scholarly journals The Impact of Hyperglycemia on Risk of Severe Infections during Early Period of Induction Therapy in Patients with Newly Diagnosed Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Sung-Hoon Jung ◽  
Hee-Chang Jang ◽  
Seung-Shin Lee ◽  
Jae-Sook Ahn ◽  
Deok-Hwan Yang ◽  
...  

The association between hyperglycemia and infections during induction chemotherapy has been reported in a number of hematologic disorders. This retrospective study evaluated the incidence of hyperglycemia during induction therapy in 155 patients with newly diagnosed multiple myeloma (MM) and its effect on serious infections during the first 60 days of induction. A total of 20 (12.9%) patients developed overt hyperglycemia (≥200 mg/dL) during induction therapy. Serious infections occurred in 28 (18.1%) of 155 patients and infection-related mortality within 2 months after treatment was 0.6% (1 patient). In a univariate analysis, overt hyperglycemia, poor performance status (≥2), International Staging System III, lymphopenia (<500/μL), and elevated serum creatinine (≥2 mg/dL) were found to be associated with serious infections. In multivariate analysis, only overt hyperglycemia (HR 7.846, 95% CI 2.512–24.503,P<0.001) and poor performance status (HR 5.801, 95% CI 1.974–17.050,P=0.001) remained significant. In conclusion, this study demonstrated an association between hyperglycemia and serious infections during induction therapy in patients with MM.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 614-614
Author(s):  
Jill Corre ◽  
Elodie Labat ◽  
Nicolas Espagnolle ◽  
Hervé Avet-Loiseau ◽  
Murielle Roussel ◽  
...  

Abstract Abstract 614 We previously reported that bone marrow mesenchymal stem cells (BMMSCs) from newly diagnosed multiple myeloma (MM) patients were abnormal. In particular, we showed that Growth Differentiation 15 (GDF15) expression was higher in MM BMMSCs than in normal BMMSCs. GDF15 is a divergent member of the human TGFβ superfamily. GDF15 overexpression has been described in numerous malignancies and its concentration is increased in the serum of patients with glioma, prostate, colorectal or pancreatic cancers. Contradictory data prevent to understand clearly GDF15 implication in pathophysiology of tumors. Furthermore, GDF15 has never been studied in haematological malignancies. Our first objective was thus to determine the effect of human recombinant GDF15 (rGDF15) on MOLP-6 stroma-dependent cell line and MM1.S stroma-independent cell line under serum free culture conditions. rGDF15 could significantly increase cell survival in MOLP-6 but not in MM1.S. Interestingly, rGDF15 was able to induce Akt phosphorylation on Threonine 308 in MOLP-6 and primary MM cells but not in MM1.S cells. Furthermore, pre-treatment of MOLP-6 with Akt pharmacologic inhibitor abrogated the prosurvival effect of GDF15, suggesting an Akt-dependent mechanism. In the same culture conditions, we observed that rGDF15 could abrogate toxicity of drugs classically used in MM treatment (melphalan, bortezomid and lenalidomide) for both cell lines MOLP-6 and MM1.S, suggesting that this cytoprotective effect may be Akt-independent. Because of the in vitro effects of GDF15, our second objective was to determine whether the plasma concentration of GDF15 (pGDF15) in patients with MM may be indicative of the seriousness of the disease or correlate with the response to the treatment. Thus, we investigated the pGDF15 in 131 patients with newly diagnosed MM and 13 healthy subjects. We first found that it was significantly higher for patients with MM (0.90±1.10 ng/mL) than for healthy subjects (0.25±0.08 ng/mL) (P< .001). In patients with MM, pGDF15 correlated with the main prognostic factor of the disease (i.e. International Staging System, b2 microglobulin level, presence or absence of deletion of chromosome 13, and bone status). For the 81 patients with high pGDF15 level (≥ 0.50 ng/mL), the probabilities of event-free and overall survival 30 months after diagnosis were 50% and 75%. For the 50 patients with low pGDF15 level (< 0.5 ng/mL), the probabilities were 80% and 97% (P< .0045 and P< .013, respectively). However, we did not find a clear relationship between pGDF15 and response to treatment. We analysed the impact of prognostic factors on event-free survival for the 131 patients with MM. On univariate analysis, event-free survival was significantly related to age (P= .003), b2-microglobulin level (P= .02) and pGDF-15 level (P= .003). On multivariate analysis, event-free survival was significantly related to age (P= .001) and pGDF15 level (P= .04). Our study demonstrates that GDF15 is a survival and cytoprotective factor for MM cells and that pGDF15 is related to initial parameters of the disease and survival, which specifically implicates the MM microenvironment in the pathophysiology and the prognosis of the disease. Disclosures: No relevant conflicts of interest to declare.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 183-183 ◽  
Author(s):  
I. Ohno ◽  
S. Mitsunaga ◽  
K. Nakachi ◽  
S. Shimizu ◽  
H. Takahashi ◽  
...  

183 Background: Alkaline phosphatase (ALP) is an enzyme that is elevated by various hepatobiliary diseases. Generally its elevation is thought to indicate bile stasis. There are some reports that show ALP is an important prognostic factor for several cancers such as colon, lung, and gastric cancer. Often it is speculated that ALP elevation indicates bile stasis caused by liver metastasis. However, the significance of ALP elevation in advanced pancreatic cancer (APC) patients is not well evaluated. The aim of this study was to determine the significance of elevated serum ALP as a prognostic factor in patients with APC even without jaundice and liver metastasis. Methods: Serum ALP levels were measured in 393 patients with APC receiving gemcitabine monotherapy before treatment, and according to those levels, patients were subgrouped (ALP<upper normal limit (UNL), UNL-500 U/L, 501-700 U/L, 701-1000 U/L, 1000U/L < ALP). The clinical data of each group were analyzed to see characteristics of elevated ALP patients. The relationship between ALP level and survival, response were also examined. Results: The elevated ALP group included poor performance status (PS>1) patients (41.3%, p=0.001), and associated with low serum albumin (3.31±0.38, p<0.01). The elevated ALP group (median survival time (MST) 112 days) showed significantly worse prognosis and lower disease control rate compared to the normal ALP group (MST 217days) (p<0.001, p<0.001). Multivariate analysis revealed ALP (p<0.001), CRP (p<0.001), ascites (p<0.001), distant metastasis (p=0.003), white blood cell count (p=0.005), PS (p=0.020), AST (p=0.020), and ALT (p=0.020) were independent prognostic factors. Similar results were seen in liver metastasis free patients without jaundice. Conclusions: Elevated serum ALP level correlated with poor performance status and low serum albumin. ALP was also the independent prognostic factor in liver metastasis free APC patients without jaundice. No significant financial relationships to disclose.


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.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Sung Min Kim ◽  
Moon Jin Kim ◽  
Hyun Ae Jung ◽  
Kihyun Kim ◽  
Seok Jin Kim ◽  
...  

Multiple myeloma occurs primarily in elderly patients. Considering the high prevalence of comorbidities, comorbidity is an important issue for the management of myeloma. However, the impact of comorbidity on clinical outcomes has not been fully investigated. We retrospectively analyzed patients with newly diagnosed myeloma. Comorbidities were assessed based on the Charlson comorbidity index (CCI) and the Freiburg comorbidity index (FCI). The CCI is a summary measure of 19 comorbid conditions. FCI is determined by performance status, renal impairment, and lung disease. This study included 127 patients with a median age of 71 years. Approximately half of the patients had additional disorders at the time of diagnosis, and diabetes mellitus was the most frequent diagnosis (18.9%). The most significant factors for prognosis among patient-related conditions were a history of solid cancer and performance status (ECOG ≥ 2). The FCI score was divided into 3 groups (0, 1, and 2-3), and the CCI score was divided into 2 groups (2-3 and ≥4). FCI was a strong prognostic tool for OS (P>0.001) and predicted clinical outcome better than CCI (P=0.059). In conclusion, FCI was more useful than CCI in predicting overall survival in elderly patients with myeloma.


Author(s):  
Nimish A. Mohile ◽  
Hans Messersmith ◽  
Na Tosha Gatson ◽  
Andreas F. Hottinger ◽  
Andrew Lassman ◽  
...  

PURPOSE To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults. METHODS ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature. RESULTS Fifty-nine randomized trials focusing on therapeutic management were identified. RECOMMENDATIONS Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)–mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMT promoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines .


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 317-317
Author(s):  
Darren M. C. Poon ◽  
Chan Kuen ◽  
S.H. Lee ◽  
T.W. Chan ◽  
Chun-Kin Sze ◽  
...  

317 Background: Visceral metastases or poor performance status (ECOG 2 or above) were the major exclusion criteria in the COU-AA-302 study, and hence the efficacy of abiraterone acetate (AA) in chemo-naïve mCRPC patients with these characteristics remain undetermined. Our study compares the clinical efficacy of AA in chemo-naïve mCRPC patients with or without the aforementioned characteristics. Methods: The clinical records of chemo-naïve mCRPC patients from all 6 public oncology centers in Hong Kong between August 2011 and December 2014 were reviewed. Patients with visceral disease who were medically unfit for, or who declined, chemotherapy, were allowed for AA in the study period. The median overall survival (OS), progression-free survival (PFS), patient and disease characteristics were compared between groups which satisfied, and did not satisfy, the inclusion criteria of COU-AA-302 study. Results: Fifty-eight consecutive chemo-naïve mCRPC patients had received AA in the review period, of which 29 fulfilled the inclusion criteria for the COU-AA-302 study (Group Eligible). All the remaining patients (Group Ineligible) had ECOG 2 or above, including 3 who had non-nodal visceral metastases. Group Ineligible had higher baseline PSA, haemoglobin and alkaline phosphatase level than Group Eligible, but otherwise there was no significant difference in the baseline characteristics between the groups for age, Gleason score, and co-morbidities. Group Ineligible had significantly shorter OS than Group Eligible (7.7 vs 25.0 months, p = 0.0095) and also a shorter PFS that did not reach statistical significance (5.3 vs 9.8 months, p = 0.2936). The duration of use of AA, and frequency of employment of post-AA treatment were comparable between the groups. Conclusions: Our study demonstrated a poor efficacy of AA in chemo-naïve patients who did not fulfil the inclusion criteria for COU-AA-302 study, by virtue of poor performance status or presence of visceral metastases. The impact of AA in this group of patients warrants further examination in clinical trials before its routine clinical use in this subgroup.


2021 ◽  
Author(s):  
Nimish A Mohile ◽  
Hans Messersmith ◽  
Na Tosha N Gatson ◽  
Andreas F Hottinger ◽  
Andrew B Lassman ◽  
...  

Abstract Purpose To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults. Methods ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature. Results Fifty-nine randomized trials focusing on therapeutic management were identified. Recommendations Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)–mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMTpromoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3861-3861
Author(s):  
Ricardo S. Bigni ◽  
Eduardo D. Velasco ◽  
Jane A. Dobbin

Abstract Between January 2001 and June 2005 a prospective cohort study of hospitalized patients with hematological malignancies including 47 adults and 30 children with candidemia was conducted at a tertiary oncology care center in Brazil in order to compare the epidemiological characteristics, concurrent illnesses and the clinical microbiological data of both groups that may influence the outcome. The crude mortality was higher in the adult population than in children (46,8% vs. 20,0%) (figure 1). A univariate analysis indicated that in the adult population were lymphoma, neutropenia, presence of comorbidities, a non-removed central venous catheter (CVC), a poor performance status, lack of CVC, use of steroid, hepatic dysfunction, previous surgery, hypotension and severe respiratory dysfunction were risk factors significantly associated with death. Among children the predictors of mortality were acute leukemia, neutropenia, presence of comorbidities, lack of CVC, poor performance status, hypotension, concomitant infected sites, pulmonary infiltrates and severe respiratory dysfunction. Although no major differences was detected in survival rates following fungemia with C. albicans and all Candida non-albicans species, episodes with Candida glabrata, krusei and tropicalis subgroup species had the highest crude death rate compared with C. albicans and other isolates (59,4% vs. 35,3% vs. 10,7%; P&lt;0.01) (figure 2). Candidemia due to C. parapsilosis was associated with the lowest mortality rate. Two variables remained statistically associated with mortality among adults in the multivariate analysis: CVC retention (OR 6.41; 95% CI 1.04–39.55) and presence of comorbidities (OR 2.17; 95% CI 1.33–3.53). Among children only the presence of comorbidities (OR 2.61; 95% CI 1.46–4.66) affected independently the outcome. Our data demonstrate children had a significant lower mortality rate than adults, despite the higher incidence of candidemia in this lower age subjects. There were significant differences of epidemiological, clinical characteristics and other risk factors between both groups. Concurrent comorbidities were the most important independent prognostic factor in both groups of patients.


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