Background Patients with cancer have been shown to have a higher risk of clinical severity and mortality compared to non-cancer patients with COVID-19. Patients with hematologic malignancies typically are known to have higher levels of immunosuppression and may develop more severe respiratory viral infections than patients with solid tumors. Data on COVID-19 in patients with hematologic malignancies are limited. Here we characterize disease severity and mortality and evaluate potential prognostic factors for mortality. Methods In this population-based registry study, we collected de-identified data on clinical characteristics, treatment and outcomes in adult patients with hematologic malignancies and confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection within the Madrid region of Spain. Our case series included all patients admitted to 22 regional health service hospitals and 5 private healthcare centers between February 28 and May 25, 2020. The primary study outcome was all-cause mortality. We assessed the association between mortality and potential prognostic factors using Cox regression analyses adjusted for age, sex, comorbidities, hematologic malignancy and recent active cancer therapy. Results Of 833 patients reported, 697 were included in the analyses. Median age was 72 years (IQR 60–79), 413 (60%) patients were male and 479 (69%) and 218 (31%) had lymphoid and myeloid malignancies, respectively. Clinical severity of COVID-19 was severe/critical in 429 (62%) patients. At data cutoff, 230 (33%) patients had died. Age ≥ 60 years (hazard ratios 3.17–10.1 vs < 50 years), > 2 comorbidities (1.41 vs ≤ 2), acute myeloid leukemia (2.22 vs non-Hodgkin lymphoma) and active antineoplastic treatment with monoclonal antibodies (2·02) were associated with increased mortality; conventional chemotherapy showed borderline significance (1.50 vs no active therapy). Conversely, Ph-negative myeloproliferative neoplasms (0.33) and active treatment with hypomethylating agents (0.47) were associated with lower mortality. Overall, 574 (82%) patients received antiviral therapy. Mortality with severe/critical COVID-19 was higher with no therapy vs any antiviral combination therapy (2.20). Conclusions In this series of patients with hematologic malignancies and COVID-19, mortality was associated with higher age, more comorbidities, type of hematological malignancy and type of antineoplastic therapy. Further studies and long-term follow-up are required to validate these criteria for risk stratification.
Patients with cancer are poorly represented in coronavirus disease 2019 (COVID-19) series, and heterogeneous series concerning hematology patients have been published. This study aimed to analyze the impact of COVID-19 in patients with lymphoma. We present a multicenter retrospective study from 19 centers in Madrid, Spain, evaluating risk factors for mortality in adult patients with COVID-19 and lymphoma. About 177 patients (55.9% male) were included with a median follow-up of 27 days and a median age of 70 years. At the time of COVID-19 diagnosis, 49.7% of patients were on active treatment. The overall mortality rate was 34.5%. Age >70 years, confusion, urea concentration, respiratory rate, blood pressure, and age >65 score ≥2, heart disease, and chronic kidney disease were associated with higher mortality risk ( P < 0.05). Active disease significantly increased the risk of death (hazard ratio, 2.43; 95% confidence interval, 1.23-4.77; P = 0.01). However, active treatment did not modify mortality risk and no differences were found between the different therapeutic regimens. The persistence of severe acute respiratory syndrome coronavirus 2-positive polymerase chain reaction after week 6 was significantly associated with mortality (54.5% versus 1.4%; P < 0.001). We confirm an increased mortality compared with the general population. In view of our results, any interruption or delay in the start of treatment should be questioned given that active treatment has not been demonstrated to increase mortality risk and that achieving disease remission could lead to better outcomes.
The aims of this study were to evaluate the clinical characteristics of HIV-negative patients affected by lymphoproliferative disorders (LPD) who developed progressive multifocal leukoencephalopathy (PML), to delineate the risk factors, and to analyze whether the new antineoplastic therapies are changing the natural history of this infectious disease. We retrospectively analyzed 46 cases with confirmed LPD-associated PML published from 1958 to 2004. Patients were stratified according to two different time periods: group A included patients diagnosed before 1989, and group B included patients diagnosed since 1990, after introduction of purine analogues. Group A patients (n = 22) had received alkylating agents and/or radiotherapy, and the majority (63.6%) had advanced Hodgkin disease. At univariate analysis, uncontrolled Hodgkin disease was the only risk factor for PML. In group B patients (n = 24), the most frequent treatments received were purine analogues (58.3%) and high-dose therapy with hematopoietic stem cell transplantation (33.3%; HDT/HSCT). B-cell chronic lymphocytic leukemia (45.8%) and aggressive non-Hodgkin lymphoma (24.9%) were the most frequent underlying LPDs. Patients treated with purine analogues were more likely to have active LPD, lower CD4 cell counts, and to be older and male than were HSCT recipients. The median interval from purine analogues or HDT/HSCT to PML was 11 months. In HDT/HSCT recipients, this interval was delayed for 10 months when peri-transplantation rituximab was used. Univariate analysis identified age >55 years, male sex, and CD4 cell counts £0.2 · 10 9 /L as risk factors for PML in patients treated with purine analogues. Mortality rates were 95.4% (group A patients), 90% (purine analogues), and 62.5% (HDT/HSCT recipients). At univariate analysis, the only factor that significantly correlated with recovery from infection was female sex. Our findings indicate (1) the possible reduction in reported cases associated with Hodgkin disease and the increasing number of published cases associated with the new antineoplastic therapies (purine analogues and HDT/ HSCT); (2) among patients treated with purine analogues, PML is more common in male patients with CD4 cell counts £0.2 · 10 9 /L; (3) the use of rituximab after HDT/ HSCT seems to delay the onset of PML; and (4) the prognosis is slightly better in transplant recipients. Am.
Summary. Hepatitis C virus (HCV) has been proposed as a possible causative agent of chronic thrombocytopenia. We investigated HCV infection in a series of 51 unselected Spanish patients with chronic acquired thrombocytopenia. Anti-HCV and HCV viraemia were detected in 13/51 (22´5%) of cases; this prevalence was particularly significant when compared with HCV seropositivity in agematched controls (0´4%). Anti-HCV-positive patients, four men and nine women with a median age of 59´3 years (range 36±72), had a mean platelet count of 55´8 Â 10 9 /l (range 12±96). Only one of our HCV-positive thrombocytopenic patients had hypersplenism. Platelet-associated IgG (PAIgG) was negative, as measured by immunofluorescent flow cytometric analysis in 11/13 HCV-positive thrombocytopenic patients. Thus, thrombocytopenia in our HCV-positive patients appeared to be non-autoimmune mediated. In six patients, a trial of recombinant a2b-interferon (IFN-a) given at a dose of 3 MU three times per week for 6±24 months gave a durable (. 1 year) and significant increase in platelet count in all six patients. The maximum increase occurred after 6 months of IFN-a therapy. In conclusion, the ability of IFN-a to increase platelet counts in HCV-positive thrombocytopenic patients supports mechanisms involving a direct role for HCV inhibiting platelet production.
Rhodotorula spp. are emergent opportunistic pathogens, particularly in haematological patients. However, no systematic review of this infection has been undertaken in this high-risk patient group. The aim of this study was to review all reported cases of Rhodotorula infection to determine the epidemiology and outcome of this infection in this high-risk population. The 29 reported cases were fungaemias. The most common underlying haematological disorder was the presence of acute leukaemia (65.5%). Rhodotorula mucilaginosa was the species found more frequently (79.3%). Most cases (58.6%) had several risk factors (≥ 3) simultaneously. The most common predisposing factors were the presence of central venous catheter (CVC, 100%) and neutropenia (62.1%). A substantial number of patients (81.5%) received antifungal treatment with amphotericin B. The overall mortality was higher (13.8%) than that described in non-haematological patients (5.8% in solid-organ neoplasms and 9% in AIDS or other chronic diseases). Patients with acute leukaemia had a higher mortality rate (15.7%) than patients with non-Hodgkin's lymphoma (0%). Our data suggest that patients with acute leukaemia might be managed as high-risk patients and intensive measures might be taken. In addition, it appears that the subgroup of patients without acute leukaemia have a good outcome and might be managed as low-risk patients with a less intensive approach.
Summary This study was designed to assess the efficacy and safety of an infusional DA‐EPOCH (dose‐adjusted etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) and rituximab (DA‐EPOCH‐R) regimen for patients with poor prognosis diffuse large B‐cell lymphoma (DLBCL). Thirty‐three patients, aged 21–76 years, with an age‐adjusted International Prognostic Index (IPI) of 2 or 3, were enrolled, and 31/33 patients were evaluable for response. Consolidative radiation therapy was given to eight patients with bulky (≥10 cm) disease at presentation. Overall, 26 patients (83·8%) achieved a complete remission (CR), four patients (12·9%) achieved a partial remission, and one patient (3·2%) died during induction. Two patients relapsed (7·6%) within 15 months. Grade 3–4 neutropenia developed in 52% of cycles and neutropenic fever in 14% of cycles (51% of patients). The estimates for event‐free survival (EFS) and overall survival at 2 years were 68% and 75% respectively. The only factor related to poor EFS was the presence of three age‐adjusted IPI‐risk factors. We conclude that DA‐EPOCH‐R has clinically significant activity with a favourable toxicity profile for poor‐prognostic DLBCL patients. The administration of DA‐EPOCH‐R as an outpatient regimen by using a single portable infusion pump may be a feasible alternative to improve the compliance and to reduce the total cost of this very effective regimen.
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