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5-Azacytidine is an effective therapy in high risk MDS and oligoblastic AML. This “real life” analysis was made on 185 patients treated with 5-azacytidine in 10 centers afferent to REL (“Rete Ematologica Lombarda”), a network in Lombardia region. The aim was to assess the influence of disease and comorbidity risk assessments on the survival. The results confirm the utility of 5-azacitidine in prolonging OS regardless of advanced age and the presence of comorbidities. They also encourage an early treatment since patients with IPSS-R High risk MDS have better outcome with respect to Very High risk ones. According to the IPSS cytogenetic risk, there was no difference in the outcome between Intermediate and High risk patients. Nevertheless, a poorer cytogenetic risk, according to the IPSS-R cytogenetic stratification, negatively influenced the outcome. [ABSTRACT FROM AUTHOR]

Objective The medullar blast count is a milestone in the prognostic assessment in myelodysplastic syndromes ( MDS). The optical microscopy ( OM) may sometimes be inaccurate in this disease. The aim of this work is to test the flow immunocytometric ( FCM) determinations of medullar immature cells ( CD45±) and the expression, among them, of CD33, CD34, and CD117 markers, for their prognostic relevance. Methods In a retrospective analysis of 98 patients affected by MDS, the IPSS was re-calculated by means of the FCM determination of blasts. Survival of patients at low or intermediate-1 IPSS risk was compared with the survival of patients at intermediate-2 or high IPSS risk. In the 64 cases with OM blast count lower than 5%, the survival of patients with the FCM count of medullar blasts ≤2% was compared with that of patients with FCM count >2%. Results Each single marker had a prognostic weight comparable to the optical blast count. The FCM blast count was particularly efficient in distinguishing the risk of having up to 2% or more than 2% of blasts in patients without OM excess of blasts. Conclusion This method is interesting as prognostic tool, especially in patients without excess of blast. [ABSTRACT FROM AUTHOR]

Abstract: To analyze the unpredicted event of hematological improvement (HI) during iron-chelation therapy (ICT), we reviewed a series of 53 myelodysplastic patients with transfusion dependency in a retrospective study involving 8 centers afferent to the “Rete Ematologica Lombarda”. According to the IWG response criteria published in the year 2000, we observed erythroid responses in 19 patients (35.1%), 5 major (9.2%) and 14 minor (25.9%). In the assessable patients, platelet response was 8/13 (61%) and neutrophil response was 13/17 (76.4%). Only in patients with erythroid improvement, multilineage responses were observed. Apparently, patients with greater erythropoiesis dysfunction may take more advantage. [Copyright &y& Elsevier]

Simple Summary: In older AML patients, their clinical fitness is of utmost importance for choosing the most appropriate therapy. Therefore, treatment-specific fitness criteria were devised in 2013 by SIE/SIES/GITMO to select patients deemed unfit for intensive chemotherapy (ICT) or even hypomethylating agents (HMAs). Since then, the therapeutic armamentarium for patients unfit for ICT has been enriched. In the present analysis of over 500 patients treated in REL centres, venetoclax/HMAs emerged as the most frequently used treatment. Considering its unique toxicity profile, an update of treatment-specific fitness criteria for selecting candidates for venetoclax/HMAs would be desirable. REL hematologists, who have gained experience with the combination over the last years, were asked if they actually restrict SIE/SIES/GITMO fitness criteria for HMAs when candidating patients to venetoclax/HMAs. A broad consensus emerged on limiting its choice to patients younger than 80–85, with a cardiac EF > 40%, without significant pulmonary comorbidities, and with an adequate caregiver. A retrospective survey was conducted in hematologic centres of the Rete Ematologica Lombarda (REL) on 529 older AML patients seen between 2020–2022. Compared to 2008–2016, the use of intensive chemotherapy (ICT) decreased from 40% to 18.1% and of hypomethylating agents (HMAs) from 19.5% to 13%, whereas the combination of Venetoclax/HMA, initially not available, increased from 0% to 36.7%. Objective treatment-specific fitness criteria proposed by SIE/SIES/GITMO in 2013 allow an appropriate choice between ICT and HMAs by balancing their efficacy and toxicity. Venetoclax/HMA, registered for patients unfit to ICT, has a unique toxicity profile because of prolonged granulocytopenia and increased infectious risk. Aiming at defining specific fitness criteria for the safe use of Venetoclax/HMA, a preliminary investigation was conducted among expert REL hematologists, asking for modifications of SIE/SIES/GITMO criteria they used to select candidates for Venetoclax/HMA. While opinions among experts varied, a general consensus emerged on restricting SIE/SIES/GITMO criteria for ICT-unfit patients to an age limit of 80–85, cardiac function > 40%, and absence of recurrent lung infections, bronchiectasis, or exacerbating COPD. Also, the presence of an adequate caregiver was considered mandatory. Such expert opinions may be clinically useful and may be considered when treatment-specific fitness criteria are updated to include Venetoclax/HMA. [ABSTRACT FROM AUTHOR]

Chronic Myeloid Leukemia is a clonal disorder characterized by the presence of the Ph‐chromosome and the BCR‐ABL tyrosine‐kinase (TK). Target‐therapy with Imatinib has greatly improved its outcome. Deeper and faster responses are reported with the second‐generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+/lin−Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in‐vivo activity and timecourse of first‐line Nilotinib therapy on BM CD34+/lin−Ph+ cells clearance. Eighty‐seven CP‐CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12 months of treatment. FISH analysis of unstimulated CD34+/lin− cells in CCyR patients were positive in 8/65 (12.3%), 5/71 (7%), 0/69 (0%) evaluable tests, respectively. Per‐Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36 months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin− cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12 months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK‐STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed. [ABSTRACT FROM AUTHOR]

The article focuses on a study which analyzes somatic mutations and haematological response to iron chelation in myelodysplastic syndromes (MDS). Topics being presented include the molecular mechanisms associated with haematological improvement during iron chelating treatment in MDS and the use of oral iron chelator deferasirox according to guidelines in patients with MDS or primary myelofibrosis.

Invasive fungal infections (IFIs) seem to be a relevant cause of morbidity and mortality in patients with chronic lymphoproliferative disorders. We studied retrospectively the epidemiology, clinical manifestations and outcome of invasive fungal infections in 42 patients with lymphoproliferative diseases, treated between January 2004 and February 2012 for probable or proven IFI. In our entire population (1355 patients) of chronic lymphoproliferative malignancies, the incidence of probable/proven IFI was 3% (molds 2.3%, yeasts 0.5%, mixed infections 0.2%). Eight patients developed a yeast infection documented by blood cultures in seven cases and by the microscopic observation of Candida spp. in the vitreum after vitrectomy in one case. Among molds we diagnosed three proven infections by histologic evidence of Aspergillus spp. ( n = 2) and Mucor ( n = 1) in the lung and 28 probable mycoses. Three mixed infections from both molds and yeasts were also observed. Twenty-two cases showed positivity of galactomannan antigen in the serum ( n = 16), in bronchoalveolar lavage (BAL) fluid ( n = 4) or in both ( n = 2). Cultures were positive in 11 cases. The overall rate of response to therapy was 64%. Fungal-attributable mortality rate was 17%, with a significant difference between molds and yeasts (16% vs. 25%, p = 0.03). At univariate analysis, the only risk factors related to mortality were severe and prolonged neutropenia ( p = 0.003) and age ( p = 0.03). Among molds, the rapid start of antifungals was probably partially responsible, together with new drugs, for the reduction of mortality, despite the severe immunosuppression of these patients. [ABSTRACT FROM AUTHOR]

Background In the absence of randomized, controlled trial data to support iron chelation therapy in transfusion-dependent patients with myelodysplastic syndromes ( MDS), continued evidence from large prospective clinical trials evaluating the efficacy and safety of iron chelation therapy in this patient population is warranted. Methods The safety and efficacy of deferasirox was examined in a prospective, open-label, single-arm, multicenter trial of transfusion-dependent patients with International Prognostic Scoring System low- or intermediate-1-risk MDS and evidence of transfusion-related iron overload. The effects of deferasirox therapy on hematological response and disease progression were also examined. Results Of 159 participants enrolled from 37 Italian centers, 152 received ≥1 dose of deferasirox (initiated at 10-20 mg/kg/day and titrated as appropriate), and 68 completed the study. Of 84 patients who discontinued deferasirox therapy, 22 died during the trial, and 28 withdrew due to an adverse event ( AE). Fourteen treatment-related grade 3 AEs occurred in 11 patients, whereas no grade 4 or 5 drug-related AEs were reported. Significant risks for dropout were a higher serum ferritin level at baseline, a higher MDS-Specific Comorbidity Index, and a shorter diagnosis-enrollment interval. Median serum ferritin level fell from 1966 ng/mL to 1475 ng/mL ( P < 0.0001). The cumulative incidence of transfusion independence, adjusted for death and disease progression, was 2.6%, 12.3%, and 15.5% after 6, 9, and 12 months, respectively. Conclusions Deferasirox therapy in transfusion-dependent patients with MDS was moderately well tolerated and effectively lowered serum ferritin levels. Positive hematological responses were observed, and a subset of patients achieved transfusion independence. [ABSTRACT FROM AUTHOR]

Abstract: We studied circulating (C)CD34+ cells by flow cytometry in 96 patients with myelodisplastic syndromes (MDS) at diagnosis, and in a subset of 35 cases during follow-up. CCD34+ counts were stratified within both International Prognostic Scoring System (IPSS) and World Health Organization (WHO) categories. Counts >10/μl were associated with poorer leukemia-free survival, a prognostic value for evolution independent from that of WHO, and a higher progression probability within intermediate-risk IPSS and WHO classes. When serial measurements were performed, counts >10/μl more frequently correlated to evolution. Separating newly diagnosed patients on the basis of 10/μl cut-off of circulating CD34+ cells retains prognostic utility, especially in intermediate-risk MDS. [Copyright &y& Elsevier]

Jak inhibitors are potent anti-inflammatory drugs that have the potential to dampen the hyperactive inflammatory response associated with severe COVID-19. We reviewed the clinical outcomes of 218 patients with COVID-19 hospitalized for severe pneumonia and treated with ruxolitinib through a compassionate use program. Data on the duration of treatment; outcomes at 4, 7, 14, and 28 days; oxygen support requirements; clinical status; and laboratory parameters were retrospectively collected. Overall, according to the physician evaluation, 66.5% of patients showed improvement at follow-up; of these, 83.5% showed improvement by day 7. Oxygen support status also showed improvement, and by day 7, 21.6% of patients were on ambient air, compared with 1.4% at baseline, which increased to 48.2% by day 28. Significant decreases in C-reactive protein and increases in the lymphocyte total count were already observed by day 4, which seemed to correlate with a positive outcome. At the end of the observation period, 87.2% of patients were alive. No unexpected safety findings were observed, and grade 3/4 adverse events were reported in 6.9% of patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of a 27-year-old woman with an history of confusion, vomiting, and headaches in which the patient was diagnosed with cerebral hemorrhage using cerebral computed tomography (CT) scan.