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.

Navigating 'grey areas' and challenges during evaluation of transplant eligibility in specific myelofibrosis populations: a perspective on behalf of the Chronic Malignancies Working Party of the EBMT.

Significant efforts have been made to effectively select myelofibrosis (MF) patients who can benefit from allogeneic hematopoietic cell transplantation (allo-HCT), the only current cure for MF. The recent EBMT/ELN 2024 recommendations offer valuable guidance for hematologists and transplant physicians. However, several grey areas remain in day-to-day clinical practice regarding the feasibility and optimal preparation for transplantation in patients with this disease.

Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial.

Background: Access to allogeneic haematopoietic stem-cell transplantation (HSCT) remains challenging for older patients (aged >60 years) with acute myeloid leukaemia. We aimed to evaluate the efficacy of venetoclax plus decitabine as first-line therapy and bridge to transplantation in this patient population.

Methods: This multicentre, single-arm, phase 2 trial was conducted in 20 Gruppo Italiano Trapianto Midollo Osseo (GITMO) centres in Italy.

Hematopoietic stem cell transplantation for CTLA-4 insufficiency across Europe: A European Society for Blood and Marrow Transplantation Inborn Errors Working Party study.

Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) insufficiency causes a primary immune regulatory disorder characterized by lymphoproliferation, dysgammaglobulinemia, and multiorgan autoimmunity including cytopenias and colitis.

Objective: We examined the outcome of hematopoietic stem cell transplantation (HSCT) for CTLA-4 insufficiency and study the impact of pre-HSCT CTLA-4 fusion protein (CTLA-4-Ig) therapy and pre-HSCT immune dysregulation on survival and immunologic outcome.

Methods: This was a retrospective study of HSCT for CTLA-4 insufficiency and 2q33.

Successful CAR-T cell therapy in a refractory MCL patient with bacterial, fungal and COVID-19 infection: a case report.

Background: The COVID-19 pandemic has had a significant impact on the management and care of onco-hematological patients, particularly those with lymphoproliferative disorders who are at higher risk for COVID-19 associated bacterial and fungal superinfections.

Case Presentation: We present the successful treatment of a 44-year-old male patient with refractory mantle cell lymphoma treated with chimeric antigen receptor T (CAR-T) cell therapy, despite concurrent COVID-19 infection. The patient developed grade II cytokine release syndrome, requiring admission to the intensive care unit.

Donor Lymphocyte Infusion in the Treatment of Post-Transplant Relapse of Acute Myeloid Leukemias and Myelodysplastic Syndromes Significantly Improves Overall Survival: A French-Italian Experience of 134 Patients.

Background: Disease relapse after allogeneic stem cell transplantation (allo-SCT) is the main challenge for curing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We investigated the overall survival (OS) after allo-SCT relapse according to different therapeutic approaches.

Methods: We analyzed 134 patients who relapsed after allo-SCT performed between 2015 and 2021 at Saint-Antoine University Hospital, Paris and Spedali Civili di Brescia, Brescia.

Evaluation of Circulating Endothelial Cells as Direct Marker of Endothelial Damage in Allo-Transplant Recipients at High Risk of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome.

Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a rare but potentially fatal complication following allogenic hematopoietic cell transplantation (allo-HCT). Timely identification of SOS/VOD to allow for prompt treatment is critical, but identifying a VOD-predictive biomarker remains challenging. Given the pivotal role of endothelial dysfunction in SOS/VOD pathophysiology, the CECinVOD study prospectively evaluated levels of circulating endothelial cells (CECs) in patients undergoing allo-HCT with a myeloablative conditioning (MAC) regimen to investigate the potential of CEC level in predicting and diagnosing SOS/VOD.

Nutritional Strategies To Improve VRE Control.

The rise of Vancomycin-resistant enterococci (VRE) strains among cellular therapy recipients raises concerns due to increased morbidity, mortality, and hospitalization costs, particularly impacting transplanted patients with diminished survival expectations. Recent research linking lactose to Enterococcus growth and graft-versus-host disease (GVHD) emphasizes the need for data on reducing lactose in the diets of VRE-carrying patients, especially in cellular therapy contexts like CAR-T or allogeneic hematopoietic stem cell transplantation. Responding to elevated VRE positivity rates in rectal swabs among patients in our BMT Unit, a unique nutritional strategy was implemented, introducing lactose-free milk and strictly enforcing lactose-free diets.

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.

Twenty years of evolution of CML therapy: how the treatment goal is moving from disease to patient.

The introduction of imatinib in 2000 opened the era of tyrosine kinase inhibitors (TKIs) for CML therapy and has revolutionized the life expectancy of CML patients, which is now quite like the one of the healthy aged population. Over the last 20 years, both the TKI therapy itself and the objectives have undergone evolutions highlighted and discussed in this review. The main objective of the CML therapy in the first 10 years after TKI introduction was to abolish the disease progression from the chronic to the blastic phase and guarantee the long-term survival of the great majority of patients.

Nutritional intervention with TGF-beta enriched food for special medical purposes (TGF-FSMP) is associated with a reduction of malnutrition, acute GVHD, pneumonia and may improve overall survival in patients undergoing allogeneic hematopoietic stem transplantation.

Malnutrition in allogeneic stem cell transplant (allo-SCT) is associated with poor outcomes. Supplementation with Foods for Special Medical Purposes may be a valid alternative to enteral nutrition or total parental nutrition to reduce malnutrition in allo-SCT. In this study, 133 patients consecutively allo-transplanted were assessed for nutritional status by Patient- Generated Subjective Global Assessment (PG-SGA) and supplemented with TGF-beta enriched Food for Special Medical Purposes (TGF-FSMP).

Minimal Residual Disease Detection at RNA and Leukemic Stem Cell (LSC) Levels: Comparison of RT-qPCR, d-PCR and CD26+ Stem Cell Measurements in Chronic Myeloid Leukemia (CML) Patients in Deep Molecular Response (DMR).

A Deep Molecular Response (DMR), defined as a transcript at levels ≤ 0.01% by RT-qPCR, is the prerequisite for the successful interruption of treatment among patients with Chronic Myeloid Leukemia (CML). However, approximately 50% of patients in Treatment-Free Remission (TFR) studies had to resume therapy after their transcript levels rose above the 0.

Bone marrow CD34+ molecular chimerism as an early predictor of relapse after allogeneic stem cell transplantation in patients with acute myeloid leukemia.

Background: Minimal residual disease (MRD) monitoring is an important tool to optimally address post-transplant management of acute myeloid leukemia (AML) patients.

Methods: We retrospectively analyzed the impact of bone marrow CD34+ molecular chimerism and on the outcome of a consecutive series of 168 AML patients submitted to allogeneic stem cell transplantation.

Results: The cumulative incidence of relapse (CIR) was significantly lower in patients with donor chimerism on CD34+ cells ≥ 97.

Busulfan or Treosulfan Conditioning Platform for Allogeneic Stem Cell Transplantation in Patients Aged >60 Y With Acute Myeloid Leukemia/Myelodysplastic Syndrome: A Subanalysis of the GITMO AlloEld Study.

Unlabelled: The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing.

Methods: With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%).

High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review.

Background: Chimeric antigen receptor (CAR) T-cell therapy represents the most advanced immunotherapy against relapsed/refractory B cell malignancies. While cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome are distinctive, known CAR T-cell acute adverse events, hematological toxicity has been increasingly reported. Cytopenia following CAR T-cell treatment is attributed in most cases to lymphodepletion regimens, bridging chemotherapy, or radiotherapy.

Timely Leukapheresis May Interfere with the "Fitness" of Lymphocytes Collected for CAR-T Treatment in High Risk DLBCL Patients.

The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematological diseases. However, approximately 60% of patients relapse after CAR-T cell therapy, and no clear cause for this failure has been identified. The objective of the Bio-CAR-T BS study (ClinicalTrials.