Is Short-Course Antibiotic Therapy Suitable for Pseudomonas aeruginosa Bloodstream Infections in Onco-hematology Patients With Febrile Neutropenia? Results of a Multi-institutional Analysis.

BACKGROUND: Several studies have suggested that short-course antibiotic therapy was effective in Pseudomonas aeruginosa (PA) bloodstream infections (BSI) in immunocompetent patients. But similar studies in patients with hematological malignancies were rare. METHODS: This cohort study included onco-hematology patients at 2 hematology centers in China. Inverse probability of treatment weighting was used to balance the confounding factors. Multivariate regression model was used to evaluate the effect of short-course antibiotic therapy on clinical outcomes. RESULTS: In total, 434 patients met eligibility criteria (short-course, 7-11 days, n = 229; prolonged, 12-21 days, n = 205). In the weighted cohort, the univariate and multivariate analysis indicated that short course antibiotic therapy had similar outcomes to the prolonged course. The recurrent PA infection at any site or mortality within 30 days of completing therapy occurred in 8 (3.9%) patients in the short-course group and in 10 (4.9%) in the prolonged-course group (P = .979). The recurrent infection within 90 days occurred in 20 (9.8%) patients in the short-course group and in 13 (6.3%) patients in the prolonged-course group (P = .139), and the recurrent fever within 7 days occurred in 17 (8.3%) patients in the short-course group and in 15 (7.4%) in the prolonged-course group (P = .957). On average, patients who received short-course antibiotic therapy spent 3.3 fewer days in the hospital (P < .001). CONCLUSIONS: In the study, short-course therapy was non-inferior to prolonged-course therapy in terms of clinical outcomes. However, due to its biases and limitations, further prospective randomized controlled trials are needed to generalize our findings.

The application of nanopore targeted sequencing in the diagnosis and antimicrobial treatment guidance of bloodstream infection of febrile neutropenia patients with hematologic disease.

Traditional microbiological methodology has limited sensitivity, detection range, and turnaround times in diagnosis of bloodstream infection in Febrile Neutropenia (FN) patients. A more rapid and sensitive detection technology is urgently needed. Here we used the newly developed Nanapore targeted sequencing (NTS) to diagnose the pathogens in blood samples. The diagnostic performance (sensitivity, specificity and turnaround time) of NTS detection of 202 blood samples from FN patients with hematologic disease was evaluated in comparison to blood culture and nested Polymerase Chain Reaction (PCR) followed by sanger sequence. The impact of NTS results on antibiotic treatment modification, the effectivity and mortality of the patients under the guidance of NTS results were assessed. The data showed that NTS had clinical sensitivity of 92.11%, clinical specificity of 78.41% compared with the blood culture and PCR combination. Importantly, the turnaround time for NTS was <24 h for all specimens, and the pre-report time within 6 h in emergency cases was possible in clinical practice. Among 118 NTS positive patients, 98.3% patients' antibiotic regimens were guided according to NTS results. There was no significant difference in effectivity and mortality rate between Antibiotic regimen switched according to NTS group and Antibiotic regimen covering pathogens detected by NTS group. Therefore, NTS could yield a higher sensitivity, specificity and shorter turnaround time for broad-spectrum pathogens identification in blood samples detection compared with traditional tests. It's also a good guidance in clinical targeted antibiotic treatment for FN patients with hematologic disease, thereby emerging as a promising technology for detecting infectious disease.

A Visualized Mortality Prediction Score Model in Hematological Malignancies Patients with Carbapenem-Resistant Organisms Bloodstream Infection.

Background: Bloodstream infection (BSI) due to carbapenem-resistant organisms (CROs) has emerged as a worldwide problem associated with high mortality. This study aimed to evaluate the risk factors associated with mortality in HM patients with CROs BSI and to establish a scoring model for early mortality prediction. Methods: We conducted a retrospective cohort study at our hematological department from January 2018 to December 2021, including all HM patients with CROs BSI. The outcome measured was death within 30-day of BSI onset. Survivor and non-survivor subgroups were compared to identify predictors of mortality. Univariate and multivariate Cox regression analyses were used to identify prognostic risk factors and develop a nomogram. Results: In total, 150 HM patients were included in the study showing an overall 30-day mortality rate of 56%. Klebsiella pneumonia was the dominant episode. Cox regression analysis showed that pre-infection length of stay was >14 days (score 41), Pitt score >4 (score 100), mucositis (score 41), CAR (The ratio of C-reactive protein to albumin) >8.8 (score 57), early definitive therapy (score 44), and long-duration (score 78) were positive independent risk predictors associated with 30-day mortality, all of which were selected into the nomogram. Furthermore, all patients were divided into the high-risk group (≥160 points) or the low-risk group based on the prediction score model. The mortality of the high-risk group was 8 times more than the low-risk group. Kaplan-Meier analysis showed that empirical polymyxin B therapy was associated with a lower 30-day mortality rate, which was identified as a good prognostic factor in the high-risk group. In comparison, empirical carbapenems and tigecycline were poor prognostic factors in a low-risk group. Conclusion: Our score model can accurately predict 30-day mortality in HM patients with CROs BSI. Early administration of CROs-targeted therapy in the high-risk group is strongly recommended to decrease mortality.

A Novel Risk Predictive Scoring Model for Predicting Subsequent Infection After Carbapenem-Resistant Gram-Negative Bacteria Colonization in Hematological Malignancy Patients.

Background: This study investigated the high-risk factors associated with the increased vulnerability for subsequent clinical CR-GNB infection in carbapenem-resistant Gram-negative bacteria (CR-GNB)-colonized hematological malignancy (HM) patients and built a statistical model to predict subsequent infection. Method: All adult HM patients with positive rectoanal swabs culture for CR-GNB between January 2018 and June 2020 were prospectively followed to assess for any subsequent CR-GNB infections and to investigate the risk factors and clinical features of subsequent infection. Results: A total of 392 HM patients were enrolled. Of them, 46.7% developed a subsequent clinical CR-GNB infection, with 42 (10.7%) cases of confirmed infection and 141 (36%) cases of clinically diagnosed infection. Klebsiella pneumoniae was the dominant species. The overall mortality rate of patients colonized and infected with CR-GNB was 8.6% and 43.7%. A multivariate analysis showed that remission induction chemotherapy and the duration of agranulocytosis, mucositis, and hypoalbuminemia were significant predictors of subsequent infection after CR-GNB colonization. According to our novel risk-predictive scoring model, the high-risk group were >3 times more likely to develop a subsequent infection in comparison with the low-risk group. Conclusion: Our risk-predictive scoring model can early and accurately predict a subsequent CR-GNB infection in HM patients with CR-GNB colonization. The early administration of CR-GNB-targeted empirical therapy in the high-risk group is strongly recommended to decrease their mortality.

Prognostic Significance of Comprehensive Gene Mutations and Clinical Characteristics in Adult T-Cell Acute Lymphoblastic Leukemia Based on Next-Generation Sequencing.

Background: Adult T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignant tumor with poor prognosis. However, accurate prognostic stratification factors are still unclear. Methods: Data from 90 adult T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients were collected. The association of gene mutations detected by next-generation sequencing and clinical characteristics with the outcomes of T-ALL/LBL patients were retrospectively analyzed to build three novel risk stratification models through Cox proportional hazards model. Results: Forty-seven mutated genes were identified. Here, 73.3% of patients had at least one mutation, and 36.7% had ≥3 mutations. The genes with higher mutation frequency were NOTCH1, FBXW7, and DNMT3A. The most frequently altered signaling pathways were NOTCH pathway, transcriptional regulation pathway, and DNA methylation pathway. Age (45 years old), platelet (PLT) (50 G/L), actate dehydrogenase (LDH) (600 U/L), response in D19-BMR detection, TP53 and cell cycle signaling pathway alterations, and hematopoietic stem cell transplantation (HSCT) were integrated into a risk stratification model of event-free survival (EFS). Age (45 years old), white blood cell (WBC) count (30 G/L), response in D19-BMR detection, TP53 and cell cycle signaling pathway alterations, and HSCT were integrated into a risk stratification model of overall survival (OS). According to our risk stratification models, the 1-year EFS and OS rates in the low-risk group were significantly higher than those in the high-risk group. Conclusions: Our risk stratification models exhibited good prognostic roles in adult T-ALL/LBL patients and might guide individualized treatment and ultimately improve their outcomes.

[A Propensity Score Matching Study of Autologous Hematopoietic Stem Cell Transplantation and New Drug Chemotherapy for Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To compare the clinical efficacy, survival, and prognosis of autologous hematopoietic stem cell transplantation (ASCT) with new drug chemotherapy in the treatment of newly diagnosed multiple myeloma (NDMM) in the new drug era. METHODS: The clinical data of 149 patients with NDMM treated with new drug induction regimen in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2012 to December 2019 were retrospectively analyzed. Twenty-four patients who received ASCT were in ASCT group, and 125 patients who did not receive ASCT were in non-ASCT group. The median follow-up time was 43 (1-90) months. The propensity score matching (PSM) method was used to balance confounding factors, then depth of response, overall survival (OS), and progression-free survival (PFS) between the two groups were compared and subgroup analysis was performed. RESULTS: After matching, the covariates were balanced between the two groups. Fifty-one patients (15 cases in ASCT group and 36 cases in non-ASCT group) were included. ASCT patients had a better complete response (CR) rate than non-ASCT patients receiving maintenance therapy (93.3% vs 42.3%, P=0.004), while there were no statistical differences in deep response rate and overall response rate (ORR) between the two groups (93.3% vs 65.4%, P=0.103; 93.3% vs 96.2%, P=1.000). Before matching, the 3 and 5-year PFS rate and median PFS (mPFS) in ASCT group and non-ASCT group were [89.6% vs 66.5%, P=0.024; 69.8% vs 42.7%; non-response (NR) vs 51.0 months], and the 3 and 5-year OS rate and median OS (mOS) were (100% vs 70.6%, P=0.002; 92.3% vs 49.6%; NR vs 54.0 months). After matching, the 3 and 5-year PFS rate and mPFS in ASCT group and non-ASCT group were (83.6% vs 61.7%, P=0.182; 62.7% vs 45.7%; NR vs 51.0 months), the 3 and 5-year OS rate and mOS were (100% vs 65.6%, P=0.018; 88.9% vs 46.9%; NR vs 51.0 months). Subgroup analysis showed that patients with mSMART 3.0 high risk stratification, the 3-year PFS rate and mPFS in ASCT group and non-ASCT group were (83.3% vs 41.5%, P=0.091; NR vs 34.0 months), and the 3-year OS rate and mOS were (100% vs 41.5%, P=0.034; NR vs 34.0 months). Patients with mSMART 3.0 standard risk stratification, the 3-year PFS rate and OS rate in ASCT group and non-ASCT group were (83.3% vs 76.8%, P=0.672; 100% vs 87.2%, P=0.155). The 3-year PFS and OS rate in MM patients who achieved deep response within 3 months after transplantation compared with non-ASCT patients who achieved deep response after receiving maintenance therapy were (83.1% vs 56.7%, P=0.323; 100% vs 60.5%, P=0.042), and the 3-year PFS and OS rate in patients who achieved overall response in both groups were (83.1% vs 62.5%, P=0.433; 100% vs 68.1%, P=0.082). After matching, Cox multivariate regression analysis showed that mSMART 3.0 risk stratification and ASCT were independent prognostic factors for OS. CONCLUSION: In the new drug era, ASCT can increase CR rate and prolong OS of NDMM patients. ASCT patients who are mSMART 3.0 high risk stratification or achieved deep response within 3 months after transplantation have better OS than non-ASCT patients receiving new drug chemotherapy. ASCT and mSMART 3.0 risk stratification are independent prognostic factors for OS in NDMM patients.