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.

Eltrombopag for Low-Risk Myelodysplastic Syndromes With Thrombocytopenia: Interim Results of a Phase II, Randomized, Placebo-Controlled Clinical Trial (EQOL-MDS).

Purpose: In myelodysplastic syndromes (MDS), severe thrombocytopenia is associated with poor prognosis. This multicenter trial presents the second-part long-term efficacy and safety results of eltrombopag in patients with low-risk MDS and severe thrombocytopenia.

Methods: In this single-blind, randomized, placebo-controlled, phase-II trial of adult patients with International Prognostic Scoring System low- or intermediate-1-risk MDS, patients with a stable platelet (PLT) count (<30 × 10/mm) received eltrombopag or placebo until disease progression.

Long-term quality of life of patients with acute promyelocytic leukemia treated with arsenic trioxide vs chemotherapy.

The main objective of this study was to compare the long-term health-related quality of life of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) vs ATRA plus standard chemotherapy. Patients previously enrolled in the randomized controlled trial APL0406 were considered eligible for this follow-up study. The following patient-reported outcome measures were used: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20), and the Short Form Health Survey 36 (SF-36).

A multicenter total therapy strategy for adult Philadelphia chromosome positive acute lymphoblastic leukemia patients: final results of the GIMEMA LAL1509 protocol.

The GIMEMA LAL1509 protocol, designed for adult (≥18-60 years) de novo Ph+ acute lymphoblastic leukemia patients, was based on a dasatinib plus steroids induction - with central nervous system prophylaxis - followed by dasatinib alone in patients in complete molecular response or chemotherapy and/or allogeneic transplantation in patients not reaching a complete molecular response. Sixty patients (median age 41.9 years) were enrolled: 33 were p190+, 18 p210+ and 9 p190/p210+.

Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.

Background: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor.

Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle.

Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP.

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR).

Management of early stage chronic myeloid leukemia: state-of-the-art approach and future perspectives.

Tyrosin kinase inhibitors (TKI), have dramatically changed the natural history of chronic myeloid leukemia (CML) leading to an impressive increase in overall survival rates and allowing many CML patients to achieve a close-to-normal life expectancy. Unfortunately, there is growing evidence that these drugs are not curative, about 30-35% of the patients who receive imatinib become resistant or discontinue the drug because of side effects; moreover, 15% of all patients become resistant to all TKIs, a condition which represents the biggest challenge in CML treatment. Recent progresses in CML stem cell biology have identified new agents and therapeutic strategies that can be used to target the CML stem cell compartment.

WT1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia.

We reviewed the frequency and prognostic significance of FLT3 (fms-like tyrosine kinase receptor-3) and NPM (nucleophosmin) gene mutations and WT1 (Wilms' tumor) and BAALC (brain and acute leukemia, cytoplasmic) gene expression in 100 consecutive patients with intermediate and poor cytogenetic risk de novo acute myeloid leukemia (AML) receiving conventional anthracycline-AraC based therapy. We observed a strict relationship between unfavorable karyotype and BAALC >1000 (p = 0.0001).

Reduced intensity conditioning for allograft after cytoreductive autograft in metastatic breast cancer.

The benefits of allografting noted in some malignant diseases might be safely extended to metastatic breast cancer by a combination of cytoreduction with high-dose chemotherapy (HDT) and autologous stem-cell transplant (ASCT) with graft-versus-tumour effect mediated by transplanted donor immune cells with nonmyeloablative allografting (reduced intensity conditioning transplantation, RICT). 17 patients with heavily pretreated disease were given tandem transplants. 13 patients sustained donor engraftment.

A reduced intensity conditioning regimen for allografting following autografting is feasible and has strong anti-myeloma activity.

Sixteen patients with stage III multiple myeloma (MM) and a median age of 51 years were treated with autografting followed by reduced intensity conditioning allotransplantation (RICT). Nine patients are alive in remission at a median of 30 months after their transplants, one patient is alive in relapse and 6 patients died of progressive disease (5) or extensive chronic graft-versus-host disease, infections and progressive disease (1). We suggest that this two-step approach is feasible and it has strong anti-myeloma activity.

Autografting in chronic myeloid leukemia.

Autografting (or autologous stem cell transplant [ASCT]) followed by "rescue" with Philadelphia chromosome (Ph)-negative hematopoietic progenitor cells (HPC) remains a good procedure to guarantee prolonged survival for patients mobilized and autografted soon after diagnosis. Among 50 autografted patients who were treated with interferon alpha (IFN-alpha) and imatinib (for cytogenetic relapse after IFN-alpha), 41 are alive at a median of 51 months (range, 8 to 106 months). Twenty-eight (56%) patients maintain major cytogenetic remission after ASCT + IFN-alpha +/- imatinib.