of newborn screening. This contemporary standard-of-care study of patients with pHLH reveals that first-line etoposide-based therapy is better than previously reported, providing a benchmark for novel treatment regimes.
- MeSH
- etoposid terapeutické užití MeSH
- lidé MeSH
- lymfohistiocytóza hemofagocytární * farmakoterapie diagnóza MeSH
- lymfoproliferativní nemoci * etiologie MeSH
- novorozenec MeSH
- transplantace hematopoetických kmenových buněk * metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- lidé MeSH
- lymfohistiocytóza hemofagocytární * diagnóza farmakoterapie komplikace terapie MeSH
- nemoci imunitního systému imunologie patologie MeSH
- sepse diagnóza etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
We report a case of an 8-year-old girl who underwent a SARS-CoV-2 infection manifesting with atypical symptoms spearheaded by abdominal discomfort and systemic inflammation and partially mimicking hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS), which however did not fulfill the HLH/MAS diagnostic criteria. In this case of what has since been described as Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-COV-2 (PIMS-TS) we documented excellent clinical response to immunosuppression with systemic corticosteroids and intravenous immunoglobulins. We show a detailed longitudinal development of neutrophil immunophenotype which suggests activation and engagement of neutrophils during PIMS-TS with compensatory contraction of the response and contra-regulation of neutrophil phenotype during recovery.
- MeSH
- Betacoronavirus * imunologie metabolismus MeSH
- dítě MeSH
- hormony kůry nadledvin aplikace a dávkování MeSH
- imunosupresivní léčba * MeSH
- intravenózní imunoglobuliny aplikace a dávkování MeSH
- koronavirové infekce * krev diagnóza farmakoterapie imunologie MeSH
- lidé MeSH
- lymfohistiocytóza hemofagocytární * diagnóza farmakoterapie imunologie MeSH
- neutrofily MeSH
- pandemie * MeSH
- syndrom aktivovaných makrofágů * diagnóza farmakoterapie imunologie MeSH
- virová pneumonie * krev diagnóza farmakoterapie imunologie MeSH
- zánět diagnóza farmakoterapie imunologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
Anaplastic large cell lymphomas are an aggressive subtype of peripheral T-cell lymphomas that can manifest with a variety of symptoms. Our case highlights the importance of prompt tissue sampling, especially if an associated hemophagocytic lymphohistiocytosis is detected and no clinical improvement is observed upon glucocorticoid treatment.
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- MeSH
- Erdheimova-Chesterova nemoc diagnóza farmakoterapie patofyziologie MeSH
- histiocytární poruchy maligní klasifikace MeSH
- histiocytóza z Langerhansových buněk * diagnóza farmakoterapie patofyziologie MeSH
- juvenilní xantogranulom patofyziologie MeSH
- lidé MeSH
- lymfohistiocytóza hemofagocytární * diagnóza etiologie farmakoterapie MeSH
- nekrobiotický xantogranulom patofyziologie MeSH
- sinusová histiocytóza * diagnóza farmakoterapie patofyziologie MeSH
- vzácné nemoci MeSH
- Check Tag
- lidé MeSH
Histiocytózy jsou hematologická onemocnění, která mohou mít jak zcela benigní, tak život ohrožující průběh. Je proto nutné na ně myslet, ačkoliv jejich výskyt je vzácný. Současná klasifikace histiocytóz vychází z patogeneze onemocnění, a umožňuje tak odhadnout prognózu pacienta a rozhodnout o terapii. Intenzita terapie se pohybuje od pouhého sledování pacienta až po chemoterapii a transplantaci hematopoetických buněk. Článek je zaměřen na nejčastější formy histiocytóz, a to histiocytózu z Langerhansových buněk (LCH – Langerhans cell histiocytosis) a hemofagocytující lymfohistiocytózu (HLH). Závěrečná tabulka srovnává tyto dvě jednotky.
Histiocytoses are hematologic diseases that can be benign as well as life-threatening disorder. It is necessary to consider these diseases despite of their rare incidence. Present classification considers patogenesis of these disorders that is useful to predict prognosis and planning therapy. This article is concerned on the most common clinical histiocytic disorders which is Langerhans cell histiocytosis and hemophagocytic lymphohistiocytosis.
- MeSH
- biopsie MeSH
- dítě MeSH
- farmakoterapie metody MeSH
- histiocytóza z Langerhansových buněk * diagnóza etiologie farmakoterapie komplikace krev terapie MeSH
- histiocytóza * diagnóza epidemiologie etiologie farmakoterapie komplikace krev terapie MeSH
- komorbidita MeSH
- lidé MeSH
- lymfohistiocytóza hemofagocytární * diagnóza etiologie farmakoterapie komplikace krev terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis. We report the final results of HLH-94, the largest prospective diagnostic/therapeutic HLH study so far. The treatment includes immunosuppressive and cytotoxic therapy aiming at clinical remission, followed by HSCT in patients with familial, persistent, or recurrent disease. Altogether, 249 patients fulfilled inclusion criteria and started HLH-94 therapy (July 1994-December 2003); 227 (91%) were followed-up for ≥ 5 years. At 6.2 years median follow-up, estimated 5-year probability of survival was 54% ± 6%. Seventy-two patients (29%) died before HSCT, 64 within 1 year, 97% of whom had active disease. In 124 patients who underwent HSCT, 5-year survival was 66 ± 8%; tendency to increased survival (P = .064) in patients with nonactive disease at HSCT. Patients with familial disease had a 5-year survival of 50% ± 13%; none survived without HSCT. Patients deceased during the first 2 months more often had jaundice, edema, and elevated creatinine. Forty-nine patients (20%) were alive without signs of HLH activity and off-therapy > 1-year without HSCT; they presented at older age (P < .001), were more often female (P = .011), and less often had CNS disease (P < .001) or hepatomegaly (P = .007). To conclude, HLH-94 chemoimmunotherapy has considerably improved outcome in HLH. Collaborative efforts are needed to further reduce early mortality, HSCT-related mortality, and neurologic late effects.
- MeSH
- analýza přežití MeSH
- časové faktory MeSH
- cytotoxiny aplikace a dávkování škodlivé účinky MeSH
- dítě MeSH
- fixní kombinace léků MeSH
- imunosupresiva aplikace a dávkování škodlivé účinky MeSH
- imunoterapie metody škodlivé účinky MeSH
- klinické protokoly MeSH
- kojenec MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- lymfohistiocytóza hemofagocytární diagnóza farmakoterapie mortalita terapie MeSH
- mladiství MeSH
- následné studie MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- transplantace hematopoetických kmenových buněk MeSH
- udržovací chemoterapie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- souhrny MeSH
