Idelalisib (PI3Kδ inhibitor) therapy for patients with relapsed/refractory chronic lymphocytic leukemia: A Swedish nation-wide real-world report on consecutively identified patients.

OBJECTIVES: We examined the efficacy and toxicity of the PI3Kδ inhibitor idelalisib in combination with rituximab salvage therapy in consecutively identified Swedish patients with chronic lymphocytic leukemia (CLL). METHODS AND RESULTS: Thirty-seven patients with relapsed/refractory disease were included. The median number of prior lines of therapy was 3 (range 1-11); the median age was 69 years (range 50-89); 22% had Cumulative Illness Rating Scale (CIRS) >6 and 51% had del(17p)/TP53 mutation. The overall response rate was 65% (all but one was partial response [PR]). The median duration of therapy was 9.8 months (range 0.9-44.8). The median progression-free survival was 16.4 months (95% CI: 10.4-26.3) and median overall survival had not been reached (75% remained alive at 24 months of follow-up). The most common reason for cessation of therapy was colitis (n = 8, of which seven patients experienced grade ≥3 colitis). The most common serious adverse event was grade ≥3 infection, which occurred in 24 patients (65%). CONCLUSIONS: Our real-world results suggest that idelalisib is an effective and relatively safe treatment for patients with advanced-stage CLL when no other therapies exist. Alternative dosing regimens and new PI3K inhibitors should be explored, particularly in patients who are double-refractory to inhibitors of BTK and Bcl-2.

Covid-19 in patients with chronic lymphocytic leukemia: clinical outcome and B- and T-cell immunity during 13 months in consecutive patients.

We studied clinical and immunological outcome of Covid-19 in consecutive CLL patients from a well-defined area during month 1-13 of the pandemic. Sixty patients (median age 71 y, range 43-97) were identified. Median CIRS was eight (4-20). Patients had indolent CLL (n = 38), had completed (n = 12) or ongoing therapy (n = 10). Forty-six patients (77%) were hospitalized due to severe Covid-19 and 11 were admitted to ICU. Severe Covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except CIRS (p < 0.05). Fourteen patients (23%) died; age ≥75 y was the only significant risk factor (p < 0.05, multivariate analysis with limited power). Comparing month 1-6 vs 7-13 of the pandemic, deaths were numerically reduced from 32% to 18%, ICU admission from 37% to 15% whereas hospitalizations remained frequent (86% vs 71%). Seroconversion occurred in 33/40 patients (82%) and anti-SARS-CoV-2 antibodies were detectable at six and 12 months in 17/22 and 8/11 patients, respectively. Most (13/17) had neutralizing antibodies and 19/28 had antibodies in saliva. SARS-CoV-2-specific T-cells (ELISpot) were detected in 14/17 patients. Covid-19 continued to result in high admission even among consecutive and young early- stage CLL patients. A robust and durable B and/or T cell immunity was observed in most convalescents.

Bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal single-center study.

Infectious complications in chronic lymphocytic leukemia (CLL) represent a major cause of morbidity and mortality. The aim of the study was to investigate temporal trends in bloodstream infections (BSIs) among patients with CLL. Individuals with blood cultures were linked to Swedish Cancer Registry and divided into three time periods (1988-1993, 1994-1999, and 2000-2006) according to year of CLL diagnosis. CLL patients (n = 275) with 1092 blood culture episodes were identified and linked to the nationwide Cause of Death Registry and Swedish Patient Registry (to retrieve information on splenectomies). The most common causes of BSI among CLL patients were Escherichia coli (11/43, 15/78, and 9/33), Streptococcus pneumoniae (7/43, 13/78, and 6/33), Pseudomonas aeruginosa (2/43, 8/78, and 3/33), Staphylococcus aureus (1/43, 6/78, and 6/33), and Viridans streptococci (5/43, 6/78, and 2/33). Coagulase-negative staphylococci was the most frequent microorganism found in blood cultures (22/70, 23/106, and 5/41, respectively) but is a frequent contaminant. Based on the largest study to date on BSI in CLL patients, we found a stable proportion of Gram-positive to Gram-negative bacteria and no temporal change of distribution was observed for BSIs 1988-2006.

Bacterial Landscape of Bloodstream Infections in Neutropenic Patients via High Throughput Sequencing.

BACKGROUND: Bloodstream infection (BSI) is a common and potentially life-threatening complication in patients with hematological malignancies and therapy-induced neutropenia. Administration of broad spectrum antibiotics has substantially decreased the mortality rate in febrile neutropenia, but bacterial infection is documented in only one-third or fewer of the cases. BSI is typically diagnosed by blood culture; however, this method can detect only culturable pathogens. METHODS: In the present study, a total of 130 blood samples from hematological patients receiving dose-intensive antitumoural treatment were subjected to 16S rRNA PCR and 62 of them were cultured. PCR positive samples were processed to high throughput sequencing by amplifying the V1-V3 regions of the 16S rRNA gene to obtain a full spectrum of bacteria present in BSI. RESULTS: Five phyla and 30 genera were identified with sequencing compared to 2 phyla and 4 genera with culture. The largest proportion of bacteria detected by sequencing belonged to Proteobacteria (55.2%), Firmicutes (33.4%) and Actinobacteria (8.6%), while Fusobacteria (0.4%) and Bacteroidetes (0.1%) were also detected. Ninety-eight percent of the bacteria identified by sequencing were opportunistic human pathogens and 65% belonged to the normal human microbiota. CONCLUSIONS: The present study indicates that BSIs in neutropenic hosts contain a much broader diversity of bacteria, likely with host origin, than previously realized. The elevated ratio of Proteobacteria in BSI corroborates the results found in other systemic inflammatory diseases, such as inflammatory bowel disease or mucosal infections. This knowledge may become of value for tailoring antimicrobial drug administration.

[Sickle cell anemia causes varied symptoms and high morbidity. Serious prognosis in the most common genetic disease in the world]. / Sicklecellanemi ger skiftande symtombild och hög morbiditet--Allvarlig prognos vid världens vanligaste genetiska sjukdom.

Sickle cell anemia is a life-threatening disease, and the most common genetic disease in the world. The prevalence of sickle cell anemia in Sweden is unknown. Sickle cell anemia is an important disease, because of its variable complications, in many medical and surgical specialties. The overview highlights common medical problems encountered in sickle cell anemia presented through a case report of a pregnant woman.

Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients.

Infections are a major cause of morbidity and mortality in patients with multiple myeloma. To estimate the risk of bacterial and viral infections in multiple myeloma patients, we used population-based data from Sweden to identify all multiple myeloma patients (n=9253) diagnosed from 1988 to 2004 with follow up to 2007 and 34,931 matched controls. Cox proportional hazard models were used to estimate the risk of infections. Overall, multiple myeloma patients had a 7-fold (hazard ratio =7.1; 95% confidence interval = 6.8-7.4) risk of developing any infection compared to matched controls. The increased risk of developing a bacterial infection was 7-fold (7.1; 6.8-7.4), and for viral infections 10-fold (10.0; 8.9-11.4). Multiple myeloma patients diagnosed in the more recent calendar periods had significantly higher risk of infections compared to controls (P<0.001). At one year of follow up, infection was the underlying cause in 22% of deaths in multiple myeloma patients. Mortality due to infections remained constant during the study period. Our findings confirm that infections represent a major threat to multiple myeloma patients. The effect on infectious complications due to novel drugs introduced in the treatment of multiple myeloma needs to be established and trials on prophylactic measures are needed.

Hematological: Low all-cause mortality and low occurrence of antimicrobial resistance in hematological patients with bacteremia receiving no antibacterial prophylaxis: a single-center study.

BACKGROUND: Bacteremia is a major cause of morbidity and mortality in patients with hematological malignancies. OBJECTIVES: The aim of this study was to define temporal trends in species distribution, antimicrobial susceptibility, and all-cause mortality in bacteremic hospitalized patients receiving no antibacterial prophylaxis during chemotherapy-induced neutropenia. METHODS: A total of 677 clinical episodes of bacteremia were identified in 463 patients during 2002-2008, and the results were compared with those published from the same institution during 1980-86 and 1988-2001. No major changes in patient selection were introduced during this period. RESULTS: Between 2002 and 2008, the dominating pathogens were Escherichia coli (18%), coagulase-negative staphylococci (15%), viridans streptococci (14%), Klebsiella spp. (10%), and Enterococcus faecium (8%). The 7-d crude mortality rate was 5.2%. Polymicrobial bacteremia was seen in 25.7% of the patients who died within 7 d and in 13.1% of the survivors (P = 0.04). Acquired resistance was rarely observed, but a statistically significant increase in ciprofloxacin resistance in E. coli was observed. Comparing 2002-2008 with historical data from the same institution, the proportion of Gram-positive isolates remained stable at 53-55% from 1988. CONCLUSIONS: The avoidance of fluoroquinolone prophylaxis may have contributed to a stable proportion of Gram-positive bacteremia. The crude mortality was low in an international perspective. Acquired resistance was uncommon, but ciprofloxacin resistance in E. coli increased significantly. We believe that an indiscriminate use of antibacterial prophylaxis could be avoided in neutropenic patients without a negative impact on mortality.