scholarly journals 1087. Evaluation of Risk Factors for Infection among Patients Receiving Ibrutinib

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S572-S573
Author(s):  
Kenneth Tham ◽  
Stacy Prelewicz ◽  
Sara deHoll ◽  
Deborah Stephens ◽  
Carlos A Gomez
Keyword(s):  
Risk Factors ◽  
Single Agent ◽  
Interleukin 2 ◽  
Significant Risk ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Cell Transplant ◽  
Serious Infection ◽  
Molecule Inhibitor ◽  
Baseline Characteristics ◽  
High Index Of Suspicion

Abstract Background Ibrutinib is a small-molecule inhibitor of Bruton tyrosine kinase (BTK) approved for various B-cell malignancies and cGVHD. Rates of serious infection—defined as requiring hospitalization or parenteral antimicrobials— and invasive fungal infection (IFI) in patients on ibrutinib are as high as 11.4% and 4.2% respectively (Varughese T, et al. Clin Infect Dis 2018;67(5):687-92), which may be related to off-target inhibition of interleukin-2-inducible T-cell kinase or macrophage function. Methods We retrospectively reviewed infection complications in patients receiving ibrutinib at our institution between 06/01/2014 and 08/31/2019, including patients who received single-agent or combination ibrutinib. In this study, serious infection was defined as above, or a diagnosis of pneumonia regardless of hospitalization or parenteral antimicrobial therapy. Logistic regression was used to identify risk factors. Results Baseline characteristics of 134 included patients are in Table 1. Infection and serious infection occurred in 96 (72%) and 48 (36%) patients, respectively. When pneumonia was not included as a criterion for serious infection, the serious infection rate was 22%. Prior allogeneic stem cell transplant (allo-HSCT) (OR 4.50; 95% CI 1.19 – 17.00) and corticosteroid use (OR 5.42; 95% CI 1.49 – 19.82) were significant risk factors for serious infection without pneumonia (Table 2). Of 37 patients (28%) who received primary HSV/VZV prophylaxis with acyclovir, there was one case of suspected herpes zoster infection (3%). IFI developed in 7 patients (5%): 5 with Pneumocystis jirovecii pneumonia (PJP), 1 with invasive aspergillosis, and 1 with a filamentous fungus, species unknown. Other identified organisms are detailed in Figure 1. Classical risk factors for IFI, including diabetes, allo-HSCT, and concurrent corticosteroid use, were not significant predictors in this group. Table 1. Baseline Characteristics Table 2. Risk Factor Analysis Figure 1. Identified Organisms in Serious Infection Conclusion Serious infections developed at a higher rate than previously reported in the literature, with IFI rates similar to those previously described. Prior allo-HSCT and steroid use were found to be risk factors for serious infection without pneumonia. Treating physicians should have a high index of suspicion for pneumonia, IFI, and PJP in this population. Disclosures All Authors: No reported disclosures

Tazemetostat (TAZ) in relapsed/refractory (R/R) follicular lymphoma (FL): Propensity-score matched analysis of E7438-G000-101 trial outcomes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18627-e18627
Author(s):  
David Proudman ◽  
Deepshekhar Gupta ◽  
Dave Nellesen ◽  
Alex Wong ◽  
Jay Yang ◽  
...  
Keyword(s):  
Propensity Score ◽  
Single Agent ◽  
Objective Response ◽  
Prior History ◽  
Cell Transplant ◽  
Phase 2 ◽  
Matched Sample ◽  
Hematopoietic Stem ◽  
Disease Characteristics ◽  
Baseline Characteristics

e18627 Background: Oncology drug development often requires the use of non-randomized, open-label, phase 2 basket studies to better understand the early activity and safety of a potential new therapy. As such, baseline demographics and disease characteristics may differ between cohorts which can impact the perception of efficacy between cohorts. TAZ, a first-in-class, oral enhancer of zeste homolog 2 (EZH2) inhibitor was approved by the US FDA after demonstrating single-agent, antitumor activity in a phase 2 study in adults with wild-type (WT) or mutant (MT) EZH2 R/R FL who had received ≥2 prior systemic therapies (NCT01897571). Differences between the cohorts in baseline characteristics known to be prognostic for clinical outcomes were noted, with the WT EZH2 cohort enrolling more patients with poor-risk features. This analysis assessed outcomes in the 2 groups after minimizing differences in baseline characteristics by creating a matched sample of directly comparable WT and MT patients. Methods: Propensity scores for each WT (n = 54) and MT (n = 45) EZH2 patient in the study were generated, based on the likelihood of being selected given their baseline characteristics. Characteristics identified for inclusion in the model were chosen if they were prognostic based on peer-reviewed literature and where larger differences were observed between cohorts at baseline: ECOG performance status, number of prior lines of anticancer therapy, progression of disease within 24 months, double refractory status, and prior history of hematopoietic stem cell transplant. Patients were matched 1:1 on propensity score, using a nearest-neighbor approach with caliper restrictions. Baseline covariates between the two matched groups were found to be sufficiently balanced. Objective response rate (ORR) point estimates were measured for the matched WT and MT EZH2 groups, and progression-free survival (PFS) was described using Kaplan-Meier analyses. Results: The propensity-matched sample included 56 patients (28 WT and 28 MT). Prior to matching, ORR was 35% (95% CI [22%, 48%]) in the WT and 69% (95% CI [55%, 83%]) in MT EZH2 groups; after matching, the ORR was 50% (95% CI [31%, 69%]) and 71% (95% CI [54%, 88%]), respectively. Median PFS was 11.1 months (95% CI [5.4, 16.7]) in the WT and 13.8 months (95% CI [11.1, 22.1]) in the MT EZH2 groups prior to matching, and 14.3 months (95% CI [11.1, inf]) and 14.8 (95% CI [10.7, inf]) months in the WT and MT EZH2 matched groups, respectively. Conclusions: As expected, efficacy remained higher in the MT EZH2 group; however, after adjustment, the ORR and PFS improved in the WT EZH2 group. This hypothesis-generating analysis suggests that outcomes in patients with WT EZH2 R/R FL treated with TAZ may have been more similar to those in the MT EZH2 group in the phase 2 trial had the baseline disease characteristics been more equally matched.

5-Azacytidine (AZA) in Combination with Ruxolitinib (RUX) As Therapy for Patients (pts) with Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPNs)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 823-823 ◽  
Author(s):  
Naval Daver ◽  
Guillermo Garcia-Manero ◽  
Jorge E. Cortes ◽  
Lingsha Zhou ◽  
Sherry Pierce ◽  
...  
Keyword(s):  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Single Agent ◽  
Myeloproliferative Neoplasm ◽  
Hematological Toxicity ◽  
Cell Transplant ◽  
Bone Marrow Biopsies ◽  
Baseline Characteristics ◽  
Grade 3

Abstract Background: Clinical trials exclusively focusing on pts with MDS/MPN are lacking. AZA is a DNA methyltransferase (DNMT) inhibitor approved for the therapy of MDS while RUX is a JAK inhibitor approved as therapy for primary myelofibrosis and polycythemia vera. RUX and AZA may target distinct clinical and pathological manifestations of MDS/MPNs. Aim: To determine the efficacy and safety of RUX + AZA in pts with MDS/MPN requiring therapy including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia BCR-ABL1 negative (aCML), and myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U)(ClinicalTrials.gov Identifier: NCT01787487). Methods: A sequential approach with single-agent RUX 15 mg orally twice daily (if platelets 100-200) or 20 mg twice daily (if platelets >200) continuously (pts with platelets below 50 were not eligible) in 28-day cycles for the first 3 cycles followed by the addition of AZA 25 mg/m2 on days 1-5 of each 28-day cycle starting cycle 4 was adopted. The AZA dosage could be gradually increased to a maximum of 75 mg/m2. The AZA could be started earlier than cycle 4 and/or at a higher dose in pts with proliferative disease or elevated blasts. Results: 24 pts were enrolled between March 1, 2013 and April 1, 2015. Baseline characteristics are summarized in table 1. 17 pts remain alive after a median (med) follow-up of 6.0 (3.7 - 21.3+) months. Responses were evaluated by the MDS/MPN IWG response criteria (Savona et al., Blood 2015, 125(12):1857-65). Responses were noted in 12 (50%) pts. Details of responses are shown in table 2. Med time to responses was 1.8 mos (0.7 - 5.5+) and the med duration of response is 7.0 mos (1.8 - 17.6+). Additionally, 9 pts had >5% pretreatment BM blasts: 6 of these pts had follow-up BM evaluations and 3 achieved a reduction in blasts to <5% with a med time to blast reduction of 5.5 mos (5.5 - 11.2+). Serial evaluation of bone marrow biopsies documented reduction in EUMNET fibrosis score in 3 of 11 (27%) evaluable pts after a med of 5.5 mos (2.1 - 5.6+) on therapy. The reduction was by one grade in all 3 pts (MF-2 to MF-1 in 2 pts, MF-1 to MF-0 in 1 pt) and was confirmed on a subsequent BM biopsy in 2 pts. No pts experienced grade 3/4 non-hematological toxicity. New onset grade 3/4 anemia and thrombocytopenia were seen in 12 (50%; of which 5 had a 2+ grade change) and 8 (31%) pts, respectively. The med overall survival is 15.1+ mos. 7 pts have died: pneumonia (n=3), sepsis (n=2), progression to AML (n=1), and transition to hospice (n=1). The AZA was started in cycle 4 in 12 pts (50%). The AZA was started earlier due to leukocytosis or increased blasts in 11 pts (46%), in cycle 1 (n=6), cycle 2 (n=4), and cycle 3 (n=1). 13 pts have discontinued protocol therapy due to leukocytosis (n=6), progression to AML (n=1), lack of response (n=3), pneumothorax (n=1), stem cell transplant (n=1), and loss of insurance (n=1), respectively. Conclusion: Concomitant administration of RUX with AZA was feasible and effective in pts with MDS/MPNs, with expected myelosuppression as the only significant toxicity. This combination warrants further evaluation. Table 1. Baseline characteristics (N = 24) Characteristic N (%) / [range] Med age, years 71 [55 - 79] Prior treatment 9 (38) Diagnosis MDS/MPN-U CMML aCML 11 (46) 10 (42) 3 (12) MF - DIPSS Int-1/ Int-2/ High 4(17)/ 11(46) / 9(37) MDS - IPSS Low/ Int-1/ Int-2/ High 9(38) /12(50) / 2(8) / 1(4) Splenomegaly 12 (50) Med WBC x 109/L 26.3 [3 - 123.2] Peripheral blood blasts >/= 1% 17 (71%) LDH 1040 [409 - 3567] EUMNET fibrosis grade MF-1/ MF-2/ MF-3 10(42)/ 6(26)/ 1(4) JAK2 + 6 (25) Med JAK2 allele burden 42.2 [3 - 90] Karyotype Diploid Abnormal 18 (75) 6 (25) 28-gene molecular panel in 23 pts*, (1 pt not done) ASXL1 DNMT3A TET2 KRAS/NRAS PTPN11 IDH 2 4 (17) 4 (17) 3 (13) 2(8) / 2(8) 2(8) 2 (8) *Mutations identified in only 1 pt included EZH2, GATA2, RUNX1, MPL, KIT. Table 2. Response evaluation by the MDS/MPN IWG 2015 criteria Response category Evaluable pts Responders/Evaluable (%) *All responses, some pts have > 1 response All 12/24 (50) Clinical improvement (CI) spleen Pts with palpable spleen > 5 cm 8/11 (73) CI total symptom score Pts with baseline TSS > 20 3/12 (25) CI Hemoglobin (HGB) Baseline HGB < 10 g/dL 1/7 (15) CI Transfusion independence History of transfusion dependence 1/5 (20) Partial marrow response Baseline and follow-up BMs 5/11 (45) Optimal marrow response Baseline and follow-up BMs 1/11 (9) *No CR or PR documented Disclosures Daver: ImmunoGen: Other: clinical trial, Research Funding. Cortes:Pfizer: Consultancy, Research Funding; BerGenBio AS: Research Funding; Teva: Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. DiNardo:Novartis: Research Funding. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding.

Evaluation of Pre–Hematopoietic Cell Transplantation (HCT) Brain MRI and Neurologic Complications of Pediatric Patients Undergoing HCT for Hematologic Malignancies

2016 ◽  
Vol 34 (1) ◽  
pp. 65-73
Author(s):  
Mara Bailey-Olson ◽  
Morton Cowan ◽  
Christopher Dvorak ◽  
Sabine Mueller ◽  
Abigail Owens ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Pediatric Patients ◽  
Brain Mri ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Hematologic Malignancies ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Neurologic Complications

Adverse neurologic complications (NC) occur commonly in pediatric patients with hematologic malignancies both pre- and post–allogeneic hematopoietic cell transplant (HCT). Given this known risk, we previously obtained pre-HCT brain magnetic resonance imaging (MRI) to document baseline abnormalities but utility of this and findings are not well described. This study aimed to ( a) determine the prevalence and risk factors for abnormal brain MRI and ( b) determine prevalence and risk factors for development of new NC during and 2 years post-HCT. Retrospective chart review included 102 patients with hematologic malignancies who underwent allogeneic HCT between 2000 and 2009 at University of California San Francisco (UCSF) Children’s Hospital and included standard HCT data, brain MRI reports, and NC and symptoms pre- and post-HCT. Forty-three percent of patients had abnormal findings on pre-MRI, most commonly nonspecific white matter changes. Neurologic symptoms pre-HCT was the only significant risk factor for abnormal MRI. Eleven patients (11%) developed post-HCT NC. Non-Caucasian race was the only significant risk factor for new NC. Although abnormal pre-HCT brain MRI is common, these findings are not predictive of subsequent NC post-HCT. Therefore routine surveillance may not be informative for that purpose, particularly when general anesthesia is required, which can have detrimental neurocognitive effects. Etiology of NC in pediatric HCT is likely multifactorial and may include genetic and ethnic predispositions.

scholarly journals 985. Fusarium Infections in Patients with Hematological Malignancies

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S583-S584
Author(s):  
Gayathri Krishnan ◽  
Anupam Pande
Keyword(s):  
Risk Factors ◽  
Statistical Analysis ◽  
Median Duration ◽  
Hematological Malignancies ◽  
Hematological Malignancy ◽  
Academic Medical Center ◽  
Significant Risk ◽  
Cell Transplant ◽  
Surgical Specimen ◽  
Exact Test

Abstract Background Fusarium is a ubiquitous mold that can cause invasive and disseminated fusariosis in immunosuppressed patients, especially those with hematological malignancies. The risk factors associated with mortality of patients with Fusarium infections have not been adequately assessed in literature. In this study, we sought to explore the characteristics, clinical outcomes, and risk factors for mortality in Fusarium infections in patients with hematological malignancies. Methods This is a retrospective study of adult hematological malignancy patients admitted to surgical/medical wards or critical units at an academic medical center from January 2010 to January 2021 and diagnosed with proven invasive Fusarium infections through positive microbiological culture data from a biopsy, surgical specimen or sterile site. Primary end point was 30-day mortality. Statistical analysis was done using Fischer’s exact test and Mann-Whitney U test. Results 31 patients with hematological malignancies were identified with proven Fusarium infections during the 10-year period (13,390 total unique patients with diagnosis of hematologic malignancies). Two were excluded due to incomplete data. Demographic characteristics, type and status of hematological malignancy, chemotherapy, exposure to steroids, neutropenia, lymphopenia, antifungal prophylaxis, and other factors were analyzed. Mean age at diagnosis was 52.6 years. 16/29 (55.2%) had undergone stem cell transplant prior to infection with median duration of 150.5 days (range 12 to 1503) prior to infection. The most common pathologies were invasive sinusitis and disseminated cutaneous infection in 13/29 (44.8%) patients. Blood culture was positive in 5/29 (17.2%). Overall mortality was 86.2% with 30-day mortality of 44.8% and 1-year mortality of 83%. Death was attributed to fusariosis in 12/25 (48%). Median duration to death was 56 days (range 2 to 1627 days). Risk factors for 30-day mortality were assessed (table 1). The table describes risk factors for 30-day mortaity for fusarium infections in patients with hematological malignancies. statistical analysis done using fischer’s exact test Conclusion Fusarium infections result in morbidity and mortality in patients with hematological malignancies. A variety of host and disease factors dictate eventual outcome of Fusarium infections in these patients. Lack of neutrophil recovery is a significant risk factor for 30-day mortality in this population. Disclosures All Authors: No reported disclosures

Evaluating Vancomycin Use at a Pediatric Hospital: New Approaches and Insights

2005 ◽  
Vol 26 (1) ◽  
pp. 47-55 ◽  
Author(s):  
Maureen K. Bolon ◽  
Alana D. Arnold ◽  
Henry A. Feldman ◽  
David H. Rehkopf ◽  
Emily F. Strong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Factor Analysis ◽  
Risk Factor ◽  
Tertiary Care ◽  
Significant Risk ◽  
Risk Factor Analysis ◽  
Cell Transplant ◽  
Care Hospital ◽  
Inappropriate Use ◽  
Tertiary Care Medical Center

AbstractObjectives:To characterize vancomycin use at a pediatric tertiary-care hospital, to discriminate between initial (≤ 72 hours) and prolonged (> 72 hours) inappropriate use, and to define patient characteristics associated with inappropriate use.Design:Vancomycin courses were retrospectively reviewed using an algorithm modeled on HICPAC guidelines. Data were collected regarding patient demographics, comorbidities, other medication use, and nosocomial infections. The association between each variable and the outcome of inappropriate use was determined by longitudinal regression analysis. A multi-variable model was constructed to assess risk factors for inappropriate initial and prolonged vancomycin use.Setting:A pediatric tertiary-care medical center.Patients:Children older than 1 year who received intravenous vancomycin from November 2000 to June 2001.Results:Three hundred twenty-seven vancomycin courses administered to 260 patients were evaluated for appropriateness. Of initial courses, 114 (35%) were considered inappropriate. Of 143 prolonged courses, 103 (72%) were considered inappropriate. Multivariable risk factor analysis identified the following variables as significantly associated with inappropriate initial use: admission to the surgery service, having a malignancy, receipt of a stem cell transplant, and having received a prior inappropriate course of vancomycin. No variables were identified as significant risk factors for inappropriate prolonged use.Conclusions:Substantial inappropriate use of vancomycin was identified. Prolonged inappropriate use was a particular problem. This risk factor analysis suggests that interventions targeting patients admitted to certain services or receiving multiple courses of vancomycin could reduce inappropriate use.

Long-Term Remissions Of Patients With Follicular Lymphoma Grade 3 Treated With Rituximab, Cyclophospamide, Doxorubicine, Vincristine and Prednisone (R-CHOP)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3028-3028
Author(s):  
Paolo Strati ◽  
Jorge Enrique Romaguera ◽  
Larry W. Kwak ◽  
Fredrick B Hagemeister ◽  
Maria Alma Rodriguez ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Follicular Lymphoma ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Single Agent ◽  
World Health ◽  
Cell Transplant ◽  
Baseline Characteristics ◽  
Grade 3

Abstract Background Follicular lymphoma grade 3 (FLG3) are recognized as a distinct entity in the World Health Organization classification of lymphoma. FLG3 are defined as > 15 centroblasts per high power field and are further subdivided into A or B on the basis of the presence of centrocytes. Their natural history is similar to that of diffuse large B cell lymphomas (DLBCL) and there is still debate about their optimal management. Methods We conducted a retroprospective analysis of 156 patients with FLG3 receiving frontline treatment at MD Anderson Cancer Center between 06/1973 and 11/2004. Multivariate analysis (MVA) was performed using Hazard Ratio (HR) Cox regression with backward stepwise selection. Logistic regression with odds ratio (OR) was used for MVA of categorical variable. Results Patient baseline characteristics are shown in the Table. Forty-five (29%) patients received R-CHOP, of which 12 (27%) received more than 6 cycles and 9 (20%) and radiation therapy as consolidation. In particular, patients with stage I/II disease (9) all received 5-6 cycles, with additional radiation therapy consolidation in 4 patients. The overall response rate was 100% and 43 (96%) patients achieved complete remission (CR). After a median follow-up of 9 (2-12) years, median PFS has not been reached with 14 (31%) patients relapsing. Nearly all relapses occurred within 3 years, except for 1 patient who relapsed after 8 years and achieved a second durable CR with single agent Rituximab (Figure). On MVA, the only characteristic associated with a shorter PFS was the presence of > 4 nodal sites (HR 4.2, p=0.03). Among relapsed patients, 3 (21%) transformed to DLBCL (1 at first relapse) and died. Six (43%) relapsed patients received stem cell transplant (1 allogeneic) and 5 (36%) received more than 2 salvage regimens. Median OS has not been reached for all R-CHOP treated and relapsed patients. On univariate analysis, the only factor associated with a shorter OS after relapse was transformation (p=0.01). Baseline characteristics associated with transformation on MVA were IPI score 3-4 (OR 1.1, p=0.004) and elevated LDH (OR 2.4, p=0.01). Nine patients died, 2 (22%) of lymphoma progression, 4 (44%) of therapy-related acute myeloid leukemia (AML) and 3 (32%) of cancer-unrelated causes On MVA, factors associated with shorter OS after R-CHOP were age > 60 years (HR 11, p=0.02) and LDH > 618 IU/L (HR 5.9, p=0.01). On univariate analysis, age > 60 years was the only factor associated with AML onset (p=0.04). Conclusions R-CHOP is an effective treatment for patients with FLG3 and small number of nodal sites, with rare late progressions. The incidence of transformation is low but is fatal. Onset of second myeloid malignancies is the main cause of death and warrants caution in elderly patients. Disclosures: No relevant conflicts of interest to declare.

Effects of obesity on overall survival (OS) of patients with acute myeloid leukemia (AML).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18510-e18510
Author(s):  
Prajwal Dhakal ◽  
Elizabeth Lyden ◽  
Andrea Lee ◽  
Joel Michalski ◽  
Zaid S. Al-Kadhimi ◽  
...  
Keyword(s):  
Cox Regression ◽  
Significant Risk ◽  
Patient Characteristics ◽  
Continuous Variable ◽  
Cell Transplant ◽  
Obese Patients ◽  
Co Morbidity ◽  
Comorbidity Burden ◽  
Baseline Characteristics ◽  
Morbidity Index

e18510 Background: The relationship between obesity and prognosis of AML has not been established. Our retrospective study aimed to determine the effect of obesity on OS of AML. Methods: AML patients diagnosed from 2000-2016 at University of Nebraska Medical Center were included. Body mass index (BMI) at the time of AML diagnosis was divided into 3 groups: normal (18.5≤25 kg/m2) or underweight (<18.5 kg/m2); over-weight (25-30 kg/m2); and obese (≥30 kg/m2). Chi-square test, Kruskal-Wallis test and ANOVA were used to look at the association of different BMI groups with other patient characteristics. Mann-Whitney test was used for pairwise comparisons of hematopoietic cell transplant (HCT) co-morbidity index and Bonferroni correction was used to adjust p-values. OS, defined as time from diagnosis to death from any cause, was determined by Kaplan-Meier method and comparisons were done using log-rank test. Cox Regression was performed to detect survival effect of BMI (as continuous variable). P<0.05 was considered statistically significant. Results: A total of 314 patients were included in the study (Table): 46% were female, 35% had adverse cytogenetics, 15% had FLT3-ITD mutation, 68% received intensive chemotherapy and 30% underwent HCT. 38% of total patients were obese. Baseline characteristics were similar in all 3 BMI groups except co-morbidity index (p=0.04). OS for normal/underweight, overweight and obese groups at 1 year was 85%, 92%, and 94% respectively (p=0.84). BMI, as a continuous variable, was not a significant risk factor for death (HR 1.00, 95% CI 0.98-1.03). Conclusions: Obese patients, compared to non-obese patients, did not differ in baseline characteristics other than increased comorbidity burden. Obesity, when adjusted for other characteristics, did not have any effect on OS of patients with AML. Patient characteristics. [Table: see text]

scholarly journals Extrapulmonary tuberculosis: risk factors

2021 ◽  
Vol 18 (4) ◽  
pp. 48-54
Author(s):  
M. A. Yudenko ◽  
I. V. Buinevich ◽  
D. Y. Rusanau ◽  
S. V. Goponiako
Keyword(s):  
Risk Factors ◽  
Retrospective Study ◽  
Pulmonary Tuberculosis ◽  
Older Persons ◽  
Extrapulmonary Tuberculosis ◽  
Significant Risk ◽  
High Index ◽  
Clinical Risk Factors ◽  
High Index Of Suspicion ◽  
Tuberculosis Risk

Objective. To identify the main demographic and clinical risk factors for the development of extrapulmonary tuberculosis (EPTB).Materials and methods. A retrospective study of tuberculosis cases registered from 2016 to 2020 in the Gomel region was conducted (330 patients with EPTB and 2,505 patients with pulmonary tuberculosis). The odds ratios were calculated to assess the risk factors for the development of EPTB.Results. The prevalence of EPTB was studied over the course of five years. The most significant risk factors for the development of tuberculosis in extrapulmonary localizations have been identified.Conclusion. The risk factors for the development of EPTB are age (EPTB often develops in children and older persons), females, and in those who have had an episode of tuberculosis previously. Awareness of the predisposing factors may help physicians maintain a high index of suspicion regarding the development of EPTB.

Post-Consolidation Immunotherapy with Histamine Dihydrochloride and Interleukin-2 in AML: Assessment of Consistency and Robustness of Treatment Benefit for Patients in First Complete Remission.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1948-1948
Author(s):  
Marc E Buyse ◽  
Pierre Squifflet ◽  
Jacob M Rowe ◽  
John K Whisnant ◽  
Dileep Bhagwat ◽  
...  
Keyword(s):  
Complete Remission ◽  
Interleukin 2 ◽  
High Dose ◽  
Cell Transplant ◽  
Histamine Dihydrochloride ◽  
Treatment Benefit ◽  
P Values ◽  
Kendall’S Τ ◽  
Baseline Characteristics ◽  
Leave One Out

Abstract Background: Data from a randomized multinational trial of 320 adults with AML demonstrated that maintenance therapy with 3-week cycles of histamine dihydrochloride plus low-dose interleukin-2 (HDC/IL-2) for up to 18 months significantly improved leukemia-free survival (LFS) for all patients in complete remission (CR) (n=320; hazard ratio [HR]=1.38; P=0.008) and for patients in first CR (CR1; n=261; HR=1.39; P=0.011) over standard-of-care (no treatment) (Brune et al, Blood, 2006). Our objective was to critically assess these trial data to verify: the consistency of treatment benefit across subsets of patients, taking into account the prognostic groups and baseline characteristics; the robustness across study centers and trial endpoints (LFS and overall survival [OS]); and the utility of LFS as a surrogate for OS in AML. Methods: Forest plots were constructed with HRs of HDC/IL-2 treatment effects versus controls for subsets of CR1 patients based on prospectively defined baseline characteristics: age &gt; or ≤60, gender, treatment initiated at &gt; or ≤6 months from CR to randomization, performance status, white blood cells at diagnosis, Southwest Oncology Group karyotypes, AML subtypes, intensive induction/consolidation with autologous stem cell transplant or high dose cytarabine, extramedullary leukemia, and country. Inconsistency coefficients and interaction tests were used to detect any differences in benefit among subsets. A “leave-one-out” analysis was carried out to assess robustness of the results to the elimination of individual study centers. Correlations were estimated between LFS and OS using a bivariate copula model, and between the HRs for LFS and OS using weighted linear regression. Results: The benefit of HDC/IL-2 over no treatment was statistically consistent across all subsets of CR1 patients regardless of baseline prognostic variables. Inconsistency coefficients and P-values of interaction tests ranged from 0% to 44% and 0.18 to 0.84, respectively. The treatment effect was robust, with statistical significance in 13 of 33 subsets analyzed. In site-specific leave-one-out analyses, P-values for the treatment benefit ranged from 0.006 to 0.031 (mean 0.013), confirming that no single site dominated the results. With regard to the surrogacy of LFS for OS, LFS and OS were correlated at the individual patient level (Kendall’s τ =0.70). More importantly, at the country level, the HRs for the effects of HDC/IL-2 on LFS and on OS were strongly correlated (R2=0.88). Conclusions: These analyses confirm the consistency and robustness of the HDC/IL-2 effect over no treatment to prolong LFS in AML patients in CR1. There was no notable heterogeneity in the HDC/IL-2 treatment benefit across baseline characteristics or country. No single study center dominated the effect. In this trial, LFS was found to be a strong surrogate for OS and may be an acceptable surrogate for OS in future AML trials.

Brentuximab-induced peripheral neuropathy: Risk factors and patient experiences.

2017 ◽  
Vol 35 (5_suppl) ◽  
pp. 120-120 ◽  
Author(s):  
Sarah Nagle ◽  
Lauren E. Strelec ◽  
Alison W. Loren ◽  
Daniel Jeffrey Landsburg ◽  
Sunita Nasta ◽  
...  
Keyword(s):  
Risk Factors ◽  
Peripheral Neuropathy ◽  
Univariate Analysis ◽  
Single Agent ◽  
Significant Risk ◽  
Progression Free Survival ◽  
Median Number ◽  
Brentuximab Vedotin ◽  
Increased Risk

120 Background: Brentuximab vedotin (BV) is an immunoconjugate used in Hodgkin lymphoma (HL) and other CD30+ lymphomas. The dose-limiting adverse effect is peripheral neuropathy (BIPN). Predictors of BIPN, effect on outcomes, and the biopsychosocial impact are not well defined. Methods: We conducted a single institution, mixed-methods study of lymphoma patients (pts) who received BV between 1/2010 and 5/2016. A retrospective analysis was conducted in all pts; an open-ended survey was given to pts seen in the prior year. A univariate analysis examined the association between BIPN and potential predictors. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan Meier method. Survey data were analyzed qualitatively via a framework approach. Results: Eighty-nine pts were eligible: 56% were male, 54% had HL, 71% had prior neurotoxic drugs, 93% received single agent BV. The median number of BV doses was 5. Forty-three (48%) pts developed BIPN. It resolved completely in 14 (33%) pts at a median follow-up of 12 mo. The median time to resolution was 13 wks. BV therapy was altered in 21 (24%) pts due to BIPN. There was no difference in PFS (6 vs. 12 mo., p = 0.09) or OS (NR vs. 26 mo., p = 0.11) in pts who had therapy altered due to BIPN. Table 1 lists significant risk factors for BIPN. No additional factors investigated (age, sex, prior neurotoxic agent, underlying neuropathy, diabetes mellitus or BMI) increased risk for BIPN. Fourteen of the 18 (78%) surveyed pts reported BIPN. At a median follow-up of 24 mo., 10 (71%) pts reported ongoing symptoms. BIPN affected quality of life in 50% and work in 20% of pts. Despite significant symptoms from BIPN, all pts were satisfied with their decision to receive BV regardless of disease response. Conclusions: BIPN is a significant adverse event and may fail to resolve in a large subset of pts. Surveyed pts reported that the benefits of BV outweigh the risks. Changes in therapy due to BIPN occur, but this did not affect outcomes in our cohort. Clinicians should be aware of the risk for BIPN and educate pts accordingly. [Table: see text]

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