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Ribavirin use for respiratory syncytial virus (RSV) infection in patients with haematologic malignancies (HM) and haematopoietic stem cell transplant (HSCT) recipients remains controversial. To summarize the current evidence of ribavirin treatment in association with mortality and progression to lower respiratory tract infection (LRTI) among patients with HM/HSCT with RSV infection. MEDLINE, Embase, and the Institute for Scientific Information Web of Science. Randomized controlled trials and observational studies investigating the effects of ribavirin, compared with treatment without ribavirin, for RSV infection. Patients with HM/HSCT. Ribavirin versus no ribavirin. The risk of bias in non-randomized studies of exposure (ROBIN-E). The random-effects model was used to calculate the pooled OR (pOR) with 95% CI for the pooled effect estimates of ribavirin benefits. Grading of recommendation assessment, development, and evaluation was used to evaluate the certainty of evidence. One randomized controlled trial and 14 observational studies were included, representing 1125 patients with HM/HSCT. Ribavirin use was not associated with lower all-cause or RSV-associated mortality with pORs [95% CI] of 0.81 [0.40, 1.66], I2 = 55% (low certainty of evidence) and 0.48 [0.11, 2.15], I2 = 64% (very low certainty of evidence), respectively. In subgroup analyses, ribavirin use was associated with lower mortality in patients with HM/HSCT with LRTI with pOR [95% CI] of 0.19 [0.07, 0.51], I2 = 0% (moderate certainty of evidence). In subgroup analyses among studies providing adjusted OR, ribavirin use was associated with lower all-cause mortality with pOR of 0.41 [0.23, 0.74], I2 = 0% (moderate certainty of evidence). In addition, aerosolized ribavirin was associated with lower progression to LRTI with pOR [95% CI] of 0.27 [0.09, 0.80], I2 = 71% (low certainty of evidence). Ribavirin may be a reasonable option to treat RSV in patients with HM/HSCT in the absence of other effective antiviral agents. [ABSTRACT FROM AUTHOR]

Patients diagnosed with haematologic malignancies (HMs) have a higher risk of developing subsequent solid tumours, such as melanoma. Patients with HM were mostly excluded from clinical trials but potentially derive less benefit from immune checkpoint inhibitors (ICIs) due to disease- or treatment-related T- or B-cell dysfunction. All advanced melanoma patients treated with anti-PD-1-based treatment or targeted therapy between 2015 and 2021 were included from the prospective nationwide Dutch Melanoma Treatment Registry. Progression-free survival (PFS) and melanoma-specific survival (MSS) were analysed for patients with HM (HM+) and without HM (HM−). A cox model was used to account for confounders associated with PFS and MSS. In total, 4638 advanced melanoma patients received first-line anti-PD-1 monotherapy (n = 1763), ipilimumab-nivolumab (n = 800), or BRAF(/MEK) inhibitors (n = 2075). Concurrent HMs were present for 46 anti-PD1-treated patients, 11 ipilimumab-nivolumab-treated patients and 43 BRAF(/MEK)-inhibitor-treated patients. In anti-PD-1-treated patients, the median PFS was 2.8 months for HM+ and 9.9 months for HM− (p = 0.01). MSS was 41.2 months for HM+ and 58.1 months for HM− (p = 0.00086). In multivariable analysis, the presence of an HM was significantly associated with higher risk of melanoma progression (HR adj 1.62; 95% confidence interval [95% CI] 1.15–2.29; p = 0.006) and melanoma-related death (HR adj 1.74; 95% CI 1.09–2.78; p = 0.020). Median PFS and MSS for first-line BRAF(/MEK-) inhibitor-treated HM+ and HM− patients were not significantly different. Patients with HM and advanced melanoma show significantly worse melanoma-related outcomes when treated with ICI, but not targeted therapy, compared to patients without HM. Clinicians should be aware of potentially altered effectiveness of ICI in patients with active HM. • Largest cohort of metastatic melanoma (MM) and haematologic malignancy (HM) patients. • Immunotherapy-treated MM patients with a concurrent HM had significantly worse PFS. • PFS was not worse for patients with HM treated with targeted therapy. [ABSTRACT FROM AUTHOR]

• The incidence of BSI and neutropenia after HM diagnosis was highest in patients with AML and ALL. • Neutropenia and HM type were risk factors for the development of BSI in HM patients. • CoNS-BSI prevalence decreased with reduced quinolone prophylaxis and changes in chemotherapy. • K. pneumoniae -BSI prevalence increased with rising quinolone and carbapenem resistance rates. • K. pneumoniae -BSI had a significantly higher 28-d mortality rate than CoNS-BSI. This study aimed to identify recent trends in the epidemiology of bloodstream infection (BSI)-causing microorganisms among patients with haematologic malignancies (HMs) between 2011 and 2021, and to determine their impact on patient outcomes. This retrospective study included 6792 patients with HMs, of whom 1308 (19.3%) developed BSI within 1 y of diagnosis. The incidence of BSI-causing microorganisms was determined, and a propensity score-matched study was performed to identify risk factors for 28-d all-cause mortality in patients with HM. A total of 6792 patients with HMs were enrolled. The cumulative incidence of BSI and neutropenia was significantly higher in the acute myeloid leukaemia and acute lymphoblastic leukaemia groups compared to other groups, and neutropenia and type of HMs were risk factors for the development of BSI. The annual incidence of coagulase-negative staphylococci (CoNS)-BSI decreased significantly (P < 0.001), whereas Klebsiella pneumoniae- BSI increased (P = 0.01). Carbapenem nonsusceptibility rates in K. pneumoniae isolates increased from 0.0% to 76.5% (P < 0.001). BSI caused by K. pneumoniae (adjusted odds ratio 2.17; 95% confidence interval 1.12–4.21) was associated with higher 28-d all-cause mortality compared to that caused by CoNS (adjusted odds ratio 0.86; 95% confidence interval 0.48–1.55). The pathogenic spectrum of BSI-causing bacteria in patients with HMs gradually shifted from Gram-positive to Gram-negative, especially from CoNS to K. pneumoniae. Considering that K. pneumoniae -BSI had a significantly higher 28-d mortality rate than CoNS-BSI, this evolving trend could adversely impact the clinical outcomes of patients with HMs. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary Background Allogeneic haematopoietic cell transplantation (HCT) is often associated with poor oral intake due to painful mucositis and gastrointestinal sequalae that occur following a preparative regimen of intensive chemotherapy and/or total body radiation. Although attractive to assume that optimal nutrition improves HCT outcomes, there are limited data to support this. It is also unclear whether artificial nutrition support should be provided as enteral tube feeding or parenteral nutrition (PN). Methods We analysed day-100 non-relapse mortality (NRM), incidence of acute graft-versus-host disease (GvHD), acute gastrointestinal GvHD, 5-year survival and GvHD-free/relapse-free survival (GRFS) according to both route and adequacy of nutritional intake prior to neutrophil engraftment, together with other known prognostic factors, in a retrospective cohort of 484 patients who underwent allogeneic HCT for haematologic malignancy between 2000 and 2014. Results Multivariate analyses showed increased NRM with inadequate nutrition (hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.2–7.2) and adequate PN (HR 2.9; 95% CI 1.6–5.4) compared to adequate enteral nutrition (EN) both P <.001. There were increased incidences of gastrointestinal GvHD of any stage and all GvHD ≥ grade 2 in patients who received PN (odds ratio (OR) 2.0; 95% CI 1.2–3.3; P =.006, and OR 1.8; 95% CI 1.1–3.0; P =.018, respectively), compared to adequate EN. Patients who received adequate PN and inadequate nutrition also had reduced probabilities of survival and GRFS at 5 years. Conclusion Adequate EN during the early transplantation course is associated with reduced NRM, improved survival and GRFS at 5 years. Furthermore, adequate EN is associated with lower incidence of overall and gut acute GvHD than PN, perhaps because of its ability to maintain mucosal integrity, modulate the immune response to intensive chemo/radiotherapy and support the gastrointestinal tract environment, including gut microflora. [ABSTRACT FROM AUTHOR]

Objectives We sought to determine the frequency at which patients with elevated voriconazole (VRC) levels but no clinically evident central nervous system (CNS) toxicity subsequently develop CNS toxicity. Methods We retrospectively reviewed the records of adult patients with haematolologic malignancy who had a VRC serum level >5.5 μg/mL at MD Anderson Cancer Center (January 2010 to December 2015). Patients with any documented CNS toxicity at the time the VRC level was obtained or patients whose VRC was discontinued as a response to high VRC level were excluded. Neurologic status was assessed using standard grading scales. Demographic and clinical characteristics, including potentially interacting medications, were correlated with the development of toxicity. Results We identified 320 such patients (mean age, 57 ± 15 years; 202 male (63%)). Subsequent CNS toxicity was documented in only 16 patients (5%). The most common CNS toxicities were visual disturbances (9/16, 56%), depressed consciousness (5/16, 31%) and cognitive disturbance (4/16, 19%). Patients with CNS toxicity tended to be older than those without (64 ± 8 vs 57 ± 15 y, p 0.08). The use of one or more neurotoxic drugs was common in patients with subsequent CNS toxicity (14/16, 88%). Reduction of VRC dose associated with the high VRC level did not correlate with less subsequent CNS toxicity. Conclusions Development of subsequent CNS toxicity is uncommon in haematolologic malignancy patients with elevated VRC levels who had no evidence of toxicity at the time the level was obtained. Automatic reduction of VRC dose out of concern for impending CNS toxicity might not be warranted. [ABSTRACT FROM AUTHOR]

In view of the poor outcomes associated with mucormycosis in patients with haematologic malignancies (HM) and haematopoietic cell transplant recipients, antifungal combinations are frequently used, yet the value of such strategy remains unclear. We reviewed the records of HM patients treated for mucormycosis from 1994 to 2014. The primary outcome was 6-week mortality after treatment initiation. Of the 106 patients identified, 44% received monotherapy and 56% received combination treatment as initial therapy. Six-week mortality was associated with disseminated mucormycosis (p 0.018), active malignancy (p <0.01), higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p <0.001), neutropenia (p 0.049), lymphopenia (p 0.0003) and intensive care unit (ICU) admission at diagnosis (p 0.0001). Survivors were more likely to have localized mucormycosis (p <0.01) and to receive hyperbaric oxygen therapy (p 0.02). There were no differences in mortality between monotherapy and combination treatment groups (43% vs. 41%; p 0.85). In multivariate analysis, lymphopenia (odds ratio (OR), 5.5; 95% confidence interval (CI), 1.9–15.9; p 0.002) and ICU admission at diagnosis (OR, 8.2; 95% CI, 2.3–29.2; p 0.001) were associated with increased mortality. Localized mucormycosis was associated with better outcome (OR, 0.06; 95% CI, 0.01–0.6; p 0.019). Initial combination treatment had no impact on mortality, even after propensity score adjustment (OR, 0.8; 95% CI, 0.3–2.4; p 0.69). A weighted mortality risk score was then calculated for each patient based on the factors independently associated with mortality and baseline APACHE II score. In the low-risk group ( n = 49), 13% of monotherapy versus 15% of combination therapy patients died within 6 weeks (p >0.99). In the high-risk group ( n = 57), 71% of monotherapy versus 61% of combination therapy patients died within 6 weeks (p 0.42). With the current status of mucormycosis diagnosis, there was no difference in mortality in HM patients, whether they received monotherapy or combination treatment as initial therapy. Earlier diagnosis and immune reconstitution are unmet needs to affect outcomes. [ABSTRACT FROM AUTHOR]