The aim of developing new tumor-inhibiting ruthenium complexes, in particular compounds which act against tumors that have been chemoresistant up to now, has led us to the synthesis of different classes of ruthenium complexes. These were selected for further evaluation on the basis of increase in survival time in the P388 tumor model and water-solubility. The water-soluble ruthenium complexes coordinated with heterocycle ligands in trans-position, HB(RuB 2 CI 4 ), and the corresponding pentachloro derivatives, (HBMRuBCI s )' were identified as being the most active ones. Their chemical properties were investigated by means of x-ray analyses, M6ssbauer spectra, NMR spectra, and other methods. Their galenic formulation was relatively easy to establish owing to their solubility in water or in physiological saline. Stability of the complexes turned out to be sufficient for infusion therapy. Antitumor activity of such compounds was confirmed not only in the P388 tumor model but also in the Walker 256 carcinosarcoma, the Stockholm Ascitic tumor, the subcutaneously growing B 16 melanoma, the intramusculary growing sarcoma 180 and the AMMN-induced colorectal tumors of the rat.In particular, the two compounds ImH(Rulm 2 Ci 4 ) and IndH(RuInd 2 CI 4 ), 1m = Imidazole, Ind = Indazole, turned out to be highly active against these tumor models, with the emphasis on activity against AMMN-induced colorectal tumors. This is a strong indication of future clinical activity against such adenotumors. The toxicological target organs turned out to be the kidneys and the liver. In addition, erythropenia and an increase in both creatinine and liver enzymes were observed. Nevertheless, in chronic application at therapeutic doses, toxicity is well tolerated. On account of these promising properties, the two compounds were selected for further toxicological studies, which are the prerequisites for the beginning of clinical studies.

Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high-risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients.

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 ofPediatric 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

Summary Background Invasive mucormycosis is a rare but frequently fatal fungal disease. The acute and rapidly progressive evolution causes unfavourable outcome in 22%‐59% of patients and its treatment represents a clinical challenge, especially in immunocompromised patients. Current data in paediatric oncological patients are limited. Objectives The infection Working Group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) analysed the episodes of invasive mucormycosis occurred between 2009 and 2016. Patients Fifteen cases of proven mucormycosis (male/female 8/7; median age 14.1 years, range 7.7‐18.6) were reported after chemotherapy for acute leukaemia and lymphoma (12) and allogeneic stem cell transplantation (3). The aetiology was Rhizopus oryzae 4, Lichtheimia corymbifera 3 and Mucor spp. 8. Results Paranasal sinus was the primary site of infection in 14/15 patients combined with orbital involvement (9), central nervous system (8), lung (4), thyroid gland and kidney (1). All patients received liposomal Amphotericin B (L‐AmB) (3‐10 mg/kg), with surgical debridement in 14/15 cases. Eleven patients received maintenance treatment with posaconazole (9) or isavuconazole (2). Eight out of fifteen patients (53.3%) died, after 3‐6 months. Conclusions Mucormycosis involved mainly the sinu‐orbital site and affected children >10 years. Despite aggressive treatment with high‐dose L‐AmB and timely surgical debridement, the mortality rate remains still high.

Our study confirms improvement of pathogenetic knowledge and treatment over the last 20 years. Age at diagnosis older than or equal to 2 years and standardized treatment are associated with improved prognoses. Multisystemic involvement, especially with "risk" organs seem to be correlated to a worse outcome.