José Fernandes

Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL

Prognosis of Philadelphia-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in the elderly has improved during the imatinib era. We investigated dasatinib, another potent tyrosine kinase inhibitor, in combination with low-intensity chemotherapy. Patients older than age 55 years were included in the European Working Group on Adult ALL (EWALL) study number 01 for Ph(+) ALL (EWALL-PH-01 international study) and were treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction. Patients in complete remission continued consolidation with dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone reinductions for 18 months followed by dasatinib until relapse or death. Seventy-one patients with a median age of 69 years were enrolled; 77% had a high comorbidity score. Complete remission rate was 96% and 65% of patients achieved a 3-log reduction in BCR-ABL1 transcript levels during consolidation. Only 7 patients underwent allogeneic hematopoietic stem cell transplantation. At 5 years, overall survival was 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24 were tested for mutation by Sanger sequencing, and 75% were T315I-positive. BCR-ABL1(T315I) was tested by allele-specific oligonucleotide reverse transcription-quantitative polymerase chain reaction in 43 patients and detection was associated with short-term relapses. Ten patients (23%) were positive before any therapy and 8 relapsed, all with this mutation. In conclusion, dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph(+) ALL. Monitoring of BCR-ABL1(T315I) from diagnosis identified patients with at high risk of early relapse and may help to personalize therapy.

Autoimmune hemolytic anemias and IgG antierythrocyte autoantibodies in Waldenström's macroglobulinemia : association with FcγRIIa polymorphism

Autoimmune hemolytic anemias and IgG antierythrocyte autoantibodies in Waldenstroms macroglobulinemia: association with Fc γ RIIa polymorphism

Molecular prognostic factors in acute myeloid leukemia receiving first-line therapy with azacitidine

Elderly patients with acute myeloid leukemia (AML), secondary AML and high-risk cytogenetics AML are generally not candidates as they respond poorly to potentially curative treatment with intensive chemotherapy (ICT) followed or not by allogeneic stem cell transplantation (allo-SCT).1 Azacitidine (AZA) has demonstrated a survival improvement in high-risk myelodysplastic syndromes (MDS) and AML with 20–30% bone marrow (BM) blasts, and is also promising in AML with >30% BM blasts.2, 3, 4 Although gene mutations are now routinely included among the prognostic factors of AML treated with ICT,5 their prognostic impact on AML treated with AZA is unknown. We report prognostic factors, including the mutational status of 18 genes assessed by next-generation sequencing (NGS), in 96 newly diagnosed AML patients who received the first line treatment with AZA.