Successful long-term hematological and immunological reconstitution by autologous cord blood transplantation combined with post-transplant immunosuppression in two children with severe aplastic anemia.

aUCBT is a valuable curative option in pediatric patients with refractory idiopathic SAA and no available matched sibling or unrelated donors. Experience in the use of autologous cord blood units in patients with SAA is limited and private for-profit cord blood-banking programs are controversial. We report the successful treatment of two patients with SAA, aged 15 and 24 months, with autologous cord blood combined with immunosuppression. After conditioning with 200 mg/kg cyclophosphamide and ATG, 7.5 mg/kg, 32.2 × 107 /kg, and 3.8 × 107 /kg autologous cord blood nucleated cells were infused, respectively. One of our patients underwent transplantation after failure of IST. Both patients received post-transplant immunosuppression with cyclosporine for 12 months. They remain disease-free 6 years post-transplantation.

Venetoclax Combination Treatment of Acute Myeloid Leukemia in Adolescents and Young Adult Patients.

Over the past two decades, the prognosis in adolescents and young adults (AYAs) diagnosed with acute myeloid leukemia (AML) has significantly improved. The standard intensive cytotoxic treatment approach for AYAs with AML, consisting of induction chemotherapy with anthracycline/cytarabine combination followed by consolidation chemotherapy or stem cell transplantation, has lately been shifting toward novel targeted therapies, mostly in the fields of clinical trials. One of the most recent advances in treating AML is the combination of the B-cell lymphoma 2 (Bcl-2) inhibitor venetoclax with hypomethylating agents, which has been studied in elderly populations and was approved by the Food and Drug Administration (FDA) for patients over 75 years of age or patients excluded from intensive chemotherapy induction schemas due to comorbidities. Regarding the AYA population, venetoclax combination therapy could be a therapeutic option for patients with refractory/relapsed (R/R) AML, although data from real-world studies are currently limited. Venetoclax is frequently used by AYAs diagnosed with advanced hematologic malignancies, mainly acute lymphoblastic leukemia and myelodysplastic syndromes, as a salvage therapeutic option with considerable efficacy and safety. Herein, we aim to summarize the evidence obtained from clinical trials and observational studies on venetoclax use in AYAs with AML. Based on the available evidence, venetoclax is a safe and effective therapeutic option for R/R AML AYA patients. However, further research in larger cohorts is needed to confirm these data, establishing the benefits of a venetoclax-based regimen for this special population.

Budget impact analysis of ustekinumab in the management of moderate to severe psoriasis in Greece.

BACKGROUND: The purpose of this study was to estimate the annual and per-patient budget impact of the treatment of moderate to severe psoriasis in Greece before and after the introduction of ustekinumab. METHODS: A budget impact model was constructed from a national health system perspective to depict the clinical and economic aspects of psoriasis treatment over 5 years. The model included drug acquisition, monitoring, and administration costs for both the induction and maintenance years for patients in a treatment mix with etanercept, adalimumab, infliximab, with or without ustekinumab. It also considered the resource utilization for non-responders. Greek treatment patterns and resource utilization data were derived from 110 interviews with dermatologists conducted in February 2009 and evaluated by an expert panel of 18 key opinion leaders. Officially published sources were used to derive the unit costs. Costs of adverse events and indirect costs were excluded from the analysis. Treatment response was defined as the probability of achieving a PASI 50, PASI 75, or PASI 90 response, based on published clinical trial data. RESULTS: The inclusion of ustekinumab in the biological treatment mix for moderate to severe psoriasis is predicted to lead to total per-patient savings of €443 and €900 in years 1 and 5 of its introduction, respectively. The cost savings were attributed to reduced administration costs, reduced hospitalizations for non-responders, and improved efficacy. These results were mainly driven by the low number of administrations required with ustekinumab over a 5 year treatment period (22 for ustekinumab, compared with 272 for etanercept, 131 for adalimumab, and 36 for infliximab). CONCLUSIONS: The inclusion of ustekinumab in the treatment of moderate to severe psoriasis in Greece is anticipated to have short- and long-term health and economic benefits, both on an annual and per-patient basis.

Transient Cytopenias as a Rare Presentation of Classic Galactosemia.

Although galactosemia can be detected through neonatal screening, some cases are characterized by rapid and severe presentation before screening results become available. We report the case of a neonate with classic galactosemia presenting with acute liver failure and cytopenias (thrombocytopenia, anemia, and neutropenia). Neonatal screening results showed increased galactose and phenylalanine levels. The diagnosis of galactosemia was confirmed by the measurement of galactose-1-phosphate uridyltransferase (GALT) activity in erythrocytes. Two mutations of the GALT gene (c.563 A>G [p. Q188R] and c.957C>A [p.H319Q]) were revealed. High clinical suspicion of galactosemia is crucial to identify, as early as possible, cases with classical or even unusual presentation, and to initiate early treatment that could change the disease course and improve outcomes. Cytopenias should be included in the broad phenotypic spectrum of galactosemia.

Fish evaluation of additional cytogenetic aberrations and hyperdiploidy in childhood Burkitt lymphoma.

Beyond MYC rearrangement, Burkitt lymphoma (BL) often presents with additional aberrations. Biopsy touch imprints from 72 children with BL were tested with interphase fluorescence in-situ hybridization (i-FISH) for MYC, BCL2, BCL6, IGH, IGK and IGL rearrangements and copy-number aberrations involving 1q21/1p32, 7cen/7q31, 9cen/9p21, 13q14/13q34 and 17cen/17p13. Diploid status deviations were investigated with chromosome enumeration probes. MYC rearrangement was demonstrated in all cases. Additional aberrations included +1q (21/72:29.2%), +7q (14/72:19.4%), 13q- (14/72:19.4%), 9p-(6/72:8.3%) and hyperdiploidy (6/72:8.3%). Advanced clinical stage IV, +7q and 9p- were associated with shorter overall survival, with stage IV and +7q retaining prognostic significance on multivariate analysis. No relapse or death was reported among the hyperdiploid cases. This i-FISH investigation provides information on the genetic profile of BL and may prove valuable for patients with no karyotype analysis. Demonstration of hyperdiploidy could evolve research on clonal evolution pathways and probably identify a subgroup of children with favorable prognosis.

Traumatic ulcerative granuloma with stromal eosinophilia: a lesion with alarming histopathologic presentation and benign clinical course.

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a chronic, benign, self-limiting lesion of the oral mucosa. Clinically, the ulceration is characterized by the presence of indurated elevated borders and may resemble pyogenic granuloma or even squamous cell carcinoma of the mouth. Pathogenesis of the lesion is unclear. Although it had been suggested that TUGSE may represent a CD30+ lymphoproliferative disorder, this theory is currently not supported by evidence. We are presenting a classic example of TUGSE, its clinical course, differential diagnosis, and treatment.

Sun exposure behavior and protection practices in a Mediterranean population: a questionnaire-based study.

OBJECTIVE: Skin cancer campaigns have only recently been implemented in a wide scale in Greece. In order to better target those individuals at risk, we aimed to explore sun exposure behaviors in a sample of the Greek population. METHODS: A total of 802 subjects, randomly selected among the residents of the two largest Greek cities, underwent a questionnaire-based telephone interview, assessing the degree of sun exposure patterns and knowledge of skin cancer risk factors. RESULTS: Females more commonly (90%) used sunscreens compared with males (67.5%), and among sunscreen users, only 8% used products with SPF <10. Almost half of the participants (48%) preferred going to the beach during the midday hours. Over exposure to the sun was mostly reported by individuals with phototypes III/IV and of younger age (18-35 years). Most participants were aware of sun exposure as a cause of skin cancer, but among those who did not, 41% were younger than 34 years of age. CONCLUSIONS: In our survey, significant differences in age, sex and phototypes were observed with regard to sun exposure patterns and sunscreen use. Educational campaigns should focus more on younger age groups, encouraging a more complete set of photoprotective measures. However, potential trial limitations inherent in self-reported measures should be taken into account.

Anaphylaxis to gadobenate dimeglumine (Multihance): a case report.

BACKGROUND: Gadolinium chelates are relatively safe contrast media used in MRI. Immediate severe adverse effects are exceptionally rare and mostly concern mild anaphylactoid reactions. We report a case of anaphylaxis to gadobenate dimeglumine (Gd-BOPTA, Multihance), a gadolinium-based contrast agent. METHODS: A 32-year-old female patient with a personal history of multiple sclerosis, while undergoing an MRI scan, developed bronchospasm and acute urticaria with diffuse giant pruritic plaques in the first minute of Gd-BOPTA infusion. The procedure was cancelled and acute treatment of the reaction took place. The patient reported 2 additional MRI scans with definite use of unknown contrast media in the past 2 years without any adverse effect. Blood samples were obtained 2 and 48 h after the reaction for measurement of serum tryptase concentration (Pharmacia Diagnostics, Uppsala, Sweden). Skin prick tests and intradermal tests were performed using 1:1,000, 1:100 and 1:10 dilution of the offending agent and alternative gadolinium-based agents [gadodiamide (Omniscan) and gadoteric acid (Dotarem)]. A group of 10 nonatopic individuals who underwent the same skin testing comprised the control group. RESULTS: Tryptase concentration was highly elevated 2 h after the reaction (21 microg/l) compared with that at 48 h (3 microg/l). Skin prick tests in our patient were all negative, while intradermal testing with 0.03 ml of 1:100 and 1:10 preparations of Multihance showed a definite positive wheal-and-flare reaction. Skin tests to the alternative agents showed no response. In the control group, all performed tests were negative. CONCLUSION: We report the first case of an allergic reaction to gadobenate dimeglumine. Besides, skin testing seems to be a precious diagnostic tool which, if positive, strongly suggests a mast cell-mediated underlying mechanism.

An atypical case of pityriasis rosea gigantea after influenza vaccination.

Pityriasis rosea is a common erythematosquamous eruption, typically presenting along the cleavage lines of the skin. A wide spectrum of atypical manifestations may challenge even the most experienced physician. Here we report a rare case of a suberythrodermic pityriasis rosea with gigantic plaques after an influenza vaccination, and we discuss the possible triggers of atypical manifestations of such a common dermatological disease in the setting of an altered immunity.

Cytogenetic abnormalities and monosomal karyotypes in children and adolescents with acute myeloid leukemia: correlations with clinical characteristics and outcome.

The whole spectrum of chromosomal abnormalities and their prognostic significance in children and adolescents with acute myeloid leukemia (AML) has not been fully elucidated yet, although a considerable amount of knowledge has been gained recently. Moreover, the incidence and prognostic impact of monosomal karyotypes (MKs), which are new cytogenetic categories reported recently in adults with AML, are currently unknown for childhood and adolescent AML. In this study, we investigated the cytogenetic and clinical characteristics of 140 children and adolescents (≤21 y) with AML, and correlated their cytogenetic features with both the clinical characteristics and outcomes of our patient cohort. The most frequent cytogenetic abnormality found in our study was the t(15;17), followed by the t(8;21). Striking differences in the genetic abnormalities and French-American-British subtypes were found among infants, children, and adolescents. Of 124 cases, 15 (12.1%) met the criteria of the MK definition, and 12 of the 15 MKs (80%) were complex karyotypes. Of 124 cases, 27 (21.8%) had cytogenetic abnormalities sufficient to be diagnosed as AML with myelodyspastic sydrome-related features. As expected, patients with the t(15;17) had the most favorable outcomes, whereas patients with 11q23 rearrangements and monosomy 7 had the worst outcomes. These data expand our knowledge by providing novel insights into the cytogenetic features and their correlations with clinical characteristics and outcomes in childhood and adolescent AML.

Cutaneous metastasis of signet-ring gastric adenocarcinoma to the breast with unusual clinicopathological features.

BACKGROUND: Cutaneous metastasis of gastric adenocarcinoma is rare and usually presents in men, as nodules over the abdomen. We present the case of a woman with cutaneous metastasis of gastric adenocarcinoma showing unusual clinicopathological features. CASE REPORT: A 37-year-old woman developed florid cutaneous metastasis over the skin of the left breast two years after total gastrectomy for a signet-ring adenocarcinoma of the diffuse type. The metastasis presented as a multinodular growth developing over erythematous skin of the left hemithorax. Microscopically, the skin tumor was predominantly made up of spindle-shaped cells, mimicking a mesenchymal/fibrohistiocytic neoplasm. A comparative immunohistochemical study of the gastric primary and the skin tumor showed an almost identical profile (keratin 7/20+; epithelial membrane antigen+, MUC-5AC+), highlighting the gastric adenocarcinoma as the origin of the skin metastasis. CONCLUSION: Although rare, cutaneous metastases of gastric adenocarcinomas can develop in women and may mimic inflammatory metastasis of breast adenocarcinoma. Immunohistochemistry is invaluable in establishing the correct diagnosis.