Publications by authors named "Giovanni Caocci"

116 Publications

Real-world use of thrombopoietin receptor agonists in elderly patients with primary immune thrombocytopenia.

Blood 2021 Apr 22. Epub 2021 Apr 22.

(Institute of Hematology, Bologna, Italy.

The efficacy and safety of thrombopoietin-receptor agonists (TRAs) in elderly patients with primary immune thrombocytopenia (ITP) is uncertain. In 384 ITP patients treated with TRAs when aged ≥60 years, we investigated TRAs response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROT). After 3 months, 82.5% and 74.3% of eltrombopag and romiplostim-treated patients achieved a response, respectively (p=0.09); 66.7% maintained the response (median follow-up: 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; while no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. During TRA, 34 major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, and were associated with thrombosis history (SHR: 2.04, p=0.05) and platelet count <20x109/L at TRA start (SHR: 1.69, p=0.04), respectively. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but one during persisting TRA treatment (incidence rate: 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRA; 53 (13.8%) patients maintained SROT, which was associated with TRA discontinuation in complete response (p<0.001). Very old age (≥75, 41.1%) was associated with more frequent TRAs start in persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in elderly ITP patients, with no fatal haemorrhages and with SROT in a significant portion of patients; in patients with thrombosis history caution is warranted and a careful risk/benefit balance should be carried out.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2021010735DOI Listing
April 2021

Ruxolitinib rechallenge in resistant or intolerant patients with myelofibrosis: Frequency, therapeutic effects, and impact on outcome.

Cancer 2021 Apr 1. Epub 2021 Apr 1.

Unit of Hematology and Clinical Immunology, University of Padua, Padua, Italy.

Background: After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities.

Methods: The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival.

Results: A total of 219 patients (31.2%) discontinued ruxolitinib for ≥14 days and survived for ≥30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for ≥14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P = .004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P < .001) and a high Total Symptom Score (TSS; P < .001). During the rechallenge, 44.6% and 48.3% of the patients had spleen and symptom improvements, respectively, with a significant increase in the number of patients with a TSS reduction (P = .01). Although the use of a ruxolitinib dose > 10 mg twice daily predicted better spleen (P = .05) and symptom improvements (P = .02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P = .004).

Conclusions: Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.33541DOI Listing
April 2021

The EORTC QLU-C10D was more efficient in detecting clinical known group differences in myelodysplastic syndromes than the EQ-5D-3L.

J Clin Epidemiol 2021 Mar 20;137:31-44. Epub 2021 Mar 20.

Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center & Health Outcomes Research Unit, Rome, Italy.

Background: The aim was to investigate the relative validity of the preference-based measure EORTC QLU-C10D in comparison with the EQ-5D-3L in myelodysplastic syndromes (MDS) patients.

Methods: We used data from an international multicentre, observational cohort study of MDS patients. Baseline EORTC QLU-C10D and EQ-5D-3L scores were used and index scores calculated for Italy, Australia, and the UK. Criterion validity was established by Spearman and intraclass correlations (ICC) and Bland-Altman plots. Construct validity was established by the instruments' ability to discriminate known groups, i.e. groups whose health status is expected to differ.

Results: We analyzed data from 619 MDS patients (61.1% male; median age 73.8 years). Correlations between theoretically corresponding domains were largely higher than between unrelated domains. ICCs and Bland-Altman plots indicated moderate to good criterion validity. Ceiling effects were lower for the QLU-C10D (4.7%) than for the EQ-5D-3L (22.6%). The EQ-5D-3L failed to discriminate known-groups in two and the QLU-C10D in one of the comparisons; the QLU-C10D's efficiency in doing so was higher in clinical known-groups. Results were comparable between the countries.

Conclusions: The QLU-C10D may be suitable to generate health utilities for economic research in MDS. Responsiveness and minimal important differences need yet to be established.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jclinepi.2021.03.015DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-021-04477-0DOI Listing
May 2021

Bosutinib in the real-life treatment of chronic myeloid leukemia patients aged >65 years resistant/intolerant to previous tyrosine-kinase inhibitors.

Hematol Oncol 2021 Feb 22. Epub 2021 Feb 22.

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

To evaluate the role of bosutinib in elderly patients aged >65 years with chronic myeloid leukemia (CML), a real-life cohort of 101 chronic-phase CML patients followed up in 23 Italian centers and treated with bosutinib in second or a subsequent line was retrospectively evaluated. Starting dose of bosutinib was 500 mg/day in 25 patients (24.8%), 400 mg/day in 7 patients (6.9%), 300 mg/day in 33 patients (32.7%), 200 mg/day in 34 patients (33.6%), and 100 mg/day in 2 patients (2.0%). Grade 3/4 hematological toxicity occurred in 7/101 patients (6.9%) and grade 3/4 extra-hematological toxicity in 19/101 patients (18.8%). Permanent bosutinib discontinuation due to toxicity was needed in 12 patients (11.9%). Among the 96 patients evaluable for response, 74 (77.0%) achieved a complete cytogenetic response (CCyR), while 64 of these 74 patients in CCyR (66.6% of all 96 evaluable patients) also achieved a molecular response (MR) (major MR [MR 3.0] in 21 [21.8%], deep MR [MR 4.0/4.5] in 43 [44.8%]). The 3-year event-free survival and overall survival of the whole patients' cohort from bosutinib start were 60.9% (CI 95% 49.3-72.5) and 86.4% (CI 95% 77.2-95.6), respectively. Our real-life data show that bosutinib is effective, with a favorable safety profile, also in elderly patients with important comorbidities and resistance and/or intolerance to previous tyrosine-kinase inhibitor treatments. As a consequence, it could play a significant role in current clinical practice for frail patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hon.2851DOI Listing
February 2021

Impact of comorbidities and body mass index on the outcome of polycythemia vera patients.

Hematol Oncol 2021 Feb 15. Epub 2021 Feb 15.

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.

In 816 patients with 2016 World Health Organization-defined polycythemia vera (PV) enrolled in a multicenter retrospective study, we investigated the predictive value of Charlson comorbidity index (CCI) and body mass index (BMI) on thrombosis, progression to post-PV myelofibrosis (PPV-MF) and survival. Patients were subgrouped according to CCI = 0 (58.1%, no comorbidities) or CCI ≥ 1 (41.9%) and according to normal/underweight (BMI < 25, 54.5%) or overweight/obesity (BMI ≥ 25, 45.5%) at PV diagnosis. BMI was available for 529 patients. Patients with CCI ≥ 1 were older and more frequently presented cardiovascular risk factors compared to patients with CCI = 0 (p < 0.001), while overweight/obese patients were more frequently males (p < 0.001). Cumulative incidence of thromboses with death as competing risk was 13.3% at 10 years. Multivariable analysis with death as competing risk showed that previous thromboses (subdistribution hazard ratio [SHR]: 2.1, p = 0.01) and hypertension (SHR: 1.77, p = 0.04) were significantly associated with a higher thrombotic risk, while BMI ≥ 25 lost statistical significance (SHR: 1.69, p = 0.05) and CCI ≥ 1 was excluded after evaluation of goodness of fit. After a median follow-up of 6.1 years, progression to PPV-MF occurred in 44 patients, and 75 patients died. BMI ≥ 25 was associated with a lower probability of progression to PPV-MF (SHR: 0.38, CI95%: 0.15-0.94, p = 0.04) and better survival (hazard ratio [HR]: 0.42, CI95%: 0.18-0.97, p = 0.04). CCI ≥ 1 did not affect progression to PPV-MF (p = 0.44) or survival (p = 0.71).  The evaluation of CCI and BMI may improve the prognostic definition of PV. In patients with hypertension an accurate evaluation of thrombotic risk is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hon.2843DOI Listing
February 2021

Cytomegalovirus reactivation in patients under immunosuppressive treatment for autoimmune haemolytic anaemia.

Ann Hematol 2021 Jan 19. Epub 2021 Jan 19.

Department of Medical, Surgical and Experimental Sciences, University of Sassari, Viale San Pietro 12, 07100, Sassari, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-021-04416-zDOI Listing
January 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-020-04392-wDOI Listing
January 2021

Occurrence of immune thrombocytopenic purpura in a patient with essential thrombocythemia: How the immune system can overcome a neoplastic clone.

Clin Case Rep 2020 Nov 17;8(11):2132-2134. Epub 2020 Jul 17.

Department of Medical, Surgical and Experimental Sciences University of Sassari Sassari Italy.

Our case highlights the possible coexistence of essential thrombocythemia (ET) and idiopathic thrombocytopenic purpura (ITP), two pathological entities with opposite clinical and laboratory manifestations. It also underlines how an autoimmune attack has been temporarily able to overcome a neoplastic clone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccr3.3121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669383PMC
November 2020

Second primary malignancy in myelofibrosis patients treated with ruxolitinib.

Br J Haematol 2021 Apr 21;193(2):356-368. Epub 2020 Nov 21.

Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, Bologna, Italy.

Ruxolitinib (RUX), the first JAK1/JAK2 inhibitor approved for myelofibrosis (MF) therapy, has recently been associated with the occurrence of second primary malignancies (SPMs), mainly lymphomas and non-melanoma skin cancers (NMSCs). We analyzed the incidence, risk factors and outcome of SPMs in 700 MF patients treated with RUX in a real-world context. Median follow-up from starting RUX was 2·9 years. Overall, 80 (11·4%) patients developed 87 SPMs after RUX start. NMSCs were the most common SPMs (50·6% of the cases). Multivariate analysis demonstrated that male sex [hazard ratio (HR): 2·37, 95% confidence interval (95%CI): 1·22-4·60, P = 0·01] and thrombocytosis> 400 × 10 /l at RUX start (HR:1·98, 95%CI: 1·10-4·60, P = 0·02) were associated with increased risk for SPMs. Risk factors for NMSC alone were male sex (HR: 3·14, 95%CI: 1·24-7·92, P = 0·02) and duration of hydroxycarbamide and RUX therapy > 5 years (HR: 3·20, 95%CI: 1·17-8·75, P = 0·02 and HR: 2·93, 95%CI: 1·39-6·17, P = 0·005 respectively). In SPMs excluding NMSCs, male sex (HR: 2·41, 95%CI: 1·11-5·25, P = 0·03), platelet > 400 × 10 /l (HR: 3·30, 95%CI: 1·67-6·50, P = 0·001) and previous arterial thromboses (HR: 3·47, 95%CI: 1·48-8·14, P = 0·004) were shown to be associated with higher risk of SPMs. While it is reassuring that no aggressive lymphoma was documented, active skin surveillance is recommended in all patients and particularly after prolonged hydroxycaramide therapy; oncological screening should be triggered by thrombocytosis and arterial thrombosis, particularly in males.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17192DOI Listing
April 2021

A Retrospective Analysis about Frequency of Monitoring in Italian Chronic Myeloid Leukemia Patients after Discontinuation.

J Clin Med 2020 Nov 17;9(11). Epub 2020 Nov 17.

Hematology Unit, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy.

Successful discontinuation of tyrosine kinase inhibitors has been achieved in patients with chronic-phase chronic myeloid leukemia (CML). Careful molecular monitoring after discontinuation warrants safe and prompt resumption of therapy. We retrospectively evaluated how molecular monitoring has been conducted in Italy in a cohort of patients who discontinued tyrosine kinase inhibitor (TKI) treatment per clinical practice. The outcome of these patients has recently been reported-281 chronic-phase CML patients were included in this subanalysis. Median follow-up since discontinuation was 2 years. Overall, 2203 analyses were performed, 17.9% in the first three months and 38.4% in the first six months. Eighty-six patients lost major molecular response (MMR) in a mean time of 5.7 months-65 pts (75.6%) during the first six months. We evaluated the number of patients who would experience a delay in diagnosis of MMR loss if a three-month monitoring schedule was adopted. In the first 6 months, 19 pts (29.2%) would have a one-month delay, 26 (40%) a 2-month delay. Very few patients would experience a delay in the following months. A less intense frequency of monitoring, particularly after the first 6 months off treatment, would not have affected the success of treatment-free remission (TFR) nor put patients at risk of progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9113692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698481PMC
November 2020

Integrated Genomic, Functional, and Prognostic Characterization of Atypical Chronic Myeloid Leukemia.

Hemasphere 2020 Dec 6;4(6):e497. Epub 2020 Nov 6.

Department of Medicine and Surgery, University of Milano - Bicocca, Monza, Italy.

Atypical chronic myeloid leukemia (aCML) is a -negative clonal disorder, which belongs to the myelodysplastic/myeloproliferative group. This disease is characterized by recurrent somatic mutations in , and genes, as well as high genetic heterogeneity, thus posing a great therapeutic challenge. To provide a comprehensive genomic characterization of aCML we applied a high-throughput sequencing strategy to 43 aCML samples, including both whole-exome and RNA-sequencing data. Our dataset identifies , , and as the most frequently mutated genes with a total of 43.2%, 29.7 and 16.2%, respectively. We characterized the clonal architecture of 7 aCML patients by means of colony assays and targeted resequencing. The results indicate that variants occur early in the clonal evolution history of aCML, while mutations often represent a late event. The presence of actionable mutations conferred both ex vivo and in vivo sensitivity to specific inhibitors with evidence of strong in vitro synergism in case of multiple targeting. In one patient, a clinical response was obtained. Stratification based on RNA-sequencing identified two different populations in terms of overall survival, and differential gene expression analysis identified 38 significantly overexpressed genes in the worse outcome group. Three genes correctly classified patients for overall survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HS9.0000000000000497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655091PMC
December 2020

Validation and reference values of the EORTC QLQ-CML24 questionnaire to assess health-related quality of life in patients with chronic myeloid leukemia.

Leuk Lymphoma 2021 03 6;62(3):669-678. Epub 2020 Nov 6.

Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Institute of Hematology "L. & A. Seràgnoli", "Sant'Orsola-Malpighi" University Hospital, University of Bologna, Bologna, Italy.

Health-related quality of life (HRQOL) assessment is important to facilitate decisions in the current treatment landscape of chronic myeloid leukemia (CML). Therefore, the availability of a validated HRQOL questionnaire, specifically developed for CML patients treated with tyrosine kinase inhibitors (TKIs), may enhance quality of research in this area. We performed an international study including 782 CML patients to assess the validity of the EORTC QLQ-CML 24 questionnaire, and to generate HRQOL reference values to facilitate interpretation of results in future studies. Internal consistency, assessed with Cronbach's alpha coefficients, ranged from 0.66 to 0.83. In the confirmatory factor analysis, all standardized factor loadings exceeded the threshold of 0.40 (range 0.49-0.97), confirming the hypothesized scale structure. Reference values stratified by age and sex were also generated. Our findings support the use of the EORTC QLQ-CML 24, in conjunction with the EORTC QLQ-C30, as a valuable measure to assess HRQOL in CML patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2020.1838509DOI Listing
March 2021

Perls Stain Grade in Bone Marrow Aspirate Correlates with Overall Survival in Low-Risk Myelodysplastic Patients.

Acta Haematol 2020 Oct 2:1-5. Epub 2020 Oct 2.

Hematology and Bone Marrow Transplant Unit, A. Businco Hospital, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

Low-risk patients with myelodysplastic syndromes (MDS) are inclined to long-term accumulation of iron in the organs due mostly to red blood cell transfusion and ineffective erythropoiesis. The effect of free toxic iron species in the liver and heart sites is well known, but recent knowledge assumes that oxidant-mediated tissue injury is also effective in the bone marrow. We aimed to investigate the predictive value of bone marrow iron accumulation as demonstrated by Perls staining on the overall survival (OS) of MDS patients. We retrospectively analyzed 114 low and intermediate-I IPSS risk MDS patients who were diagnosed at our institution in the last 20 years. The median age was 70 years (range 32-93). Two different experienced hematologists analyzed all samples. Perls Prussian blue stain was used to stain the bone marrow, which was assessed by modified Gale's grading and then correlated with the outcome. Twenty-seven patients had grade 1 (+), 31 grade 2 (++), and 56 grade 3 (+++). The 20-year OS was significantly lower in patients with a higher Perls score (6.8 ± 6.1%, median 80 ± 7 months in grade 3; 18.7 ± 9.4%, median 70 ± 17 months in grade 2; 33.2 ± 16.4%, median 144 ± 18 months in grade 1; p = 0.011); bone marrow iron overload (p = 0.003; HR 1.7) and transfusion dependency (0.001; HR 2.6) negatively impacted on survival. We suggest that a higher grade of iron storage at diagnosis can impact on the outcome in MDS patients. Perls stain, together with ferritin and the blood transfusional burden, could be another marker at diagnosis of iron-related toxicity that predicts survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000510111DOI Listing
October 2020

White Blood Cell Count Nadir and Duration of Aplasia Do Not Associate with Treatment Outcome in Adult Patients with Acute Myeloid Leukemia Undergoing Intensive Chemotherapy.

Chemotherapy 2020 18;65(3-4):110-114. Epub 2020 Sep 18.

Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy,

Introduction: Adult patients with acute myeloid leukemia (AML) are usually treated with intensive chemotherapy, leading to prolonged bone marrow aplasia. It is usually assumed that a short duration of aplasia could be a surrogate marker of poor therapeutic efficacy in clearing bone marrow blasts, especially in older patients. No studies have evaluated the usefulness of such a surrogate marker in younger AML patients treated with intensive chemotherapy.

Materials And Methods: In the present study, we retrospectively assessed the role of white blood cell (WBC) count nadir and duration of aplasia in 68 patients with AML treated with intensive chemotherapy and potentially candidate to stem cell transplantation.

Results: The median (interquartile range) bone marrow aplasia was 25 days, and the mean WBC count nadir from chemotherapy start was at day +12, whereas the median neutrophil recovery occurred at day +24. No significant differences were found between responders and nonresponders for mean aplasia duration (25 vs. 26 days, p value = 0.76), mean WBC count nadir (12 vs. 12 days, p value = 0.86), and median neutrophil recovery (24 vs. 24, p value = 0.67).

Discussion: The present study evaluated the potential prognostic role of WBC count nadir and duration of aplasia, demonstrating that they are not associated with treatment outcomes in adult patients with AML treated with intensive chemotherapy. Therefore, a short duration of aplasia seems not linked to poor therapeutic efficacy in clearing bone marrow blasts. Our findings, although needing validation in larger and more homogeneous cohorts, may offer helpful clues in the management of aplasia of AML patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509816DOI Listing
September 2020

Defibrotide in the COVID-19 coagulopathy: What is the timing?

J Thromb Haemost 2020 11;18(11):3113-3115

Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.15100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537223PMC
November 2020

Rituximab Monotherapy or in Combination with Bendamustine Is Not Inferior to Rituximab-CHOP Regimen in the Treatment of Patients with Splenic Marginal Zone Lymphoma in the Real Life.

Acta Haematol 2020 Sep 4:1-5. Epub 2020 Sep 4.

Ematologia e CTMO, Ospedale Businco, AOB, Cagliari, Italy.

Splenic marginal zone lymphoma (SMZL) is a rare lymphoma belonging to the marginal zone lymphoproliferative disorders. Usually, SMZL occurs with indolent presentation and, when required, the standard of care is represented by rituximab-based regimens. No direct comparison of different rituximab-based combinations and polychemotherapy regimens has been conducted to date. In a monocentric cohort of 68 SMLZ patients, we showed that rituximab in monotherapy or in combination with bendamustine, compared with rituximab associated with the polychemotherapy cycle cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), resulted in a higher 5-year progression-free survival (91.3 ± 9% and 75 ± 15.7% vs. 30.8 ± 12.1%, p < 0.001). Platelets at diagnosis <100 ×109/L (p = 0.034, HR = 4.3) and transformation into diffuse large B-cell lymphoma (p = 0.031, HR = 4.3) were associated with a lower overall survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509596DOI Listing
September 2020

Health Related Quality of Life in Patients with Onco-hematological Diseases.

Clin Pract Epidemiol Ment Health 2020 30;16:174-179. Epub 2020 Jul 30.

Dipartimento di Scienze Mediche e Sanita Pubblica, Universita di Cagliari, Cagliari, Italy.

Background: HRQoL is generally conceptualized as a broad multidimensional construct that refers to patients' perceptions of the impact of disease and its treatment on their physical, psychological, and social functioning and well-being. Little is known in patients with onco-hematological cancer in comparison with the general population and other chronic diseases.

Objective: We assessed HRQoL in patients diagnosed with haematological cancers in comparison with the general population and other chronic diseases.

Methods: The questionnaire Short Form (SF)-12 was administered to 62 patients with onco-hematological disease and results were compared with 702 controls (184 healthy people, 37 Major Depression, 201 Multiple Sclerosis; 23 Wilson disease; 46 Carotidal Atherosclerosis; 60 Celiac disease; 151 solid tumours).

Results: HRQoL in patients diagnosed with a haematological cancer was significantly worse in comparison with the general population (F= 43.853, p <0.00001) but similar when compared with solid tumour and other chronic diseases such as Major Depression and Carotid Atherosclerosis. In addition, HRQoL in patients diagnosed with a haematological cancer was significantly higher than that due to Celiac disease (p <0.00001) and Wilson's disease (p= 0.02), and lower than that due to Multiple Sclerosis (p= 0.032).

Conclusion: This study confirmed that haematological cancers negatively affects overall HRQoL. The results showed an impact of haematological cancers on HRQoL that is similar to what found in patients with solid tumors, Major Depression and Carotid Atherosclerosis. Current successful therapeutic strategy achieved in the treatment of haematological cancers not only positively impact on survival rate but also could improve the overall HRQoL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1745017902016010174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431682PMC
July 2020

Complement-mediated oxidative damage of red cells impairs response to eculizumab in a G6PD-deficient patient with PNH.

Blood 2020 12;136(26):3082-3085

Laboratory of Cancer Genetics and Gene Transfer, Core Research Laboratory-Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2020007780DOI Listing
December 2020

Evaluating the Thresholds for Clinical Importance of the EORTC QLQ-C15-PAL in Patients Receiving Palliative Treatment.

J Palliat Med 2021 Mar 24;24(3):397-404. Epub 2020 Aug 24.

University Hospital of Psychiatry II, Medical University of Innsbruck, Innsbruck, Austria.

The EORTC QLQ-C15-PAL is a shortened version of the widely used EORTC QLQ-C30. This questionnaire was developed to measure the symptoms and functional health of patients receiving palliative care. To enhance clinical interpretability of the EORTC QLQ-C15-PAL, our aim was to evaluate the sensitivity and specificity of thresholds for clinical importance developed previously for the QLQ-C30 when applied to the QLQ-C15-PAL scales. Cross-sectional observational study. Patients with cancer receiving any type of palliative treatment. Patients completed the EORTC QLQ-C15-PAL and anchor items on limitations, worries, and need for help for each of the health domains covered by the questionnaire. The anchor items were summarized in a binary criterion for clinical importance to calculate the sensitivity and specificity of the thresholds for clinical importance. In total, 225 patients participated in the study (mean age 64.5 years). Patients were recruited from Austria, Italy, the Netherlands, Poland, Spain, and the United Kingdom. The thresholds for clinical importance for the QLQ-C15-PAL scales showed a median sensitivity of 0.88 (range: 0.82 for sleep disturbances to 1.00 for dyspnea) and a median specificity of 0.74 (range: 0.54 for dyspnea to 0.89 for constipation). The thresholds for clinical importance showed high sensitivity and mostly high specificity in identifying clinically important symptoms and functional health impairments as assessed by the QLQ-C15-PAL. These thresholds will facilitate interpretation of EORTC QLQ-C15-PAL scores in daily clinical practice and clinical research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jpm.2020.0159DOI Listing
March 2021

Multifactorial pathogenesis of COVID-19-related coagulopathy: Can defibrotide have a role in the early phases of coagulation disorders?

J Thromb Haemost 2020 Nov;18(11):3106-3108

Department of Medical Sciences and Public Health, University of Cagliari, Hematology and Transplant Center, Businco Hospital, Azienda Ospedaliera Brotzu, Cagliari, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.15021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405280PMC
November 2020

High serum ferritin levels in newly diagnosed patients with myelodysplastic syndromes are associated with greater symptom severity.

Int J Hematol 2020 Aug 25;112(2):141-146. Epub 2020 Jun 25.

Data Center and Health Outcomes Research Unit, Italian Group for Adult Haematologic Diseases (GIMEMA), Rome, Italy.

We examined the association between serum ferritin (SF) levels and patient-reported functional aspects and symptoms, as measured by the EORTC QLQ-C30, in newly diagnosed patients with myelodysplastic syndromes (MDS). Analysis was conducted on 497 MDS patients who were classified in two groups based on the SF value of 1000 ng/mL. Clinically relevant differences of patient-reported functional and symptom scales were evaluated and classified as small, medium and large, based on established thresholds. Multivariable linear regression analysis was performed to account for potential confounding factors. Patients with SF of ≥ 1000 ng/mL reported statistically significant and clinically relevant worse outcomes across various health domains. Dyspnea was the symptom indicating the largest difference and mean scores of patients with higher and lower SF levels were 40 and 24.3, respectively (p = 0.005), indicating a large clinically relevant difference (Δ = 15.7). Further research is needed to better understand the relationship between SF levels and specific health-related quality of life domains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-020-02920-yDOI Listing
August 2020

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-020-04102-6DOI Listing
July 2020

Systemic Mastocytosis with Associated Primary Myelofibrosis.

Indian J Hematol Blood Transfus 2020 Apr 28;36(2):442-443. Epub 2019 Oct 28.

2Dipartimento di Scienze Mediche e Sanità Pubblica, SC Ematologia e CTMO, Ospedale Businco, P.O. Businco, Università di Cagliari, Azienda Ospedaliera Brotzu, Via Jenner, sn, 09124 Cagliari, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12288-019-01225-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229127PMC
April 2020

Could ruxolitinib be effective in patients with COVID-19 infection at risk of acute respiratory distress syndrome (ARDS)?

Ann Hematol 2020 Jul 14;99(7):1675-1676. Epub 2020 May 14.

Ematologia e CTMO, Ospedale Businco Azienda Ospedaliera Brotzu, Dipartimento di Scienze Mediche e Sanità Pubblica, Università di Cagliari, Via Jenner, sn, 09124, Cagliari, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-020-04067-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220809PMC
July 2020