Use of eltrombopag for patients 65 years old or older with immune thrombocytopenia

Background Eltrombopag is useful for immune thrombocytopenia (ITP). However, results of clinical trials may not accurately mirror clinical practice reality. Here we evaluated eltrombopag for primary and secondary ITP in our ≥65‐year‐old population. Methods A total of 106 primary ITP patients (16 with newly diagnosed ITP, 16 with persistent ITP, and 74 with chronic ITP) and 39 secondary ITP patients (20 with ITP secondary to immune disorders, 7 with ITP secondary to infectious diseases, and 12 with ITP secondary to lymphoproliferative disorders [LPD]) were retrospectively evaluated. Results Median age of our cohort was 76 (interquartile range, IQR, 70‐81) years. 75.9% of patients yielded a platelet response including 66.2% complete responders. Median time to platelet response was 14 (IQR, 8‐21) days. Median time on response was 320 (IQR, 147‐526) days. Sixty‐three adverse events (AEs), mainly grade 1‐2, occurred. The most common were hepatobiliary laboratory abnormalities (HBLAs) and headaches. One transient ischemic attack in a newly diagnosed ITP and two self‐limited pulmonary embolisms in secondary ITP were the only thrombotic events observed. Conclusion Eltrombopag showed efficacy and safety in ITP patients aged ≥65 years with primary and secondary ITP. However, efficacy results in LPD‐ITP were poor. A relatively high number of deaths were observed

Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome–negative adult lymphoblastic leukemia

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome–negative (Ph−) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph− adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph− adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance

Novel variants in GALE cause syndromic macrothrombocytopenia by disrupting glycosylation and thrombopoiesis

Glycosylation is recognized as a key process for proper megakaryopoiesis and platelet formation. The enzyme UDP-galactose-4-epimerase, encoded by GALE, is involved in galactose metabolism and protein glycosylation. Here, we studied three patients from two unrelated families who showed lifelong severe thrombocytopenia, bleeding diathesis, mental retardation, mitral valve prolapse, and jaundice. Whole-exome sequencing revealed four variants affecting GALE, three of them previously unreported (Pedigree A: p.Lys78ValfsX32 and p.Thr150Met; Pedigree B: p.Val128Met and p.Leu223Pro). Platelet phenotype analysis showed giant and/or grey platelets, impaired platelet aggregation, and severely reduced alpha and dense granule secretion. Enzymatic activity of the UDP-galactose-4-epimerase enzyme was severely decreased in all patients. Immunoblotting of platelet lysates revealed reduced GALE protein levels, a significant decrease of N-acetyl-lactosamine (LacNAc), demonstrating a hypoglycosylation pattern, reduced surface expression of GPIbα-IX-V complex, and mature β1 integrin, and increased apoptosis. In vitro studies performed with patients' derived megakaryocytes demonstrated normal ploidy and maturation but decreased proplatelet formation due to the impaired glycosylation of the GPIbα and β1 integrin, and reduced externalization to megakaryocyte and platelet membranes. Altered distribution of filamin A and actin and delocalization of the von Willebrand Factor were also demonstrated. Overall, this study expands our knowledge of GALE-related thrombocytopenia and emphasized the critical role of GALE in the physiological glycosylation of key proteins involved in platelet production and function

A new prognostic model identifies patients aged 80 years and older with diffuse large B-cell lymphoma who may benefit from curative treatment: A multicenter, retrospective analysis by the Spanish GELTAMO group

The means of optimally managing very elderly patients with diffuse large B-cell lymphoma (DLBCL) has not been established. We retrospectively analyzed 252 patients aged 80-100 years, diagnosed with DLBCL or grade 3B follicular lymphoma, treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze the influence of the type of treatment and comorbidity scales on progression-free survival (PFS) and overall survival (OS). One hundred sixty-three patients (63%) were treated with chemotherapy that included anthracyclines and/or rituximab, whereas 15% received no chemotherapeutic treatment. With a median follow-up of 44 months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis restricted to the 205 patients treated with any kind of chemotherapy, comorbidity scales did not influence the choice of treatment type significantly. Independent factors associated with better PFS and OS were: age  85 years, R-IPI 3-5 or CIRS > 5). In conclusion, treatment with R-CHOP-like is associated with good survival in a significant proportion of patients. We have developed a simple prognostic model that may aid the selection patients who could benefit from a curative treatment, although it needs to be validated in larger series