scholarly journals INFECTIOUS RISKS AND COMPLICATIONS IN ADULT LEUKEMIC PATIENTS RECEIVING BLINATUMOMAB

2018 ◽  
Vol 10 (1) ◽  
pp. 2018029 ◽  
Author(s):  
Wonhee So ◽  
Shuchi Pandya ◽  
Rod Quilitz ◽  
Rod Quilitz ◽  
John Greene
Keyword(s):  
Lymphoblastic Leukemia ◽  
Patient Characteristics ◽  
Underlying Disease ◽  
Mucosal Barrier ◽  
Cancer Center ◽  
Antibacterial Prophylaxis ◽  
Lower Baseline ◽  
Included Patient ◽  
Mucosal Barrier Injury ◽  
Cell Acute Lymphoblastic Leukemia

Background: Blinatumomab is an anti-CD19 immunotherapy approved for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) with significantly increased survival rate. While blinatumomab showed lower rates of infection, neutropenia and mucosal barrier injury versus chemotherapy, its infection risks are not well described. Methods: All patients who received blinatumomab for ≥ 7 days at an academic cancer center from May 2015 to April 2017 were included. Patient characteristics pertinent to infectious risks and complications were examined.Results: Twenty patients with refractory (25%), relapsed (70%), or remitted (5%) B-ALL who received a total of 35 cycles were included. Ten of the 35 cycles were interrupted, none of which were due to infections. Twenty six infections (n) were observed with lower respiratory (9), gastrointestinal (6) and bacteremia (5) being most common. Compared to patients without nodular, possible mold pneumonia (n=16), patients with nodular pneumonia (n=4) had significantly lower baseline absolute neutrophil count (ANC) (2319 v. 208/µL, p=0.011). There were no differences in baseline characteristics including ANC between bacteremic and non-bacteremic patients. One patient was discharged with no antibacterial prophylaxis since ANC recovered to >500cells/µL, but developed Pseudomonal bacteremia within a week with ANC ~100cells/µL. Conclusion: Despite blinatumomab’s relatively modest myelosuppression and the lack of mucotoxicity, host factors (e.g., duration and degree of neutropenia/lymphopenia) play a key role and should be considered when choosing anti-microbial prophylaxis. In relapsed/refractory disease, the ANC should be monitored closely post blinatumomab since neutropenia can unexpectedly develop after treatment which may be compounded by the underlying disease and recent chemotherapy effects.

scholarly journals Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Furun An ◽  
Huiping Wang ◽  
Zhenyun Liu ◽  
Fan Wu ◽  
Jiakui Zhang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Patient Characteristics ◽  
Car T ◽  
Cell Acute Lymphoblastic Leukemia

AbstractCD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.

scholarly journals Treatment failure in giant cell arteritis

2021 ◽  
pp. annrheumdis-2021-220347
Author(s):  
Sebastian H Unizony ◽  
Min Bao ◽  
Jian Han ◽  
Yves Luder ◽  
Andrey Pavlov ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Patient Characteristics ◽  
Related Factors ◽  
Intention To Treat ◽  
Lower Baseline ◽  
Included Patient ◽  
Patient Reported ◽  
Registration Number

ObjectiveIdentify predictors of treatment failure in patients with giant cell arteritis (GCA) receiving tocilizumab in combination with glucocorticoids and in patients with GCA receiving only glucocorticoids.MethodsPosthoc analysis of the Giant-Cell Arteritis Actemra trial including 250 patients who received tocilizumab every week plus a 26-week prednisone taper (n=100), tocilizumab every-other-week plus a 26-week prednisone taper (n=49) or placebo plus a 26-week (n=50) or 52-week (n=51) prednisone taper in the intention-to-treat population. Responders for this analysis were patients who maintained remission (no GCA signs/symptoms and no erythrocyte sedimentation rate elevation) through week 52. Treatment failure was defined as inability to achieve remission by week 12 or relapse between weeks 12 and 52. Predictors investigated in univariate and multivariable analyses included patient characteristics, disease-related and treatment-related factors and patient-reported outcomes (PROs).Results149 patients received tocilizumab plus prednisone (TCZ/PDN) and 101 received placebo plus prednisone (PBO+PDN). After adjustment for confounders, treatment failure was significantly less likely in the TCZ/PDN group than the PBO/PDN group (OR, 0.2; 95% CI, 0.1 to 0.3; p<0.0001). Risk for treatment failure was significantly higher in women than men in the PBO/PDN group (OR, 5.2; 95% CI, 1.6 to 17.2; p=0.007) but not in the TCZ/PDN group. Predictors of treatment failure in the TCZ/PDN group included lower baseline prednisone doses and worse PROs at baseline.ConclusionThe strongest risk factors for treatment failure in GCA are treatment with prednisone alone and female sex. Lower starting prednisone doses and impaired PROs are associated with failure to respond to tocilizumab.Trial registration numberNCT01791153.

scholarly journals Immunotherapy for T-Cell ALL and T-NHL: Highlights From SOHO 2020

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Allyson Price, MPAS, PA-C
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Cancer Center ◽  
University Of Texas ◽  
Keynote Presentation ◽  
Non Hodgkin Lymphoma ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Md Anderson ◽  
The University ◽  
Washington University

In his keynote presentation, John DiPersio, MD, PhD, of Washington University, recipient of the SOHO 2020 Distinguished Lecturer Award, discussed immunotherapy for T-cell acute lymphoblastic leukemia and T-cell non-Hodgkin lymphoma. Allyson Price, MPAS, PA-C, of The University of Texas MD Anderson Cancer Center, distills the seminal research by Dr. DiPersio and discusses implications for advanced practitioners.

scholarly journals Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With IKZF1 Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study

2018 ◽  
Vol 36 (26) ◽  
pp. 2726-2735 ◽  
Author(s):  
Allen Eng Juh Yeoh ◽  
Yi Lu ◽  
Winnie Hui Ni Chin ◽  
Edwynn Kean Hui Chiew ◽  
Evelyn Huizi Lim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lymphoblastic Leukemia ◽  
Patient Characteristics ◽  
Treatment Intensification ◽  
Significant Difference ◽  
Amplification Assay ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Impact ◽  
Risk Of Relapse ◽  
Dependent Probe

Purpose Although IKZF1 deletion ( IKZF1del) confers a higher risk of relapse in childhood B-cell acute lymphoblastic leukemia (B-ALL), it is uncertain whether treatment intensification will reverse this risk and improve outcomes. The Malaysia-Singapore ALL 2010 study (MS2010) prospectively upgraded the risk assignment of patients with IKZF1del to the next highest level and added imatinib to the treatment of all patients with BCR- ABL1 fusion. Patients and Methods In total, 823 patients with B-ALL treated in the Malyasia-Singapore ALL 2003 study (MS2003; n = 507) and MS2010 (n = 316) were screened for IKZF1del using the multiplex ligation-dependent probe amplification assay. The impact of IKZF1del on the 5-year cumulative incidence of relapse (CIR) was compared between the two studies. Results Patient characteristics were similar in both cohorts, including IKZF1del frequencies (59 of 410 [14.4%] v 50 of 275 [18.2%]; P = .2). In MS2003, where IKZF1del was not used in risk assignment, IKZF1del conferred a significantly higher 5-year CIR (30.4% v 8.1%; P = 8.7 × 10−7), particularly in the intermediate-risk group who lacked high-risk features (25.0% v 7.5%; P = .01). For patients with BCR-ABL1–negative disease, IKZF1del conferred a higher 5-year CIR (20.5% v 8.0%; P = .01). In MS2010, the 5-year CIR of patients with IKZF1del significantly decreased to 13.5% ( P = .05) and no longer showed a significant difference in patients with BCR-ABL1-negative disease (11.4% v 4.4%; P = .09). The 5-year overall survival for patients with IKZF1del improved from 69.6% in MS2003 to 91.6% in MS2010 ( P = .007). Conclusion Intensifying therapy for childhood B-ALL with IKZF1del significantly reduced the risk of relapse and improved overall survival. Incorporating IKZF1del screening significantly improved treatment outcomes in contemporary ALL therapy.

Antibacterial Prophylaxis in Patients with Neutropenia

2007 ◽  
Vol 5 (2) ◽  
pp. 235-242 ◽  
Author(s):  
Brahm H. Segal ◽  
Alison G. Freifeld
Keyword(s):  
At Risk ◽  
Bacterial Infections ◽  
Hematologic Malignancy ◽  
Lymphoblastic Leukemia ◽  
Meta Analysis ◽  
Empiric Therapy ◽  
Underlying Disease ◽  
Antibacterial Prophylaxis ◽  
Pneumocystis Jiroveci ◽  
Chemotherapy Induced Neutropenia

Patients with cancer and chemotherapy-induced neutropenia are at risk for severe bacterial infections. This risk is not uniform among all cancer patients but is dependent primarily on the depth and duration of neutropenia and the type of underlying disease. Accordingly, the decision whether to use antibacterial prophylaxis to prevent serious infections in these patients requires a balance between expected benefit and the risks for infection, adverse drug-related events, and emergence of antibiotic resistance. Although antibacterial prophylaxis has the potential to benefit all patients with chemotherapy-induced neutropenia, the benefit regarding reduction in documented infections has been firmly established only in patients with neutropenia expected to exceed 7 days. A recent meta-analysis showed enhanced survival in patients receiving antibacterial prophylaxis during neutropenia; most patients enrolled in the analyzed trials had a hematologic malignancy. Among patients with neutropenia at lower risk for infectious complications (a category that includes most patients with solid tumor malignancies), the main benefit of antibacterial prophylaxis relates to a reduction in fever rather than documented infections. The authors advise quinolone prophylaxis (levofloxacin is preferred), in patients with an expected duration of neutropenia (absolute neutrophil count < 1000/μL) of more than 7 days. Trimethoprim-sulfamethoxazole should be used in patients at risk for Pneumocystis jiroveci (formerly P carinii), such as childhood acute lymphoblastic leukemia. In patients with neutropenia expected to last 7 days or less and not receiving immunosuppressive regimens (e.g., systemic corticosteroids), the authors recommend no initial prophylaxis. However, if such patients develop fever during neutropenia, they should be considered for outpatient empiric therapy with an oral quinolone–containing regimen if they meet criteria for low risk for complications.

scholarly journals 1171. Impact of Catheter Management on the Clinical Outcome in Adult Cancer Patients with Gram-Negative Bacteremia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S419-S419
Author(s):  
Johny Fares ◽  
Melissa Khalil ◽  
Anne-Marie Hajjar Chaftari ◽  
Ying Jiang ◽  
Ray Y Hachem ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Bloodstream Infection ◽  
Mucosal Barrier ◽  
Cancer Center ◽  
Gram Negative ◽  
Mucosal Barrier Injury ◽  
Gram Negative Bacteremia ◽  
The Impact ◽  
Overall Mortality ◽  
Line Management

Abstract Background Over the last 2 decades, Gram-negative organisms have been on the rise as an etiology of bloodstream infections (BSI) in cancer patients. Management of the central venous catheter (CVC) in the setting of Gram-negative BSI remains challenging. The aim of our study was to evaluate cancer patients with different types of Gram-negative BSI, in the presence of an indwelling CVC, and assess the impact of line management on the outcome of the BSI. Methods We identified all the patients older than 14 years with CVC who had a documented BSI with a Gram-negative organism at M.D Anderson Cancer Center, from May 2017 until May 2018. Patients were divided into three groups. Group 1 (G1) included patients with central-line associated bloodstream infection and no mucosal barrier injury (non-MBI CLABSI) and/or those who met the catheter-related bloodstream infection (CRBSI) criteria; Group 2 (G2) consisted of patients who had a CLABSI with a mucosal barrier injury that did not meet the CRBSI definition; and Group 3 (G3) consisted of patients who had a non-line-related BSI. We assessed catheter management (CVC removed/exchanged or retained) at 2 days after the onset of bacteremia. We then determined the effect of line management on clinical and microbiologic outcomes through various measures. Results A total of 300 patients were included with 100 patients in each group. The univariate analyses showed that in G1, CVC removal within 2 days of bacteremia was significantly associated with higher rate of microbiologic eradiation of the bacteremia compared with delayed CVC removal (3 to 5 days) or CVC retention (98% vs. 72% vs. 78% respectively, P = 0.002; P < 0.001), and lower overall mortality rate at 3 months follow-up (3% vs. 22% vs. 17% respectively, P = 0.02; P = 0.01). By multivariate analysis, this association persisted (P = 0.018 and P = 0.016, respectively). CVC removal within 2 days of bacteremia did not affect the outcome of BSI in G2 and G3. Conclusion CVC removal within 48 hours of the onset of Gram-negative bacteremia significantly improved the infectious outcome and the overall mortality in adult cancer patients with definite CRBSI and CLABSI without MBI. Disclosures All authors: No reported disclosures.

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