Exploring the role of PARP1 inhibition in enhancing antibody-drug conjugate therapy for acute leukemias: insights from DNA damage response pathway interactions.

Background: The introduction of antibody-drug conjugates represents a significant advancement in targeted therapy of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Our study aims to investigate the role of the DNA damage response pathway and the impact of PARP1 inhibition, utilizing talazoparib, on the response of AML and ALL cells to Gemtuzumab ozogamicin (GO) and Inotuzumab ozogamicin (INO), respectively.

Methods: AML and ALL cells were treated with GO, INO and γ-calicheamicin in order to induce severe DNA damage and activate the G2/M cell-cycle checkpoint in a dose- and time-dependent manner.

Outcome of adult acute myeloid leukemia patients with extramedullary disease and treatment with venetoclax/hypomethylating agents.

We evaluated response to VEN/HMA in 46 patients with acute myeloid leukemia (AML) characterized by extramedullary disease (EMD). Median age was 65 (range, 19-81) years. Patients had a median of two EMD sites (range, 1-5) and 35 (76%) patients had concurrent bone marrow involvement.

Multiple Myeloma: The Role of Autologous Stem Cell Transplantation in the Era of Immunotherapy.

Upfront high-dose therapy with melphalan (HDM) followed by autologous stem cell transplantation (ASCT) has established itself as a core treatment for newly diagnosed multiple myeloma (NDMM) patients in the past 30 years. Induction therapy, HDM-ASCT, and subsequent consolidation and maintenance therapy comprise the current fundamental framework for MM treatment. The introduction of anti-CD38 monoclonal antibodies such as daratumumab and isatuximab has changed the treatment paradigm for transplant-eligible NDMM patients in that quadruplets have become the new standard induction therapy.

Impact of inotuzumab ozogamicin on outcome in relapsed or refractory acute B-cell lymphoblastic leukemia patients prior to allogeneic hematopoietic stem cell transplantation and risk of sinusoidal obstruction syndrome/venous occlusive disease.

We evaluated 58 patients with relapsed or refractory (r/r) acute B-lymphoblastic leukemia (B-ALL; median age 42.5 years; range, 16-69 years), treated with inotuzumab ozogamicin (INO) between 2016-2022 and who received an allogeneic hematopoietic stem cell transplantation (allo-HCT) consecutively. Forty-seven (81%) of the 58 patients were heavily pretreated receiving intensive chemotherapy +/- tyrosine kinase inhibitor, blinatumomab in 24 (41%) and allo-HCT at first-line in 11 (19%) patients.

Uncovering the expression of circPVT1 in the extracellular vesicles of acute myeloid leukemia patients.

Extracellular vesicles (EVs) act as molecular mediators in the tumor microenvironment, by shuttling information contained within malignant cells and functioning as regulators of the immune system. Circular (circ)RNAs are characterized by a closed loop-like structure that makes them more stable in the extracellular milieu and suitable to be packaged inside EVs. circPVT1 (hsa_circ_0001821) showed an oncogenic role in several cancer types and immunosuppressive properties in myeloid and lymphoid cell subsets.

Personalizing precision medicine: Patients with AML perceptions about treatment decisions.

Background: This study aims to explore patients' with acute myeloid leukemia perceptions about precision medicine and their preferences for involvement in this new area of shared decision-making.

Methods: Individual semi-structured interviews were conducted in Finland, Italy and Germany (n = 16). The study population included patients aged 24-79 years.

Regions of homozygosity confer a worse prognostic impact in myelodysplastic syndrome with normal karyotype.

Half of the myelodysplastic syndromes (MDS) have normal karyotype by conventional banding analysis. The percentage of true normal karyotype cases can be reduced by 20-30% with the complementary application of genomic microarrays. We here present a multicenter collaborative study of 163 MDS cases with a normal karyotype (≥10 metaphases) at diagnosis.

Hemophagocytic lymphohistiocytosis in gastric cancer: A rare syndrome for the oncologist. Case report and brief review.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by uncontrolled activation of the immune system. HLH is a reactive mononuclear phagocytic response that occurs in association with a constellation of conditions such as malignancies and infections. The clinical diagnosis of HLH remains challenging because HLH can present with symptoms that significantly overlap with other causes of cytopenia, such as sepsis, autoimmune diseases, hematological cancers, and multiorgan failure.

Biological therapy in elderly patients with acute myeloid leukemia.

Introduction: The introduction of target molecules and immunological therapies is changing the treatment landscape of acute myeloid leukemia (AML).

Areas Covered: We recapitulate the biological therapies that can be employed in the treatment of elderly patients with AML. Alongside small molecules inhibitors that target specific gene mutations, antibodies, tumor microenvironment modulators, and cellular therapies are being developed for the cure of the disease.

AVALON: The Italian cohort study on real-life efficacy of hypomethylating agents plus venetoclax in newly diagnosed or relapsed/refractory patients with acute myeloid leukemia.

Background: Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia.

Methods: AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax-based therapies from 2015 to 2020.

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol.

IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19−86).

Baseline cluster of differentiation 22 fluorescent intensity correlates with patient outcome after Inotuzumab Ozogamicin treatment.

Antigen-directed target therapy for B-cell acute lymphoblastic leukemia (B-ALL) is now the standard of care for relapsed/refractory (R/R) disease. A comprehensive determination of the target itself is mandatory to aid physician's choice. We determined baseline Cluster of differentiation 22 (CD22) expression percentage and fluorescent intensity on lymphoblasts of 30 patients with R/R B-ALL treated with anti-CD22 immunoconjugate drug Inotuzumab Ozogamicin (INO) and analyzed the impact of both parameters on patient outcome.

Impact of infectious comorbidity and overall time of hospitalization in total outpatient management of acute myeloid leukemia patients following venetoclax and hypomethylating agents.

Venetoclax (VEN) and hypomethylating agent (HMAs) regimens are emerging as the standard of care for unfit for chemotherapy acute myeloid leukemia (AML) patients, but the safety and feasibility of a total outpatient management have not been fully investigated. Fifty-nine AML patients with active disease received VEN and HMAs. Nineteen out of 59 (32.

Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia.

Allogeneic stem cell transplantation still represents the best curative option for most patients with acute myeloid leukemia, but relapse is still dramatically high. Due to their immunologic activity and safety profile, hypomethylating agents (HMAs) represent an interesting backbone for combination therapies. This review reports mechanism of action, safety, and efficacy data on combination strategies based on HMAs in the setting of post-allogeneic stem cell transplant relapse.

Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies.

The members of the Poly(ADP-ribose) polymerase (PARP) superfamily are involved in several biological processes and, in particular, in the DNA damage response (DDR). The most studied members, PARP1, PARP2 and PARP3, act as sensors of DNA damages, in order to activate different intracellular repair pathways, including single-strand repair, homologous recombination, conventional and alternative non-homologous end joining. This review recapitulates the functional role of PARPs in the DDR pathways, also in relationship with the cell cycle phases, which drives our knowledge of the mechanisms of action of PARP inhibitors (PARPi), encompassing inhibition of single-strand breaks and base excision repair, PARP trapping and sensitization to antileukemia immune responses.

Assessment of liver stiffness measurement and ultrasound findings change during inotuzumab ozogamicin cycles for relapsed or refractory acute lymphoblastic leukemia.

In adult patients, acute lymphoblastic leukemia (ALL) is a rare hematological cancer with a cure rate below 50% and frequent relapses. With traditional therapies, patients with relapsed or refractory (R/R) ALL have a survival that may be measured in months; in these patients, inotuzumab ozogamicin (IO) is an effective therapy. IO was linked to increased risk of veno-occlusive disease/sinusoid obstruction syndrome (VOD/SOS), liver injury, and various grade of liver-related complications during clinical trials and real-life settings; however, hepatologic monitoring protocol is not established in this population.