Risk Factors For The Development Of Severe Bacterial Infection In Patients With Multiple Myeloma During Chemotherapy With Bortezomib Containing Regimens

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5370-5370 ◽  
Author(s):  
Shin Young Hyun ◽  
Ji Eun Jang ◽  
Yundeok Kim ◽  
Doh Yu Hwang ◽  
Soo Jeong Kim ◽  
...  

Abstract Background The aim of this study is to identify risk factors associated with the development of severe bacterial infection (SBI) in patient with multiple myeloma (MM) during treatment with bortezomib-containing regimens. Methods A total of 98 patients with MM who were treated with bortezomib-based treatment between 2006 and 2012 were analyzed. Fifty three patients received bortezomib-dexamethasone, 25 patients received bortezomib-melphalan-prednisolone, 15 patients received bortezomib-doxorubicin-dexamethasone and 5 patients received other regimens. They received a total of 427 courses of treatment. The SBI was defined as at least grade 3 neutropenic/non-neutropenic infection by NCI Common Terminology Criteria for Adverse Events version 4.0. Using the logistic regression method, we analyzed risk factors for the development of SBI during each course of treatment. Results Median age of the patients was 62 years and 40.6% (30/98) of patients treated with bortezomib-containing regimens as first-line therapy. The SBI was developed in 57% (56/98) of patients and 19% (81/427) of bortezomib courses. Among 81 episodes of SBI, 42 (53%) episodes were clinically documented infection, 30 (37%) were microbiologically documented infections, and 9 (11%) were fever of unknown origin. The most common type of infection was pneumonia (60%). Poor performance status (ECOG ≥2) (Hazard Ratio [HR] 5.365, 95% Confidence Interval [CI] 2.004-14.364, P =.001) was the only risk factor for the development of SBI in 98 patients. When we analyzed the risk factors for the development of SBI which occurred during each treatment course, poor performance status (ECOG ≥2) (P <.001), early course of treatment (≤2 courses) (P <.001) and pretreatment lymphopenia (absolute lymphocyte count <1.0 x 109/L) (P = .043) were associated with increased risk for developing SBI in each course. These 3 risk factors remained independently significant in multivariate analysis: poor performance status (ECOG ≥2) (HR 3.920, 95% CI 2.305-6.666, P <.001), early course of treatment (≤2 courses) (HR 2.782, 95% CI 1.633-4.740, P <.001) and pretreatment lymphopenia (HR 1.728, 95% CI 1.016-2.937, P = .043). The probability of developing SBI in each treatment course was 5.1% in courses with no risk factor, 14.9% in 1 risk factor, 23.9% in 2 risk factors and 59.5% in 3 risk factors (P <.001, Figure 1). After treatment with bortezomib-containing regimens, patients who experienced SBI showed a significantly shorter overall survival than patients who didn't experienced SBI (median 6.1 month vs. 30.1 months, P = .004) although progression free survival was not different (median 18.1 months vs. 21.9 months, P = .418). The multivariate cox analysis demonstrated that the development of SBI was associated with inferior overall survival (HR 2.440, 95% CI 1.305-4.561, P = .005) as well as male sex (HR 2.323, 95% CI 1.236-4.367, P = .009). Conclusions In conclusion, we identified that poor performance status, early courses of treatment, and lymphopenia at the beginning of each treatment course were the risk factors for the development of SBI in patients with MM during treatment with bortezomib-containing regimens. Close monitoring for the development of SBI and appropriate treatment should be considered in the patients with risk factors. Disclosures: No relevant conflicts of interest to declare.

Author(s):  
Alvin J. X. Lee ◽  
Karin Purshouse

AbstractThe SARS-Cov-2 pandemic in 2020 has caused oncology teams around the world to adapt their practice in the aim of protecting patients. Early evidence from China indicated that patients with cancer, and particularly those who had recently received chemotherapy or surgery, were at increased risk of adverse outcomes following SARS-Cov-2 infection. Many registries of cancer patients infected with SARS-Cov-2 emerged during the first wave. We collate the evidence from these national and international studies and focus on the risk factors for patients with solid cancers and the contribution of systemic anti-cancer treatments (SACT—chemotherapy, immunotherapy, targeted and hormone therapy) to outcomes following SARS-Cov-2 infection. Patients with cancer infected with SARS-Cov-2 have a higher probability of death compared with patients without cancer. Common risk factors for mortality following COVID-19 include age, male sex, smoking history, number of comorbidities and poor performance status. Oncological features that may predict for worse outcomes include tumour stage, disease trajectory and lung cancer. Most studies did not identify an association between SACT and adverse outcomes. Recent data suggest that the timing of receipt of SACT may be associated with risk of mortality. Ongoing recruitment to these registries will enable us to provide evidence-based care.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Elena Vladimirovna Semenova ◽  
Olesia V Paina ◽  
Zhemal Zarifovna Rakhmanova ◽  
Polina Valerievna Kozhokar ◽  
Anastasia S Frolova ◽  
...  

Background: Traditionally, children with AML undergo аllo-HSCT with myeloablative conditioning (MAC). It is known that MAC is associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities. But there is no conclusive evidence to support efficacy of RIC allo-HSCT in children suffering from different malignant diseases including AML. The aim: To compare efficacy of different intensity conditioning regimens in children with high risk (HR) AML (according to AML-BFM protocols 1998 and 2004) and to identify factors which have a prognostic significance for overall survival (OS). Patients and methods: Retrospective analysis was performed in 192 patients (pts) with AML (median age of 10 years (0.5-18 y.o.), who received allo-HSCT at R.M. Gorbacheva Research Institute between 08/2000 and 09/2019. MAC (busulfan- or treosulfan-based) were used in 109 pts: 1st CR - 46 pts (MRD+ n=11), 2nd CR - 18 pts, 3rd CR - 1 pt, relapse - 44 pts. Allo-HSCT with RIC were performed in 83 pts: 1st CR - 32 pts (MRD+ n=13), 2nd CR -19 pts, 3rd CR - 4 pts, relapse -28 pts (p=0,674). RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Indication for RIC allo-HSCT was poor performance status (Lansky/Karnofsky score ≤70%), or organ dysfunction due to previous therapy, or infectious complications at the moment of allo-HSCT. Allo-HSCT from matched related donor was performed in 30 pts (16%), from matched unrelated donor - in 98 pts (51%), haploidentical - in 64 pts (33%) and the donor distribution was not different between groups (p=0,878). Post-transplant Cy was included in GVHD prophylaxis regimens in 102 pts (53%). OS were estimated using Kaplan-Meier curves. Univariate analyses were performed using the log rank test for OS, Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5 years for МАС, 4.5 years for RIC. In both groups the median time to neutrophil engraftment &gt;=0,5x109/l was D+16 (range D+8-52). Engraftment was observed in 67 pts (81%) after RIC and 94 pts (86%) after MAC (p=0,231). OS after RIC allo-HSCT in the 1st CR was 76% and after MAC - 68% (p=0,014), in 2nd CR 50% after RIC and 54% after MAC (p=0,058), in advanced disease 14% after RIC and 16% after MAC (p=0,394). The transplant-related mortality rate was 19% after RIC and 22% after MAC (p=0,546). Risk of relapse was 28% after RIC and 26% after MAC (p=0,456). Factors influencing OS after MAC were: 1) Remission status at the moment of allo-HSCT (р=0.001); 2) Presence of aGVHD grade I-II (р=0,005); 3) Relapse or MRD+ status after allo-HSCT (р=0.012); 4) Lansky score &gt;70% (р=0,024). Factors influencing OS after RIC were: 1) Remission status at the moment of allo-HSCT (1st remission) (p=0,001); 2) Lansky score &gt;70% (р=0,004). Conclusion: The effectiveness of RIC and MAC is comparable in children with HR AML, but RIC demonstrated better results in 1st CR. The presence of I-II grade aGVHD had positive effect in MAC. Factors influencing OS in both groups were disease status at the moment of allo-HSCT and performance status before allo-HSCT The use of RIC can be effective in patients, especially those who have undergone allo-HSCT in the 1st remission, while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Multicenter studies are warranted, especially for patients in the first CR, where long-term complications are of most importance. Disclosures No relevant conflicts of interest to declare.


Breast Care ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. 93-98
Author(s):  
Hartmut Link

Chemotherapy-induced anemia (CIA) in cancer patients correlates with poor performance status and decreased quality of life. Currently recommended causal therapies are erythropoiesis-stimulating agents (epoetins), iron substitution, or a combination of both. Guidelines recommend considering red blood cell (RBC) transfusions for symptomatic anemia at a hemoglobin (Hb) level of <8 g/dl. Granulocyte colony-stimulating factor (G-CSF) is recommended if the risk of febrile neutropenia (FN) following from the chosen chemotherapy protocol is ≥20%. If a chemotherapy is planned that induces a moderate FN risk (10-20%), the individual overall FN risk should be assessed prior to each chemotherapy cycle, taking into account patient- or tumor-related risk factors. G-CSF is required when risk factors such as age ≥ 65 years, advanced disease or relevant comorbidity, or previous neutropenia complications are present. Neutropenia that required a shift in chemotherapy is also an indication for G-CSF prophylaxis in subsequent cycles, in order to maintain the planned dose intensity. The use of G-CSF improves patient survival and reduces the rate of neutropenia complications.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2324-2324
Author(s):  
Jayesh Mehta ◽  
S. Singhal ◽  
M. Tallman ◽  
S. Williams ◽  
J. Winter ◽  
...  

Abstract The outcome of 63 consecutive submyeloablative allografts (27–66 y, median 52) performed for hematologic malignancies after 100 mg/m2 melphalan without (n=21; prior autograft) or with (n=42; no prior autograft) 50 mg/kg cyclophosphamide was analyzed to study the effect of pre-transplant characteristics. GVHD prophylaxis comprised cyclosporine-mycophenolate (n=37; HLA-identical sibling donors) or tacrolimus-mycophenolate (n=26, 1-locus mismatched sibling or 9–10/10 allele-matched unrelated). No growth factors were administered routinely post-transplant and supportive care was uniform. 14 patients experienced transplant-related mortality (TRM), and 32 relapsed. 24 relapsing patients died, and 7 of the other 8 are alive in CR or with declining disease. The following factors were analyzed in a Cox model for their effect on TRM and relapse: chemosensitive (n=25) vs refractory disease (n=38), age ≤55 (n=44) vs >55 (n=19), normal (n=32) vs abnormal (n=31) LDH, HLA match (n=56) vs mismatch (n=7), prior autograft or not, performance status 0–1 (n=47) vs 2–3 (n=16). Outcome Favorable factor RR (95% CI) P TRM Age ≤55 0.20 (0.04–0.86) 0.03 HLA matched 0.21 (0.05–0.89) 0.04 Performance status 0-1 0.25 (0.06–0.99) 0.05 Relape Chemosensitive disease 0.28 (0.11–0.73) 0.01 Fig 1 shows TRM for patients with 0, 1 or 2 high-risk factors for TRM. Fig 1 shows TRM for patients with 0, 1 or 2 high-risk factors for TRM. Fig 2 shows overall survival (OS) for patients with 0 or 1 high-risk factors for TRM by disease chemosensitivity. Fig 2 shows overall survival (OS) for patients with 0 or 1 high-risk factors for TRM by disease chemosensitivity. Table 2 shows the causes of death by risk factors for TRM and disease chemosensitivity. Group (n) Alive TRM Death from disease A: 2 risk factors for TRM (7) 1 (14%) 5 (71%) 1 (14%) B: 1 risk factor for TRM + Refractory (19) 2 (11%) 6 (32%) 11 (58%) C: 1 risk factor for TRM + Sensitive (9) 5 (56%) 1 (11%) 3 (33%) D: 0 risk factor for TRM + Refractory (12) 3 (25%) 1 (8%) 8 (67%) E: 0 risk factor for TRM + Sensitive (16) 13 (81%) 1 (6%) 2 (13%) These data suggest that while the current treatment approach is optimal for patients falling in Group E, modified approaches are needed for other patients. Based on the causes of failure, the following modifications appear to be warranted. Group A: A completely non-ablative regimen to reduce toxicity. Group B: A completely non-ablative regimen to reduce toxicity with augmentation of graft-vs-tumor effects by elective donor leukocyte infusions and/or abbreviated immunosuppression. Group C: Augmentation of graft-vs-tumor effects by elective donor leukocyte infusions and/or abbreviated immunosuppression. Group D: Conventional-intensity rather than reduced-intensity allogeneic HSCT.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18116-18116
Author(s):  
F. Sperandi ◽  
B. Melotti ◽  
A. A. Martoni

18116 Background: Several studies have demonstrated that the combination of CBDCA plus GEM according to various regimens appears as effective as cisplatin (CP) containing regimens. CBDCA plus GEM regimens are associated with more haematological toxicity (G3–4 leucopenia 17–40.6%, G3–4 neutropenia 29–75%, G3–4 thrombocytopenia 21–57% and G3–4 anaemia 5–33%), but with lower non-hematological toxicity as compared to CP-based regimens. Methods: The primary objective of this trial was the evaluation of the overall survival, while the secondary objectives were assessment of objective response and toxicity in elderly or poor PS pts. The eligible pts had previously untreated aNSCLC not suitable for CP-based chemotherapy. Pts received each at 3-week intervals GEM 1000 mg/sq on day 1 and 8 plus CBDCA area under the curve of 5 on day 2. Between April 2004 and January 2007, 54 consecutive pts were accrued in the study. Pt characteristics were: 42 (78%) males and 12 (22%) females; median age 72 years (range: 56–84 years) with 67% of pts = 70 years; median Karnofsky PS 90 (range: 50–100) with 33% of pts = 80; stage disease: IIB not suitable for surgery in 1 (2%) pt, IIIA in 5 (9%), IIIB in 10 (19%), IV in 33 (61%) and recurrent disease in 5 (9%); histologic subtype: adenocarcinoma in 30 (56%) pts, epidermoid in 11 (20%), bronchioalveolar carcinoma in 2 (4%) and other histologic subtypes in 11 (20%). Results: A median of 4 courses was administered (range 1–8). Dose- intensity was 98.7% (range 50–100%) for CBDCA and 87.2% (range 60–100%) for GEM. Objective response according to intention-to-treat analysis was as follows: 15 (28%) pts had PR, 16 (29%) had SD, 14 (27%) had PD and 9 (16%) were not assessable because lost to follow-up or too early. Median overall survival was 10 months. WHO G3 leucopenia was observed in 5 (9%) pts, G3–4 neutropenia in 15 (28%), G3 thrombocytopenia in 7 (13%) and G3 anaemia in 2 (4%). No WHO G3–4 non-hematological toxicity was observed. Conclusions: This regimen is feasible and active in elderly or poor PS pts. It can be administered in a outpatient setting because toxicity is moderate and manageable. No significant financial relationships to disclose.


2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 9628-9628 ◽  
Author(s):  
R. Nair ◽  
M. Shirodkar ◽  
M. Mallath ◽  
A. D’Cruz ◽  
P. Shukla ◽  
...  

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 534-534
Author(s):  
Hui-li Wong ◽  
Kathryn M Field ◽  
Jeanne Tie ◽  
Suzanne Kosmider ◽  
Jeremy David Shapiro ◽  
...  

534 Background: The management of patients with poor performance status (PS) remains challenging in the absence of data on optimal treatment. Here we assessed the treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with poor Eastern Cooperative Oncology Group (ECOG) PS (≥ 2) in routine clinical care. Methods: Analysis of patients prospectively entered onto the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed initiative to collect comprehensive data on consecutive patients with mCRC from sites across Australia. Data collection commenced in July 2009 and is ongoing at 14 participating public and private centres. Results: Of the 679 patients entered, 129 (19.0%) had an ECOG PS ≥ 2. In total, 77 (11.3%) were PS 2, 41 (6.0%) PS 3 and 11 (1.6%) PS 4. Chemotherapy was administered to 55 (71.4%) PS 2 and 15 (36.6%) PS 3 patients, with none of the PS 4 patients being treated. Overall, poor PS patients were significantly less likely to receive any chemotherapy compared to their good PS (PS 0-1) counterparts (55.0% versus 86.8%, p<0.0001) and, when chemotherapy was given, significantly less likely to receive combination chemotherapy (38.0% vs 71.6%, p<0.0001) or bevacizumab (15.5% vs 46.9%, p<0.0001). Overall survival (OS) was reduced with declining PS, with medians of 31.2, 9.0, 3.0 and 0.8 months for PS 0-1, 2, 3 and 4 patients respectively (p<0.0001). Poor PS patients treated with chemotherapy had a better OS outcome (9.8 vs 4.1 months for untreated patients, p<0.0001). At one and two years, 22 (31.4%) and 8 (11.4%) treated poor PS patients were alive. Conclusions: In routine practice many patients with a poor PS, particularly those that are PS 2, receive active treatment. Although overall survival for poor PS patients is poor, some patients appear to benefit from treatment. Further data analysis, particularly to define subsets that may benefit most from treatment, is planned as further sites around Australia contribute data to the project.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 224-224
Author(s):  
Marina Dusevic Kaymakcalan ◽  
Sherri Stuver ◽  
Christopher Sweeney ◽  
Toni K. Choueiri ◽  
Aymen Elfiky

224 Background: Cabazitaxel can offer a survival advantage in patients (pts) with metastatic castration resistant prostate cancer (mCRPC). Febrile neutropenia (FN) has emerged as a serious complication, with a rate of 8% in the TROPIC trial (de Bono, Lancet 2010). Prophylaxis with pegfilgrastim (P) can decrease the risk of FN, although predictors of FN continue to evolve. We performed an analysis on the effect of prophylactic P use on FN and the impact of certain risk factors on FN rates. Methods: We conducted a retrospective analysis of mCRPC patients treated with cabazitaxel from June 2010 to August 2013 at Dana-Farber Cancer Institute. Patient clinical and treatment variables were extracted. Fisher’s exact test was used to evaluate the association between potential risk factors and FN. Results: A total of 89 patients were treated at our institution and included in this analysis. All patients received at least one dose of cabazitaxel and received a mean of four cycles. Five pts (5.6%) developed FN; 3 out of 70 (4.3%) receiving P and 2 out of 19 (10.5%) not receiving P (p=0.3). Of the 24 patients that started cabazitaxel at a reduced dose, none developed FN. No toxic death was reported. Among several risk factors including P use, age older than 65, pre-existing neutropenia, prior chemotherapy, pre-existing infection, poor performance status, liver and renal dysfunction, and recent surgery, only a prior history of palliative radiation had a significant association with FN (p=.002). Conclusions: The rate of FN in a large academic practice is similar to what was reported in the TROPIC trial. Prior radiation may be a risk factor for FN in cabazitaxel-treated mCRPC patients. Other factors that may help better predict the risk of FN in different groups of patients receiving cabazitaxel must be identified.


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