Favourable outcomes for high-risk diffuse large B-cell lymphoma (IPI 3-5) treated with front-line R-CODOX-M/R-IVAC chemotherapy: results of a phase 2 UK NCRI trial.

BACKGROUND: Outcomes for patients with high-risk diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP chemotherapy are suboptimal but, to date, no alternative regimen has been shown to improve survival rates. This phase 2 trial aimed to assess the efficacy of a Burkitt-like approach for high-risk DLBCL using the dose-intense R-CODOX-M/R-IVAC regimen. PATIENTS AND METHODS: Eligible patients were aged 18-65 years with stage II-IV untreated DLBCL and an International Prognostic Index (IPI) score of 3-5. Patients received alternating cycles of CODOX-M (cyclophosphamide, vincristine, doxorubicin and high-dose methotrexate) alternating with IVAC chemotherapy (ifosfamide, etoposide and high-dose cytarabine) plus eight doses of rituximab. Response was assessed by computed tomography after completing all four cycles of chemotherapy. The primary end point was 2-year progression-free survival (PFS). RESULTS: A total of 111 eligible patients were registered; median age was 50 years, IPI score was 3 (60.4%) or 4/5 (39.6%), 54% had a performance status ≥2 and 9% had central nervous system involvement. A total of 85 patients (76.6%) completed all four cycles of chemotherapy. There were five treatment-related deaths (4.3%), all in patients with performance status of 3 and aged >50 years. Two-year PFS for the whole cohort was 67.9% [90% confidence interval (CI) 59.9-74.6] and 2-year overall survival was 76.0% (90% CI 68.5-82.0). The ability to tolerate and complete treatment was lower in patients with performance status ≥2 who were aged >50 years, where 2-year PFS was 43.5% (90% CI 27.9-58.0). CONCLUSIONS: This trial demonstrates that R-CODOX-M/R-IVAC is a feasible and effective regimen for the treatment of younger and/or fit patients with high-risk DLBCL. These encouraging survival rates demonstrate that this regimen warrants further investigation against standard of care. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00974792) and EudraCT (2005-003479-19)

Favourable outcomes for high-risk diffuse large B-cell lymphoma (IPI 3–5) treated with front-line R-CODOX-M/R-IVAC chemotherapy: results of a phase 2 UK NCRI trial

Background: Outcomes for patients with high-risk diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP chemotherapy are suboptimal but, to date, no alternative regimen has been shown to improve survival rates. This phase 2 trial aimed to assess the efficacy of a Burkitt-like approach for high-risk DLBCL using the dose-intense R-CODOX-M/R-IVAC regimen. / Patients and methods: Eligible patients were aged 18–65 years with stage II–IV untreated DLBCL and an International Prognostic Index (IPI) score of 3–5. Patients received alternating cycles of CODOX-M (cyclophosphamide, vincristine, doxorubicin and high-dose methotrexate) alternating with IVAC chemotherapy (ifosfamide, etoposide and high-dose cytarabine) plus eight doses of rituximab. Response was assessed by computed tomography after completing all four cycles of chemotherapy. The primary end point was 2-year progression-free survival (PFS). / Results: A total of 111 eligible patients were registered; median age was 50 years, IPI score was 3 (60.4%) or 4/5 (39.6%), 54% had a performance status ≥2 and 9% had central nervous system involvement. A total of 85 patients (76.6%) completed all four cycles of chemotherapy. There were five treatment-related deaths (4.3%), all in patients with performance status of 3 and aged >50 years. Two-year PFS for the whole cohort was 67.9% [90% confidence interval (CI) 59.9–74.6] and 2-year overall survival was 76.0% (90% CI 68.5–82.0). The ability to tolerate and complete treatment was lower in patients with performance status ≥2 who were aged >50 years, where 2-year PFS was 43.5% (90% CI 27.9–58.0). / Conclusions: This trial demonstrates that R-CODOX-M/R-IVAC is a feasible and effective regimen for the treatment of younger and/or fit patients with high-risk DLBCL. These encouraging survival rates demonstrate that this regimen warrants further investigation against standard of care. / Trial Registration: ClinicalTrials.gov (NCT00974792) and EudraCT (2005-003479-19)

Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

[Abstract] Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study design and setting: This was an observational, retrospective study. Patient sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006-2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%-58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%-65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients with acute traumatic SCI admitted to the ICU, and renal dysfunction occurs in half of the cases. Creatinine values should be requested starting at the admission while neither the peak CPK values nor the hemodynamic SOFA scores could be used to properly discriminate between patients with and without renal dysfunction

Risks factors of mechanical ventilation in acute traumatic cervical spinal cord injured patients

[Abstract] Study design. Descriptive retrospective study. Objectives. To analyze risk factors associated with mechanical ventilation (MV) in cases of acute traumatic Cervical Spinal Cord Injury (tCSCI). Setting. Unidad de Lesionados Medulares, Complejo Hospitalario Universitario A Coruña, in Galicia (Spain). Methods. The study included patients with tCSCI who were hospitalized between January 2010 and December 2014. The following variables were analyzed: age, gender, etiology, neurological level, ASIA (American Spinal Injury Association) grade, associated injuries, injury severity score (ISS), ASIA motor score (AMS) at admission and mortality. Results. A total of 146 patients met the study’s inclusion criteria. The majority were men (74.7%) with mean age of 62.6 (s.d. ± 18.8) years. Sixty patients (41.1%) required MV. Mean age of ventilated vs. non-ventilated patients was 57.3 vs. 65.7. Men were more likely to require MV than women, ASIA grades A and B were also more likely to need MV than grades C and D, as well as patients with associated injuries. The AMS of patients receiving MV was lower than that of those who did not require MV (20.1 vs. 54.3). Moreover, the ISS was higher in patients receiving MV (31.2 vs. 13.4). An AMS ≤ 37 and an ISS ≥ 13 increased the risk of requiring MV by a factor of 11.98 and 7.28, respectively. Conclusions. Isolated factors associated with a greater risk of MV in tCSCI were: age, gender, ASIA grade, ISS and AMS. However, the only factor with a significant discriminatory ability to determine the need for MV was the AMS at admission

P82 238. ¿Es segura la reintervención dejando los injertos arteriales permeables sin clampar?

ObjetivoEl objetivo de no dañar la arteria mamaria evitando su disección y clampaje supone un reto para la protección miocárdica debido al lavado de la cardioplejía.Presentamos nuestra experiencia en reintervenciones sin disecar ni clampar los injertos arteriales.Material y métodosDesde septiembre de 2000 hasta febrero de 2010 se realizaron 29 reintervenciones en 28 pacientes, (89,7% varones), edad media 73,17±7,38años. Las causas de reoperación fueron: progresión de valvulopatía 17 pacientes (58,6%), endocarditis 10 (34,4%), disfunción protésica no estructural 2 (6,9%). La mediana del EuroS-CORE logístico fue 14,84 (4-77,25). La cirugía fue urgente en 7 pacientes. Se realizó sustitución valvular aórtica aislada en 18 y se asoció revascularización en 4, sustitución/plastia mitral en 4, sustitución de aorta en 2; sustitución mitral aislada en 1.La protección miocárdica se realizó con cardioplejía hemática con esmolol, K+ y Mg+, administrándola siempre que no dificultaba el trabajo quirúrgico (intervalos nunca > 20min). Temperatura sistémica media 32,26±3,23 °C.ResultadosLa mediana del tiempo de circulación extracorpórea (CEC) fue 153 (91-494) y de clampaje 103 (71-430)min. Presentaron infarto postoperatorio 1 paciente (3,4%) y síndrome de bajo gasto postoperatorio 2 pacientes (6,5%). La mediana de troponina I postoperatoria fue 7,03ng/ml (1,84-109,5). La mortalidad hospitalaria fue 3 pacientes (10,3%) (cirugía urgente por endocarditis). Las causas de mortalidad fueron: daño neurológico irreversible (1 paciente), sepsis y bajo gasto (2 pacientes). La mediana de estancia hospitalaria fue 7 (1-33) días.ConclusiónEn nuestra experiencia, sin clampar los injertos arteriales y con la estrategia descrita, la protección miocárdica parece adecuada y la mortalidad hospitalaria aceptable

T-cell project: an international, longitudinal, observational study of patients with aggressive peripheral T-cell lymphoma

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of neoplasms that are derived from post-thymic lymphoid cells at different stages of differentiation and with different morphological patterns, phenotypes, and clinical presentations. PTCLs are highly diverse, reflecting the diverse cells from which they can originate and are currently sub-classified using World Health Organization (WHO) 2008 criteria. Peripheral T-Cell Lymphomas account for 5%-10% of all lymphoproliferative disorders in the Western hemisphere, with an overall incidence of 0.5-2 per 100,000 individuals per year, and have a striking epidemiological distribution, with higher incidence in Asia. The clinical features of PTCL are extremely heterogeneous. PTCLs express even more clinical diversity than B-cell non-Hodgkin's lymphomas, and there is a close, though not absolute, relationship between some unusual clinical features and certain histological subtypes

Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma

We are indebted to the patients for donating tumor specimens as part of this study. The authors thank the Centre de Ressources Biologiques (CRB)-Santé of Rennes (BB-0033-00056) for patient samples, Queen Mary University of London Genome Centre for Illumina Miseq sequencing, and the support by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London for Illumina Hiseq sequencing. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. This work was supported by grants from the Kay Kendall Leukaemia Fund (KKL 757 awarded to J.O.), Cancer Research UK (22742 awarded to J.O., 15968 awarded to J.F., Clinical Research Fellowship awarded to S.A.), Bloodwise through funding of the Precision Medicine for Aggressive Lymphoma (PMAL) consortium, Centre for Genomic Health, Queen Mary University of London, Carte d’Identité des Tumeurs (CIT), Ligue National contre le Cancer, Pôle de biologie hospital universitaire de Rennes, CRB-Santé of Rennes (BB-0033-00056), and CeVi/Carnot program

Life expectancy of young adults with follicular lymphoma

FL patients younger than 40 have a median OS of 24 years and their outcome improved over time. However, they still have a significantly shorter life expectancy when compared with that of an age-matched general healthy population. FL in young adults, differently from paediatric FL, does not seem to represent a distinct entit

Primary refractory follicular lymphoma: a poor outcome entity with high risk of transformation to aggressive B cell lymphoma

Background: Primary refractory (PREF) follicular lymphoma (FL) has a completely different clinical course from that of FL that responds to front-line treatments. In addition to having poor responses to salvage therapies, it seems that patients with PREF are at increased risk of histological transformation (HT). The Aristotle consortium presented the opportunity of investigating the risk of HT in a very large series of cases. Thus, we investigated the risk of HT in patients with PREF FL compared with that of responding patients or in stable disease and ultimately their outcome. Methods: Six thousand three hundred thirty-nine patients from the Aristotle database were included in the analysis. These patients had a histologically confirmed grade 1, 2 or 3a FL diagnosed between 1997 and 2013. The primary end-points were the cumulative incidence (CI) of HT at the first progression or relapse and the survival after transformation. Findings.: The 5-year CI of HT among patients with PREF was 34% (95% confidence interval (CI): 27–43), whilst it was 7.1% (95% CI: 6.0–8.5) in the group of patients with partial response (PR) or stable disease (SD) (PR + SD) and 3.5% (95% CI: 3.0–4.2) in the group of patients achieving complete response (CR). The 5-year survival after relapse (SAR) was 33% (95% CI: 28–39) for the PREF group, 57% (95% CI 54–61) in patients with PR, 51% (95% CI 43–58) in the SD group after first-line therapy and 63% (95% CI: 66–72) in patients with CR after initial treatment (p-value <0.001). The 5-year SAR for those patients with PREF who developed HT was 21% (95% CI: 12–31), clearly diminished when compared with those patients with PREF who did not experience HT (38% [95% CI: 31–44]) (p-value = 0.001). Interpretation.: Patients with PREF FL have a dismal outcome and an associated very high rate of HT that further worsens their poor prognosis