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- Dhakal, Binod, et al.
(author)
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Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era
- 2020
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In: Leukemia. - : SPRINGERNATURE. - 0887-6924 .- 1476-5551. ; 34:12, s. 3338-3347
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Journal article (peer-reviewed)abstract
- The outcomes of patients with primary plasma cell leukemia (pPCL) after undergoing hematopoietic cell transplantation (HCT) in the novel agent era are unknown. We report outcomes of 348 patients with pPCL receiving autologous (auto-) HCT (n = 277) and allogeneic (allo-) HCT (n = 71) between 2008 and 2015. Median age was 60 years and 56 years for auto- and allo-HCT respectively. For auto-HCT, the 4-year outcomes were: non-relapse mortality (NRM) 7% (4-11%), relapse (REL) 76% (69-82%), progression-free survival (PFS) 17% (13-23%), and overall survival (OS) 28% (22-35%). Karnofsky performance status (KPS) > 90 and >= very good partial response (VGPR) predicted superior OS in multi-variate analysis for auto-HCT. For allo-HCT, the 4-year outcomes were: NRM 12% (5-21%), REL 69% (56-81%), PFS 19% (10-31%), and OS 31% (19-44%). Compared with prior CIBMTR pPCL patients (1995-2006), inferior survival was noted in the current cohort (3-year OS, 39% vs. 38% in allo-HCT, and 62% vs. 35% in auto-HCT) respectively. However, we noted an increased HCT utilization, from 12% (7-21%) in 1995 to 46% (34-64%) in 2009 using SEER data (available till 2009). Despite modern induction translating to higher proportion receiving HCT, the outcomes remain poor in pPCL patients, mainly derived by high relapse rates post-HCT.
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| 2. |
- Haycock, Philip C., et al.
(author)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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In: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Journal article (peer-reviewed)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 3. |
- Munshi, Pashna N., et al.
(author)
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Age no bar : A CIBMTR analysis of elderly patients undergoing autologous hematopoietic cell transplantation for multiple myeloma
- 2020
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In: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 126:23, s. 5077-5087
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Journal article (peer-reviewed)abstract
- Background Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. Methods The authors investigated the outcomes of AHCT in patients with MM who were aged >= 70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged >= 70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, aPvalue <.01 was considered to be statistically significant a priori. Results An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged >= 70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m(2)overall, 58% of the patients aged >= 70 years received Mel at a dose of 140 mg/m(2). On multivariate analysis, patients aged >= 70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1-1.7 [P = .06]), REL (HR, 1.03; 99% CI, 0.9-1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1-1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1-1.4 [P = .02]) compared with the reference group (those aged 60-69 years). In patients aged >= 70 years, Mel administered at a dose of 140 mg/m(2)was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m(2), including day 100 NRM (1% [95% CI, 1%-2%] vs 0% [95% CI, 0%-1%];P = .003]), 2-year PFS (64% [95% CI, 60%-67%] vs 69% [95% CI, 66%-73%];P = .003), and 2-year OS (85% [95% CI, 82%-87%] vs 89% [95% CI, 86%-91%];P = .01]), likely representing frailty. Conclusions The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.
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