due to the discovery of their role in intra-cellular communications, exosomes, which carry information specific to the cell of origin, have garnered considerable attention in cancer research. Moreover, there is evidence to suggest the possibility of isolating different exosome sub-populations based on target antigens at the cell surface. Philadelphia chromosome-positive (Ph +) chronic myeloid leukemia (cML) is a clonal myeloproliferative neoplasia characterized by the breakpoint cluster region-proto-oncogene 1 tyrosine-protein kinase (BcR-ABL1) fusion-gene, derived from the t (9;22) translocation. Tyrosine kinase inhibitors (TKIs) target BcR-ABL1 protein and induce major or deep molecular responses in the majority of patients. despite the fact that several studies have demonstrated the persistence of leukemic cells in the bone marrow niche, even following treatment, TKIs prolong patient survival time and facilitate treatment-free remission. These characteristics render cML a plausible model for investigating the feasibility of tumor-derived exosome fraction enrichment. In the present study, patients in the chronic phase (cP) of CML were treated with TKIs, and the quantification of the BCR-ABL1 exosomal transcript was performed using digital PcR (dPcR). The possibility of tumor-derived exosomes enrichment was confirmed, and for the first time, to the best of our knowledge, the detection of the BcR-ABL1 transcript highlighted the presence of active leukemic cells in patients with CP-CML. According to these findings, tumor-derived exosomes may be considered a novel tool for the identification of active leukemic cells, and for the assessment of innovative monitoring focused on the biological functions of exosomes in cML.

Changes in CEC count can represent a promising marker to monitor endothelial damage in patients undergoing allo-HSCT and could become a valuable tool in the diagnostic definition of GvHD.

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.

To evaluate if WT1 expression may predict relapse after allo-SCT, we analyzed WT1 levels on peripheral blood (PB) and bone marrow (BM) before and after allo-SCT in 24 AML patients with WT1 overexpression at diagnosis. Five copies of WT1/ABL × 104 from PB were identified as the threshold value that correlated with relapse after allo-SCT. The same correlation was not identified when WT1 expression was assessed from bone marrow (BM). Eight out of 11 (73%) patients with a pre-allo-SCT PB-WT1 ≥ 5 and 4/13 (31%) patients with a pre-allo-SCT PB-WT1 < 5 relapsed, respectively (P = 0.04). The incidence of relapse was higher in patients with PB-WT1 ≥ 5 measured after allo-SCT, at the 3rd (56% versus 38%; P = 0.43) and at the 6th month (71% versus 20%; P = 0.03). Patients with pretransplant PB-WT1 < 5 had significantly better 2-year OS and LFS than patients with a PB-WT1 ≥ 5 (81% versus 0% and 63% versus 20%) (P = 0.02). Our data suggest the usefulness of WT1 monitoring from PB to predict the relapse in allotransplanted AML patients and to modulate the intensity of conditioning and/or the posttransplant immunosuppression in an attempt to reduce the posttransplant relapse risk.