Does human bocavirus infection depend on helper viruses? A challenging case report

A case of severe diarrhoea associated with synergistic human bocavirus type 1 (HBoV) and human herpes virus type 6 (HHV6) is reported. The case supports the hypotheses that HBoV infection under clinical conditions may depend on helper viruses, or that HBoV replicates by a mechanism that is atypical for parvoviruses, or that HBoV infection can be specifically treated with cidofovir

Clinical characteristics and outcome of 60 pediatric patients with malignant melanoma registered with the German Pediatric Rare Tumor Registry (STEP)

BACKGROUND: Malignant melanoma (MM) is a common malignancy in adults while it is rare in children. Thus, information on clinical behavior of pediatric MM is incomplete. PATIENTS: The German Pediatric Rare Tumor Registry (STEP) presents a prospective analysis of 60 childhood MM cases diagnosed between June 2006 and December 2014. METHODS: Patients' ages ranged between 0 and 17 years at initial diagnosis (median age 9.6 years). Information on patient's and tumor characteristics was obtained by standardized documentation. Three-year overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier test. RESULTS: Follow-up ranged from 0 to 116 months with a median of 36.5 months, however, univariate analysis was performed for 46 cases with a follow-up > 3 months, only. Cases with spitzoid histotype (40%) did not show a significantly different outcome compared to cases with non-spitzoid MM. Breslow thickness ≤ 2.00 mm was identified in 30% of the cases and 18% were Clark level I to III. Adjuvant therapy was used in 45% of cases. OS at 3 years was 100%, EFS 95.2%. CONCLUSION: We present a series of cases with a high number of spitzoid malignant melanoma and advanced pediatric melanoma, but surprisingly good overall survival rates. Spitzoid and non-spitzoid MM do not differ in clinical behavior and survival

Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation

Böhm S, Wustrau K, Pachlopnik Schmid J, et al. Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation. Blood. 2024;143(10):872-881.ABSTRACT: 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. © 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies

Survival in primary hemophagocytic lymphohistiocytosis 2016-2021: etoposide is better than its reputation

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 50-59% 5-year survival. Contemporary data are lacking. We evaluated 88 pHLH patients documented in the international HLH Registry between 2016-2021 with follow-up until 6/2023. In 12/88 patients, the diagnosis was made without HLH activity, based on index siblings or partial albinism. Major HLH-directed drugs (etoposide, ATG, alemtuzumab, emapalumab, ruxolitinib) were given to 66/76 symptomatic patients (86% first-line etoposide); 16/57 etoposide-treated and 3/9 patients with other first-line treatment received salvage therapy. HSCT was performed in 75 patients, 7 symptomatic patients died before HSCT. 3-year probability of survival (pSU) was 82% (CI 72%-88%) for the entire cohort and 77% (CI 64-86%) for symptomatic patients receiving first-line etoposide. Compared to the HLH-2004 study, both pre-HSCT survival (83% to 91%) and post-HSCT survival of patients receiving first-line etoposide improved (70% to 88%). Differences to HLH-2004 included preferential use of reduced-toxicity conditioning and reduced time from diagnosis to HSCT (148 to 88 days). 3-year pSU was lower with haploidentical (44%, 4/9 patients) than with other types of donors (94%, 4/66, p&lt;0.001). Importantly, also in this study, early HSCT of asymptomatic patients resulted in excellent survival (100%), emphasizing the potential benefit of newborn screening. This contemporary standard-of-care study of pHLH patients reveals that first-line etoposide-based therapy is better than previously reported, providing a benchmark for novel treatment regimes

Lung Infection by Human Bocavirus Induces the Release of Profibrotic Mediator Cytokines In Vivo and In Vitro

Human Bocavirus subtype 1 (HBoV1) is associated with respiratory diseases and may contribute to chronic lung diseases by persisting in the infected host. Here the question was addressed if HBoV infections could contribute to fibrogenesis processes as suggested by previously published clinical observations. Cytokine profiles induced by HBoV infection in CuFi-8 air-liquid interphase cell cultures and in bronchoalveolar lavage fluid (BALF) of 20 HBoV-positive and 12 HBoV-negative patients were analysed by semi-quantitative Western spot blot analyses. Although lots of cytokines were regulated independently of HBoV status, several cytokines associated with lung fibrosis and tumour development, e.g., EGF, VEGF, TARC (CCL17), TNF-alpha, TNF-beta, TIMP-1, were clearly upregulated in the HBoV-positive cohort. These findings suggest that the development of lung fibrosis might be triggered by HBoV induced cytokine expression