Autoimmune hematological diseases after allogeneic hematopoietic stem cell transplantation in children: An Italian multicenter experience

AbstractAutoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic stem cell transplantation (HSCT), but reports on these complications in large cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574 consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%), and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5% (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of alternative donor and nonmalignant disease was statistically associated with AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained complete remission was achieved in 87% of cases with the anti-CD20 monoclonal antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans' syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD diagnosis as a direct or indirect consequence of their disorder. Our data suggest that AHDs are a relatively rare complication occurring after HSCT that usually respond to treatment with rituximab

Risk of Seizures in Children Receiving Busulphan-Containing Regimens for Stem Cell Transplantation

Busulphan (BU) is associated with neurotoxicity and risk of seizures. Hence, seizure prophylaxis is routinely utilized during BU administration for stem cell transplantation (SCT). We collected data on the incidence of seizures among children undergoing SCT in Italy. Fourteen pediatric transplantation centers agreed to report unselected data on children receiving BU as part of the conditioning regimen for SCT between 2005 and 2012. Data on 954 pediatric transplantation procedures were collected; of them, 66% of the patients received BU orally, and the remaining 34%, i.v. All the patients received prophylaxis of seizures, according to local protocols, consisting of different schedules and drugs. A total of 13 patients (1.3%) developed seizures; of them, 3 had a history of epilepsy (or other seizure-related pre-existing condition); 3 had documented brain lesions potentially causing seizures per se; 1 had febrile seizures, 1 severe hypo-osmolality. In the remaining 5 patients, seizures were considered not explained and, thus, potentially related to BU administration. The incidence of seizures in children receiving BU-containing regimen was very low (1.3%); furthermore, most of them had at least 1deither pre-existing or concurrentdassociated risk factor for seizures. 2014 American Society for Blood and Marrow Transplantation

The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series

IntroductionStroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (>= 500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and MethodsWe retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. ResultsThe underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4-34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (+/- 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (+/- 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. ConclusionsSLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management

First Occurrence of Eustrongylides spp. (Nematoda: Dioctophymatidae) in a Subalpine Lake in Northwest Italy: New Data on Distribution and Host Range

The genus Eustrongylides includes nematodes that infect fish species and fish-eating birds inhabiting freshwater ecosystems. Nematodes belonging to the genus Eustrongylides are potentially pathogenic for humans; infection occurs after the consumption of raw or undercooked fish. In the two-year period 2019\u20132020, a total of 292 fish belonging to eight species were examined for the occurrence of Eustrongylides spp. from Lake San Michele, a small subalpine lake in northwest Italy. The prevalence of infestation was 18.3% in Lepomis gibbosus, 16.7% in Micropterus salmoides, and 10% in Perca fluviatilis. The other five fish species (Ameiurus melas, Ictalurus punctatus, Squalius cephalus, Carassius carassius, and Scardinius erythrophthalmus) were all negative for parasite presence. There were no significant differences in prevalence between the three fish species (Fisher\u2019s exact test; p = 0.744). The mean intensity of infestation ranged from 1 (M. salmoides and P. fluviatilis) to 1.15 (L. gibbosus), and the mean abundance ranged from 0.1 (P. fluviatilis) to 0.28 (L. gibbosus). There were significant differences in the infestation site between the four muscle quadrants (anterior ventral, anterior dorsal, posterior ventral, and posterior dorsal) and the visceral cavity (Kruskal\u2013Wallis test; p = 0.0008). The study findings advance our knowledge about the distribution and host range of this parasite in Italy

Occurrence and Spatial Distribution of Dibothriocephalus Latus (Cestoda: Diphyllobothriidea) in Lake Iseo (Northern Italy): An Update

Dibothriocephalus latus (Linnaeus, 1758) (Cestoda: Diphyllobothriidea; syn. Diphyllobothrium latum), is a fish-borne zoonotic parasite responsible for diphyllobothriasis in humans. Although D. latus has long been studied, many aspects of its epidemiology and distribution remain unknown. The aim of this study was to investigate the prevalence, mean intensity of infestation, and mean abundance of plerocercoid larvae of D. latus in European perch (Perca fluviatilis) and its spatial distribution in three commercial fishing areas in Lake Iseo (Northern Italy). A total of 598 specimens of P. fluviatilis were caught in 2019. The total prevalence of D. latus was 6.5%. However, there were significant differences between areas (10.2% North; 7.3% Center; 1.5% South) (Chi-square test, p = 0.0018). The mean intensity of infestation ranged from 1 larva in southern area to 1.2 larvae in both the central and northern (Pisogne) areas. In addition, the mean abundance ranged from 0.02 in the southern area to 0.26 in the northern area (Pisogne). The total number of larvae (anterior dorsal\u2014AD = 21; anterior ventral\u2014AV = 1; posterior dorsal\u2014PD = 15; posterior ventral\u2014PV = 5) differed significantly between the four anatomical quadrants (Kruskal\u2013Wallis test; p = 0.0001). The prevalence of D. latus plerocercoid larvae in European perch from Lake Iseo has long been investigated, but without an appropriate sampling design. With the present study, a broader analysis in spatial distribution has been added to the existing literature, revealing new information about D. latus distribution and occurrence in Lake Iseo, with new data that will be useful for health authorities and future studies

Occurrence of ascaridoid nematodes in Illex coindetii, a commercially relevant cephalopod species from the Ligurian Sea (Northwest Mediterranean Sea)

International audienceIn this study we investigated the occurrence of larval ascaridoid nematodes in Illex coindetii, a commercially relevant cephalopod, via a cross-sectional prevalence study (January 2015 to February 2018) in two fishing areas (Savona and Piombino) in the Ligurian Sea (northwest Mediterranean Sea). A total of 745 specimens of I. coindetii were caught by local fisherman through bottom trawling. Parasitological examination revealed ascaridoid nematodes (L3) larvae (n = 9): Hysterothylacium sp. (n = 6) and Anisakis spp. (n = 3). All larvae morphologically referred to the genus Anisakis were identified by PCR-RFLP as A. pegreffii. The prevalence of Hysterothylacium sp. infestation was 0.88% for the Savona and 0.56% for the Piombino sampling site; the prevalence of A. pegreffii was 0.18% for Savona and 1.11% for Piombino and did not differ between the two sampling sites (chi-square test; p = 0.0848). Better knowledge of the distribution of ascaridoid nematodes, especially of Anisakis species is essential for defining their epidemiological role and the potential risk for consumer health

Different behavior of erythrovirus B19 and torquetenovirus in response to a single step of albumin purification

12noneBACKGROUND: The safety of human serum albumin (HSA) is of special interest with respect to virus transmission because of the wide use of this blood product as a therapeutic agent and also, added to other products, as an excipient or a stabilizer. Conflicting data are reported concerning HSA contamination by small, naked viruses such as the erythrovirus B19 (B19V) and the anellovirus torquetenovirus (TTV). This study has been performed to assess the effect of the HSA purification procedures on the viral contamination. STUDY DESIGN AND METHODS: Known concentrations of B19V and TTV virus were spiked in raw Fraction V, the starting material from fractionated human plasma for HSA purification, which was subsequently submitted to the depth filtration procedure. After spiking, B19V and TTV genome copies were determined by real-time quantitative polymerase chain reaction assays in the mixture at the end of Fraction V dissolution, to determine the virus concentration achieved, in the HSA solution after the filtration step, in the filtered postwashing fluid, and in the supernatant of resuspended Celite. RESULTS: B19V was completely adsorbed by the Celite used as a filter aid in the depth filtration process and was thus undetectable in the resulting HSA-containing fraction. In contrast, in 2 out of 3 experiments, TTV was detected in all samples. CONCLUSION: The different behavior of the two viruses might be a reflection of their different surface charge.mixedAzzi, Alberta; Maggi, Fabrizio; Zakrzewska, Krystyna; Menconi, Maria Carla; Di Pietro, Niccolò; Salotti, Vittorio; Farina, Claudio; Andreoli, Elisabetta; Fiorentino, Bruno; Angelini, Cristina; Corcioli, Fabiana; Bendinelli, MauroAzzi, Alberta; Maggi, Fabrizio; Zakrzewska, Krystyna; Menconi, Maria Carla; Di Pietro, Niccolò; Salotti, Vittorio; Farina, Claudio; Andreoli, Elisabetta; Fiorentino, Bruno; Angelini, Cristina; Corcioli, Fabiana; Bendinelli, Maur

Long-term outcome after allogeneic hematopoietic stem cell transplantation for Shwachman-Diamond syndrome: a retrospective analysis and a review of the literature by the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (SAAWP-EBMT)

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative procedure in patients with Shwachman-Diamond syndrome (SDS) with bone marrow abnormalities. The results of 74 patients with SDS (6 acute myeloid leukemia, 7 myelodysplastic syndrome, and 61 bone marrow failure) treated with HSCT between 1988 and 2016 are reported. The donor source was: 24% sibling, 8% parent, and 68% unrelated donor. The stem cell source was: 70% bone marrow, 19% peripheral blood stem cells, and 11% cord blood. The conditioning regimen was myeloablative in 54% and reduced intensity in 46%. Neutrophil engraftment was achieved in 84% of patients after a median time of 17.5 days. Graft failure occurred in 15% of HSCTs. Grades I-IV acute and chronic GVHD were observed in 55% and 20% of patients, respectively. After a median follow-up of 7.3 years (95% CI 4.8-10.2), 28 patients died for progression/relapse (7) or toxicity (21). The 5-year overall survival and nonrelapse mortality were 63.3% (95% CI 50.8-73.4) and 19.8% (95% CI 10.8-30.8), respectively. In conclusion, this is the largest series so far reported and confirms that HSCT is a suitable option for patients with SDS. Further efforts are needed to lower transplant-related toxicity and reduce graft failure