Pegaspargase administration and tolerability in patients aged 55 years or older with acute lymphoblastic leukemia treated with the LAL1913 program. A subanalysis of the Campus ALL group.

The adoption of pediatric-inspired regimens for the treatment of Ph-negative acute lymphoblastic leukemia (ALL) in adults has improved prognosis. However, the feasibility of these intensive regimens in older patients is limited, due to the increased incidence of therapy-related side effects, including those related to asparaginase. In this sub-analysis carried out by the Campus ALL network, 90 ALL patients aged 55 or more (median age 59 years) homogeneously treated in real-life according to the GIMEMA LAL1913 program, were analyzed to evaluate the feasibility and tolerability of pegaspargase (PEG-ASP) treatment.

PNH clones prevalence study in ph-negative myeloproliferative neoplasms: a multicenter Italian study.

The prevalence of paroxysmal nocturnal hemoglobinuria (PNH) clones is little investigated in myeloproliferative neoplasms (MPN) patients. The aim of this multicenter study was to evaluate the prevalence of PNH clones (glycosyl-phosphatidyl-inositol lacking) in 119 Ph- negative MPN patients having anemia, LDH elevation, asthenia and history of thrombosis. All the participating centers performed the standardized diagnostic test by using a single lyophilized template for granulocytes, monocytes, and erythrocytes.

Revised "iRR6" model in intermediate-1 risk myelofibrosis patients treated with ruxolitinib.

Background: The response to ruxolitinib after 6 months (RR6) model allows early identification of ruxolitinib-treated myelofibrosis (MF) patients with poorer overall survival (OS); however, it is less applicable to lower-risk patients.

Methods: To further explore this, the authors performed a subanalysis of the "RUX-MF" study (NCT06516406) with an aim to validate the RR6 and to develop a score specific for intermediate-1 DIPSS/MYSEC-PM risk patients.

Results: Among the 776 evaluable patients, 34.

Recommendations for best management of polycythemia vera in Italy: a Delphi consensus statement.

A two-round Delphi panel study assessed consensus among Italian healthcare professionals on the management of polycythemia vera (PV). Six hematologists with expertise in PV developed an online questionnaire containing 39 statements covering PV diagnosis and prognosis, treatment, management of complications, patient referral between transfusionist and hematologist, and patient education/psychosocial support. An Expert Panel of 18 transfusionists/hematologists rated their level of agreement with each statement on a 5-point Likert scale.

Chronic myeloid leukemia outcomes according to baseline risk and first-line treatment in real-world settings: Data from the Italian Network/CML Campus.

Background: Improved outcome has been reported in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) in sponsored trials.

Methods: This is a multicenter prospective cohort study of consecutive patients with newly diagnosed chronic phase CML from 19 regions in Italy. Baseline treatments and prognostic factors on time to first optimal molecular response (≥ molecular response 3, MR3), time to disease progression, time to death from CML, and overall survival (OS) were analyzed using multivariable Fine and Gray models.

Outcomes of allogeneic stem cell transplant in adult Philadelphia negative acute lymphoblastic leukemia patients treated with the pediatric-inspired GIMEMA 1913 protocol. A Campus ALL study.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the best consolidative treatment for high-risk acute lymphoblastic leukemia (ALL). The Campus ALL study group analyzed the clinical outcomes of patients treated in the real-life with the pediatric-inspired and minimal/measurable residual disease (MRD)-oriented GIMEMA LAL1913 protocol who underwent alloHSCT. Key factors impacting on outcomes were MRD and remission status (1 complete remission vs 2 complete remission) at transplant.

SETD2 loss of function is a recurrent event in advanced-phase chronic myeloid leukemia and contributes to genomic instability: SETD2 loss in Chronic Myeloid Leukemia.

The SETD2 tumour suppressor encodes a histone methyltransferase that specifically trimethylates histone H3 on lysine 36 (H3K36me3), a key histone mark implicated in the maintenance of genomic integrity among other functions. We found that SETD2 protein deficiency, mirrored by H3K36me3 deficiency, is a nearly universal event in advanced-phase chronic myeloid leukemia (CML) patients. Similarly, K562 and KCL22 cell lines exhibited markedly reduced or undetectable SETD2/H3K36me3 levels, respectively.

Disease Phenotype Significantly Influences the Outcome After Discontinuation of Ruxolitinib in Chronic Phase Myelofibrosis.

Introduction: In patients with myelofibrosis (MF), overall survival (OS) after ruxolitinib discontinuation is poor, with leukemic transformation, clonal evolution and thrombocytopenia as the main factors worsening prognosis.

Patients And Methods: To assess the impact of disease phenotype on outcome after ruxolitinib discontinuation in chronic phase patients, we performed a sub-analysis of the "RUX-MF" study (NCT06516406), which now includes 1055 MF patients who received ruxolitinib in a real-life context.

Results: After a median follow-up of 3.

Dosing and clinical outcomes of ruxolitinib in patients with myelofibrosis in a real-world setting: Interim results of the Italian observational study (ROMEI).

Background: Myelofibrosis (MF) significantly impacts patients' overall survival (OS) and quality of life (QOL). This prospective study analyzed ruxolitinib dosing patterns and associated clinical outcomes in patients with MF over 12 months.

Methods: ROMEI, a multicenter, observational, ongoing study, enrolled 508 adult patients with MF treated with ruxolitinib.

Uncovering two neutrophil-committed progenitors that immediately precede promyelocytes during human neutropoiesis.

Technological advances have greatly improved our knowledge of myelopoiesis, for example, with the discovery of granulocyte‒monocyte‒dendritic cell (DC) progenitors (GMDPs), monocyte‒DC progenitors (MDPs), common DC progenitors (CDPs) and common monocyte progenitors (cMoPs) on the basis of flow cytometry approaches. Concomitantly, some progress has been made in characterizing the very early phases of human neutropoiesis with the description of novel CD66b progenitors, including eNePs, PMs w/o eNePs, ProNeus, and PreNeus. More recently, we identified four SSCLinCD66bCD45CD34/CD34CD64CD115 cells as the earliest precursors specifically committed to the neutrophil lineage present in human bone marrow (BM), which we called neutrophil-committed progenitors (NCPs, from NCP1s to NCP4s).

Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy.

Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation.

Digital PCR (dPCR) is able to anticipate the achievement of stable deep molecular response in adult chronic myeloid leukemia patients: results of the DEMONSTRATE study.

Chronic Myeloid Leukemia (CML) is marked by the BCR::ABL1 fusion gene. Monitoring tyrosine kinase inhibitor (TKI) therapy response is crucial for treatment management, thus, limitations in Reverse Transcription quantitative PCR's (RT-qPCR) accuracy and sensitivity led to the exploration of alternative methods like digital PCR (dPCR). This study evaluated dPCR efficacy in detecting Minimal Residual Disease (MRD) in CML patients undergoing TKI therapy.

Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study.

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph- ALL) has significantly improved patients' prognosis. Within the Campus ALL network, we analyzed the outcome of adult Ph- ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial to compare the real-life data with the study results. We included 421 consecutive patients; median age 42 years.

Underlying systemic mastocytosis in patients with unexplained osteoporosis: score proposal.

Background: A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking.

Objective: This study aimed at identifying criteria able to predict the diagnosis of SM without skin involvement and provide an indication for bone marrow (BM) assessment.

Methods: We included 139 adult patients with unexplained osteoporosis and suspected SM.

Serum chemistry profiling and prognostication in systemic mastocytosis: a registry-based study of the ECNM and GREM.

Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter.

The Italian Multicentric Randomized OPTkIMA Trial on Fixed vs Progressive Intermittent TKI Therapy in CML Elderly Patients: 3-Years of Molecular Response and Quality of Life Monitoring After Completing the Treatment Plan.

Background: Intermittent treatment with tyrosine kinase inhibitors (TKIs) is an option for elderly chronic myeloid leukemia (CML) patients who are often candidates for life-long treatment.

Materials And Methods: The Italian phase III multicentric randomized Optimize TKIs Multiple Approaches (OPTkIMA) study aimed to evaluate if a progressive de-escalation of TKIs is able to maintain the molecular remission (MR) and to improve Health-Related Quality of Life (HRQoL) in CML elderly patients.

Results: A total of 215 patients in stable MR/MR were randomized to receive an intermittent TKI schedule 1 month ON-1 month OFF for 3 years (FIXED arm; n = 111) vs.

Ropeginterferon versus Standard Therapy for Low-Risk Patients with Polycythemia Vera.

BACKGROUND: Whether phlebotomy alone can adequately maintain target hematocrit in patients with low-risk polycythemia vera (PV) remains elusive. METHODS: In a phase 2 open-label randomized trial, we compared ropeginterferon alfa-2b (ropeg; 100 μg every 2 weeks) with phlebotomy only regarding maintenance of a median hematocrit level (≤45%) over 12 months in the absence of progressive disease (primary end point). In follow-up, crossover to the alternative treatment group was allowed if the primary end point was not met.

Long-Term Results of the Dasatinib-Blinatumomab Protocol for Adult Philadelphia-Positive ALL.

JCO We report the long-term results of the frontline trial with dasatinib and blinatumomab in induction/consolidation (GIMEMA LAL2116, D-ALBA) for adult Philadelphia-positive ALL (Ph+ ALL), which enrolled 63 patients of all ages. At a median follow-up of 53 months, disease-free survival, overall survival, and event-free survival are 75.8%, 80.