Myelodysplastic syndromes (MDS) are hematopoietic disorders rare in childhood, often occurring in patients with inherited bone marrow failure syndromes or germinal predisposition syndromes. Among the latter, one of the most frequent involves the gene GATA binding protein 2 (GATA2), coding for a transcriptional regulator of hematopoiesis. The genetic lesion as well as the clinical phenotype are extremely variable; many patients present hematological malignancies, especially MDS with the possibility to evolve into acute myeloid leukemia. Variable immune dysfunction, especially resulting in B- and NK-cell lymphopenia, lead to severe infections, including generalized warts and mycobacterial infection. Defects of alveolar macrophages lead to pulmonary alveolar proteinosis through inadequate clearance of surfactant proteins. Currently, there are no clear guidelines for the monitoring and treatment of patients with GATA2 mutations. In patients with MDS, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT) that restores normal hematopoiesis preventing the progression to acute myeloid leukemia and clears long-standing infections. However, to date, the donor type, conditioning regimen, and the optimal time to proceed to HSCT, as well as the level of chimerism needed to reverse the phenotype, remain unclear highlighting the need for consensus guidelines.

CMV represents one of the most serious life-threatening complications of allogeneic stem cell transplantaion (allo-SCT). Pre-emptive treatment is highly effective, but toxicity and repetitive reactivation of CMV represent a major challenge in the clinical practice. The use of anti-CMV specific immunoglobulins (Megalotect) is controversial. We retrospectively collected data on 92 patients submitted to allo-SCT for hematological malignancies, in whom Megalotect was used either for prophylaxis (n=14) or with pre-emptive therapy (n=78). All the patients were considered at high-risk of developing CMV reactivation and CMV disease. The treatment was well tolerated, with no reported infusion reactions, nor other adverse events. None of the 14 cases treated with Megalotect as prophylaxis developed CMV reactivation. 51/78 (65%) patients who received Megalotect during pre-emptive treatment achieved complete clearance of CMV viremia, and 14/51 patients (29%) developed a breakthroug CMV infection. 7/78 patients (9%) developed CMV disease. The projected 1-year OS, 1-year TRM and 1-year RR is 74%, 15% and 19%, respectively. No differences were observed in terms of OS, TRM and RR by comparing patients who achieved a complete response after treatment versus those who did not.. These retrospective data suggest that Megalotect is safe and well tolerated. When used as prophylaxis, no CMV reactivation was recorded. We have no conclusive data regarding its efficacy in reducing the cumulative dose of anti-CMV specific drugs in the pre-emptive setting. Further prospective trials are warrented to identify the best setting of patients who can benefit from Megalotect alone or in addition to anti-CMV specific drugs.

Background Central venous catheters (CVC) are essential for the management of patients with hematologic malignancies, facilitating chemotherapy infusion, antibiotics, parenteral nutrition, blood products, and blood samples collection. In this population, peripherally inserted central catheters (PICC) seem to be associated with lower complications, compared with conventional percutaneously inserted devices (CICC). Data on the PICC in allogeneic hematopoietic stem cell recipients (allo-HSCT) are limited. Methods We have prospectively evaluated the safety and efficacy of 100 polyurethanes or silicone PICC, inserted into 100 adult allo-HSCT recipients, at the Hematology of Sapienza University of Rome (Italy), between October 2012 and August 2017. ResultsThe median duration of PICC placement was 117 days. Overall, 68% of patients maintained the device for the entire transplant procedure and PICC were removed after day 100 from allo-HSCT; of these, 44% did not experienced any PICC-related complications. Catheter-related bloodstream infections (CRBSI) occurred in 32% of patients (2.5/1000 PICC days), associated with thrombosis in 8 cases. CRBSI were observed in 42% of patients with polyurethane and 20% with silicone PICC (p = 0.02). Catheter-related thrombosis occurred in 9% of patients, never requiring anticipated PICC removal. Mechanical complications occurred in 15% of cases (1.2/1000 PICC days). On the whole, adverse events were manageable and did not affect transplant outcome. No deaths related to PICC-complications were observed. Conclusions PICC are a safe and reliable long-term venous access in allo-HSCT recipients.

Iron overload is a pathological condition resulting from a congenital impairment of its regulation, increased intestinal iron absorption secondary to bone marrow erythroid hyperplasia, or a chronic transfusional regimen. In normal conditions, intracellular and systemic mechanisms contribute to maintaining iron balance. When this complex homeostatic mechanism fails, an iron overload could be present. Detecting an iron overload is not easy. The gold standard remains the liver biopsy, even if it is invasive and dangerous.Identifying iron using noninvasive techniques allowed a better understanding of the rate of iron overload in different organs, with a low risk for the patient. Estimating serum ferritin (mg/L) is the easiest and, consequently, the most employed diagnostic tool for assessing body iron stores, even if it could be a not specific method. The most common hematological causes of iron overload are myelodysplastic syndromes, sickle cell disease, and thalassemia. In all of these conditions, three drugs have been approved for the treatment of iron overload: deferiprone, deferoxamine, and deferasirox. These chelators have been demonstrated to help lower tissue iron levels and prevent iron overload complications, improving event-free survival (EFS). Nowadays, the decision to start chelation and which chelator to choose remains the joint decision of the clinician and patient.chelation therapy, iron metabolism, iron overload Novelty statementsConsidering the new diagnostic and therapeutic frontiers of iron chelation, we have conducted an accurate review of the literature to provide the clinician with indications for managing patients with iron accumulation. | INTRODUCTIONIron overload may result from a congenital impairment of regulation mechanisms, increased intestinal iron absorption (secondary to bone marrow erythroid hyperplasia), or a chronic transfusional regimen.A single unit of packed red cells, derived from 420 mL of whole blood, contains roughly 200 mg of iron. The transfusion regimens commonly employed, that is, in patients with thalassemia major or patients with myelodysplastic syndromes (MDS), deliver a total amount of 100-200 mL/kg of erythrocytes/year, leading to an annual iron burden of about 116-232 mg/kg. 1In hereditary iron overload, the primary treatment is represented by venesection. In contrast, iron-chelating therapy is the only Massimo Gentile and Ernesto Vigna contributed equally as senior authors.