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Elderly patients represent the most challenging and hard-to-treat patient population due to dismal characteristics of the disease, such as secondary-acute myeloid leukemia (AML), enrichment of unfavorable molecular genes (TP53) and comorbidities. We conducted a multicentric retrospective study to evaluate activity and safety in a real-life setting of hypomethylating drugs (HMAs) in patients older than 75 years with AML. Between September 2010 and December 2021, 220 patients were treated, 164 (74.5%) received AZAcitidine and 56 DECitabine; most patients (57.8%), received more than four cycles of HMAs. The best response obtained was CR in 51 patients (23.2%), PR in 23 (10.5%) and SD in 45 (20.5%); overall transfusion independence was obtained in 47 patients (34%), after a median of 3.5 months. The median OS (mOs) was 8 months (95% CI 5.9–10.2), with 1- and 2-years OS of 39.4% (95% CI 32.7–46) and 17.4% (95% CI 11.7–23.1), respectively; similar mOS was observed according to HMA treatment (AZA 8.3 vs. DEC 7.8 months, p = 0.810). A subset of 57 long survivors (44 in AZA group and 13 in DEC group) received at least 12 cycles of HMAs, their mOS was 24.3 months. In multivariate analysis, age (≥80), Charlson comorbidity index (≥3), creatinine clearance and the type of best response (≥PR) during treatment maintained independent significance in predicting survival. Infectious complications, most frequently pneumonia (35) and septic shock (12), were lethal in 49 patients (22.2%). Our data show that HMAs have similar efficacy compared to pivotal trials and are well tolerated in a setting of very elderly patients with several co-comorbidities.

Aims: To define the peculiar features of patients with the deletion of the chromosome 20 long arm (del20q), data from 69 patients with myelodysplastic syndromes (MDSs) and isolated del20q, followed by the Gruppo Romano-Laziale Sindromi Mielodisplastiche (GROM-L) and Ospedale Torrette of Ancona, were collected and compared with those of 502 MDS patients with normal karyotype (NK-MDS). Results: Compared to the NK-MDS group, patients with del20q at diagnosis were older (p = 0.020) and mainly male (p = 0.006). They also had a higher rate of bone marrow blast < 5% (p = 0.004), a higher proportion of low and int-1 risk according to IPSS score (p = 0.023), and lower median platelet (PLT) count (p < 0.001). To date, in the del20q cohort, 21 patients (30.4%) received no treatment, 42 (61.0%) were treated with erythropoiesis-stimulating agents (ESA), 3 (4.3%) with hypomethylating agents, and 3 (4.3%) with other treatments. Among 34 patients evaluable for response to ESA, 21 (61.7%) achieved stable erythroid response according to IWG 2006 criteria and 13 (38.2%) were resistant. Nine patients (13.0%) progressed to acute myeloid leukaemia (AML) after a median time from diagnosis of 28 months (IR 4.1–51.7). The median overall survival (OS) of the entire cohort was 60.6 months (95% CI 54.7–66.4). the 5-year cumulative OS was 55.9% (95% CI 40.6–71.2). Conclusion: According to our results, we hypothesize that MDSs with isolated del 20q may represent a distinct biological entity, with peculiar clinical and prognostic features. The physio-pathological mechanisms underlying the deletion of the chromosome 20 long arm are still unclear and warrant future molecular analysis.

Background: Candidaemia is an important infectious complication for haematological malignancy patients. Antifungal prophylaxis reduces the incidence of candidaemia but may be associated with breakthrough candidaemia. Objective: To analyse the Candida species’ distribution and relative antifungal susceptibility profiles of candidaemia episodes in relation to the use of antifungal prophylaxis among Italian SEIFEM haematology centres. Methodology: This multicentre retrospective observational SEIFEM study included 133 single-species candidaemia episodes of haematological malignancy patients for whom antifungal susceptibility testing results of blood Candida isolates were available between 2011 and 2015. Each participating centre provided both clinical and microbiological data. Results: Non-Candida albicans Candida (NCAC) species were the mostly isolated species (89, 66.9%), which accounted for C parapsilosis (35, 26.3%), C glabrata (16, 12.0%), C krusei (14, 10.5%), C tropicalis (13, 9.8%) and uncommon species (11, 8.3%). C albicans caused the remaining 44 (33.1%) episodes. Excluding 2 C albicans isolates, 23 of 25 fluconazole-resistant isolates were NCAC species (14 C krusei, 6 C glabrata, 2 C parapsilosis and 1 C tropicalis). Fifty-six (42.1%) of 133 patients developed breakthrough candidaemia. Systemic antifungal prophylaxis consisted of azoles, especially fluconazole and posaconazole, in 50 (89.3%) of 56 patients in whom a breakthrough candidaemia occurred. Interestingly, all these patients tended to develop a C krusei infection (10/56, P =.02) or a fluconazole-resistant isolate’s infection (14/50, P =.04) compared to patients (4/77 and 10/77, respectively) who did not have a breakthrough candidaemia. Conclusions: Optimisation of prophylactic strategies is necessary to limit the occurrence of breakthrough candidaemia and, importantly, the emergence of fluconazole-resistant NCAC isolates’ infections in haematological malignancy patients.

Background: In ‘real-life', the Nordic score guides ESA use in lower-risk MDS with predicted response rates of 25% or 74%. As new treatments emerge, a more discriminating score is needed. Objectives: To validate existing ESA predictive scores and develop a new score that identifies non-responders. Methods: ESA-treated patients were identified in 3 MDS registries in Italy and Canada (FISM 555, GROM 233, MDS-CAN 208). Clinical and disease-related variables were captured. Nordic, MDS-CAN and IPSS-R-based ESA scores were calculated and documented ESA responses compared. Results: 996 ESA-treated patients were identified. Overall response rate(ORR) was 59%. The database was randomly divided into balanced derivation (n=463) and validation (n=462) cohorts. By multivariate analysis, transfusion independence, erythropoietin level

Nausea and vomiting induced by chemotherapy (CINV) occur in 70-80% of onco-haematological patients undergoing antiblastic therapy. The anti-emetic therapy chosen according to the guidelines and characteristics of the single patient solve CINV in about 80% of cases. The concept of supportive care, which includes the treatment of CINV, has been formalized by the Multinational Association Supportive Care in Cancer (MASCC) to prevent and manage the side effects of antiblastic therapy. The evaluation of co-morbidities makes it possible to choose the most suitable antiemetic drug in compliance with multi-drug non-oncology therapies. The most immediate benefits are an improvement in the quality of life (QoL), a greater adherence of the patient to cancer therapy, and a lower interaction between drugs.

The Gruppo Romano Mielodisplasie (GROM) conducted a retrospective study in 543 patients with myelodysplastic syndromes (MDS) to evaluate the safety and efficacy of erythropoiesis-stimulating agents (ESAs) in "real-life" clinical practice. The 40.000-UI/week erythropoietin (EPO)-alpha and 30.000-UI/week EPO-beta starting dose were defined "standard," and 80,000 UI/week EPO-alpha and 60.000 UI/week EPO-beta were defined "high." Response was defined according to International Working Group (IWG) 2006 criteria. At ESA's start, median age was 74.2 years (interquartile range (IR) 67.8-79.5) and median hemoglobin was 8.9 g/dl (IR 8.2-9.6). Median time from diagnosis to ESAs start was 3.8 months (IR 0.8-13.2). ESA starting dose was "standard" in 361 patients (66.5 %) and "high" in 182 patients (33.5 %). Erythroid response was observed in 82/185 (44.3 %) transfusion dependent (TD) patients as compared with 226/329 (68.6 %) transfusion independent (TI) ones (p

Objective Azacitidine is the standard of care for higher-risk myelodysplastic syndromes (MDS). We evaluated factors affecting the outcome of azacitidine treatment in 196 ‘real-world’ patients, retrospectively collected by two Italian cooperative groups. Methods The study included 184 MDS and 12 low blast count acute myeloid leukemia (AML). Azacitidine was administered at the standard dose of 75 mg/m2/d for 7 d (SD) in 163 patients and 100 mg/d for 5–7 d in 33 patients. Results After a median of 4.5 azacitidine cycles (range 7–15 cycles), 182 patients were evaluable for response. Nineteen percent achieved complete remission (CR), 17% partial remission (PR), and 21% hematological improvement (HI). The disease was stable or progressive in 29% and 14% of patients, respectively. The probability of response was significantly higher in patients who received the 75 mg/m2/7 d compared with 100 mg through 5–7 d dose (CR/PR/HI: 63 vs. 29%, P = 0.0005). Median overall survival was 17.1 months. Low MDS-CI and achievement of CR/PR/HI were significant predictors of survival in the multivariable analysis. Conclusions Our data show that maximal azacitidine efficacy is associated with the standard dose and with prolonged treatment, beyond 4–6 cycles, with the goal of also improving the ‘quality’ of response. Lower MDS-CI and IPSS-R scores, hematologic response and disease stability, are associated with longer survival. The risk of febrile events is highest during the first treatment cycles and is associated with active disease.

Deferasirox (DFX) is an orally administered iron chelator approved for use in patients with transfusion-dependent iron overload due to myelodysplastic syndromes (MDS). The safety and efficacy of DFX has been explored in clinical trial settings, but there is little data on unselected patients with MDS. The aim of this study was to retrospectively evaluate the safety, compliance, efficacy and effect on haematopoiesis of DFX in a large 'real-world' MDS population. One hundred and eighteen patients with transfusion-dependent MDS were treated with DFX across 11 centres in Italy. Serum ferritin levels, haematological response, dosing, adverse events and transfusion dependence were recorded at baseline, 3, 6, 12 and 24 months following initiation of treatment. DFX reduced mean serum ferritin levels from 1790 to 1140 ng/mL (P < 0.001), with 7.1% of patients achieving transfusion independence. Significant haematological improvement was seen in erythroid (17.6%), platelet (5.9%) and neutrophil counts (7.1%). Adverse events were reported in 47.5% of patients, including gastrointestinal and renal toxicity. Regression analysis showed that higher starting doses of DFX are associated with transfusion independence at 24 months. DFX is a safe, effective treatment for transfusion-dependent MDS that can lead to transfusion independence and haematological improvement in a subset of patients.

Purpose The definition of disease-specific prognostic scores plays a fundamental role in the treatment decision-making process in myelodysplastic syndrome (MDS), a group of myeloid disorders characterized by a heterogeneous clinical behavior. Patients and Methods We applied the recently published Revised International Prognostic Scoring System (IPSS-R) to 380 patients with MDS, registered in an Italian regional database, recruiting patients from the city of Rome (Gruppo Romano Mielodisplasie). Patients were selected based on the availability of IPSS-R prognostic factors, including complete peripheral-blood and bone marrow counts, informative cytogenetics, and follow-up data. Results We validated the IPSS-R score as a significant predictor of overall survival (OS) and leukemia-free survival (LFS) in MDS (P < .001 for both). When comparing the prognostic value of the International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and IPSS-R, using the Cox regression model and the likelihood ratio test, a significantly higher predictive power for LFS and OS became evident for the IPSS-R, compared with the IPSS and WPSS (P < .001 for both). The multivariate analysis, including IPSS, WPSS, age, lactate dehydrogenase, ferritin concentration, Eastern Cooperative Oncology Group performance status, transfusion dependency, and type of therapy, confirmed the significant prognostic value of IPSS-R subgroups for LFS and OS. Treatment with lenalidomide and erythropoiesis-stimulating agents was shown to be an independent predictor of survival in the multivariate analysis. Conclusion Our data confirm that the IPSS-R is an excellent prognostic tool in MDS in the era of disease-modifying treatments. The early recognition of patients at high risk of progression to aggressive disease may optimize treatment timing in MDS.

Azacitidine (AZA) is the standard of care for higher-risk myelodysplastic syndromes (MDS). Cytopenias are a major problem during the first treatment cycles due to MDS itself and to the mechanism of action of the drug, which includes not only demethylation, but also cytotoxicity and apoptosis. We evaluated the incidence of infectious complication during AZA treatment in 200 “real life” patients, collected retrospectively by the italian cooperative groups Gruppo Romano MDS (GROM) and Basilicata MDS Registry. Patients gave informed consent and the study was approved by the Ethycal Committes of partecipating Centers. Patient started AZA between 3/2006 and 3/2014. Median age at treatment start was 71 years (range 33-93 yrs, 66 females, 134 males). There were 182 MDS (up to 20% BM-Blasts) and 18 AML (median BM-blasts 23%, range 21-60% BM-blasts). In MDS, IPSS stratification (n=178) was: low: 4%, Int-1: 19%, Int-2: 60%, high 17%, and according to R-IPSS (n=123 pts): low: 4%, intermediate: 20%, high: 51%, very-high: 20%. MDS-specific comorbidity index (MDS-CI) was available for 154 patients: 50 patients were classified as low-risk (0), 85 as intermediate (1-2), and 19 as high risk (>2). Azacitidine was started at a median of 1.4 months from initial diagnosis. One-hundred-sixty-six patients received AZA at the standard dose of 75 mg/sqm (7 days continuously: 22%, 5-2-2 days: 64%, 6-1-1: 4%) while 34 patients received AZA at 50 mg/sqm for 5- 7 days. Response, according to IWG 2006 criteria, was evaluable in 188 patients: 27 obtained complete remission (CR, 14%), marrow CR was achieved in 6 (3%), partial remission (PR) in 30 (16%), hematological improvement (HI) in 40 (21%), disease was reported stable (SD) in 54 (29%), whereas 31 patients presented progressive disease (16%). A median of 10 (range 1-62) cycles of AZA were delivered. Probability of response was independent from age, IPSS, IPSS-R, MDS-CI, and was associated to a shorter time from diagnosis to therapy initiation (p=0.04) and to the 75 mg/sqm through 7 days vs 50 mg/sqm through 5 -7 days schedule (60 vs 30% CR/PR/HI, p=0.007). With a median follow-up of 14.8 months (range 0-100 months), 57 patients are alive, resulting into a median overall survival of 17.2 months. IPSS and MDS-CI did not predict survival, while grouping according to IPSS-R was associated to a significantly different survival probability (p=0.0007). Across delivery of a total of 1547 AZA cycles, 213 (13%) febrile events were recorded. Fever of unknown origin was diagnosed in 20 patients (10%). Of 193 clinically documented events, a positive microbiologic test was available in 49 cases (25%, 44 for bacteria, 5 for viruses). A single episode of infection was recorded in 124 patients (62%) at a median of 3.8 months from therapy initiation (0-53 months), 53 (26.5%) patients suffered from a second infectious event and 28 (14%) patients from a third one (at 5.6 and 8.3 months from AZA start, respectively). Infections were the attributable cause of death in 30 patients (15%, 3 in CR, 17 with progressive disease and 10 SD). Most frequent infection sites were lungs (45%), cutis (9%), mouth (9%), bowel or peri-anal region (7%). The risk of infectious complications was lower in IPSS low-risk (p=0.05) or IPSS-R low/int MDS (p=0.01), and in patients with MDS-CI 0-2 (p=0.0001). Our data indicate that treatment with AZA is associated with a relatively high probability to develop infectious complications, especially pneumonia, which is however rarely the cause of death. The risk to develop infections is the highest during the first courses of AZA delivery and correlates to baseline patients’ characteristics, including disease stage and comorbidities. Once the infectious episode has occurred, the outcome depends on the disease status. Disclosures Voso: Celgene: Consultancy. Venditti:celgene: Consultancy. Breccia:novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy.

Abstract 4958 Erythropoietin (EPO) have been widely employed in the treatment of patients with low-risk Myelodysplastic Syndromes (MDS) and anemia, with response rates ranging from 30 to 60%. These data, however, have been derived only from controlled clinical trials or unicentric single-arm studies; it is still lacking a wider survey evaluating the use of EPO in the real-life clinical practice. To address this issue, the Gruppo Romano Mielodisplasie (GROM) revised retrospectively 394 MDS patients (M/F 225/169, median age at diagnosis 73. 9 yrs, IR 67. 0 – 79. 3) treated with EPO from 1/2002 to 12/2010 by 11 Hematological Centers (5 university hospitals and 6 community-based hospitals) in the metropolitan area of Rome. According to WHO classification, there were 81 (20. 6%) patients with RA, 7 (1. 8 %) with SA, 160 (40. 7%) with RCMD, 17 (4. 3%) with RCMD-S, 75(19. 0%) with RAEB-1, 27 (6. 8%) with RAEB-2 and 27 (6. 8%) with isolated del5q. The IPSS score was calculated in the 307 patients with an available karyotype: 145 (47. 2%) patients were low-risk, 135 (44. 0%) int-1, 24 (7. 8%) int-2 and 3 (1. 0%) high-risk. Median interval from diagnosis to EPO start was 3. 7 months (IR 0. 9 – 12. 1). At EPO start, median age was 74. 5 yrs (IR 68. 3 – 79. 9) with a median haemoglobin level of 8. 9 g/dl (IR 8. 2 – 9. 6). Creatinine level was elevated in 64 (16. 2%) cases: 138 patients (35. 3%) had a previous transfusion requirement. Median serum EPO level was 50. 0 mU/L (IR 26. 2 – 110. 0). The initial doses of EPO were ≤ 40. 000 UI/week in 259 patients (65. 7%) (standard doses, α-EPO in 104 patients, β-EPO in 143 patients, darbepoietin in 12 patients) and 80000 UI/week in 135 patients (34. 3%) (high doses, α-EPO in 130 patients, β-EPO in 5 patients). An erythroid response was observed in 228 (57. 9%) patients, with Hb increase > 1. 5 g/dl in 210 patients (53. 3%) and disappearance of transfusion requirement in 18 (4. 6%): patients receiving initial high doses had a higher response rate compared to patients receiving standard doses [94/135 (69. 6%) vs 134/259 (51. 7%), p=0. 002]. Only 5 thrombotic events (1. 2%) were reported during the treatment. Predicting factors for erythroid response were no previous transfusion requirement (p 8 g/dl (p=0. 017). Median overall survival from EPO start was 70. 7 months (CI 95% 52. 5 – 88. 8) in responders versus 41. 7 months (CI 95% 27, 6 – 55, 7) in resistant patients (p= 0. 018). Our real-life data from a single homogeneous geographic area outline that EPO treatment is safe and effective also in the current clinical practice, beyond controlled clinical trials. However, this latter type of studies is warranted to define the best initial dose of EPO in such patients. Disclosures: No relevant conflicts of interest to declare.

We measured serum levels of total alkaline phosphatase activity, osteocalcin, car☐y-terminal propeptide of human type I procollagen (PICP), tartrate-resistant acid phosphatase activity (TRAP), and the fasting urinary hydroxyproline/creatinine ratio (OHPr/Cr) in seven affected members (four men, three women; age, 43.3 ± 16.6 years [mean ± SD]) of a family with clinically diagnosed type I-A osteogenesis imperfecta (OI) and in eight (five men, three women) normal age-matched (38.2 ± 10.3) relatives. Three boys with OI and three normal girls of the same family were also studied, although they were excluded from statistical analysis. Bone mineral density was also determined at four different skeletal sites. Serum levels of PICP were measured with a radioimmunoassay (Farmos Diagnostica, Turku, Finland). There were no significant differences in mean values of the biomarkers studied between OI patients and normal relatives, with the only exception being serum levels of PICP (35 ± 7.5 v 219 ± 107.5μ/L, P < .001). A significant reduction of BMD was found in OI patients compared with normal relatives at the lumbar (L) spine (680 ± 61 v 1,128 ± 92mg/cm2, P < .001), at the ultradistal radius ([UDR] 323 ± 85 v 458 ± 76, P < .006), at the femoral neck ([F] 494 ± 140 v 791 ± 104, P < .001), and at the junction of the distal and middle third of the radius ([MR] 639 ± 71 v 717 ± 52, P < .029). When the patients and control subjects were combined, there were significant positive correlations between serum PICP and BMD values at various skeletal sites (L, P < .006; F, P < .05; UDR, P < .005; MR, P < .007). Our results suggest that decreased levels of serum PICP are typical of OI type I patients, or at least of this family. This should be ascribed to a decreased amount of collagen produced, although the possibility of an abnormal sequence not recognized by the antiserum used should also be considered. Densitometric results indicate that quantitative or qualitative defects of collagen structure may contribute to the fragility of OI bone by interfering with complete mineralization and/or normal tissue structure.

The treatment of multiple myeloma (MM), a B-cell neoplasm characterized by a clonal expansion of plasma cell in the bone marrow, remains unsuccessful in a significant proportion of patients. The majority of MM patients fail to achieve a complete response (CR) with standard therapy. Bortezomib is a new drug that has been shown to induce a complete response (CR) in 10% of pre-treated patients and continues to show benefit in relapsing/refractory myeloma treatment. We report a case of 72 year-old women with IgAl and IgGK MM who resulted refractory to two different line therapies. Patient was diagnosed with MM in March 2005 following the admission to our clinic for bone pain and weight loss. Laboratory blood tests were: total protein 9,4 gr/dl; IgAl and IgGK monoclonal spike (IgG: 917; IgA: 2990, IgM