Francesco Mendicino

Older and unfit patients with Acute Myeloid Leukemia (AML), which are uneligible for standard induction therapy, have limited treatment options. The therapeutic approach in these cases is based on the use of hypomethylating agents, either decitabine or azacitidine, or Low-Dose Cytarabine (LDAC). However, despite the extensive use of these agents, there is no consensus regarding the extent of their efficacy, and clinical benefit deriving from their use is very modest. We present a case of FLT3- and TP53-mutated AML in an unfit patient with congenital agammaglobulinemia, responsive to single agent decitabine, with a response duration of over 20 months.

CLL is frequently complicated by autoimmune phenomena (up to 25% of patients) which are sustained by dysfunctions of the immune system. AIHA results the commonest form. In the past decade small molecules had dramatically change the therapeutic scenario of CLL. Their role in the setting of autoimmune phenomena has to be still elucidated. Here we report the case of a CLL patient harboring del (17p) in relapse of disease during ibrutinib therapy who experienced AIHA. Patient, refractory to steroids, achieved benefit from the administration of rituximab and venetoclax. The patient reached stable and long-lasting stabilization of hemoglobin values.

Splenomegaly, which may range from a few centimeters below the left costal border to massive dimensions, is one of the most characteristic features in patients with advanced myelofibrosis (MF). Splenectomy may offer an effective therapeutic option for treating massive splenomegaly in patients with MF, and especially in cases of disease refractory to conventional drugs, but it is associated with a number of complications as well as substantial morbidity and mortality. Whether splenectomy should be performed before allogeneic hematopoietic stem-cell transplantation is also controversial, and there is a lack of prospective randomized clinical trials that assess the role of splenectomy before hematopoietic stem-cell transplantation in patients with MF. Although splenectomy is not routinely performed before transplantation, it may be appropriate in patients with massive splenomegaly and related symptoms, so long as the higher risk of graft failure in such cases is taken into account. This review aims to describe the efficacy, indications, and complications of splenectomy in patients with MF; and to evaluate the long-term impact of splenectomy on patient survival and risk of disease transformation.

Background. The International prognostic index (IPI), since its publication in 1993, became the primary prognostic tool for patients with DIFFUSE LARGE B-CELL LTMPHOMA (DLBCL). However, the introduction of rituximab (R) has improved patients outcomes and has partially changed the predictive capacity of IPI. In 2007, in the R era, a most accurate prognostic index, termed revised IPI (R-IPI) was proposed by Sehn et al. More recently, Cox et al. showed that absolute lymphocyte count (ALC), at diagnosis has a prognostic impact and it is independent from R-IPI. Thus, they have built-up a score, termed ALC/R-IPI, incorporating both parameters (low risk=ALC 650.84 109/L and R-IPI very good or good, intermediate risk= ALCUNL, 16% a PS>1, 26% had extranodal sites>1 and 26% presented with ALC<0.84 109/L. The distribution of patients in R-IPI was 7%, 48% and 45% in very good (VG), good (G) and poor (P) groups, respectively. The distribution in ALC/R-IPI was 47%, 42% and 11% in low (L), intermediate (I) and high (H) risk groups, respectively. The OS at 3-years was 88%, 64% and 39% in L, I and H risk groups, with significative differences (p<0.001). The HR were: I vs L = 3.7 (p<0.001); H vs I = 2.1 (p=0.012), while the c-Harrell was = 0.71 (CI95% 0.65-0.76). Conclusions. The ALC/R-IPI showed a good ability to discriminate the prognosis of patients in term of OS in our data base. ALC was confirmed as a specific prognostic factor for DLBCL in R er

The advent of high‐dose melphalan with autologous stem‐cell transplantation (ASCT), the availability of novel agents such as thalidomide, lenalidomide (immunomodulatory drugs or IMiDs) and bortezomib (proteasome inhibitor) and improvements in supportive care have allowed to increase overall survival in multiple myeloma (MM) patients; nevertheless, MM remains an incurable pathology. For this reason, newer agents are required for continued disease control. Bendamustine is an old drug rediscovered in the last decade. In fact, its unique mechanism of action with structural similarities to both alkylating agents and antimetabolities, but which is not cross‐resistant to alkylating agents, has reawakened interest in the use of this drug in the treatment of MM. Studies have proven the safety and efficacy of bendamustine administered alone or in combination with new drugs in both upfront and relapse/refractory settings of MM patients, including those with renal impairment. Moreover, bendamustine has been successfully used as conditioning for autologous stem‐cell transplantation. Finally, the use of bendamustine does not compromise peripheral blood stem‐cell collection. This drug is generally well tolerated, with the majority of adverse events being due to myelosuppression. Non‐haematological adverse events are infrequent and usually mild.

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.

Introduction: Hydroxyurea (HU) is the most used cytoreductive therapy (tx) for patients (pts) with polycythemia vera (PV). However, many pts may have suboptimal responses (SubOR) and/or toxicity (TOX) to HU. After HU, Ruxolitinib (RUX) may achieve hematocrit (HCT) and spleen reductions, but other tx are also available, mainly busulfan (BUS) and interferons (IFN). Aims: In a large cohort of PV pts, we investigated if: 1) type of SubOR to HU influenced subsequent tx strategy; 2) differential tx had an impact on overall survival (OS). Methods: After IRB approval, clinical/laboratory data of 2016 WHO-defined PV pts from 21 European Hematology Centers were retrospectively collected. SubOR included ≥1 of the following criteria after ≥3 mos of HU: WBC/PLT count >10/400 x109/l, need for phlebotomies (PHL); splenomegaly and/or symptoms persistence/occurrence (Barosi G et al, Blood 2009). Only pts with stable SubOR were included in this analysis. Since a complete response was never achieved, the index date (ID) was set at 3 mos from HU start in all pts (Barosi G et al, BJH 2009). OS was calculated from the ID by Cox analysis with age>80, adjusted with left truncation from PV diagnosis. Results: At data cut-off date (June 2020), 808 PV pts were collected; 688 received HU. Among the 452 (65.7%) pts who presented a stable SubOR to HU, 41 did not receive any tx for PV due to early death or progression to BP/MF and were excluded from this analysis. Baseline characteristics of the 411 evaluable pts were: median age: 65 yrs (21- 87); males: 54%; median (range) WBC/PLT count, x109/l: 10 (1.1-38)/465 (139-1209); median Hb (g/dl)/HCT (%): 18.6/56 (males); 17.6/54 (females); palpable splenomegaly: 38%; symptoms: 80.5%; pruritus: 42%. A previous thrombosis occurred in 104 (25.3%) pts. At least one cardiovascular risk factor (CVRF: smoke, diabetes, hypertension, dyslipidemia and overweight) was present in 325 pts (79.1%). After a median follow-up of 4.8 yrs (0.5-27.6) from HU start, 104 (25.3%) switched to RUX (HU-RUX), 18 (4.4%) switched to another agent (HU-other, including IFN, BUS, PHL only), and 289 (70.3%) continued HU (HU-alone). Pts with baseline palpable spleen (p<0.001) and pruritus (p=0.01) more frequently switched to RUX. Conversely, pts ≥80y more frequently received HU-alone/other (p=0.03). Notably, Charlson Comorbidity Index and CVRF had no impact on tx strategy. Median HU daily dose was 0.65 g (≥2 g/d: 8.7% of pts) and was higher in HU-RUX pts (1 vs 0.6 g/d in HU-alone/other pts, p=0.004). While 331 (80.5%) pts had a stable SubOR without TOX, 80 (19.5%) had also TOX. Notably, pts with only SubOR more frequently continued HU (p<0.001). Conversely, the co-occurrence of TOX was significantly associated to RUX switch (p<0.001) (Fig. 1a). In 45.5% of pts, the SubOR was related only to uncontrolled WBC/PLT/HCT, while 16.1% of pts had an optimal hematological control but presented spleen/symptoms; the remaining 38.4% of pts had both uncontrolled myeloproliferation and spleen/symptoms. The presence of both uncontrolled myeloproliferation and spleen/symptoms significantly predicted RUX switch (p<0.001). Investigating the SubOR criteria individually among the HU-alone/other and the HU-RUX groups, we found that uncontrolled leukocytosis and/or thrombocytosis (p<0.001), rather than PHL need (p=0.13), was significantly associated with RUX switch. Moreover, the persistence/occurrence of symptoms (p=0.001) or splenomegaly (p=0.005) were significantly associated with RUX use (Fig. 1b). After the ID, 31 pts died. HU-RUX pts presented increased OS compared to HU-alone/other pts (p=0.03). Conclusions. This study revealed a high rate of SubOR to HU, possibly also affected by low HU doses, and a lack of urgency to change the tx in these pts, with >70% of pts continuing HU despite the stable SubOR. Particularly, good tolerance to HU, absence of splenomegaly and pruritus, and older age were the main factors against a tx change. Notably, despite HCT>45% is associated with worse outcome (Marchioli R, NEJM 2013), PHL need did not significantly trigger tx change. The better OS in the HU-RUX group is presumably multifactorial and requires further confirmation. Overall, this analysis points out the need to improve HU management and response evaluations, weighing appropriate tx strategies in case of SubOR. Disclosures Palandri: Novartis: Consultancy, Honoraria. Benevolo:Amgen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Breccia:Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Abbvie: Consultancy; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Cavazzini:Pfize: Honoraria; Novartis: Honoraria; Incyte: Honoraria. Heidel:Celgene: Consultancy; CTI: Consultancy; Novartis: Consultancy, Research Funding. Crugnola:BMS: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Pane:Daiichi Sankyo: Consultancy, Other: Travel Expenses; Janssen: Other:…

Myelodysplastic syndromes (MDS) are acquired bone marrow malignant disorders characterized by ineffective hematopoiesis, resulting from a complex interaction between genetic and epigenetic mutations, alterations of the marrow microenvironment, and the immune system. In 2001, the World Health Organization (WHO) proposed a classification that integrates morphologic and genetic information, considering the MDS with ring sideroblasts (MDS‐RS) as a distinct entity. Considering the strong association between MDS‐RS and SF3B1 mutation and its importance in the development of MDS, the last WHO classification replaced the prior entity of MDS‐RS with MDS with SF3B1 mutation. Several studies were performed to explore this genotype‐phenotype correlation. Mutant SF3B1 protein deregulates the expression of genes implicated in developing hematopoietic stem and progenitor cells. Of paramount importance are PPOX and ABCB7 involved in iron metabolism. Another essential role in hemopoiesis is played by the transforming growth factor‐beta (TGF‐β) receptor. This gene exerts its effects on SMAD pathways, regulating hematopoiesis through effects on balancing proliferation and apoptosis cell inactivity, differentiation, and migration. Luspatercept (ACE‐536) is a soluble fusion protein that inhibits molecules in the TGF‐β superfamily. Since its structure resembles the TGF‐β family receptor, it catches TGF‐β superfamily ligands before binding to the receptor, resulting in reduced activation of SMAD signaling, thus enabling erythroid maturation. Luspatercept was investigated in the phase III trial MEDALIST, showing promising efficacy in treating anemia compared to placebo. Nowadays, further studies are needed to explore the real potential of luspatercept, investigating the biological features likely associated with treatment response, the potential use in combination treatments, and its role in the treatment of naïve MDS.

Multiple myeloma (MM) represents the second-most common hematologic malignancy. In the 1980s, induction therapy with alkylating agents, such as anthracyclines and steroids, as well as high-dose chemotherapy followed by autologous stem cell transplantation were the main therapeutic approaches for MM. Since the introduction of more effective drugs, such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies and histone deacetylase inhibitor, the new therapeutic algorithm allows of achieving a significantly improvement of prognosis. Numerous regimens, which differently combine these new agents, have been developed and tested in clinical trials. The results of these new regimens are reported each year. In this variegated new contest, old chemotherapeutic drugs still maintain an overriding weight, especially when beneficially combined with new drugs. Also, this is particular true in specific situations, such as extramedullary manifestations, in which tumor mass reduction becomes an urgent clinical need,, or in case of chemotherapy-induced stem-cell mobilization. Moreover, melphalan represents the gold standard conditioning regimen since 2002, either alone or, possibly in the next future, in combination with busulfan. Finally, new chemotherapeutic agents with new mechanisms of action, such as melflufen, are in early experimental phase.

2622 Poster Board II-598 Introduction: Genetic alterations reported in myelodysplastic syndromes (MDS) are not disease-specific and the underlying molecular causes of the disease remain poorly understood. It has been suggested that one or more of the genes mapping within the commonly deleted region of the 5q syndrome, together with other distant genes, may be critical to the development of the 5q syndrome. Potential candidate genes have been identified including the tumor suppressor gene SPARC, and the ribosomial protein gene, RPS14. Haploinsufficiency of RPS14 has been demonstrated and recent evidence indicates RPS14 as a causal gene for the 5q syndrome. Lenalidomide has proven efficacy in MDS patients with del(5q). Rapid and durable responses include transfusion-independence, with a rise in Hb, suppression of the 5q-deletion clone and improvement in bone marrow morphologic features. Methods: In a multicenter Italian phase II trial to evaluate safety, changes in quality of life and...

The JAK1 and JAK2 inhibitor ruxolitinib has approved indications in myelofibrosis, a BCR-AB1-negative myeloproliferative neoplasm associated with progressive bone marrow fibrosis and shortened survival. In Phase III clinical studies, ruxolitinib provided rapid and durable improvement of myelofibrosis-related splenomegaly and symptoms irrespective of mutation status, and was associated with a survival advantage compared with placebo or best available therapy. Because of dose-dependent cytopenias, blood count monitoring and dose titration are important to optimize therapy. Specific precautions apply to the treatment of patients with or at risk of serious infections. Discontinuation of ruxolitinib generally leads to symptom return within 1 week. Ruxolitinib also is approved for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

The paper discusses the role that sociology and digital social research methods could play in developing E-health and Telemedicine, specifically after the COVID-19 pandemic, and the possibility of dealing with new pandemics. In this article, we will reflect on an interdisciplinary research pilot project carried out by a team of sociologists, medical doctors, and software engineers at The University of Calabria (Italy), to give a proof of concept of the importance to develop Telemedicine through the contribution of digital social research. We apply a web and app survey to administrate a structured questionnaire to a self-selected sample of the University Community. Digital social research has highlighted socioeconomic and cultural gaps that affect the perception of Telemedicine in the University Community. In particular, gender, age, educational, and professional levels influence medical choices and behaviors during Covid-19. There is often an unconscious involvement in Telemedicine ...