Allogeneic stem cell transplantation still represents the best curative option for most patients with acute myeloid leukemia, but relapse is still dramatically high. Due to their immunologic activity and safety profile, hypomethylating agents (HMAs) represent an interesting backbone for combination therapies. This review reports mechanism of action, safety, and efficacy data on combination strategies based on HMAs in the setting of post-allogeneic stem cell transplant relapse. Several studies highlighted how HMAs and donor lymphocyte infusion (DLI) combination may be advantageous. The combination strategy of HMA with venetoclax, possibly in association with DLI, is showing excellent results in terms of response rate, including molecular responses. Lenalidomide, despite its well-known high rates of severe graft-versus-host disease in post-transplant settings, is showing an acceptable safety profile in association with HMAs with a competitive response rate. Regarding FLT3 internal tandem duplication (ITD) mutant AML, tyrosine kinase inhibitors and particularly sorafenib have promising results as monotherapy and in combination with HMAs. Conversely, combination strategies with gemtuzumab ozogamicin or immune checkpoint inhibitors did not show competitive response rates and seem to be currently less attractive strategies. Associations with histone deacetylase inhibitors and isocitrate dehydrogenase 1 and 2 (IDH1/2) inhibitors represent new possible strategies that need to be better investigated.

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Aim: There is lack of evidence of the role of sacral root neuromodulation (SNM) in the management of chronic pelvic pain syndrome (CPPS). We evaluated the effectiveness of cycling sacral root neuromodulation (CSNM) in the management of CPPS in patients non responders to conservative treatment. Methods:A prospective, single center, cohort study was carried out on all patients with CPPS refractory to conventional treatment, who underwent test stimulation using the tined lead between February 2012 and March 2016. During test stimulation the tine lead was positioned along the third sacral nerve, on the side where they reported more pain. Success was defined as >50% improvement of pain and concurrent urinary symptoms. After a successful SNM test period of 4 weeks, patients received a permanent implant. We also included 9 more patients already with a permanent implant and partial responders to continuous mode in neuromodulator programming. To assess pain and quality of life, all patients filled-in a VAS scale and SF-36 and McGill questionnaires, at baseline, after the 4-week test period ad after the permanent implant.Results: Overall 22 consecutive adult patients were suitable to undergo a cycling test stimulation; 19 out of them (86.3%) underwent a permanent implant after a satisfactory test phase, using a codified cycling mode of programming. Eighteen naive patients out of nineteen (94.7%) maintained the benefits of the test stimulation at a mean follow up of 21.3 months. VAS scale, McGill and SF-36 questionnaires scores improved significantly in all domains with a 95% satisfaction rate; 7 out of the 9 already implanted patients (77.7%) significantly improved their pain control.Conclusion: CSRN appears to be effectiveness in treating CPPS in both naïve and previous implanted partial responder patients.

Objectives During the lockdown that started in Italy on 10 March 2020 to address the COVID-19 pandemic, aggressive procedures were implemented to prevent SARS-CoV-2 transmission in SARS-CoV-2-negative patients with haematological malignancies. These efforts progressively reduced Klebsiella pneumonia carbapenemase-producing K. pneumoniae (KPC-KP) spread among these patients. Here we evaluated the potential effects of measures against COVID-19 that reduced KPC-KP transmission. Patients and methods We analysed KPC-KP spread among 123 patients with haematological malignancies, hospitalized between March and August 2020, who were managed using measures against COVID-19. Their outcomes were compared with those of 80 patients hospitalized during the preceding 4 months (November 2019–February 2020). Results During March–August 2020, 15.5% of hospitalized patients were KPC-KP positive, compared with 52.5% in November 2019–February 2020 ( P < 0.0001); 8% and 27.5% of patients in these two groups were newly KPC-KP positive, respectively ( P = 0.0003). There were eight new KPC-KP-positive patients during January 2020 and none during June 2020. The weekly rate of hospitalized KPC-KP-positive patients decreased from 50% during March 2020 to 17% during August 2020. Four KPC-KP bloodstream infections (BSIs) were experienced by 123 patients (3%) in March–August 2020, and seven BSIs (one fatal) by 80 patients (8%) in November 2019–February 2020 ( P = 0.02). Consumption and expense of ceftazidime/avibactam administered to KPC-KP-positive patients significantly decreased in March–August 2020. Conclusions Aggressive strategies to prevent SARS-CoV-2 transmission were applied to all hospitalized patients, characterized by high levels of KPC-KP endemicity and nosocomial transmission. Such measures prevented SARS-CoV-2 infection acquisition and KPC-KP horizontal transmission. Reduced KPC-KP spread, fewer associated clinical complications and decreased ceftazidime/avibactam consumption represented unexpected ‘collateral benefits’ of strategies to prevent COVID-19.

The oncometabolite 2-hydroxyglutarate (2-HG) plays a key role in differentiation blockade and metabolic reprogramming of cancer cells. Approximatively 20–30% of acute myeloid leukemia (AML) cases carry mutations in the isocitrate dehydrogenase (IDH) enzymes, leading to a reduction in the Krebs cycle intermediate α-ketoglutarate (α-KG) to 2-HG. Relapse and chemoresistance of AML blasts following initial good response to standard therapy account for the very poor outcome of this pathology, which represents a great challenge for hematologists. The decrease of 2-HG levels through pharmacological inhibition of mutated IDH enzymes induces the differentiation of AML blasts and sensitizes leukemic cells to several anticancer drugs. In this review, we provide an overview of the main genetic mutations in AML, with a focus on IDH mutants and the role of 2-HG in AML pathogenesis. Moreover, we discuss the impact of high levels of 2-HG on the response of AML cells to antileukemic therapies and recent evidence for highly efficient combinations of mutant IDH inhibitors with other drugs for the management of relapsed/refractory (R/R) AML.

Background: Despite that the unfavorable prognostic role of a high Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma has been demonstrated, the role of SUVmax alone at baseline PET/CT could have a different prognostic role. Patients and Methods: We performed a retrospective observational monocentric cohort study. All patients affected by FL who underwent a basal PET/CT were included. Two subgroups were identified and compared in terms of PFS and OS: (A) Basal SUVmax ≤ 6; and (B) Basal SUVmax > 6. Results: Ninety-four patients were included, 34 in group A (36.2%) and 60 in group B (63.8%). The PFS at two years was comparable in the two groups (97%). The five-year PFS was 73.5% for group A and 95% for group B (p 0.005). The five-year PFS in the whole cohort was 87.5%. A clear advantage was confirmed in group A in the absence of other risk factors. Patients with SUVmax ≤ 6 and no risk factors showed a 5-year PFS of 73% against 83% for patients with SUVmax > 6 and at least two risk factors. Conclusion: A high FDG uptake favorably correlated with PFS. A low basal SUVmax reflected a higher rate of late relapse requiring a prolonged follow-up. The basal SUVmax is an approachable parameter with prognostic implications.

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