Results of the PETHEMA ALL-96 trial in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common malignant disease in children, but the frequency of this malignancy in the adult population is low. Most of the studies on the treatment of adult ALL exclude older patients because of the presence of co-morbid disorders or poor performance status. This implies that, in most of the cases, these patients are managed with conservative or individualized strategies outside clinical trials. Thus, the number of trials on elderly ALL published is scarce and frequently, the schedules are not homogenous over Abstract Background and aim: Only 20-30% of elderly patients with acute lymphoblastic leukemia (ALL) are enrolled in clinical trials because of co-morbid disorders or poor performance status. We present the results of treatment of Philadelphia chromosome-negative (Ph)) ALL patients over 55 yr treated in the PETHEMA ALL-96 trial. Patients and methods: From 1996 to 2006, 33 patients P55 yr with Ph) ALL were included. Induction therapy was vincristine, daunorubicin, prednisone, asparaginase, and cyclophosphamide over 5 weeks. Central nervous system (CNS) prophylaxis involved triple intrathecal (IT) therapy, 14 doses over the first year. Consolidation-1 included mercaptopurine, methotrexate, teniposide and cytarabine, followed by one consolidation-2 cycle similar to the induction cycle. Maintenance consisted of mercaptopurine and methotrexate up to 2 yr in complete remission (CR) with monthly reinduction cycles (vincristine, prednisone and asparaginase) during the first year. Results: Median (range) age was 65 yr (56-77). Phenotype (30 patients): early-pre-B 7, common/pre-B 18, T 5. Cytogenetics (28 patients): normal 12, complex 10, t(4;11) 2 and other 4. CR was achieved in 19/33 (57.6%) patients, early death occurred in 12 (36.4%) and 2 (6%) were resistant. Overall survival and disease-free survival probabilities (2 yr, 95% CI) were 39% (21%-57%) and 46% (22%-70%), respectively (median follow up of 24 months). Removal of asparaginase and cyclophosphamide from the induction decreased induction death (OR 0.119, CI 95% 0.022-0.637, P = 0.013) and increased survival (20% vs. 52%, P = 0.05). Conclusions: The prognosis of elderly Ph) ALL patients is poor. In this study, less intensive induction decreased toxic death, allowing delivery of planned consolidation therapy and increased survival probability

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry

Aim To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Genetic and phenotypic characterisation of HIV-associated aggressive B-cell non-Hodgkin lymphomas, which do not occur specifically in this population: diagnostic and prognostic implications

The frequency of aggressive subtypes of B-cell non-Hodgkin lymphoma (B-NHL), such as high-grade B-cell lymphomas (HGBL) with MYC and BCL2 and/or BCL6 rearrangement (HGBL-DH/TH) or Burkitt-like lymphoma (BL) with 11q aberration, is not well known in the HIV setting. We aimed to characterise HIV-associated aggressive B-NHL according to the 2017 WHO criteria, and to identify genotypic and phenotypic features with prognostic impact. Seventy-five HIV-associated aggressive B-NHL were studied by immunohistochemistry (CD10, BCL2, BCL6, MUM1, MYC, and CD30), EBV-encoded RNAs (EBERs), and fluorescence in situ hybridisation (FISH) to evaluate the status of the MYC, BCL2, and BCL6 genes and chromosome 11q. The 2017 WHO classification criteria and the Hans algorithm, for the cell-of-origin classification of diffuse large B-cell lymphomas (DLBCL), were applied. In DLBCL cases, the frequencies of MYC and BCL6 rearrangements (14.9 and 27.7%, respectively) were similar to those described in HIV-negative patients, but BCL2 rearrangements were infrequent (4.3%). MYC expression was identified in 23.4% of DLBCL cases, and coexpression of MYC and BCL2 in 13.0%, which was associated with a worse prognosis. As for BL cases, the expression of MUM1 (30.4%) conferred a worse prognosis. Finally, the prevalence of HGBL-DH/TH and BL-like with 11q aberration are reported in the HIV setting. The phenotypic and genotypic characteristics of HIV-associated aggressive B-NHL are similar to those of the general population, except for the low frequency of BCL2 rearrangements in DLBCL. MYC and BCL2 coexpression in DLBCL, and MUM-1 expression in BL, have a negative prognostic impact on HIV-infected individuals

Efficacy of SARS-CoV-2 vaccination in patients with monoclonal gammopathies: A cross sectional study

SARS-CoV-2 vaccination is the most effective strategy to protect individuals with haematologic malignancies against severe COVID-19, while eliciting limited vaccine responses. We characterized the humoral responses following 3 mo after mRNA-based vaccines in individuals at different plasma-cell disease stages: monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma on first-line therapy (MM), compared with a healthy population. Plasma samples from uninfected MM patients showed lower SARS-CoV-2-specific antibody levels and neutralization capacity compared with MGUS, SMM, and healthy individuals. Importantly, COVID-19 recovered MM individuals presented significantly higher plasma neutralization capacity compared with their uninfected counterparts, highlighting that hybrid immunity elicit stronger immunity even in this immunocompromised population. No differences in the vaccine-induced humoral responses were observed between uninfected MGUS, SMM and healthy individuals. In conclusion, MGUS and SMM patients could be SARS-CoV-2 vaccinated following the vaccine recommendations for the general population, whereas a tailored monitoring of the vaccine-induced immune responses should be considered in uninfected MM patients.This work was partially funded by Grifols, the Departament de Salut of the Generalitat de Catalunya (grant DSL0016 to J Blanco and Grant DSL015 to J Carrillo), the Spanish Health Institute Carlos III (Grant PI17/01518 and PI20/00093 to J Blanco and PI18/01332 to J Carrillo), Fundació Gloria Soler, and the crowdfunding initiatives https://www.yomecorono.com, BonPreu/Esclat and Correos. M Trigueros was supported by a doctoral fellowship from the Departament de Salut from Generalitat de Catalunya (SLT017/20/000095). F Muñoz-Lopez is supported by a doctoral grant from Sorigué Foundation. E Pradenas was supported by a doctoral grant from ANID, Chile: Grant 72180406. M Massanella was granted with RYC2020-028934-I/AEI/10.13039/501100011033 from Spanish Ministry of Science and Innovation and State Research Agency, MCIN/AEI/10.13039/501100011033 and the European Social Fund “investing in your future.

Successfully non-surgical management of flail chest as first manifestation of multiple myeloma: a case report

Background: Multiple myeloma is a malignant neoplasm of the bone marrow characterized by neoplastic proliferation of monoclonal plasma cells with a high relationship with destructive bone disease. We present a case of a patient diagnosed with multiple myeloma and sternal fracture in association with multiple bilateral rib fractures and thoracic kyphosis, who developed a severe acute respiratory failure, thus complicating the initial presentation of multiple myeloma. We discuss the therapeutic implications of this uncommon presentation. Case summary: A 56-year-old man presented to Hematological Department after he had been experiencing worsening back pain over the last five months, with easy fatigability and progressive weight loss. He had no history of previous trauma. The chemical blood tests were compatible with a diagnosis of multiple myeloma. A radiographic bone survey of all major bones revealed, in addition to multiple bilateral rib fractures, a sternal fracture and compression fracture at T9, T10, T11 and L1 vertebrae. Subcutaneous fat biopsy was positive for amyloid. We started treatment with bortezomib and dexamethasone. After 24 h of treatment, he presented dyspnea secondary to flail chest. He required urgent intubation and ventilatory support being transferred to intensive care unit for further management. The patient remained connected to mechanical ventilation (positive pressure) as treatment which stabilized the thorax. A second cycle of bortezomib plus dexamethasone was started and analgesia was optimized. The condition of the patient improved, as evidenced by callus formation on successive computed tomography scans. The patient was taken off the ventilator one month later, and he was extubated successfully, being able to breathe unaided without paradoxical motion. Conclusion: This case highlights the importance of combination between bortezomib and dexamethasone to induce remission of multiple myeloma and the initiation of positive airway pressure with mechanical ventilation to stabilize chest wall to solve the respiratory failure. This combined approach allowed to obtain a quick and complete resolution of the clinical situation