Post-engraftment Bloodstream Infections After Allogeneic Hematopoietic Cell Transplantation: Risk Factors and Association with Mortality.

BACKGROUND: Bloodstream infections (BSIs) are major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to analyze the incidence, etiology, risk factors and outcomes of post-engraftment BSI in allo-HCT recipients. MATERIALS AND METHODS: The retrospective study included 261 patients with documented engraftment after first allo-HCT performed from January 2018 till September 2021. RESULTS: Of 261 patients 29 (11.1%) developed at least one post-engraftment BSIs episode with a median time to post-engraftment BSI of 49 days (range, 1 - 158 days from the engraftment). A total of 45 pathogens were isolated from blood - 64.4% (n = 29) were represented by Gram-negative bacteria, and 35.6% (n = 16) - by Gram-positive bacteria. Secondary graft failure (hazard ratio [HR]: 39.93; 95% confidence interval [CI]: 7.64-208.74; P <0.001), secondary poor graft function (HR: 18.07; 95% CI: 3.53 - 92.44; P <0.001), and acute gut graft-versus-host-disease (GvHD) grade II-IV (HR: 29.86; 95% CI: 10.53 - 84.68; P <0.001) were associated with the higher risk of Gram-negative post-engraftment BSIs. Overall 30-day survival after post-engraftment BSIs was 71.4%. By multivariate analysis post-engraftment BSIs (HR: 3.09; 95% CI: 1.29 - 7.38; P = 0.011), and acute gut GvHD grade II-IV (HR: 6.60; 95% CI: 2.78 - 15.68; P <0.001) were associated with the higher 180-day non-relapse mortality risk. CONCLUSION: Gram-negative bacteria prevailed in the etiology of post-engraftment BSIs with secondary graft failure. secondary poor graft function. and acute gut GvHD being the main predisposing factors for their development. Post-engraftment BSIs were associated with the higher risk of non-relapse mortality after allo-HCT.

Impact of fluoroquinolone administration and gut mucosal colonization on the risk of pre-engraftment bloodstream infections after allogeneic hematopoietic cell transplantation.

Fluoroquinolones (FQ) has been used after allogeneic hematopoietic stem cell transplantation (allo-HCT) for decades. This study on 284 allo-HCT recipients aimed to analyze the impact of FQ on pre-engraftment BSI. A total of 154 patients were colonized with resistant gram-negative bacteria, and 130 patients were not. Colonized patients did not receive FQ (n = 147) except 7 who received FQ as sequential therapy; 98 non-colonized patients received FQ, whereas 32 did not. Gram-negative (p < 0.0001), and ESBL-E BSI (p < 0.0001) were higher in colonized patients receiving FQ. No difference was found in gram-positive BSI (p = 0.452). In multivariate analysis colonized patients with (p < 0.0001) or without FQ (p = 0.007), omission of FQ in non-colonized patients (p = 0.038), and active disease (p = 0.042) were associated with gram-negative BSI, whereas mismatched unrelated donor transplantations - with gram-positive BSI (p = 0.009). Colonized patients with FQ have a higher risk of gram-negative BSI. In non-colonized patients, FQ prophylaxis is effective approach significantly reducing gram-negative BSI risk.

Recurrent bloodstream infections after allogeneic hematopoietic cell transplantation.

BACKGROUND: Although colonization is an established risk factor for bloodstream infection (BSI) due to identical strain, prior infection with resistant bacteria should also be considered during the management of febrile neutropenia. This study aimed to analyze the rate and etiology of recurrent BSI in allogeneic hematopoietic cell transplant (allo-HCT) recipients to determine its potential impact on decision-making. MATERIALS AND METHODS: The retrospective study included 284 allo-HCT recipients. Recurrent BSI was defined as a new BSI episode occurring in a period of more than 72 hours after antibiotic withdrawal. RESULTS: Overall, 104 patients (36.6%) developed at least one BSI, and 23 of them (22.1%) experienced recurrent BSI episodes (n = 30). Median time to recurrent BSI was 41 days (range 5-526 days). Recurrent BSI was associated with second allo-HCT (p < 0.0001), primary (p = 0.021), and secondary graft failure (p = 0.024). Carbapenem-resistant gram-negative bacteria were more common during recurrent BSI episodes (23.7% vs. 6.0%; p = 0.003). In only 17.5% patients experiencing recurrent BSI episode and in only 3.9% of patients with at least one BSI episode phenotypically identical recurring pathogen was isolated. CONCLUSIONS: In view of low rate of recurrent BSI due to identical pathogen, empirical antimicrobial therapy should not be based on data on previous BSI episodes.

Incidence, etiology, risk factors, and outcomes of pre-engraftment bloodstream infections after first and second allogeneic hematopoietic cell transplantation.

INTRODUCTION: With an increasing number of allogeneic hematopoietic cell transplantations (allo-HCT) bloodstream infections (BSI) are still among the most common and serious complications. This study aimed to analyze the incidence, etiology, risk factors, and outcomes of pre-engraftment BSI after the first and the second allo-HCT. MATERIALS AND METHODS: This is a retrospective study of 284 patients who underwent the first allo-HCT and 37 patients after the second allo-HCT at the National Research Center for Hematology in Moscow, Russia, from January 2018 till September 2021. RESULTS: Cumulative incidence of pre-engraftment BSI was 29.9% after the first allo-HCT and 35.1% after the second (p = .805). The median time to the first BSI was 9 days (range 0-61 days) after the first and 16 days (range 1-28 days) after the second allo-HCT (p = .014). A total of 113 pathogens were isolated during 94 BSI episodes after the first allo-HCT (gram-negative bacteria 52.2%; gram-positive bacteria 47.7%). Fourteen pathogens were isolated during 14 BSI episodes after the second allo-HCT (gram-negative bacteria 50.0%; gram-positive bacteria 50.0%). The only significant difference was found in the rate of carbapenem-resistant gram-negative bacteria, which was higher after the second allo-HCT compared to the first (57.1% vs. 13.6%; p = .048). Mismatched unrelated donor (hazards ratio [HR] 3.01; 95% confidence interval [CI]: 1.62-5.60; p < .0001) and haploidentical donor transplantations (HR 1.84; 95% CI: 1.02-3.33; p = .042) were the only independent risk factors associated with the higher risk of pre-engraftment BSI. Overall 30-day survival after all BSI episodes was 94.4%. Survival was lower after BSI during the second allo-HCT compared to the first (71.4% vs. 97.9%; p < .0001), particularly after BSI was caused by carbapenem-resistant gram-negative bacteria (25.0% vs. 100.0%; p = .0023). The non-relapse mortality rate at day +60 was 4.0%, and the risk was highly associated with primary graft failure (HR 9.62; 95% CI: 1.33-71.43), second allo-HCT (HR 6.80; 95% CI: 1.36-34.48), and pre-engraftment BSI caused by carbapenem-resistant gram-negative bacteria (HR 32.11; 95% CI: 4.91-210.15). CONCLUSIONS: Pre-engraftment BSI is still a common complication after allo-HCT, particularly after mismatched unrelated and haploidentical donor transplantations. BSI incidence was slightly higher after the second allo-HCT with a significantly higher rate of carbapenem-resistant BSI. Although pre-engraftment BSI would generally follow a benign clinical course, survival was dramatically lower during the second allo-HCT, especially after carbapenem-resistant BSI.

Infectious complications in allogeneic hematopoietic cell transplant recipients: Review of transplant-related risk factors and current state of prophylaxis.

Allogeneic hematopoietic cell transplantation is a complex procedure that carries a significant risk of complications. Infections are among the most common of them. Several direct factors such as neutropenia, hypogammaglobulinemia, lymphopenia, mucosal barrier injury, and graft-versus-host disease have been shown to be associated with increased infectious risk post-transplant. Apart from direct factors, there are also indirect transplant-related factors that are the primary trigger to the formers' development. The most important of them are type of preparative regimen, graft source, donor type, graft-versus-host disease prophylaxis, and graft manipulation techniques. In this review, an attempt has been made to summarize the role of the transplant-related factors in the development of infectious complications and provide evidence underlying the current concept of infectious disease prophylaxis in patients after allogeneic hematopoietic cell transplantation.

Respiratory syncytial virus and human metapneumovirus after allogeneic hematopoietic stem cell transplantation: Impact of the immunodeficiency scoring index, viral load, and ribavirin treatment on the outcomes.

INTRODUCTION: Respiratory viral infections are a major cause of morbidity and mortality among stem cell transplant recipients. While there is a substantial amount of information on prognostic factors and response to ribavirin therapy is available for RSV infections, this information is largely lacking for hMPV. PATIENTS AND METHODS: In total, 71 patients were included in this study: 47 patients with RSV and 24 with hMPV. Forty-one patients presented as an upper respiratory tract infection (URTI) and 30 as a primary lower respiratory tract infection (LRTI). Patients were stratified as per ISI criteria into low-, moderate-, and high-risk groups. Twenty-two patients in the URTI cohort received treatment with ribavirin (mainly oral), and 19 patients received no antiviral therapy. The decision for antiviral treatment was at the discretion of the attending physician. All 30 patients with primary LRTI and 10 patients with secondary LRTI were treated with ribavirin, 95% with the intravenous formulation. 45% of these patients received additional treatment with intravenous immunoglobulins. The viral load was assessed indirectly by using the CT value of the RT-PCR. RESULTS: In the cohort, as whole 11.5% suffered a virus-associated death, 5% in the URTI group, and 20% in the LRTI group. Sixty-day mortality was significantly higher in the ISI high-risk group (log-rank P = .05). Mortality was independent of the type of virus (P = .817). Respiratory failure with an indication for mechanical ventilation developed in 11.5%, this risk was independent of the type of virus. Progression from URTI to LRTI was observed in 24% of cases with a significantly higher risk (75%) in the ISI high group (log-rank P = .001). In the ISI high-risk group, treatment with ribavirin significantly reduced the risk of progression (log-rank P < .001). Neither the type of virus nor the viral load in the nasopharyngeal swab impacted the risk of progression (P = .529 and P = .141, respectively). The detection of co-pathogens in the BAL fluid was borderline significant for mortality (P = .07). CONCLUSIONS: We could detect no differences between RSV and hMPV with respect to progression to LRTI, risk of respiratory failure or need for mechanical ventilation and virus-associated death. The ISI index is of predictive value in hMPV patients with a high ISI score and treatment with oral ribavirin has an equivalent protective effect in RSV and hMPV patients. Treatment of LRTI with intravenous ribavirin results in a similar outcome in RSV- and hMPV-infected patients. We could not detect any benefit of adjunctive treatment with immunoglobulins in both primary and secondary LRTI. No role of viral load as an independent prognostic marker could be detected either for progression to LRTI or death.

Sarcoidosis imitating breast cancer metastasis: a case report and literature review.

Sarcoidosis is a benign systematic granulomatous disorder of unknown etiology and is associated with various malignancies. However, granulomatous and metastatic lymph node lesions are difficult to distinguish even when using precise and modern diagnostic methods, such as positron emission tomography. Thus, histological verification is the only method that can be used to accurately describe the nature of this disease. In this article, we report a case of non-luminal HER-2/neu-positive breast cancer in a patient without history of sarcoidosis and suspected to have metastatic disease.

Work-up and management of a high-risk patient with primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare disorder that, in 95% of cases, represents diffuse large B-cell lymphoma. As such, making an accurate diagnosis is important. At present, stereotactic-guided biopsy is a recognized method of choice for tissue analysis. However, the diagnostic work-up for high-risk patients is determined by their performance status. Here, we report a case of PCNSL in a high-risk patient, for whom diagnosis was established by cerebrospinal fluid cytology and flow cytometry, which significantly shortened a diagnostic work-up period and allowed for the immediate treatment of the patient.