Long-term follow-up of Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) in children and adolescents managed at a single institution over a 20-year period

Chronic myeloid leukaemia (CML) is rare in childhood. In our Institution we managed 30 consecutive Ph+CML patients aged <18 years, according to our adults’ guidelines. Patients with HLA-identical related donor (RD) underwent stem cell transplant (SCT). Since 1989, patients without RD were systematically treated with -interferon (IFN) (median dosage: 6 MU/day). Of 18/19 evaluable patients, 17 (94.5%) achieved haematologic response (HR), 11/17 (65%) cytogenetic response (CyR), complete (CCyR) in 4 (23.5%). Three patients remain in CCyR, 2 achieved BCR-ABL transcript disappearance. Of 13 patients without CCyR, 5 underwent SCT, 4 switched to STI571, 4 progressed. All patients receiving STI571 in chronic phase (CP) obtained sustained CCyR and 3 a persistent molecular response. 8-year survival among IFN-treated patients, censored or not for subsequent therapies, is 62% and 63%. Overall, 13/30 patients underwent SCT: 5 HLA-identical-RD, 5 matched unrelated donor, 2 mismatched-RD, 1 unrelated mismatched umbilical cord blood. Eight allotransplanted patients (6/6 in 1st CP) are in cytogenetic and molecular remission with 8-year survival of 61% from SCT and 69% from diagnosis. In our 20-year experience, the use of IFN in children without matched RD led to prolonged cytogenetic and molecular responses and long-term survival, without impairing the outcome of subsequent SCT

Sustained molecular remission after low dose gemtuzumab-ozogamicin in elderly patients with advanced acute promyelocytic leukemia.

We report here a preliminary experience with gemtuzumab ozogamicin (GO) used at low dosage (3 mg/m2) in 3 elderly patients with acute promyelocytic leukaemia (APL) who presented molecular relapse and were unfit for intensive chemotherapy

Prospective Assessment of Health-Related Quality of Life in Pediatric Patients with Beta-Thalassemia following Hematopoietic Stem Cell Transplantation

Although hematopoietic stem cell transplantation (HSCT) has been widely used to treat pediatric patients with beta-thalassemia major, evidence showing whether this treatment improves health-related quality of life (HRQoL) is lacking. We used child-self and parent-proxy reports to prospectively evaluate HRQoL in 28 children with beta-thalassemia from Middle Eastern countries who underwent allogeneic HSCT in Italy. The PedsQL 4.0 Generic Core Scales were administered to patients and their parents 1 month before and 3, 6, and 18 months after transplantation. Two-year overall survival, thalassemia-free survival, mortality, and rejection were 89.3%, 78.6%, 10.9% and 14.3%, respectively. The cumulative incidence of acute and chronic graft-versus-host disease (GVHD) was 36% and 18%, respectively. Physical functioning declined significantly from baseline to 3 months after HSCT (median PedsQL score, 81.3 vs 62.5; P = .02), but then increased significantly up to 18 months after HSCT (median score, 93.7; P = .04). Agreement between child-self and parent-proxy ratings was high. Chronic GVHD was the most significant factor associated with lower HRQoL scores over time ( P = .02). The child-self and parent-proxy reports showed improved HRQoL in the children with beta-thalassemia after HSCT. Overall, our study provides preliminary evidence-based data to further support clinical decision making in this area

Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience

Abstract In idiopathic thrombocytopenic purpura (ITP), corticosteroids have been widely recognized as the most appropriate first-line treatment, even if the best therapeutic approach is still a matter of debate. Recently, a single high-dose dexamethasone (HD-DXM) course was administered as first-line therapy in adult patients with ITP. In this paper we show the results of 2 prospective pilot studies (monocentric and multicentric, respectively) concerning the use of repeated pulses of HD-DXM in untreated ITP patients. In the monocenter study, 37 patients with severe ITP, age at least 20 years and no more than 65 years, were enrolled. HD-DXM was given in 4-day pulses every 28 days, for 6 cycles. Response rate was 89.2%; relapse-free survival (RFS) was 90% at 15 months; long-term responses, lasting for a median time of 26 months (range 6-77 months) were 25 of 37 (67.6%). In the multicenter study, 95 patients with severe ITP, age at least 2 years and no more than 70 years, were enrolled. HD-DXM was given in 4-day pulses every 14 days, for 4 cycles; 90 patients completed 4 cycles. Response rate (85.6%) was similar in patients classified by age (< 18 years, 36 of 42 = 85.7%; ≥ 18 years, 41 of 48 = 85.4%, P = not significant), with a statistically significant difference between the second and third cycle (75.8% vs 89%, P = .018). RFS at 15 months 81%; long-term responses, lasting for a median time of 8 months (range 4-24 months) were 67 of 90 (74.4%). In both studies, therapy was well tolerated. A schedule of 3 cycles of HD-DXM pulses will be compared with standard prednisone therapy (eg, 1 mg/kg per day) in the next randomized Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) trial

Prevalence, severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes

The primary objective of this study was to investigate factors associated with fatigue severity in newly diagnosed patients with higher-risk myelodysplastic syndromes (MDS). The secondary objectives were to assess symptom prevalence and to examine the relationships between fatigue, quality of life (QoL) and overall symptom burden in these patients. The analyses were conducted in 280 higher-risk MDS patients. Pre-treatment patient-reported fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Female gender (P = 0·018), poor performance status (i.e., ECOG of 2-4) (P < 0·001) and lower levels of haemoglobin (Hb) (P = 0·026) were independently associated with higher fatigue severity. The three most prevalent symptoms were as follows: fatigue (92%), dyspnoea (63%) and pain (55%). Patients with higher levels of fatigue also had greater overall symptom burdens. The mean global QoL scores of patients with the highest versus those with the lowest levels of fatigue were 29·2 [standard deviation (SD), 18·3] and 69·0 (SD, 18·8), respectively and this difference was four times the magnitude of a clinically meaningful difference. Patient-reported fatigue severity revealed the effects of disease burden on overall QoL more accurately than did degree of anaemia. Special attention should be given to the female patients in the management of fatigue

ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia

Abstract Extracellular signal-regulated kinase-1/2 (ERK1/2) is frequently found constitutively activated (p-ERK1/2) in hematopoietic diseases, suggesting a role in leukemogenesis. The aim of this study was to assess the expression and clinical role of p-ERK1/2 in adult acute lymphoblastic leukemia (ALL). In 131 primary samples from adult de novo ALL patients enrolled in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) Leucemia Acute Linfoide (LAL) 2000 protocol and evaluated by flow cytometry, constitutive ERK1/2 activation was found in 34.5% of cases; these results were significantly associated with higher white blood cell (WBC) values (P = .013). In a multivariate analysis, p-ERK1/2 expression was an independent predictor of complete remission achievement (P = .027). Effective approaches toward MEK inhibition need to be explored in order to evaluate whether this may represent a new therapeutic strategy for adult ALL patients

The contribution of rat studies to contemporary knowledge of Major Depressive Disorder: Results from citation analysis

Funding: This study was financed by Animalfree Research—Switzerland, a grant from the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) and by Portuguese National Funds through FCT—Fundação para a Ciência e a Tecnologia, within the CFCUL Unit funding UIDB/00678/2020. TM thanks partial support by CEAUL (funded by FCT—Fundação para a Ciência e a Tecnologia, Portugal, through the project UID/MAT/00006/2019). FP thanks FCT/MCTES for the financial support to CESAM (UIDP/50017/2020 and UIDB/50017/2020), through national funds. Open access publication costs were covered by Animalfree Research-Switzerland and by funding provided by the Ketty and Leif Hjordt Foundation.Major depressive disorder (MDD) is the most severe depression type and one of the leading causes of morbidity worldwide. Animal models are widely used to understand MDD etiology, pathogenesis, and treatment, but the efficacy of this research for patients has barely been systematically evaluated. Such evaluation is important given the resource consumption and ethical concerns incurred by animal use. We used the citation tracking facilities within Web of Science and Scopus to locate citations of original research papers on rats related to MDD published prior to 2013—to allow adequate time for citations—identified in PubMed and Scopus by relevant search terms. Resulting citations were thematically coded in eight categories, and descriptive statistics were calculated. 178 publications describing relevant rat studies were identified. They were cited 8,712 times. More than half (4,633) of their citations were by other animal studies. 794 (less than 10%) were by human medical papers. Citation analysis indicates that rat model research has contributed very little to the contemporary clinical understanding of MDD. This suggests a misuse of limited funding hence supporting a change in allocation of research and development funds targeting this disorder to maximise benefits for patients.Publisher PDFPeer reviewe

Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups

The most effective post-remission treatment to maintain complete remission (CR) in adults aged between 46 and 60 years with acute myeloid leukaemia (AML) is uncertain. Previously untreated patients with AML in CR after induction chemotherapy with daunorubicin and cytarabine were randomized between two intensive courses of consolidation therapy containing high-dose cytarabine, combined with amsacrine or daunorubicin and a standard consolidation and maintenance therapy containing standard dose cytarabine and daunorubicin. One hundred fifty-eight CR patients were assigned to the intensive group and 157 patients to the standard group. After a median follow-up of 7.5 years, the 4-year survival rate was 32 % in the intensive group versus 34 % in the standard group (P = 0.29). In the intensive group, the 4-year relapse incidence was lower than in the standard group: 55 and 75 %, respectively (P = 0.0003), whereas treatment-related mortality incidence was higher: 22 versus 3 % (P < 0.0001). Two intensive consolidation courses containing high-dose cytarabine as post-remission treatment in patients with AML aged between 46 and 60 years old did not translate in better long-term outcome despite a 20 % lower relapse incidence. Better supportive care and prevention of treatment-related complications may improve the overall survival after intensified post-remission therapy in this age group

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p &lt; 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription