Translational Research on Azacitidine Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2).

The achievement of complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undertaking curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong disease-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) to best supportive care (BSC) in elderly AML patients who achieved CR following intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next-Generation Sequencing (NGS).

FLT3-Mutated Leukemic Stem Cells: Mechanisms of Resistance and New Therapeutic Targets.

Despite the availability of target drugs in the first and second line, only 30% of FLT3mut AMLs are cured. Among the multiple mechanisms of resistance, those of FLT3mut LSC are the most difficult to eradicate because of their metabolic and genomic characteristics. Reactivation of glycogen synthesis, inhibition of the RAS/MAPK pathway, and degradation of FLT3 may be potential aids to fight the resistance of LSC to FLT3i.

Azacitidine Post-Remission Therapy for Elderly Patients with AML: A Randomized Phase-3 Trial (QoLESS AZA-AMLE).

This phase-3 randomized multicenter trial evaluated the efficacy of subcutaneous azacitidine (AZA) post-remission therapy vs. best supportive care (BSC) in elderly acute myeloid leukemia (AML) patients. The primary endpoint was the difference in disease-free survival (DFS) from complete remission (CR) to relapse/death.

Overcoming Resistance: FLT3 Inhibitors Past, Present, Future and the Challenge of Cure.

FLT3 ITD and TKD mutations occur in 20% and 10% of Acute Myeloid Leukemia (AML), respectively, and they represent the target of the first approved anti-leukemic therapies in the 2000s. Type I and type II FLT3 inhibitors (FLT3i) are active against FLT3 TKD/ITD and FLT3 ITD mutations alone respectively, but they still fail remissions in 30-40% of patients due to primary and secondary mechanisms of resistance, with variable relapse rate of 30-50%, influenced by NPM status and FLT3 allelic ratio. Mechanisms of resistance to FLT3i have recently been analyzed through NGS and single cell assays that have identified and elucidated the polyclonal nature of relapse in clinical and preclinical studies, summarized here.

The Time Has Come for Targeted Therapies for AML: Lights and Shadows.

Acute myeloid leukemia (AML) is a complex disease characterized by genetic and clinical heterogeneity and high mortality. After 40 years during which the standard of care for patients evolved very little, the therapeutic landscape has recently seen rapid changes, with the approval of eight new drugs by the Food and Drug Administration (FDA) within the last 2 years, providing new opportunities, as well as new challenges, for treating clinicians. These therapies include FLT3 inhibitors midostaurin and gilteritinib, CPX-351 (liposomal cytarabine and daunorubicin), gemtuzumab ozogamicin (GO, anti-CD33 monoclonal antibody conjugated with calicheamicin), IDH1/IDH2 inhibitors ivosidenib and enasidenib, Hedgehog inhibitor glasdegib, and BCL-2 inhibitor venetoclax.

A novel method to evaluate prethawing viability of cryopreserved CD34+ hematopoietic stem cells for autologous transplantation.

Background: Cryopreservation of CD34+ hematopoietic stem cells (HSCs) is associated with variable loss of viability. Although postfreezing CD34+ cell viability can be assessed on the sampling tube (bag tail) directly connected to the main bag (mother bag), results often underestimate the actual viability observed when the mother bag is thawed and reinfused. We assessed a novel method to measure postfreezing CD34+ cell viability, based on small bag (minibag) samples; results were compared with those obtained on the corresponding mother bags and bag tails.

Feasibility and Outcome of a Phase II Study of Intensive Induction Chemotherapy in 91 Elderly Patients with AML Evaluated Using a Simplified Multidimensional Geriatric Assessment.

Introduction: We prospectively tested in a phase II study high-dose aracytin and idarubicin plus amifostine as induction regimen in 149 patients with acute myeloid leukaemia (AML) aged ≥ 60 years, evaluated by a simplified multidimensional geriatric assessment (MGA).

Methods: Ninety-one fully or partially fit patients (61%) were allocated to intensive chemotherapy and 58 (39%) frail patients to best supportive care (BSC). Intensively treated patients, showing early death and complete response (CR) rate respectively of 5.

GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia.

We designed a trial in which postremission therapy of young patients with de novo acute myeloid leukemia (AML) was decided combining cytogenetics/genetics and postconsolidation levels of minimal residual disease (MRD). After induction and consolidation, favorable-risk patients (FR) were to receive autologous stem cell transplant (AuSCT) and poor-risk patients (PR) allogeneic stem cell transplant (AlloSCT). Intermediate-risk patients (IR) were to receive AuSCT or AlloSCT depending on the postconsolidation levels of MRD.

Primary B-cell lymphoblastic lymphoma of the testis.

We present a rare case of primary lymphoblastic B-cell lymphoma of the testis focusing on ultrasonographic and pathological features and clinical implications. Pathological examination revealed primary testicular lymphoblastic B-cell lymphoma which was treated with adjuvant chemotherapy, including rachicentesis with administration of chemotherapy and with radiotherapy of contralateral testis. Primary testicular lymphoblastic B cell lymphoma is an aggressive disease and it is necessary a multimodal therapy (surgery, chemotherapy and radiotherapy) to prevent metastasis.

Mobilization-driven postconsolidation therapy in elderly patients with acute myeloid leukemia: feasibility and efficacy of autologous stem cell transplantation versus low-dose gemtuzumab ozogamicin.

We prospectively evaluated 2 postconsolidation strategies, administered according to the mobilization outcome, in 72 acute myeloid leukemia (AML) fit elderly patients, achieving complete remission after the first high-dose cytarabine-based induction. Autologous stem cell transplantation (ASCT) was performed in patients collecting ≥3 × 10(6) CD34(+)/kg and low-dose gemtuzumab ozogamicin (GO) was performed in poor mobilizers (collecting <3 × 10(6) CD34(+)/kg). Fifty-five patients (76.

Immunostaining for nucleophosmin in bone marrow trephine biopsy specimens in acute myeloid leukemias.

Objective: To evaluate the technicalfeasibility of nucleophosmin (NPM) staining and the problems of interpretations by pathologists in an academic regional hospital in Italy.

Study Design: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells that presents genetic abnormalities in several genes, including NPM. Mutations of the NPM gene occur in 35% of patients with AML with normal karyotype, causing cytoplasmic rather than nuclear localization of the protein.

A new intensive induction schedule, including high-dose Idarubicin, high-dose Aracytin and Amifostine, in older AML patients: feasibility and long-term results in 42 patients.

Objective: We evaluated the feasibility of a new regimen in elderly patients with acute myeloid leukemia (AML). The main end points were overall response rate (ORR) and toxicity; secondary end points were feasibility of peripheral blood stem cells (PBSC) collection, leukemia-free survival, and overall survival (OS).

Patients And Methods: We treated 42 fit elderly patients with high-dose (HD) idarubicin plus HD-cytarabine (Ara-C), with amifostine.

Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma.

We present the results of a phase 2 study using thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) in the treatment of 50 patients older than 65 years with newly diagnosed multiple myeloma. Thalidomide 100 mg was administered orally at bedtime continuously, dexamethasone 40 mg was administered orally on days 1 to 4 and 9 to 12, and pegylated liposomal doxorubicin 40 mg/m2 was administered intravenously on day 1 over the 28-day cycle. Response was assessed according to the EBMT criteria.

Low-dose thalidomide with pegylated liposomal doxorubicin and high-dose dexamethasone for relapsed/refractory multiple myeloma: a prospective, multicenter, phase II study.

The aim of this prospective, multicenter, phase II study was to investigate the combination of pegylated liposomal doxorubicin (Caelyx) 40 mg/m2 on day 1 every 28 days, dexamethasone 40 mg p.o. on days 1-4 and 9-12 and thalidomide 100 mg daily in 50 patients with advanced multiple myeloma.