zithromax and Hematologic-Neoplasms

Early administration of azithromycin after allogeneic hematopoietic stem cell transplantation was shown to increase the relapse of hematological malignancies. To determine the impact of azithromycin on the post-transplant gut ecosystem and its influence on relapse, we characterized overtime gut bacteriome, virome, and metabolome of 55 patients treated with azithromycin or a placebo. We describe four enterotypes and the network of associated bacteriophage species and metabolic pathways. One enterotype associates with sustained remission. One taxon from Bacteroides specifically associates with relapse, while two from Bacteroides and Prevotella correlate with complete remission. These taxa are associated with lipid, pentose, and branched-chain amino acid metabolic pathways and several bacteriophage species. Enterotypes and taxa associate with exhausted T cells and the functional status of circulating immune cells. These results illustrate how an antibiotic influences a complex network of gut bacteria, viruses, and metabolites and may promote cancer relapse through modifications of immune cells.

Topics: Azithromycin; Ecosystem; Hematologic Neoplasms; Humans; Neoplasm Recurrence, Local; T-Lymphocytes

Bronchiolitis obliterans syndrome has been associated with increased morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). Previous studies have suggested that azithromycin may reduce the incidence of post-lung transplant bronchiolitis obliterans syndrome.. To evaluate if the early administration of azithromycin can improve airflow decline-free survival after allogeneic HSCT.. The ALLOZITHRO parallel-group trial conducted in 19 French academic transplant centers and involving participants who were at least 16 years old, had undergone allogeneic HSCT for a hematological malignancy, and had available pretransplant pulmonary function test results. Enrollment was from February 2014 to August 2015 with follow-up through April 26, 2017.. Patients were randomly assigned to receive 3 times a week either 250 mg of azithromycin (n = 243) or placebo (n = 237) for 2 years, starting at the time of the conditioning regimen.. The primary efficacy end point was airflow decline-free survival at 2 years after randomization. Main secondary end points were overall survival and bronchiolitis obliterans syndrome at 2 years.. Thirteen months after enrollment, the independent data and safety monitoring board detected an unanticipated imbalance across blinded groups in the number of hematological relapses, and the treatment was stopped December 26, 2016. Among 480 randomized participants, 465 (97%) were included in the modified intention-to-treat analysis (mean age, 52 [SD, 14] years; 75 women [35%]). At the time of data cutoff, 104 patients (22%; 54 azithromycin vs 50 placebo) had experienced an airflow decline; 138 patients (30%) died (78 azithromycin vs 60 placebo). Two-year airflow decline-free survival was 32.8% (95% CI, 25.9%-41.7%) with azithromycin and 41.3% (95% CI, 34.1%-50.1%) with placebo (unadjusted hazard ratio [HR], 1.3; 95% CI, 1.02-1.70; P = .03). Of the 22 patients (5%) who experienced bronchiolitis obliterans syndrome, 15 (6%) were in the azithromycin group and 7 (3%) in the placebo group (P = .08). The azithromycin group had increased mortality, with a 2-year survival of 56.6% (95% CI, 50.2%-63.7%) vs 70.1% (95% CI, 64.2%-76.5%) in the placebo group (unadjusted HR, 1.5; 95% CI, 1.1-2.0; P = .02). In a post hoc analysis, the 2-year cumulative incidence of hematological relapse was 33.5% (95% CI, 27.3%-39.7%) with azithromycin vs 22.3% (95% CI, 16.4%-28.2%) with placebo (unadjusted cause-specific HR, 1.7; 95% CI, 1.2-2.4; P = .002).. Among patients undergoing allogeneic HSCT for hematological malignancy, early administration of azithromycin resulted in worse airflow decline-free survival than did placebo; these findings are limited by early trial termination. The potential for harm related to relapse requires further investigation.. clinicaltrials.gov Identifier: NCT01959100.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bronchiolitis Obliterans; Disease-Free Survival; Double-Blind Method; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Intention to Treat Analysis; Male; Middle Aged; Recurrence; Respiratory Function Tests; Transplantation Conditioning; Transplantation, Homologous; Treatment Failure

Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.

Topics: Acetates; Adult; Aged; Anti-Inflammatory Agents; Azithromycin; Bronchiolitis Obliterans; Cyclopropanes; Disease Progression; Fluticasone; Forced Expiratory Volume; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Lung; Male; Middle Aged; Quality of Life; Quinolines; Sulfides; Survival Analysis; Transplantation, Homologous; Treatment Outcome

Bronchiolitis obliterans syndrome (BOS) is an important complication after hematopoietic SCT (HSCT). Recent observations suggested that azithromycin might improve lung function in BOS after HSCT. We conducted a randomized double-blinded placebo-controlled study on azithromycin in patients with BOS after HSCT. The treatment group (n=10) received oral azithromycin 250 mg daily while the control group (n=12) received placebo daily for 12 weeks. Respiratory symptoms were assessed by the St George Respiratory Questionnaires and spirometry at baseline (drug commencement), 1, 2, 3 (drug cessation) and 4 months (1 month after drug cessation). There was no significant difference in the baseline demographic characteristics between the treatment and the control groups in age, gender, time from HSCT to BOS, time since diagnosis of BOS, chronic GVHD, baseline respiratory symptom scores and baseline forced expiratory volume in 1 s (FEV(1)). Throughout and after 3 months of treatment, there were no significant changes in respiratory symptom scores and FEV(1) measurements between the treatment and the control groups. In conclusion, there was no significant benefit of 3 months of oral azithromycin on the respiratory symptoms and lung function in patients with relatively late BOS after HSCT in this randomized placebo-controlled study.

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Bronchiolitis Obliterans; Chronic Disease; Double-Blind Method; Female; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Syndrome; Time Factors; Transplantation, Homologous

Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey.. In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection.. Forty four patients were asymptomatic at diagnosis of SARS-CoV- 2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixty-nine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use.. Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.. Solid malignite hastalarının şiddetli akut solunum yolu enfeksiyonu-koronavirüs-2 (SARS-CoV-2) enfeksiyonuna sağlıklı bireylerden daha yatkın oldukları gösterilmiştir. Bu verilerin ardından oldukça yoğun immünosupresif olan hematolojik malignite hastalarında SARS-CoV-2 infeksiyonu sonuçları ilgi konusu olmuştur. Biz de bu makalede Türkiye’de hematolojik malignite tanısı ile takip ve tedavi edilirken SARS-CoV-2 enfeksiyonu saptanan hastaların semptom, komplikasyon, yoğun bakım ünitesine yatış ve mortalite oranlarını değerlendirmeyi amaçladık.. Çok merkezli çalışmamıza Mart-Kasım 2020 tarihleri arasında SARS-CoV-2 enfeksiyonu tanısı alan erişkin ve pediatrik 340 hastayı dahil ettik. Hastaların hematolojik malignite tanıları, hastalık statusları, tedavileri, son tedaviden enfeksiyona kadar geçen süre, komorbiditeleri, yaşam beklentileri değerlendirildi. Semptomları, oluşan komplikasyonlar ve sonuçlar analiz edildi.. Kırk-dört hasta semptomsuz olarak enfeksiyonu geçirirken, semptomatik hastaların ateş, öksürük, ve dispne oranları sırasıyla %62,6, %48,8 ve %41,8 idi. Altmış altı hasta (%20) hastalığı hafif geçirirken, orta, ciddi ve kritik hastalık tanısı alanların oranı sırasıyla %29, %20 ve %16 idi. Tüm kohortta ölüm oranı %26,6 idi; ölüm hafif hastalığı olanlarda %4,4 , orta derece hastalık geçirenlerde %12 ve ciddi/kritik hastalık geçirenlerde ise %83 olarak saptandı. Aktif hematolojik hastalık olması, primer hematolojik hastalığa bağlı düşük hayat beklentisi, SARS-CoV-2 tanısı aldığında nötropenik olmak, yoğun bakıma alınmış olmak ve ilk sıra koronavirüs hastalığı-2019 tedavisi yüksek ölüm riski ile ilişkilendirilen faktörlerdendi. Tek başına veya azitromisin ile kombine olarak hidroksiklorokin kullanan hastaların sadece favipiravir kullananlara göre ölüm riskleri daha yüksek saptandı.. SARS-CoV-2 infeksiyonu geçiren hematolojik malignite hastalarında daha yüksek oranda ciddi hastalık ve ölüm riski gözlenmektedir.

Topics: Adult; Amides; Azithromycin; Child; COVID-19; Hematologic Neoplasms; Humans; Hydroxychloroquine; Pyrazines; SARS-CoV-2; Turkey

Topics: Azithromycin; Child; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Neoplasm Recurrence, Local; Transplant Recipients; Transplantation Conditioning

Topics: Antilymphocyte Serum; Azithromycin; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Recurrence; Transplant Recipients; Transplantation Conditioning; Unrelated Donors

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Disease-Free Survival; Female; Follow-Up Studies; Hematologic Neoplasms; Humans; Hydroxychloroquine; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Survival Rate

Coronavirus disease 2019 (COVID-19) is an illness resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019. Patients with cancer, and especially those with hematologic malignancies, may be at especially high risk of adverse outcomes, including mortality resulting from COVID-19 infection. The ASH Research Collaborative COVID-19 Registry for Hematology was developed to study features and outcomes of COVID-19 infection in patients with underlying blood disorders, such as hematologic malignancies. At the time of this report, data from 250 patients with blood cancers from 74 sites around the world had been entered into the registry. The most commonly represented malignancies were acute leukemia (33%), non-Hodgkin lymphoma (27%), and myeloma or amyloidosis (16%). Patients presented with a myriad of symptoms, most frequently fever (73%), cough (67%), dyspnea (50%), and fatigue (40%). Use of COVID-19-directed therapies, such as hydroxychloroquine (n = 76) or azithromycin (n = 59), was common. Overall mortality was 28%. Patients with a physician-estimated prognosis from the underlying hematologic malignancy of <12 months at the time of COVID-19 diagnosis and those with relapsed/refractory disease experienced a higher proportion of moderate/severe COVID-19 disease and death. In some instances, death occurred after a decision was made to forgo intensive care unit admission in favor of a palliative approach. Taken together, these data support the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality resulting from COVID-19 infection. Batch submissions from sites with high incidence of COVID-19 infection are planned to support future analyses.

Topics: Adolescent; Adult; Aged; Azithromycin; COVID-19; COVID-19 Drug Treatment; Female; Hematologic Neoplasms; Humans; Hydroxychloroquine; Male; Middle Aged; Prognosis; Registries; SARS-CoV-2; Severity of Illness Index; Survival Rate; Treatment Outcome; Young Adult

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiolitis Obliterans; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male