Publications by authors named "Emilia Scalzulli"

37 Publications

Measuring prognosis in chronic myeloid leukemia: what's new?

Expert Rev Hematol 2021 Jun 14:1-9. Epub 2021 Jun 14.

Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Rome, Italy.

The outcome of chronic myeloid leukemia (CML) patients in chronic phase has changed after the introduction of tyrosine kinase inhibitors (TKIs). The life expectancy is actually similar to that of the general population. Prognostic stratification at baseline is part of a patient-centered approach to decide the best therapeutic approach. In this review, the current prognostic factors examined at baseline are detailed and the meaning is explained. A broad research on Medline, Embase and archives from EHA and ASH congresses, was performed. Prognostic factors have been divided into patient-related (age, gender, comorbidities, etc.) and disease-related (additional cytogenetic abnormalities, type of transcript, etc). New information about genomic data and the potential role of patient-reported outcomes is also discussed. Prognostic factors at baseline should be considered to evaluate the long-term probability of disease-related death, the possible toxicity, and the projected long-term overall survival. The genomic assessment would provide the basis for a genomic-based risk and help in oriented decision-making process.
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http://dx.doi.org/10.1080/17474086.2021.1938534DOI Listing
June 2021

Long-term follow-up of late chronic phase chronic myeloid leukemia patients treated with imatinib after interferon failure: a single center experience.

Leuk Lymphoma 2021 Mar 16:1-6. Epub 2021 Mar 16.

Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University, Rome, Italy.

We report the long-term outcome of 139 patients treated with imatinib in late chronic phase after IFN failure. Median follow-up was 16.6 years and the estimated 18-year OS was 64.8%. 18-year EFS and PFS were 69% and 64.4%, respectively. Fifty (36%) patients stopped imatinib, 72% received a second line. b2a2 transcript was associated with a significantly inferior 18-year OS ( = 0.008), FFS ( = 0.036), PFS ( = 0.013) compared to the b3a2 type, whilst the type of transcript did not influence the time to response achievement. Failure to achieve MMR at 12 months significantly reduced the chance of reaching a DMR ( = 0.001). Imatinib discontinuation after achieving a sustained deep molecular response was attempted in 14 patients; 12 (86%) are still in treatment-free remission (TFR) at the last follow-up. Our experience confirms the long-term efficacy of imatinib after IFNα failure in real-life setting and documents the possibility of attempting a TFR in this subset of patients.
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http://dx.doi.org/10.1080/10428194.2021.1901094DOI Listing
March 2021

Real-life comparison of nilotinib versus dasatinib as second-line therapy in chronic phase chronic myeloid leukemia patients.

Ann Hematol 2021 May 7;100(5):1213-1219. Epub 2021 Mar 7.

Hematology, Department of Translational and Precision Medicine, Policlinico Umberto 1, Sapienza University, Rome, Italy.

Tyrosine kinase inhibitors (TKIs), the backbone of treatment for chronic phase chronic myeloid leukemia patients (CP-CML), have changed the long-term outcome of the disease. Nonetheless, over 20% of patients fail front-line therapy due to intolerance or resistance. A head-to-head comparison of dasatinib and nilotinib as second-line treatment outside of sponsored clinical trials has not been reported. We retrospectively analyzed 131 CP-CML patients who, after front-line imatinib failure, switched to a second-line therapy with nilotinib (59, 45%) or dasatinib (72, 55%). Median duration of second-line treatment was 33 months (range 2-100). The reason for switching therapy was resistance in 83.2% and intolerance in 16.8% of patients. The overall survival of the entire cohort at 7 years was 78.9%, while it was 72% and 85.6% for patients treated with dasatinib and nilotinib, respectively (p=0.287). With regard to efficacy after 12 months of treatment, 108 patients were evaluable for molecular response: 47% achieved a major molecular response and 18.2% a deep molecular response with dasatinib, compared to 38% and 16.2% with nilotinib (p=ns). We observed 35% of grade 3-4 adverse events, more frequently in the dasatinib group (47%) compared to the nilotinib group (22%), without affecting molecular responses. Our study suggests that, in the real-life setting, dasatinib and nilotinib used as second-line treatment in CP-CML are equally effective, with high molecular response rates and an acceptable tolerability.
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http://dx.doi.org/10.1007/s00277-021-04477-0DOI Listing
May 2021

Optimizing health-related quality of life in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.

Expert Rev Hematol 2021 Mar 9;14(3):293-302. Epub 2021 Mar 9.

Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome, Italy.

: The current treatment landscape of chronic myeloid leukemia (CML) is challenging for several reasons, and health-related quality of life (HRQOL) data may be of critical importance to help physicians and patients make more informed decisions.: A systematic literature search was performed in PubMed to identify the most recent studies (between April 2016 and June 2020) assessing the impact of tyrosine kinase inhibitors (TKIs) on adult CML patients' HRQOL. Studies assessing treatment discontinuation were also considered. For each study, we evaluated characteristics of CML patients included, treatment information and basic HRQOL data, including questionnaires used, and summary findings.: Valuable information can be gleaned from recent CML studies including a HRQOL assessment; however, major gaps remain in our knowledge. These include, for example, a better understanding of the impact of second- and third-generation TKIs on patients' HRQOL compared to imatinib therapy. Also, the benefits of TKI treatment discontinuation, in terms of symptom burden and HRQOL, are yet to be fully elucidated. More research efforts are needed in this area to generate high-quality evidence that can facilitate decision-making.
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http://dx.doi.org/10.1080/17474086.2021.1886918DOI Listing
March 2021

Low-density lipoprotein (LDL) levels and risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib.

Ann Hematol 2021 Jan 3. Epub 2021 Jan 3.

Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Recommendations for dyslipidemia management aimed at reducing arterial occlusive events (AOEs) have been recently published. So far, no data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib. We investigated 369 CML adult patients, stratified according to the new Systematic Coronary Risk Evaluation (SCORE) scoring system. Plasma levels of cholesterol, HDL, LDL, and triglycerides were measured prior to the start of nilotinib and after 3, 6, and 12 months. The 5-year cumulative incidence of AOEs was 15.9%. Patients with cholesterol levels > 200 mg/dL and LDL > 70 mg/dL 3 months after treatment showed a significantly higher incidence of AOEs (21.9 ± 4.6% vs 6.2 ± 2.5, P = 0.003). Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (34.4 ± 6% vs 10 ± 2.1%, P < 0.001). In multivariate analysis, both high cholesterol and LDL levels and a high and very high SCORE risk remained significantly associated with the risk of AOEs (P = 0.008; HR = 3.5; 95% CI = 1.4-8.7 and P < 0.001; HR = 4.4; 95% CI = 2-9.8, respectively). Overall, 78 patients (21.1%) presented dyslipidemia at the time of CML diagnosis and 88 (23.3%) after starting nilotinib, but only 26 of them (29.5%) were treated with statins.Low LDL and cholesterol plasma levels are associated with a significant lower risk of AOEs in CML patients treated with nilotinib in the real life.
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http://dx.doi.org/10.1007/s00277-020-04392-wDOI Listing
January 2021

Clinical and Prognostic Features of Essential Thrombocythemia: Comparison of 2001 WHO Versus 2008/2016 WHO Criteria in a Large Single-center Cohort.

Clin Lymphoma Myeloma Leuk 2021 Apr 6;21(4):e328-e333. Epub 2020 Nov 6.

Department of Translational and Precision Medicine, University "Sapienza" of Rome, Rome, Italy. Electronic address:

Background: According to 2008/2016 classification of the World Health Organization (WHO), a platelet (PLT) count ≥ 450 × 10/L, reduced from the previously published WHO 2001 indicated level ≥ 600 × 10/L, was considered the new PLT threshold for the diagnosis of essential thrombocythemia (ET).

Patients And Methods: To validate this important diagnostic change in a setting of current clinical practice, we retrospectively analyzed clinical and hematologic features at diagnosis and during follow-up of 162 patients with ET, diagnosed in our center from January 2008 to December 2017. We subdivided patients according to PLT value at baseline into Group A (PLT ≥ 600 × 10/L) (124 patients; 76.5%) and Group B (PLT ≥ 450 × 10/L < 600 × 10/L) (38 patients; 23.5%).

Results: Among clinical features, only the median value of leukocytes (P < .001) was significantly higher in Group A. Cytostatic treatment was administered in 103 patients, with a significantly higher rate in patients of group A (P < .001). After a median follow-up of 42.4 months (interquartile range, 22.1-70.6 months), 8 thrombotic events were recorded in the entire cohort, without differences between the 2 groups (P = .336). The 5-year overall survival (OS) of the entire cohort was 96.9% (95% confidence interval, 92.6%-100%), without differences between the 2 groups (P = .255).

Conclusions: Our data indicate a substantial homogeneity among patients with ET regardless of the PLT count at diagnosis, thus confirming the usefulness of the 2008/2016 WHO diagnostic criteria.
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http://dx.doi.org/10.1016/j.clml.2020.11.003DOI Listing
April 2021

Digital droplet PCR as a predictive tool for successful discontinuation outcome in chronic myeloid leukemia: Is it time to introduce it in the clinical practice?

Crit Rev Oncol Hematol 2021 Jan 12;157:103163. Epub 2020 Nov 12.

Hematology, Department of Translational and Precision Medicine, Sapienza University, Azienda Policlinico Umberto 1, Rome, Italy. Electronic address:

Tyrosine kinase inhibitors (TKIs) have drastically changed the outcome of chronic myeloid leukemia (CML) patients. A sustained and deep molecular response achieved over time paves the way to therapy discontinuation, and is a pre-requisite to attempt treatment-free remission. Monitoring of the molecular response during treatment discontinuation is routinely carried out by RQ-PCR, but it may not be the optimal tool to monitor minimal residual disease at the time of stopping treatment and during treatment discontinuation. Different digital PCR platforms (such as droplet dPCR) are available, a method based on water-emulsion droplet technology in which the sample is partitioned into 20,000 droplets and PCR amplification of the template subsequently occurs in each individual droplet. The consequent high sensitivity and precision with a very reliable quantification without the need of a calibration curve and the exquisite reproducibility makes this procedure as an ideal alternative method for the detection of very low levels of disease. Aim of this review is to describe and discuss the recent use of dPCR/ddPCR in CML, focusing in particular on its role in TKI treatment discontinuation strategies.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103163DOI Listing
January 2021

Tyrosine kinase inhibitor discontinuation in the management of chronic myeloid leukemia: a critical review of the current practice.

Expert Rev Hematol 2020 12 1;13(12):1311-1318. Epub 2020 Dec 1.

Hematology, Department of Translational and Precision Medicine, Azienda Policlinico Umberto I, Sapienza University , Rome, Italy.

: Tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity, have significantly prolonged the overall survival of patients affected by chronic myeloid leukemia (CML) and changed drastically the outcome. Evidences from several studies suggest that in patients who have achieved a sustained, stable and deep molecular response, TKI treatment can be safely discontinued with a close subsequent monitoring. Thus, a stable deep molecular response (DMR) has become a feasible treatment goal in CML. : In this review, the main findings extrapolated from sponsored and real-life evidences regarding TKI discontinuation were discussed, through a broad research on Medline, Embase and archives from EHA and ASH congresses (including words such as discontinuation, treatment-free remission, TFR, etc). Moreover, suggestions emerged from international guidelines about treatment-free remission (TFR) are presented. : With the growing availability of clinical trials and real-life data on TFR, in recent years the possibility of offering to CML patients a safe, informed and shorter path to TFR, through the achievement of a stable deep molecular response (DMR), has become an increasing option. However, many controversial aspects remain regarding treatment choices and timings, predictive factors, patient communication and optimal strategies aimed at achieving a successful TFR.
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http://dx.doi.org/10.1080/17474086.2021.1852924DOI Listing
December 2020

Concomitant Administration of Direct Oral Anticoagulants in Chronic Phase Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors.

Clin Drug Investig 2020 Dec 22;40(12):1177-1181. Epub 2020 Oct 22.

Department of Translational and Precision Medicine, Hematology, Sapienza University of Rome, 00161, Rome, Italy.

Background And Objective: In the last decades, the chronic myeloid leukemia (CML) therapeutic landscape has changed dramatically with the introduction of tyrosine kinase inhibitors (TKIs), with 10-year survival rates improving to up to 80%. Long-lasting TKI treatment, in particular with second-generation TKIs, has enabled clinicians to manage the onset of several side effects and other co-morbidities, such as atrial fibrillation or venous thromboembolism (VTE).

Methods: We retrospectively evaluated nine CML patients treated with TKIs between 2017 and 2020 who experienced atrial fibrillation or VTE and received concomitant administration of TKIs and direct oral anticoagulants (DOACs) outside clinical trials, to evaluate the efficacy and safety of this combination.

Results: Median age was 66 years at CML diagnosis (range 52-73 years) and 69 years at the time of starting DOACs. A female predominance was observed. The median follow-up of concomitant DOAC and TKI administration was 8.5 months; edoxaban was administered in six patients and apixaban in two patients, and one patient received rivaroxaban. Regarding CML treatment, four patients received imatinib, two patients bosutinib, and three nilotinib. In eight patients DOACs were started for atrial fibrillation and in one patient for VTE. In none of the patients treated with the combination were additional symptomatic thrombotic adverse events or major bleedings reported.

Conclusion: In this small case series, the use of DOACs in CML patients seemed feasible. Additional data on long-term outcomes including a larger cohort of CML patients treated with DOACs are, however, needed.
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http://dx.doi.org/10.1007/s40261-020-00980-wDOI Listing
December 2020

The advantages and risks of ruxolitinib for the treatment of polycythemia vera.

Expert Rev Hematol 2020 10 11;13(10):1067-1072. Epub 2020 Sep 11.

Hematology, Department of Translational and Precision Medicine, Sapienza University Azienda Policlinico Umberto 1 , Rome, Italy.

Introduction: Polycythemia vera is a myeloproliferative neoplasm characterized by an increased red blood cell mass, risk of thromboembolic events, and of transformation into secondary myelofibrosis and acute leukemia. The goal of treatment is to reduce the risk of fatal cardiovascular events reducing the hematocrit level with phlebotomies and low-dose aspirin. In high-risk patients (age >60 years or previous thromboembolic events) cytoreductive therapy is indicated. In this setting, resistance and/or intolerance is common.

Areas Covered: Authors searched Medline, Embase, archives from the EHA and the ASH annual congresses from 2014 onward about ruxolitinib treatment in PV patients. Two trials (RESPONSE and RESPONSE2) have documented the efficacy and safety of ruxolitinib. The drug is able to persistently control the hematocrit level and symptoms (due to increased cytokine levels, increased viscosity, and increased splenomegaly), to reduce WBC counts and the rate of thromboembolic events, to increase the quality of life.

Expert Opinion: Although ruxolitinib has entered into the clinical practice, the real-life incidence of resistant/intolerant patients, the long-term safety, and the activity on thromboembolic events (associated or not to a reduction of the molecular burden) remains to be conclusively determined. More information extrapolated by registries are required to shed light on the missing information.
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http://dx.doi.org/10.1080/17474086.2020.1816819DOI Listing
October 2020

Balanced and unbalanced chromosomal translocations in myelodysplastic syndromes: clinical and prognostic significance.

Leuk Lymphoma 2020 12 1;61(14):3476-3483. Epub 2020 Sep 1.

Hematology, Dipartimento Medicina Traslazionale e di Precisione, AOU Policlinico Umberto I Sapienza University of Rome, Rome, Italy.

Prognostic role of chromosomal translocations (CT) in myelodysplasia (MDS) was retrospectively analyzed in 77 patients from GROM-L registry. Forty (51.9%) balanced, 28 (36.4%) unbalanced and 9 (11.7%) concomitant balanced and unbalanced CT were identified. Five-year overall survival (OS) of the entire cohort was 34.5% (CI 95% 22.5-46.5). Five-year OS of patients with unbalanced CT was significantly shorter than that of patients carrying balanced CT [22.3% (CI 95% 4.0-40.6) vs 44.0% (CI 95% 26.7-61.3) ( = 0.042)]. Five-year OS of patients with CT included in complex karyotype (CK) was significantly shorter than that of patients with isolated CT or CT with another abnormality [5.5% (CI 95% 0-15.7) vs 42.9% (CI 95% 21.3-64.5) and vs 4% (CI 95% 31.6-79.2) ( < 0.001)]. Presence of CT in MDS characterizes a more aggressive outcome only when associated with CK.
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http://dx.doi.org/10.1080/10428194.2020.1811861DOI Listing
December 2020

Management of myelofibrosis and concomitant advanced cutaneous squamous cell carcinoma with ruxolitinib associated with cemiplimab.

Ann Hematol 2020 Aug 27. Epub 2020 Aug 27.

Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto 1, Sapienza University, Via Benevento 6, 00161, Rome, Italy.

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http://dx.doi.org/10.1007/s00277-020-04236-7DOI Listing
August 2020

Predictive factors for response and survival in elderly acute myeloid leukemia patients treated with hypomethylating agents: a real-life experience.

Ann Hematol 2020 Oct 19;99(10):2405-2416. Epub 2020 Aug 19.

Hematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University, Via Benevento 6, 00161, Rome, Italy.

Predictive factors of response to hypomethylating agents (HMA) in elderly acute myeloid leukemia (AML) patients remain unclear in the real-life setting and no direct comparison between azacitidine (AZA) and decitabine (DEC) has been carried out. We retrospectively evaluated 110 AML patients treated with HMA (78 AZA, 32 DEC) as first-line therapy outside of clinical trials. Median age was 75 years (range 58-87). The median overall survival (OS) of the entire cohort was 8.0 months (95% CI 6.1-10), without significant differences among the subgroups: AZA 8.8 months vs DEC 6.3 months (p = 0.291). HMA treatment yielded an overall response rate (ORR) of 40% (AZA 37% vs DEC 47%, p = 0.237). A stable disease (SD) after 4 HMA cycles was not associated with a worse survival outcome compared with an early optimal response. Factors independently associated with a better OS were transfusion independence during treatment (p = 0.049), achievement of an optimal response to treatment (p < 0.001), and a baseline hemoglobin level ≥ 9.25 (p = 0.018). A bone marrow (BM) blast count ≥ 30% (p < 0.001) and a therapy-related AML (p = 0.008) remain poor survival predictors. Of the available biologic features, an adverse risk category according to the ELN classification was significantly associated with a shorter survival over the intermediate risk category (p = 0.034). Disease progression remains the primary cause of death. Infectious complications were more severe (p = 0.036) and occurred earlier (p = 0.006) in the DEC group compared with that of the AZA group. In conclusion, clinical prognostic factors associated to response and survival have been identified without significant associations concerning overall outcomes between the two HMAs.
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http://dx.doi.org/10.1007/s00277-020-04217-wDOI Listing
October 2020

Early intracranial haemorrhages in acute promyelocytic leukaemia: analysis of neuroradiological and clinico-biological parameters.

Br J Haematol 2021 Apr 10;193(1):129-132. Epub 2020 Aug 10.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Acute promyelocytic leukaemia (APL) represents a modern success of precision medicine. However, fatalities occurring within the first 30 days of induction treatment, in particular intracranial haemorrhage (ICH), remain the main causes of death. We studied the clinico-biological characteristics of 13 patients with APL who experienced ICH. Compared to 85 patients without this complication, patients with ICH were older and more frequently had high-risk APL. Moreover, positivity for the 'swirl' sign at neuroradiological imaging and hydrocephalus were predictors of a fatal outcome, together with lower fibrinogen, prolonged international normalized ratio (INR) and higher lactate dehydrogenase levels.
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http://dx.doi.org/10.1111/bjh.17018DOI Listing
April 2021

Renin angiotensin system inhibitors reduce the incidence of arterial thrombotic events in patients with hypertension and chronic myeloid leukemia treated with second- or third-generation tyrosine kinase inhibitors.

Ann Hematol 2020 Jul 30;99(7):1525-1530. Epub 2020 May 30.

Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy.

Hypertension is a commonly reported comorbidity in patients diagnosed with chronic myeloid leukemia (CML), and its management represents a challenge in patients treated with 2nd- or 3rd-generation tyrosine kinase inhibitors (TKIs), considering their additional cardiovascular (CV) toxicity. The renin angiotensin system (RAS) contributes to hypertension genesis and plays an important role in atherosclerosis development, proliferation, and differentiation of myeloid hematopoietic cells. We analyzed a cohort of 192 patients with hypertension at CML diagnosis, who were treated with 2nd- or 3rd-generation TKIs, and evaluated the efficacy of RAS inhibitors (angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs)) in the prevention of arterial occlusive events (AOEs), as compared with other drug classes. The 5-year cumulative incidence of AOEs was 32.7 ± 4.2%. Patients with SCORE ≥ 5% (high-very-high) showed a significantly higher incidence of AOEs (33.7 ± 7.6% vs 13.6 ± 4.8%, p = 0.006). The AOE incidence was significantly lower in patients treated with RAS inhibitors (14.8 ± 4.2% vs 44 ± 1%, p < 0.001, HR = 0.283). The difference in the low and intermediate Sokal risk group was confirmed but not in the high-risk group, where a lower RAS expression has been reported. Our data suggest that RAS inhibitors may represent an optimal treatment in patients with hypertension and CML, treated with 2nd or 3rd TKIs.
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http://dx.doi.org/10.1007/s00277-020-04102-6DOI Listing
July 2020

Switch from branded to generic imatinib: impact on molecular responses and safety in chronic-phase chronic myeloid leukemia patients.

Ann Hematol 2020 Dec 28;99(12):2773-2777. Epub 2020 May 28.

Hematology, Department of Precision and Translational Medicine, Policlinico Umberto 1, Sapienza University, Via Benevento 6, 00161, Rome, Italy.

Since July 2017, different generic imatinib formulations have been introduced in Italy for the treatment of patients with chronic myeloid leukemia (CML). We analyzed 168 chronic phase CML patients treated with branded imatinib for a median of 12 years (range 1-16) at a single institution who switched to a single generic formulation in order to assess the safety and impact on molecular response. The Sokal risk was low/intermediate/high in 63%, 33%, and 4% of patients, respectively. The median duration of generic imatinib treatment was 19 months (range 4-22). Twenty-seven percent of patients were in MMR and 73% were in deep molecular responses (MR4-4.5) at the time of the switch. After 12 months of treatment with generic imatinib, 140 patients were evaluable for response: 23.6% and 76.4% were respectively in MMR and in deep molecular response. When the degree of response was compared with the best molecular response observed with branded imatinib, it was found that 84% of patients maintained the response previously achieved, 6% improved it, and 10% of patients had a molecular fluctuation from the previous deep molecular response to MMR. Only 1 patient lost the MMR and no patient switched to another TKI for inefficacy. In terms of safety, 20% of patients reported new or worsening side effects, but only 2 patients returned to branded imatinib for toxicity. Our data show that the switch to generic imatinib in patients who have been previously treated with branded imatinib appears to maintain efficacy, although a proportion of patients experience new or worsening side effects.
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http://dx.doi.org/10.1007/s00277-020-04096-1DOI Listing
December 2020

Erythropoietin treatment in chronic phase chronic myeloid leukemia patients treated with frontline imatinib who developed late anemia.

Eur J Haematol 2020 Sep 22;105(3):286-291. Epub 2020 May 22.

Department of Translational and Precision Medicine, University "La Sapienza" of Rome, Rome, Italy.

Background: Role of erythropoietin (EPO) in the treatment of late anemia in patients with Chronic Myeloid Leukemia (CML) is still undefined.

Methods: Fifty CML patients treated at 14 institutions with frontline imatinib for at least 12 months and in stable complete cytogenetic response who developed a late chronic anemia treated with EPO were retrospectively evaluated.

Results: Median time from imatinib start to EPO treatment was 42.2 months [interquartile range (IQR) 20.8-91.9]. Median Hb value at EPO starting time was 9.9 g/dL (IQR 8.9-10.3): Eleven patients (22.0%) were transfusion dependent. Alpha-EPO (40 000 UI weekly) was employed in 37 patients, beta-EPO (30 000 UI weekly) in 9 patients, zeta-EPO (40 000 UI weekly) in 2 patients, and darbepoetin (150 mcg/weekly) in the remaining 2 patients. On the whole, 41 patients (82.0%) achieved an erythroid response, defined as a stable (>3 months) improvement >1.5 g/dL of Hb level, and 9 patients (18.0%) indeed resulted resistant. Among responding patients, 10 relapsed after a median time from EPO start of 20.7 months (IQR 10.8-63.7). No EPO-related toxicity was observed.

Conclusions: Results of EPO treatment for late chronic anemia during long-lasting imatinib therapy are encouraging, with a high rate of response.
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http://dx.doi.org/10.1111/ejh.13436DOI Listing
September 2020

Therapeutic strategies in low and high-risk MDS: What does the future have to offer?

Blood Rev 2021 Jan 31;45:100689. Epub 2020 Mar 31.

Hematology, Department of Translational and Precision Medicine, Sapienza University, Az. Policlinico Umberto 1, Rome, Italy. Electronic address:

Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterized by cytopenias and increased risk of acute leukemia transformation. Prognosis of MDS patients can be assessed by various scoring systems, the most common being the International Prognostic Scoring System (IPSS) now refined by the revised version (IPSS-R). Genomic information at baseline, that is currently not included in clinical prognostic scores, will, in the future, help us to stratify patients with various prognoses. Therapy of MDS is based on risk stratification. The aim of therapy in low-risk MDS is to improve anemia or thrombocytopenia, decrease transfusion needs, improve quality of life, attempt to prolong overall survival, and reduce the risk of progression. In higher-risk MDS, the goal of therapy is to prolong survival and reduce the risk of transformation into acute leukemia. Only a few drugs are currently available for treatment, but more drugs are now under clinical investigation, in line with new, recently discovered molecular and immunological pathways. This review describes potential new drugs for low and high-risk MDS. The increasing knowledge of immunological and signalling pathways in MDS will assist us in identifying targeted patient-oriented treatments. In the near future, initial molecular stratification will lead the way to a personalized approach and targeted therapy.
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http://dx.doi.org/10.1016/j.blre.2020.100689DOI Listing
January 2021

Hemorrhagic Complications in Patients Treated With Azacitidine and Direct Oral Anticoagulants.

Am J Ther 2020 02 17. Epub 2020 Feb 17.

Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.

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http://dx.doi.org/10.1097/MJT.0000000000001105DOI Listing
February 2020

Incidence of Clinically Significant (≤10 g/dL) Late Anemia in Elderly Patients with Newly Diagnosed Chronic Myeloid Leukemia Treated with Imatinib.

Oncol Res Treat 2019 8;42(12):660-664. Epub 2019 Oct 8.

Hematology, Department of Precision and Translational Medicine, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy,

Background: In elderly patients with chronic myeloid leukemia (CML) responsive to imatinib, the incidence of clinically significant (CS) late chronic anemia is still unknown.

Materials And Methods: To highlight this issue, we revised retrospectively 81 CML patients aged >60 years treated at our Institution with front-line imatinib for at least 24 months in durable complete cytogenetic response (CCyR). CS late chronic anemia was defined as the presence of persistent (>6 months) and otherwise unexplained Hb levels ≤10 g/dL, which occurred >6 months from imatinib start.

Results: A condition of CS late chronic anemia occurred in 22 out of 81 patients (27.2%) at different intervals from imatinib start. Seven out of 22 patients (31.8%) needed packed red cell transfusions during the follow-up. At diagnosis, patients who developed CS late chronic anemia were significantly older and had a lower Hb median level. Six out of 22 patients with CS late chronic anemia received subcutaneous recombinant alpha-erythropoietin (EPO) at the standard dosage of 40,000 IU weekly: all 6 patients achieved an erythroid response. A significantly worse event-free survival (EFS) in patients with untreated CS late chronic anemia was observed (p = 0.012).

Conclusions: CS late chronic anemia during long-term treatment with imatinib is a common complication in responsive elderly patients, with worse EFS if untreated. Results with EPO are encouraging, but larger studies are warranted to define its role.
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http://dx.doi.org/10.1159/000502801DOI Listing
April 2020

Digital droplet PCR at the time of TKI discontinuation in chronic-phase chronic myeloid leukemia patients is predictive of treatment-free remission outcome.

Hematol Oncol 2019 Dec 5;37(5):652-654. Epub 2019 Aug 5.

Hematology, Department of Translational and Precision Medicine, University 'Sapienza' and Policlinico Umberto 1, Rome, Italy.

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http://dx.doi.org/10.1002/hon.2650DOI Listing
December 2019

Efficacy and safety of ruxolitinib and hydroxyurea combination in patients with hyperproliferative myelofibrosis.

Ann Hematol 2019 Aug 14;98(8):1933-1936. Epub 2019 Jun 14.

Institute of Hematology "L. and A. Seràgnoli", Sant'Orsola-Malpighi University Hospital, Bologna, Italy.

Ruxolitinib is the only commercially available JAK1/2 inhibitor approved for the treatment of myelofibrosis-related splenomegaly and symptoms. During treatment, as rare conditions, leukocytosis and/or thrombocytosis could develop and the management of these situations is not well established. We report here 53 myelofibrosis patients that received a combination of hydroxyurea and ruxolitinib because of uncontrolled myeloproliferation. Both drugs were administered outside clinical trials. At 48 weeks, a significant reduction in leucocyte and platelet counts was observed (p = 0.02 and p = 0.04, respectively). Additionally, the spleen volume decreased from a median value of 10 cm below the left costal margin (range, 0-10) to 6 cm (range, 0-15). The rate of spleen response increased from 14% at the start of the combination to 45% after 48 weeks. The safety profile of the combination was consistent with that observed with ruxolitinib single agent. These data require further confirmation in large cohorts of patients prospectively assessed.
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http://dx.doi.org/10.1007/s00277-019-03727-6DOI Listing
August 2019

Identification of predictive factors for overall survival at baseline and during azacitidine treatment in high-risk myelodysplastic syndrome patients treated in the clinical practice.

Ann Hematol 2019 Aug 5;98(8):1919-1925. Epub 2019 Jun 5.

Hematology, Department of Precision and Translational Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University, Via Benevento 6, 00161, Rome, Italy.

The outcome of high-risk myelodysplastic syndrome (MDS) patients treated with 5-azacitidine (5-AZA) in the real-life setting remains largely unknown. We evaluated 110 MDS patients (IPSS intermediate 2/high) treated outside of clinical trials at a single institution between September 2003 and January 2017. Median duration of therapy was 9.5 cycles. The overall survival (OS) of the whole cohort was 66.1% at 1 year and 38.3% at 2 years. No differences in terms of OS were observed with regard to gender (p = 0.622) and age at baseline (< 65 years, 65-75, and > 75 years, p = 0.075). According to the IPSS-R, the very high-risk group had an inferior 2-year OS (17%) compared with intermediate-group patients (64%, p < 0.001). Transfusion independency at baseline was identified as a favorable prognostic factor on 1-year (66.8%) and 2-year OS (43.4%) (p < 0.001). After four cycles, the persistence of bone marrow blasts > 10% identified patients with a worse outcome, with a 2-year OS of 9.4% (p = 0.002). The occurrence of an infection during the first four cycles impacted on the 2-year OS (31.6% vs 58.3% in patients without infections, p = 0.032). Patients receiving at least 24 cycles of the drug have a 5-year OS of 38.2%. This analysis allowed to identify features at baseline or during treatment with 5-AZA associated with a different 2-year OS.
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http://dx.doi.org/10.1007/s00277-019-03724-9DOI Listing
August 2019

Ten-year outcome of chronic-phase chronic myeloid leukemia patients treated with imatinib in real life.

Ann Hematol 2019 Aug 11;98(8):1891-1904. Epub 2019 May 11.

Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161, Rome, Italy.

Imatinib, the first BCR/ABL kinase inhibitor approved for the treatment of chronic myeloid leukemia (CML), has changed the long-term outcome of patients affected by this disease. The aim of our analysis was to report, after a median follow-up of 10.2 years (range 5.8-14.8), the long-term outcome, efficacy, and safety of imatinib treatment (frontline and after interferon failure) in a single institution cohort of 459 patients with CML in chronic phase treated outside of clinical trials. The 10-year overall survival of the whole cohort was 77.1%, while the 10-year probability of dying due to CML and other causes was 7.8% and 16%, respectively. The prognostic value of the BCR-ABL1 ratio at 3 months (⩽ 10%) and of complete cytogenetic response and major molecular response at 1 year was confirmed also in the real-life practice. The EUTOS long-term survival score better stratified the baseline risk of dying of CML compared with other risk scores. Two hundred thirty-six (51.4%) patients achieved a deep molecular response during imatinib treatment after a median time of 4.57 years, and 95 (20.6%) had a stable deep molecular response maintained for at least 2 consecutive years. Imatinib was associated with a low rate of serious cardiovascular events and second neoplasia. This 10-year real-life follow-up study shows that imatinib maintains efficacy over time and that long-term administration of imatinib is not associated with notable cumulative or late toxic effects.
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http://dx.doi.org/10.1007/s00277-019-03706-xDOI Listing
August 2019

Recurrent arterial occlusive events in patients with chronic myeloid leukemia treated with second- and third-generation tyrosine kinase inhibitors and role of secondary prevention.

Int J Cardiol 2019 08 17;288:124-127. Epub 2019 Apr 17.

Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.

Background: Risk of death is particularly high in patients with a previous history of arterial occlusive events (AOEs) and the probability for a recurrent event is around 20%. Little is known about recurrent AOE and the role of secondary prevention in patients with Chronic Myeloid Leukemia (CML) with previous AOE, treated with second- and third-generation tyrosine kinase inhibitors (2/3 TKIs), nilotinib, dasatinib, bosutinib and ponatinib.

Methods: We identified a real-life cohort of 57 consecutive adult CML patients treated with 2/3 TKI. All patients had a previous history of AOE. Ongoing use of secondary prevention of AOE (including antiplatelet agents, anticoagulant therapy, and statins) before starting a 2/3 TKI was recorded, as well as CV risk factors.

Results: The 60-month cumulative incidence rate of recurrent AOEs was 47.8 ± 10.9%. Despite a history of AOE, 10 patients (16%) were not receiving secondary preventative measures. Patients treated with nilotinib and ponatinib showed a higher incidence of recurrent AOEs (76.7 ± 14.3% and 64 ± 20.1%, respectively) than those treated with dasatinib and bosutinib (44 ± 24.2% and 30.5 ± 15.5%, respectively) (p = 0.01). Only treatment with a 2/3 TKI given as second or subsequent line therapy showed a significant association with an increased incidence of recurrent AOE (p = 0.039). Overall, 17 recurrent AOEs were observed; 3 CV-related deaths were reported.

Conclusion: CML patients with a previous history of AOE treated with 2/3 TKI represent a particular patient population with a higher probability of experiencing a recurrent AOE; individualized treatment is needed to optimize secondary prevention.
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http://dx.doi.org/10.1016/j.ijcard.2019.04.051DOI Listing
August 2019