Organizing pneumonia in a patient with hodgkin's lymphoma and large B cell lymphoma: a rare association

Organizing Pneumonia (OP) is classified as an Idiopathic Interstitial Pneumonia (IIP).1 Clinically, the patients present dyspnea, cough, and low fever, and usually respond well to corticosteroids, reaching clinical and radiologic resolution in a short timeframe. However, sometimes infiltrates do recur and may not resolve. Radiologically, migratory consolidations are identified in high-resolution computed tomography (HRCT), sometimes associated with progressive fibrosis with reticulation and areas of persistent consolidation.1 The histology reveals “proliferation of fibroblastic tissue within small airways, alveolar ducts, and alveolar spaces”.2 OP can be secondary to other pathologies such as common variable immunodeficiency3 and malignant disease among others.4 At times no etiology is identified and the term Cryptogenic Organizing Pneumonia (COP) is used.1 Furthermore, OP could coexist or mimic a malignant disease.4,

Combined treatment with anti-CD20 (rituximab) and CHOP in relapsed advanced-stage follicular lymphomas

We studied the safety and efficacy of combined treatment with rituximab plus CHOP in 16 patients with relapsed advanced-stage follicular lymphomas. The intent-to-treat overall response rate (ORR) was 88%, 75% complete remissions (CR) and 13% partial remissions (PR). At a median follow-up of 18 months, 63% of the patients are alive (50% CR). The combination of rituximab and CHOP in relapsed advanced-stage follicular lymphomas achieves high ORRs and CRs, with low toxicity except for in previously autografted patients

Clinical characteristics and risk of relapse for patients with stage I-II diffuse large B cell lymphoma treated in first line with immunochemotherapy

Diffuse large b-cell lymphoma (DLBCL) is an aggressive and potentially curable lymphoma that presents itself as stage I-II in 30% of all cases. It is known that in these localized stages, 15-20% of patients treated without rituximab eventually relapse, but less data exist regarding rituximab era. We have analyzed clinico-pathological features and risk of relapse in 98 patients with I-II stage DLBCL in complete response (CR) or unconfirmed CR (CRu) after first-line treatment consisting of immunochemotherapy. Twelve patients (12.2%) eventually relapsed. Late relapse, more than two years after diagnosis, occurred in three patients, and early relapse, less than two years after diagnosis, was documented in nine patients. Median time from diagnosis to relapse was 0.61 years for patients with early relapse and 3.66 years for patients with late relapse. The second CR rate obtained was similar in the late and in early relapsing patients, being 33% versus 44% (p = 0.072), respectively. Three-year overall survival (OS) was 22% for early relapsing patients and 33% for late relapsing patients (p = 0.65). In conclusion, patients who are diagnosed with stage I-II DLBCL and achieve a CR/CRu with first line immunochemotherapy have a good prognosis. However, a proportion of patients relapse, and this is less frequent in patients treated with first line with immunochemotherapy. These patients have a poor prognosis

Comparison of different automatic methods for the delineation of the total metabolic tumor volume in I-II stage Hodgkin Lymphoma

Total metabolic tumor volume (TMTV) is a promising quantitative biomarker for therapy assessment and prognosis in Hodgkin Lymphoma affected patients that allows prediction of patient outcome. The aim of this study was to evaluate the TMTV reproducibility between different sources of variability in tumor delimitation such as SUV-based thresholds (2.5, 41% and 50%) and software tools (Beth Israel plugin (BI) and LIFEx). Effect of contouring procedure both including single and multiple regions of interest was also studied in patients with multiple lesions, and optimal cut-offs for each studied method were displayed to compare the effect on prognosis. Strong alikeness in TMTV was found for 2.5 under software choice. Best accuracy in contouring compared to visual assessment of the disease was found for BI multiple ROI and LIFEx single ROI drawing. Similar cut-offs were found between both software for all considered thresholds, but best resemblance and highest cut-off due to an overestimation of the TMTV was found for 2.5 SUV. Our findings suggest that optimal reproducibility in TMTV is found for SUV>2.5 threshold under choice of contouring methodology or software tool, meaning that overestimation of the TMTV threshold using 2.5 looks to be preferable than underestimation with 41% and 50%

Post-transplant lymphomas: a 20-year epidemiologic, clinical and pathologic study in a single center

Background and objectives: to study the incidence, clinical presentation, pathologic features and outcome of post-transplant lymphomas (PTL) during the past 20 years. Design and methods: we undertook a descriptive study of all biopsy-proven cases of PTL diagnosed in our hospital from 1979 through 1999. The average annual incidence rate of PTL was analyzed at 5-year intervals from 1979 to 1999. Risk ratios were estimated by comparing the incidence of PTL among transplanted patients with that of lymphoma observed in the general population of the region. Survival analysis was performed at the univariate level using the Kaplan Meier technique and at the multivariate level by Cox hazard models. Results: seventeen of 1,860 transplanted patients developed a PTL (0.9%). The risk of PTL was calculated to be almost 8-fold higher than the risk of lymphoma in the general population. The risk was highest among those who had received a heart transplant (RR=35.6). The mean time between transplant and the diagnosis of PTL was 31 +/- 29 months. Of all PTL, 88% were of B-cell origin and 53% of the cases tested were Epstein-Barr virus (EBV)-positive. The median survival was 24 months. The majority of patients with allograft involvement died within the 2 months following diagnosis (hazard ratio 5.3; 95% CI 1.4-20.7). Interpretation and conclusions: organ transplantation is a major risk factor for the development of lymphoma, a disease with a particularly bad prognosis when it develops at the site of the allograft. Early diagnosis and more specific treatment may improve PTL survival

The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-HematologicalPatients. Antibiotics (Basel).

Objectives: to assess the current epidemiology, antibiotic therapy and outcomes of oncohematological patients with bacteremic skin and soft-tissue infections (SSTIs), and to identify the risk factors for Gram-negative bacilli (GNB) infection and for early and overall mortality. Methods: episodes of bacteremic SSTIs occurring in cancer patients at two hospitals were prospectively recorded and retrospectively analyzed. Results: Of 164 episodes of bacteremic SSTIs, 53% occurred in patients with solid tumors and 47% with hematological malignancies. GNB represented 45.5% of all episodes, led by Pseudomonas aeruginosa (37.8%). Multidrug resistance rate was 16%. Inadequate empirical antibiotic therapy (IEAT) occurred in 17.7% of episodes, rising to 34.6% in those due to resistant bacteria. Independent risk factors for GNB infection were corticosteroid therapy and skin necrosis. Early and overall case-fatality rates were 12% and 21%, respectively. Risk factors for early mortality were older age, septic shock, and IEAT, and for overall mortality were older age, septic shock and resistant bacteria. Conclusions: GNB bacteremic SSTI was common, particularly if corticosteroid therapy or skin necrosis. IEAT was frequent in resistant bacteria infections. Mortality occurred mainly in older patients with septic shock, resistant bacteria and IEAT. These results might guide empirical antibiotic therapy in this high-risk population

The direct and indirect effects of COVID‐19 pandemic in a real‐life hematological setting

Background: Clinical outcomes of novel coronavirus 2019 disease (COVID-19) in onco-hematological patients are unknown. When compared to non-immunocompromised patients, onco-hematological patients seem to have higher mortality rates. Aims: We describe the characteristics and outcomes of a consecutive cohort of 24 onco-hematological patients with COVID-19 during the first month of the pandemic. We also describe variations in healthcare resource utilization within our hematology department. Methods and results: Data from patients between the first month of the pandemic were retrospectively collected. Clinical and logistic data were also collected and compared with the average values from the prior 3 months of activity. Prevalence of COVID-19 in our hematological population was 0.4%. Baseline characteristics were as follows: male sex: 83%, lymphoid diseases: 46%, median age: 69 (22-82) years. Median follow-up in survivors was 14 (9-28) days and inpatient mortality rate was 46%. Average time to moderate/severe respiratory insufficiency and death were 3 (1-10) and 10 (3-18) days, respectively. Only 1 out of every 12 patients who developed moderate to severe respiratory insufficiency recovered. Upon univariate analysis, the following factors were associated with higher mortality: age ≥ 70 years (P = .01) and D-dimer ≥900 mcg/L (P = .04). With respect to indirect effects during the COVID-19 pandemic, and when compared with the prior 3 months of activity, inpatient mortality (excluding patients with COVID-19 included in the study) increased by 56%. This was associated with a more frequent use of vasoactive drugs (+300%) and advanced respiratory support (+133%) in the hematology ward. In the outpatient setting, there was a reduction in initial visits (-55%) and chemotherapy sessions (-19%). A significant increase in phone visits was reported (+581%). Conclusion: COVID-19 pandemic is associated with elevated mortality in hematological patients. Negative indirect effects are also evident within this setting

A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma

In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the anti-programmed death-1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly prominent role in treatment. The CD30/CD16A-bispecific antibody AFM13 is an innate immune cell engager, a first-in-class, tetravalent antibody, designed to create a bridge between CD30 on HL cells and the CD16A receptor on natural killer cells and macrophages, to induce tumor cell killing. Early studies of AFM13 have demonstrated signs of efficacy as monotherapy for patients with R/RHL and the combination of AFM13 with pembrolizumab represents a rational new treatment modality. Here, we describe a phase 1b, dose-escalation study to assess the safety and preliminary efficacy of AFM13 in combination with pembrolizumab in patients with R/R HL. The primary objective was estimating the maximum tolerated dose; the secondary objectives were to assess safety, tolerability, antitumor efficacy, pharmacokinetics, and pharmacodynamics. In this heavily pretreated patient population, treatment with the combination of AFM13 and pembrolizumab was generally well tolerated, with similar safety profiles compared to the known profiles of each agent alone. The combination of AFM13 with pembrolizumab demonstrated an objective response rate of 88% at the highest treatment dose, with an 83% overall response rate for the overall population. Pharmacokinetic assessment of AFM13 in the combination setting revealed a half-life of up to 20.6 hours. This proof-of-concept study holds promise as a novel immunotherapy combination worthy of further investigation

Prospective phase II trial of extended treatment with rituximab in patients with B-cell post-transplant lymphoproliferative disease

Background and Objectives The elective treatment of patients with post-transplant lymphoproliferative disorders is controversial. The purpose of this trial was to evaluate the efficacy of treatment with extended doses of rituximab adapted to the response in patients with post-transplant lymphoproliferative disorders after solid organ transplantation. Design and Methods This was a prospective, multicenter, phase 11 trial. Patients were treated with reduction of immunosuppression and four weekly infusions of rituximab. Those patients who did not achieve complete remission (CR) received a second course of four rituximab infusions. The primary end-point of the study was the CR rate. Results Thirty-eight patients were assesable. One episode of grade 4 neutropenia was the only severe adverse event observed. After the first course of rituximab, 13 (34.2%) patients achieved CR, 8 patients did not respond, and 17 patients achieved partial remission. Among those 17 patients, 12 could be treated with a second course of rituximab, and 10 (83.3%) achieved CR, yielding an intention-to-treat CR rate of 60.5%. Eight patients excluded from the trial because of absence of CR were treated with rituximab combined with chemotherapy, and six (75%) achieved CR. Event-free survival was 42% and overall survival was 47% at 27.5 months. Fourteen patients died, ten of progression of their post-transplant lymphoproliferative disorder. Interpretation and Conclusions These results confirm that extended treatment with rituximab can obtain a high rate of CR in patients with post-transplant lymphoproliferative disorders after solid organ transplantation without increasing toxicity, and should be recommended as initial therapy for these patients

Clinical and pathological characteristics of peripheral T‐cell lymphomas in a Spanish population: a retrospective study

We investigated the clinicopathological features and prognostic factors of patients with peripheral T-cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune-related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy-treated carcinomas 19%). The median progression-free survival (PFS) and overall survival (OS) were 7·9 and 15·8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P 15% of cells were positive in anaplastic lymphoma kinase-positive and -negative anaplastic large-cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re-evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological sub-classification, and response level to first-line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors