Pre-Transplant Variables Affecting the Outcome of Submyeloablative Allogeneic HSCT in Uniformly Treated Patients with Hematologic Malignancies.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2324-2324
Author(s):  
Jayesh Mehta ◽  
S. Singhal ◽  
M. Tallman ◽  
S. Williams ◽  
J. Winter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Risk Factor ◽  
High Risk ◽  
Cox Model ◽  
Performance Status ◽  
Hematologic Malignancies ◽  
Current Treatment ◽  
Allogeneic Hsct ◽  
High Risk Factors

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.

Efficacy and toxicity of postoperative external beam radiotherapy or chemoradiation for early-stage cervical cancer

2020 ◽  
Vol 30 (12) ◽  
pp. 1878-1886
Author(s):  
Mick J E van den Akker ◽  
Nanda Horeweg ◽  
Jogchum Jan Beltman ◽  
Carien L Creutzberg ◽  
Remi A Nout
Keyword(s):  
Risk Factors ◽  
Cervical Cancer ◽  
Overall Survival ◽  
Risk Factor ◽  
High Risk ◽  
Early Stage ◽  
Free Survival ◽  
High Risk Factors ◽  
Early Stage Cervical Cancer ◽  
Risk Factors For Recurrence

ObjectiveThe aim of this study was to assess the impact of the evolving role of the addition of chemotherapy to postoperative radiotherapy on oncological outcomes and toxicity in patients with early-stage cervical cancer after radical hysterectomy.MethodsRetrospective cohort study of patients with stage IB1–IIB FIGO 2009 cervical cancer treated from November 1999 to May 2015 by primary surgery and radiotherapy (46–50.4 Gy in 1.8–2.0 Gy fractions) with or without concurrent cisplatin (40 mg/m2, 5–6 weekly cycles) with or without a brachytherapy boost. Chemotherapy was allocated depending on the risk factors for recurrence. Incidences of all outcomes were calculated using Kaplan–Meier’s methodology and compared by log-rank tests. Risk factors for recurrence and survival were identified using Cox’s proportional hazards models.ResultsA total of 154 patients were included, median follow-up was 9.6 years (IQR: 6.1–12.8). Five-year pelvic recurrence-free survival was 75.3%; 74.7% in patients with high-risk factors treated with radiotherapy; and 77.3% in those treated with chemoradiation (P=0.43). Distant metastasis-free survival at 5 years was 63.4%; 63.6% in high-risk patients after radiotherapy; and 57.1% after chemoradiation (P=0.36). Five-year overall survival was 63.9%: 66.8% and 51.6% after radiotherapy and after chemoradiation in patients with high-risk factors (P=0.37), respectively. Large tumor size was a risk factor for vaginal and pelvic recurrence, ≥2 involved lymph nodes was a significant risk factor for para-aortic recurrence and death. Mild treatment-related late toxicity was observed in 53.9% of the patients. Five-year severe (grade 3–5) late rectal, bladder, bowel, and vaginal toxicities were, respectively, 1.3%, 0%, 3.4%, and 0.9%. Any late severe toxicity was observed in 5.5% of patients treated with radiotherapy and in 15.3% of those treated with chemoradiation (P=0.07).ConclusionPostoperative (chemo)radiation for early-stage cervical cancer patients with risk factors for recurrence yields adequate pelvic tumor control, but overall survival is limited due to distant metastasis.

scholarly journals Perineural Invasion Should Be Regarded as an Intermediate-Risk Factor for Recurrence in Surgically Treated Cervical Cancer: A Propensity Score Matching Study

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ting Wan ◽  
Hua Tu ◽  
Lili Liu ◽  
He Huang ◽  
Yanling Feng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cervical Cancer ◽  
Overall Survival ◽  
Risk Factor ◽  
High Risk ◽  
Propensity Score ◽  
Cancer Patients ◽  
Perineural Invasion ◽  
Intermediate Risk ◽  
High Risk Factors

Background. Perineural invasion (PNI) is considered as a poor prognostic factor in cervical cancer, but there has been no postoperative adjuvant therapy for it, because whether it belongs to high- or intermediate-risk factors has not been determined, this study intends to provide evidences to solve this problem. Methods. We conducted a retrospective analysis of cervical cancer patients who underwent radical surgery and be reported PNI from January 2012 to June 2017 at the Sun Yat-sen University Cancer Center. After 1 : 1 propensity score matching (PSM), a group of patients without PNI was matched according to the clinical pathological features. Postoperative pathological parameters and prognosis were evaluated between the PNI and the matched groups. Results. 1836 patients were screened, of which 162 (8.8%) diagnosed as stages IB1 to IIB reported PNI. Comparing to the matched group, more PNI (+) patients had deep outer cervix stromal invasion, cervical tunica adventitia invasion, positive lymph nodes, and positive margins. Among patients without high-risk factors, PNI (+) patients had worse 3-year overall survival (90.8% vs. 98.1%, P = 0.02 ), PNI (+) patients with single intermediate-risk factor and PNI (-) patients who meet with SEDLIS criteria had similar progress free survival ( P = 0.63 ) and overall survival ( P = 0.63 ), even similar survival curves. Conclusion. PNI is related to a worse overall survival among cervical cancer patients without high-risk factors and play the role as an intermediate-risk factor.

Abstract 18634: Favorable Cardiovascular Health and the Compression of Morbidity: Findings From the Chicago Heart Detection Project in Industry Study

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Norrina B Allen ◽  
Lihui Zhao ◽  
Lei Liu ◽  
Martha Daviglus ◽  
Kiang Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
High Risk ◽  
Healthcare Costs ◽  
Cardiovascular Health ◽  
Heart Association ◽  
Baseline Risk ◽  
Compression Of Morbidity ◽  
High Risk Factors ◽  
Morbidity Score

Introduction: We sought to determine the association of CV health at younger ages with the proportion of life lived free of morbidity, the cumulative burden of morbidity, and average healthcare costs at older ages. Methods: The Chicago Heart Association (CHA) study is a longitudinal cohort of employed men and women aged 18-59 years at baseline exam in 1967-1973. Baseline risk factor levels included blood pressure, cholesterol, diabetes, BMI and smoking. Individuals were classified into one of four strata: favorable levels of all factors, 0 factors high but 1+ elevated, 1 high, and ≥2 high risk factors. Linked CMS/NDI data from 1984-2010 were used to determine morbidity in older age providing up to 40 years of follow-up. We included participants who were age 65+ between 1984 and 2010 and enrolled in Medicare FFS. All-cause morbidity was defined using the Gagne score. A CV morbidity score was defined as the sum of 4 CVDs including CHD (includes MI), PVD, cerebrovascular disease and CHF. Results: We included 25,390 participants (43% female, 90% White, mean age 44 at baseline); 6% had favorable levels, 19% had 1+ risk factors at elevated levels, 40% had 1 high risk factor and 35% had 2+ high risk factors. As compared to those with 2+ high risk factors, favorable CV health had lower levels of all-cause and CV morbidity from age 65-90 years, and a lower cumulative morbidity burden (p<0.001) translating to lower average annual healthcare costs ($15,905 vs $20,791 per year, p<0.001). Favorable CV health postponed the onset of all-cause morbidity by 4.5 years, the onset of CV morbidity by almost 7 years and extended life by almost 4 years resulting in a compression of morbidity on both the absolute and relative scale (see figure). Conclusion: Individuals in favorable CV health live a longer, healthier life and a greater proportion of life free of morbidity. These findings provide support for prevention efforts aimed at preserving cardiovascular health and reducing the burden of disease in older ages.

scholarly journals Objective screening of hearing impairment using brainstem evoked response audiometry in children below 5 years of age and assessing the high risk factors

2018 ◽  
Vol 4 (4) ◽  
pp. 923 ◽  
Author(s):  
Mallikarjun Patil ◽  
Prakash Handi ◽  
K. R. Prasenkumar ◽  
Kranti Gouripur
Keyword(s):  
Risk Factors ◽  
Hearing Loss ◽  
Risk Factor ◽  
High Risk ◽  
Hearing Impairment ◽  
Hearing Threshold ◽  
Evoked Response ◽  
Common Risk Factor ◽  
High Risk Factors ◽  
Evoked Response Audiometry

<p class="abstract"><strong>Background:</strong> Hearing impairment is a common disability in children. This study is to evaluate the common high risk factors for hearing loss in our locality and to estimate hearing threshold by brain stem evoked response audiometry.</p><p class="abstract"><strong>Methods:</strong> 100 children under five years were subjected to brainstem evoked response audiometry. Wave V morphology was studied and hearing threshold estimated. The high risk factor(s) were analysed and degree of hearing impairment assessed.  </p><p class="abstract"><strong>Results:</strong> 38 children were found to have hearing impairment. Most of the children had bilateral hearing impairment. Of them 30 children (79%) had profound hearing loss. Consanguineous marriage was the most common risk factor.</p><p class="abstract"><strong>Conclusions:</strong> Since consanguinity is the most common risk factor, health education and genetic counselling will help to decrease the incidence of autosomal recessive nonsyndromic deafness. Improvement in immunization for rubella can decrease the hearing impairment due to these infections. Due to availability of medical facilities hearing impairment due to perinatal factors have decreased.</p>

Abstract P058: Cardiovascular Health Screening In 26,063 Adolescent Blood Donors

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Maria Odette Gore ◽  
Stephen J Eason ◽  
Colby R Ayers ◽  
Jarett D Berry ◽  
Amit Khera ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
High Risk ◽  
School District ◽  
Cardiovascular Risk Factors ◽  
Low Income ◽  
Blood Donors ◽  
Socioeconomic Characteristics ◽  
High Risk Factors

Introduction and Objective: Cardiovascular risk factors in adolescents track into adulthood and are associated with morbidity and early mortality. As part of a pilot health screening program implemented by Carter BloodCare, the largest independent blood program in Texas, we screened a large adolescent blood donor population for key cardiovascular risk factors. Methods: Blood pressure (SBP and DBP), total cholesterol and hemoglobin A1C (HbA1C) were measured in 26,063 volunteer high-school blood donors, 16-19 years of age, between 2011 and 2013. Cardiovascular risk factors were classified as high risk (SBP ≥ 140 mm Hg and/or DBP ≥ 90 mm Hg, cholesterol ≥ 200 mg/dL, HbA1C ≥ 6.5%) and intermediate or high risk (SBP ≥ 120 mm Hg and/or DBP ≥ 80 mm Hg, cholesterol ≥ 170 mg/dL, HbA1C ≥ 5.7%). The main study measures were the prevalence of 1, 2 or 3 risk factors within the same individual in the study population, with stratification by age, sex, race/ethnicity, and school district socioeconomic characteristics. Results: In the overall cohort, 66.5% of donors had at least one and 20.3% had at least two intermediate or high risk factors, and 15.3% had at least one high risk factor (Table). The percentage of donors in each non-zero category of intermediate or high risk factors increased with age (Ptrend<0.001), was higher in ethnic minorities (P<0.001 each for Asian, Black and Hispanic vs. White), and there were more boys than girls in all non-zero risk categories (P<0.001 for all). There were no statistically significant relationships between risk factor categories and socioeconomic characteristics (urban vs. rural and low-income vs. not low-income donor school district). Conclusions: The prevalence of cardiovascular risk factors among adolescent blood donors is common, with two or more concomitant risk factors identifiable in many donors. Blood donation programs may provide a unique portal for early screening and targeted preventive intervention in youth, with potential for cardiovascular disease prevention in the community.

Submyeloablative Allogeneic HSCT for Hematologic Malignancies: Effect of Body Weight.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2949-2949 ◽  
Author(s):  
Seema Singhal ◽  
Leo Gordon ◽  
Martin Tallman ◽  
Jane Winter ◽  
Stephanie Williams ◽  
...  
Keyword(s):  
Body Weight ◽  
Cox Model ◽  
Performance Status ◽  
Hematologic Malignancies ◽  
Donor Age ◽  
Ideal Weight ◽  
Allogeneic Hsct ◽  
Actual Weight ◽  
Weight Difference ◽  
Related Mortality

Abstract Being underweight or markedly overweight is associated with poorer outcome after myeloablative allogeneic HSCT. The role of body weight after reduced-intensity HSCT is unknown. The outcome of 91 patients (19–71 y, median 53) with hematologic malignancies undergoing submyeloablative allogeneic HSCT was studied to determine the effect of weight. 8 patients were >10% underweight (A), 33 were from ≤10% underweight to ≤10% overweight (B), 41 were >10% but ≤50% overweight (C), and 9 were >50% overweight (D). Donors were HLA-matched siblings (n=51), 10/10 allele-matched unrelated (n=29), or 1-locus/allele mismatched (n=11). The conditioning comprised 100 mg/m2 melphalan with (n=50; no prior auto) or without (n=41; prior auto) 50 mg/kg cyclophosphamide. Cyclophosphamide dose was based on actual weight in underweight patients and adjusted ideal weight [ideal + 0.25(actual-ideal)] in overweight patients, while melphalan dose was usually based on the actual weight if it did not exceed ideal weight by >20%. Above that, adjusted ideal weight was used. GVHD prophylaxis comprised cyclosporine-mycophenolate (HLA-matched sibs) or tacrolimus-mycophenolate (others). G/GM-CSF were not given routinely. Supportive care was uniform. As the figure above shows, weight affected overall (OS) and disease-free (DFS) survival significantly. When analyzed as a continuous variable, increasing difference between actual and ideal weight (i.e. increasing overweight) had a detrimental effect on OS (RR 1.0017; 95% CI 1.0036–1.0198; P=0.005) and DFS (RR 1.0092; 95% CI 1.0012–1.0173; P=0.023). Weight difference was also analyzed in a Cox model with chemosensitivity (refractory or not), performance status (PS; 0/1 or 2/3), donor age (<45 or ≥45), and LDH (elevated or not) - variables shown to affect outcome significantly in this group of patients (Mehta et al. ASH 2006, BMT 2006). The 4 known prognostic factors retained their significance, and weight difference was also found to affect DFS and OS significantly. Transplant-related mortality was not affected by weight but relapse was - as shown in the figure below. Further Cox analysis showed that relapse was significantly affected by chemosensitivity, donor age, and weight difference. Transplant-related mortality was affected by donor age and LDH. The effect of PS on TRM disappeared when weight difference was introduced in the model although there was no correlation between weight difference and PS. This observation of lower weights affecting outcome favorably through lower relapse is somewhat unexpected, and requires confirmation in other series of patients undergoing submyeloablative allografts. Possible reasons for this may be a greater amount of chemotherapy delivered based on actual weight in group A compared to groups B, C and D, and leptin-mediated immunomodulation with attenuation of graft-vs-tumor effects with increasing weight. Figure Figure Figure Figure

Allograft After Pediatric-Inspired Therapy Does Not Improve Young patient's Outcome with High Risk Philadelphia- Chromosome-Negative Acute Lymphoblastic Leukemia (Ph-ALL). A Single Center Report

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3528-3528
Author(s):  
Thibaut Leguay ◽  
Arnaud Pigneux ◽  
Reza Tabrizi ◽  
Mathieu Sauvezie ◽  
Krimo Bouabdallah ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
High Risk ◽  
Maintenance Therapy ◽  
Induction Chemotherapy ◽  
Fusion Transcript ◽  
Low Risk ◽  
Multicentric Study ◽  
High Risk Factors ◽  
The Impact

Abstract Abstract 3528 Allogeneic stem cells transplant (allo-SCT) is currently the preferred therapeutic option for young adults with Ph- ALL in first CR. However, the results of different studies suggested that pediatric-inspired therapy have markedly improved the outcome of these patients. In our monocentric study, we analyzed the impact of the allo-SCT on outcome in adults treated within these pediatric-inspired trials. Between April 2002 and March 2010, 75 young adult patients with Ph- ALL were treated in our clinical unit. 70 patients (49 men and 21 women) were in complete remission (CR) (93%) after induction chemotherapy (4 after two courses), 2 died before evaluation (3%) and 3 patients were refractory and died with progressive disease (4%). The median age of the population was 33 years (range, 16–59). Among the 70 patients in CR, 54 (77%) were considered at high-risk ALL and therefore eligible for allo-SCT after 1 or 2 consolidation courses. Baseline high-risk factors were: WBC count of ≥ 30 × 109/L for B-lineage ALL, clinical and/or morphologic CNS involvement, t(4;11) and/or MLL-AF4 fusion transcript, t(1;19) and/or E2A-PBX1 fusion transcript and low hypodiploidy and/or near-triploidy. Fourteen patients with low-risk ALL received chemotherapy alone with late intensification followed by maintenance therapy. With a median follow-up of 36.5 months, median overall survival (OS) for the entire population was not reached and the estimated OS at five years was 75% (70-80%). The high-risk factors as previously defined could separate two different groups with statistically different outcome. In the low-risk (LR) group, none patient died or relapsed during this study. While, in the high-risk (HR) group, 11 of 54 patients (20%) relapsed and 14 patients (26%) died. For the LR group and the HR group, the estimated OS at five years was respectively 100% and 69% (64-74%) (p=0.04) and the estimated disease free survival (DFS) was respectively 100% and 61% (56-66%) (p=0.02). In the HR group, 30 of the 54 patients (55.5%) had donor and had received allogeneic SCT, 28 of 30 patients after myeloablative conditioning regimen, 12 patients with related donor and 18 patients with unrelated donor. The 24 other patients without donor had received the same chemotherapy than patients in the LR group with late intensification and maintenance therapy. There was no difference between the two subgroups for death: 6 patients with donor (D+) and 8 without donor (D-). Nevertheless, there was more relapses in the subgroup D- (8 relapses) than in the subgroup D+ (3 relapses) (p=0.006). At five years, in the subgroup D+, the estimated OS and DFS were respectively 75 % (68-82) and 72 % (66-78). In the subgroup D-, the estimated OS and DFS were respectively 62 % (55-69) and 48 % (41-55). There was no difference between two subgroups D+ and D- for OS (p=0.4) and DFS (p=0.19). In addition, there was no difference for age, sex, risk factor and initial characteristic of the disease. These results suggest that allograft might not improve the outcome of patient with high-risk Ph- ALL. One explanation is that pediatric-inspired induction chemotherapy improves the outcome of the whole population (75% of overall survival) and this advantage decreases the impact of the allo-SCT. Nevertheless, allo-SCT decreased the risk of relapse but did not modify OS and DFS. However, more patients are necessary to confirm these results in a multicentric study. Disclosures: No relevant conflicts of interest to declare.

European Collaborative Study of Treatment Outcomes in 347 Patients with Systemic AL Amyloidosis with Mayo Stage III Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 995-995 ◽  
Author(s):  
Ashutosh Wechalekar ◽  
Stefan O Schonland ◽  
Efstathios Kastritis ◽  
Philip N Hawkins ◽  
Meletios A. Dimopoulos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Clinical Trials ◽  
High Risk ◽  
Cardiac Involvement ◽  
Staging System ◽  
Stage Iii ◽  
Al Amyloidosis ◽  
High Risk Factors ◽  
Intent To Treat

Abstract Abstract 995 N-terminal fragment of BNP (NT-proBNP) and cardiac troponin –T (TnT) or I (TnI) form a useful staging system in AL amyloidosis and poor outcomes have been reported in stage III patients treated before routine use of novel agents. These patients are routinely excluded from clinical trials and prospective outcome data is limited but recent studies suggest that some such patients may have better outcomes. We report the outcomes of 347 patients with Mayo stage III AL amyloidosis seen at the amyloid centres in London (UK), Pavia (Italy), Heidelberg (Germany) and Athens (Greece). Organ involvement and responses are defined according to 2005 amyloidosis consensus criteria. Presenting features were [n (%)/median (range)]: cardiac, renal and liver involvement in 338 (97%), 216 (62%) and 77 (22%) respectively, NT-proBNP 9106 ng/L (379–216187); TnI – 0.18 ng/ml (0.1–12); TnT −0.09 ng/ml (0.04–8.2) and IVS 15 mm (7–24). Treatments given were: Bortezomib combinations - 23 (7%), MDex - 150 (43%), thalidomide combinations - 96 (28%), lenalidomide combinations - 13 (4%). 30 (8%) were deemed too ill for treatment or died prior to treatment initiation. Only 37% completed the planned treatment course. The haematological responses on an intention to treat basis were seen in (Overall response rate/complete response (CR)/partial response (PR))(n(%)): MDex – 63(42%)/24 (16%)/39 (26%); Thalidomide combinations 31(32%)/11(12%)/20(21%), bortezomib combinations 10(43%)/6 (23%)/4 (17%), lenalidomide combination 5(38%)/0(0%)/5(38%). The median overall survival (OS) was 7.1 mos. The overall survival at 12 months from response evaluation was 74% for CR, 52% for PR and 18% for NR and from diagnosis was (median): CR – 59 mo, PR 28 mo, NR 10 mo and not assessable for response 2.9 mos. Stage III patients without echocardiographic evidence of cardiac involvement had excellent outcomes with 80% estimated 2 year OS. Using best fit cut-off, in multivariate model (including NT-proBNP., systolic blood pressure (SBP), ejection fraction, NYHA, ECOG, dFLC, LV wall thickness), NT-proBNP > 8000 ng/L (HR 2.3; p <0.0001) and SBP < 100 mm of Hg (HR 1.6; p<0.0001) were the only independent predictors of poor outcome. Using NT-proBNP >8000 ng/L and SPB <100 mm of Hg as high risk criteria, stage III patients can be further subdivided based on presence of none, one or two criteria with OS of 25 mo, 6 mo and 3 mo respectively. Using these criteria, on intent to treat basis, OS by CR/PR/NR was: no high risk factors – median not reached/69 mo/7 mo and one high risk factor - 59 mo/23 mo/4 mos respectively and too few patients for patients with two high risk factors making comparison unreliable. In conclusion, outcomes amyloidosis patients with stage III disease remain poor. However, stage III patients are heterogeneous and combination of NT-proBNP and SBP can usefully sub-classify these patients. Patients with abnormal biomarkers just due to renal failure in absence of cardiac involvement should be excluded from the current Mayo staging system. Although, treatment responses of stage III patients, on intent to treat basis, are poor with all regimes, it is encouraging that haematological responses improve outcomes and patients who achieve a CR have best outcomes. Clinical trials are urgently needed in patients with stage III disease to confirm these findings and define optimal treatment options. Disclosures: No relevant conflicts of interest to declare.

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 ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Risk Factor ◽  
Bacterial Infection ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Severe Bacterial Infection ◽  
Early Course

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.

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