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Introduction: Caustic substances ingestion results in a complex syndrome. The patient characteristics and severity of injury are important prognostic predictors. The monitoring of clinical changes and the multidisciplinary approach are necessary to prevent death in the early stages of the poisoning., Case Description: The case report describes the suicide of a woman by ingestion of a large amount of 15% sulfuric acid for suicidal purposes (15-20 ml). The initial conditions were stable, and no changes were found on a CT scan. However, the main sign was a severe metabolic acidosis. After 7 hours, haematemesis and oedema of the larynx appeared, and oro-tracheal intubation and ICU admission were necessary. Consequent progressive haemodynamic deterioration with persistent severe metabolic acidosis, increasing lactates and septic shock appeared. A new CT scan with contrast was performed 22 hours later detecting diffuse perforations and liquid in pleurae and abdomen. A pleural sample showed necrotic liquid. The death was 24 hours after ingestion and no surgical treatment was performed because of the diffuse lesions to the thoracoabdominal districts., Conclusions: Early detection of gastroenteric lesions and the monitoring of clinical changes are mandatory to avoid the death of the patient. Gastroenteric perforations require an immediate radiological evaluation and surgical treatment. The clinical case report states the severity of prognosis was related to high doses of sulfuric acid ingestion. The immediate metabolic acidosis is related to quick subsequent severe systemic pathological lesions of the gastrointestinal tract. The severity of absorption metabolic acidosis, consequently, may be an early and prognostic sign of the late chest and abdominal lesions., Learning Points: Severity of metabolic acidosis after sulfuric acid ingestion may anticipate late damage to the gastrointestinal tract., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder of lymphocyte homeostasis classically due to mutation of FAS, FASL, and CASP10 genes (ALPS-FAS/CASP10). Despite recent progress, about one-third of ALPS patients does not carry classical mutations and still remains gene orphan (ALPS-U, undetermined genetic defects). The aims of the present study were to compare the clinical and immunological features of ALPS-FAS/CASP10 versus those of ALPS-U affected subjects and to deepen the genetic characteristics of this latter group. Demographical, anamnestic, biochemical data were retrieved from medical record of 46 ALPS subjects. An enlarged panel of genes (next-generation sequencing) was applied to the ALPS-U group. ALPS-U subjects showed a more complex phenotype if compared to ALPS-FAS/CASP10 group, characterized by multiorgan involvement ( P = 0.001) and positivity of autoimmune markers ( P = 0.02). Multilineage cytopenia was present in both groups without differences with the exception of lymphocytopenia and autoimmune neutropenia that were more frequent in ALPS-U than in the ALPS-FAS/CASP10 group ( P = 0.01 and P = 0.04). First- and second-line treatments were able to control the symptoms in 100% of the ALPS-FAS/CASP10 patients, while 63% of ALPS-U needed >2 lines of treatment and remission in some cases was obtained only after target therapy. In the ALPS-U group, we found in 14 of 28 (50%) patients 19 variants; of these, 4 of 19 (21%) were known as pathogenic and 8 of 19 (42%) as likely pathogenic. A characteristic flow cytometry panel including CD3CD4-CD8-+TCRαβ+, CD3+CD25+/CD3HLADR+, TCR αβ+ B220+, and CD19+CD27+ identified the ALPS-FAS/CASP10 group. ALPS-U seems to represent a distinct entity from ALPS-FAS/CASP10; this is relevant for management and tailored treatments whenever available., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

We investigated MYB rearrangements (MYB-R) and the levels of MYB expression, in 331 pediatric and adult patients with T-cell acute lymphoblastic leukemia (T-ALL). MYB-R were detected in 17 cases and consisted of MYB tandem duplication (tdup) (= 14) or T cell receptor beta locus (TRB)-MYB (= 3). As previously reported, TRB-MYB was found only in children (1.6%) while MYB tdup occurred in both age groups, although it was slightly more frequent in children (5.2% vs 2.8%). Shared features of MYB-R T-ALL were a non-early T-cell precursor (ETP) phenotype, a high incidence of NOTCH1/FBXW7 mutations (81%) and CDKN2AB deletions (70.5%). Moreover, they mainly belonged to HOXA (=8), NKX2-1/2-2/TLX1 (=4), and TLX3 (=3) homeobox-related subgroups. Overall, MYB-R cases had significantly higher levels of MYB expression than MYB wild type (MYB-wt) cases, although high levels of MYB were detected in ~ 30% of MYB-wt T-ALL. Consistent with the transcriptional regulatory networks, cases with high MYB expression were significantly enriched within the TAL/LMO subgroup (P = .017). Interestingly, analysis of paired diagnosis/remission samples demonstrated that a high MYB expression was restricted to the leukemic clone. Our study has indicated that different mechanisms underlie MYB deregulation in 30%-40% of T-ALL and highlighted that, MYB has potential as predictive/prognostic marker and/or target for tailored therapy., (© 2021 Wiley Periodicals LLC.)

Primary autoimmune neutropenia (pAN) is typified by onset in early infancy and a mild/moderate phenotype that resolves within 3 years of diagnosis. In contrast, secondary AN is classically an adult disease associated with malignancy, autoimmunity, immunodeficiency, viral infection, or drugs. This study describes a cohort of 79 children from the Italian Registry who, although resembling pAN, did not fully match the criteria for pAN because neutropenia either appeared after age 5 years (LO-Np) or lasted longer than 3 years (LL-Np). These 2 categories compared with classical pAN showed a far inferior rate of resolution (P < .001), lower severity of neutropenia (P = .03), leukopenia (P < .001), lymphopenia (P < .001) with low B+ (P = .001), increased need of granulocyte colony-stimulating factor (P = .04), and increased frequency of autoimmunity over the disease course (P < .001). A paired comparison between LO-Np and LL-Np suggested that LO-Np had a lower rate of resolution (P < .001) and lower white blood cell (P < .001) and lymphocyte (P < .001) values, higher occurrence of apthae (P = .008), and a stronger association with autoimmune diseases/markers (P = .001) than LL-Np, thus suggesting a more pronounced autoimmune signature for LO-Np. A next-generation sequencing panel applied in a small subgroup of LO-Np and LL-Np patients identified variants related to immune dysregulations. Overall, these findings indicate that there are important differences among pAN LL-Np and LO-Np. Forms rising after 3 years of age, with low tendency to resolution, require tight monitoring and extensive immune investigations aimed to early identify underlying immunologic disease., (© 2020 by The American Society of Hematology.)

Background: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known., Objective: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use., Methods: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded., Results: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID., Conclusions: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective of the Study: In this study we aimed to retrospectively evaluate how centers, belonging to the Associazione Italiana Ematologia e Oncologia Pediatrica (AIEOP), manage severe acquired hypofibrinogenemia in children with acute lymphoblastic leukemia, particularly evaluating the therapeutic role of human fibrinogen concentrate (HFC) and fresh frozen plasma (FFP)., Methods: We conducted a survey among AIEOP centers; thereafter, we collected and analyzed data with regard to the treatment of episodes of severe acquired hypofibrinogenemia occurring during the induction and reinduction phases of the AIEOP-BFM ALL 2009 protocol., Results: In total, 15 of the 37 AIEOP centers invited to join the survey agreed to collect the data, with 10 and 5 centers declaring to react to severe acquired hypofibrinogenemia (<70 mg/dL) by administering HFC or FFP, respectively. Of the 150 episodes of severe hypofibrinogenemia occurring in 101 patients, 47.3% were treated with HFC and 52.7% with FFP, with a normalization of fibrinogen levels achieved in greater proportion and in a shorter amount of time in the HFC group as compared with the FFP group. None of the patients presented with bleeding or thrombosis during the observation period., Conclusions: Even with the limitations of the retrospective nature of this study, HFC seems to be a safe and effective alternative to FFP for replacement therapy in case of severe hypofibrinogenemia in children with acute lymphoblastic leukemia.

Autoimmune neutropenia of infancy (AIN) is characterized by low risk of severe infection, tendency to spontaneously resolve and typically onset at ≤4-5 years of age; it is due to auto-antibodies whose detection is often difficult. In case of negativity of 4 antineutrophils autoantibody tests, after having excluded ethnic, postinfection, drug induced, or congenital neutropenia, according to the Italian guidelines the patients will be defined as affected by "idiopathic neutropenia" (IN). We describe the characteristics of 85 IN patients enrolled in the Italian neutropenia registry: they were compared with 336 children affected by AIN. The 2 groups were clinically very similar and the main differences were detection age (later in IN), length of disease (longer in IN) and, among recovered patients, age of spontaneous recovery: the median age at resolution was 2.13 years in AINs and 3.03 years in INs (P = .00002). At bivariate analysis among AIN patients earlier detection age (P = .00013), male sex (P = .000748), absence of leucopenia (P = .0045), and absence of monocytosis (P = .0419) were significantly associated with earlier recovery; in the IN group only detection age (P = .013) and absence of monocytosis (P = .0333) were significant. At multivariate analysis detection age and absence of monocytosis were independently significant (P = 6.7e-05 and 4.4e-03, respectively) in the AIN group, whereas in the IN group only detection age stayed significant (P = .013)., (© 2018 Wiley Periodicals, Inc.)

Objectives: Posterior reversible encephalopathy syndrome (PRES) is one of the most common neurological complications in hematology-oncology pediatric patients. Despite an increasingly recognized occurrence, no clear consensus exists regarding how best to manage the syndrome, because most cases of PRES have reported in single-case reports or small series. Aim of this paper is to identify incidence, clinical features, management, and outcome of PRES in a large series of hematology-oncology pediatric patients., Methods: The cases of PRES occurred in twelve centers of the Italian Association of Pediatric Hematology and Oncology were reported., Results: One hundred and twenty-four cases of PRES in 112 pediatric patients were recorded with an incidence of 2.1% and 4.7%, respectively, in acute lymphoblastic leukemia in first complete remission and hematopoietic stem cell transplantation (HSCT). The majority of cases occurred after a cycle of chemotherapy rather than after stem cell transplant. PRES after chemotherapy significantly differs from that after HSCT for diagnosis, time of presentation, risk factors, management, and outcome., Conclusions: This study demonstrates that PRES is a common neurological complication and occurring preferentially in course of induction treatment of some hematologic malignancies, as ALL and after HSCT. It also highlights great clinical differences in the management and outcome in patients with PRES occurring after chemotherapy or after HSCT., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We analyzed 97 Fanconi anemia patients from a clinic/biological database for genotype, somatic, and hematologic phenotype, adverse hematological events, solid tumors, and treatment. Seventy-two patients belonged to complementation group A. Eighty percent of patients presented with mild/moderate somatic phenotype and most with cytopenia. No correlation was seen between somatic/hematologic phenotype and number of missense mutations of FANCA alleles. Over follow-up, 33% of patients improved or maintained mild/moderate cytopenia or normal blood count, whereas remaining worsened cytopenia. Eleven patients developed a hematological adverse event (MDS, AML, pathological cytogenetics) and three developed solid tumors. 10 years cumulative risk of death of the whole cohort was 25.6% with median follow-up 5.8 years. In patients eligible to hematopoietic stem cell transplantation because of moderate cytopenia, mortality was significantly higher in subjects transplanted from matched unrelated donor over nontransplanted subjects, whereas there was no significant difference between matched sibling donor transplants and nontransplanted patients. In patients eligible to transplant because of severe cytopenia and clonal disease, mortality risk was not significantly different in transplanted from matched unrelated versus matched sibling donor versus nontransplanted subjects. The decision to transplant should rely on various elements including, type of donor, HLA matching, patient comorbidities, impairment, and clonal evolution of hematopoiesis. Am. J. Hematol. 91:666-671, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Congenital or acquired severe aplastic anaemia (SAA) is cured by bone marrow transplantation (BMT) from a histocompatible leukocyte antigen- (HLA-) identical sibling. The best conditioning regimen is cyclophosphamide (CTX) with or without antithymocyte globulin (ATG), followed by short-term methotrexate (MTX) and cyclosporine A (CsA) to prevent graft-versus-host disease (GvHD). In our pediatric oncology-hematology unit, a 5-year-old girl with SAA was treated with two BMT from the same HLA-identical sibling donor. Severe CsA-induced adverse events (severe hypertension and PRES) after the first BMT led necessarily to CSA withdrawal. Alternative immunosuppressive treatment for GvHD prevention as tacrolimus and mycophenolate were not tolerated by our patient because toxicity > grade II. For this reason we decided to administrate sirolimus alone as GvHD prophylaxis and to prevent disease relapse after the rescue BMT. Here we report the successful use of sirolimus alone for GvHD prophylaxis after the second transplant in a pediatric BMT setting for SAA.

We describe the incidence and characteristics of infections in children with severe congenital neutropenia (SCN), autoimmune neutropenia (AN) and idiopathic neutropenia (IN). Data extracted from the Italian Neutropenia Registry on 73 patients with 108 episodes of infections were collected from 2000 to 2009. All SCN patients with SCN and one third of AN and IN experienced at least 1 infectious episode, equating to 5.7 infections/patient in SCN and approximately 0.6 in AN and IN. The rate of infections before diagnosis of neutropenia was 6.35/1000 patient-days at risk in SCN, 0.48 in AN and 0.71 in IN (P < 0.001) and significantly decreased after diagnosis. Skin and subcutaneous abscesses and cellulitis were the most frequent types of infection encountered, followed by pneumonia. Infections are an important clinical issue in the management of neutropenic patients, even in those considered at lower risk.

Cytotoxic T lymphocytes, natural killer cells, and NKT cells are effector cells able to kill infected cells. In some inherited human disorders, a defect in selected proteins involved in the cellular cytotoxicity mechanism results in specific clinical syndromes, grouped under the name of familial hemophagocytic lymphohistiocytosis. Recent advances in genetic studies of these patients has allowed the identification of different genetic subsets. Additional genetic immune deficiencies may also induce a similar clinical picture. International cooperation and prospective trials resulted in refining the diagnostic and therapeutic approach to these rare diseases with improved outcome but also with improved knowledge of the mechanisms underlying granule-mediated cellular cytotoxicity in humans.

Background: A 68-year-old man diagnosed with primary plasma-cell leukemia was given thalidomide maintenance treatment for his disease. He had previously failed induction therapy with cyclophosphamide, vincristine, adriamycin, and dexamethasone, but achieved complete remission after melphalan therapy. Multiple syncopal episodes started to occur during thalidomide treatment, and a Holter electrocardiogram showed multiple abnormalities, with an episode of sustained ventricular tachycardia., Investigations: Blood tests, peripheral blood smear, bone-marrow biopsy and aspirate, Holter electrocardiogram., Diagnosis: Sustained ventricular tachycardia possibly owing to thalidomide treatment., Management: Thalidomide withdrawal, dexamethasone maintenance therapy, monthly oral courses of combined melphalan and prednisone, salvage therapy with bortezomib.