1.
Vitamin D deficiency is not associated with graft versus host disease after hematopoietic stem cell transplantation: A meta-analysis.
Chiengthong, K, Cheungpasitporn, W, Thongprayoon, C, Lertjitbanjong, P, Cato, LD, Bathini, T, Ungprasert, P, Mao, MA, Chokesuwattanaskul, R
Journal of evidence-based medicine. 2020;(3):183-191
Abstract
OBJECTIVE Vitamin D status plays an important role in immunoregulation, and a deficiency is believed to be related to Graft Versus Host Disease (GVHD) in patients after hematopoietic stem cell transplantation (HSCT). We aim to study the association between vitamin D deficiency and GVHD after HSCT. METHODS A literature search was conducted utilizing MEDLINE, EMBASE, and The Cochrane Library Database from inception to July 2019. Eligible studies were required to1 be clinical trials or observational studies (cohort, case-control, or cross-sectional studies);2 provide data to calculate the odds ratios (OR) of GVHD in HSCT patients with vitamin D deficiency. Two reviewers independently extracted the data and assessed the risk of bias. Pooled odds ratios (OR) with 95% confidence interval (CI) were estimated using random-effects meta-analysis through the Comprehensive Meta-Analysis 3.3 software. RESULTS In total, 8 observational studies consisting of 1335 HSCT patients were enrolled in this systematic review. Overall, there was no significant association between vitamin D deficiency and acute GVHD (OR = 1.06, 95% CI 0.74-1.53, P > 0.05). There was no significant association between vitamin D deficiency and chronic GVHD (OR = 1.75, 95% CI 0.72-4.26, P > 0.05). Funnel plots and Egger regression asymmetry test were performed and showed no publication bias. CONCLUSION There is not a statistically significant association between vitamin D deficiency and neither acute nor chronic GVHD.
2.
Impact of body mass index at different transplantation stages on postoperative outcomes in patients with hematological malignancies: a meta-analysis.
Ren, G, Cai, W, Wang, L, Huang, J, Yi, S, Lu, L, Wang, J
Bone marrow transplantation. 2018;(6):708-721
Abstract
Although the association between body mass index (BMI) and overall survival (OS) has been reported in leukemia patients of different ages, whether BMI levels at different stages of hematopoietic stem cell transplantation (HSCT) have different effects on postoperative survival remains controversial. We searched four electronic databases from inception through July 2017 without any language restrictions and included studies on different types of hematological malignancies reporting both BMI time points and HSCT. Of the 1420 articles identified, 26 articles were eligible for inclusion in this meta-analysis. Three weight groups (obese, overweight and underweight) were individually compared with the normal group. Summary risk estimates for OS and event-free survival (EFS) were calculated with random- or fixed-effects models. For BMI at the pre-HSCT stage, a statistically significant positive association of increased risk of OS (RR: 1.17; 95% CI: 1.08-1.27) and EFS (RR: 1.29; 95% CI: 1-1.67) was identified in underweight individuals compared with those with normal weights. For BMI in the HSCT stage, a lower BMI was significantly associated with poorer OS (RR: 1.34; 95% CI: 1.01-1.78) and EFS (RR: 1.53; 95% CI: 1.09-2.06) compared with a normal BMI. Our results indicated that lower BMI at the pre-HSCT stage or during HSCT is associated with poorer survival.
3.
Trilateral retinoblastoma: a systematic review and meta-analysis.
de Jong, MC, Kors, WA, de Graaf, P, Castelijns, JA, Kivelä, T, Moll, AC
The Lancet. Oncology. 2014;(10):1157-67
Abstract
BACKGROUND About 5% of children with retinoblastoma from germline mutation of the RB1 gene are at risk of developing trilateral retinoblastoma--intraocular retinoblastoma combined with a histologically similar brain tumour, most commonly in the pineal gland. We aimed to provide a systematic overview of published data for trilateral retinoblastoma, and to analyse how survival has changed. METHODS We searched Medline and Embase for scientific literature published between Jan 1, 1966, and April 14, 2014, that assessed trilateral retinoblastoma cases. We undertook a meta-analysis of survival with the Kaplan-Meier method and Cox proportional hazards regression, stratified on the basis of the original study, to account for between-study heterogeneity. FINDINGS We included 90 studies, with 174 patients with trilateral retinoblastoma. 5-year survival after pineal trilateral retinoblastoma increased from 6% (95% CI 2-15) in patients diagnosed before 1995, to 44% (26-61; p<0·0001) in those diagnosed from 1995 onwards. Before 1995, no patients with non-pineal trilateral retinoblastoma survived, but from 1995 onwards, 5-year survival was 57% (30-77; p=0·035). Hazard ratios (HR) adjusted for the presence of leptomeningeal metastases and trilateral retinoblastoma location, suggested that both conventional (HR 0·059, 95% CI 0·016-0·226; p<0·0001) and high-dose chemotherapy with stem-cell rescue (0·013, 0·002-0·064; p<0·0001) most strongly contributed to this improvement. Absence of leptomeningeal metastases (HR 2·13, 95% CI 0·98-4·60; p=0·055) were associated with improved survival. Non-pineal trilateral retinoblastomas were larger than pineal tumours (median 30 mm [range 6-100] vs 22 mm [7-60]; p=0·012), but both had similar outcomes since 1995. INTERPRETATION Our results suggest that improvements in overall survival are attributable to improved chemotherapy regimens and early detection of pineal trilateral retinoblastoma. As such, successful treatment of trilateral retinoblastoma should include screening at least at the time of retinoblastoma diagnosis and chemotherapy, which would preferably be a high-dose regimen with autologous stem-cell rescue. FUNDING None.
4.
Mycophenolate mofetil versus methotrexate for prevention of graft-versus-host disease in people receiving allogeneic hematopoietic stem cell transplantation.
Kharfan-Dabaja, M, Mhaskar, R, Reljic, T, Pidala, J, Perkins, JB, Djulbegovic, B, Kumar, A
The Cochrane database of systematic reviews. 2014;(7):CD010280
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Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HCT) is associated with improved outcomes for people with various hematologic diseases; however, the morbidity and mortality resulting from acute and subsequently chronic graft-versus-host disease (GVHD) pose a serious challenge to wider applicability of allo-HCT. Intravenous methotrexate in combination with a calcineurin inhibitor, cyclosporine or tacrolimus, is a widely used regimen for the prophylaxis of acute GVHD, but the administration of methotrexate is associated with a number of adverse events. Mycophenolate mofetil, in combination with a calcineurin inhibitor, has been used extensively in people undergoing allo-HCT. Conflicting results regarding various clinical outcomes following allo-HCT have been observed when comparing mycophenolate mofetil-based regimens against methotrexate-based regimens for acute GVHD prophylaxis. PRIMARY OBJECTIVE to assess the effect of mycophenolate mofetil versus methotrexate for prevention of acute GVHD in people undergoing allo-HCT. SECONDARY OBJECTIVES to evaluate the effect of mycophenolate mofetil versus methotrexate for overall survival, prevention of chronic GVHD, incidence of relapse, treatment-related harms, nonrelapse mortality, and quality of life. SEARCH METHODS We searched Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE from inception to March 2014. We handsearched conference abstracts from the last two meetings (2011 and 2012) of relevant societies in the field. We searched ClinicalTrials.gov, Novartis clinical trials database (www.novctrd.com), Roche clinical trial protocol registry (www.roche-trials.com), Australian New Zealand Clinical Trials Registry (ANZCTR), and the metaRegister of Controlled Trials for ongoing trials. SELECTION CRITERIA Two review authors independently reviewed all titles/abstracts and selected full-text articles for inclusion. We included all references that reported results of randomized controlled trials (RCTs) of mycophenolate mofetil versus methotrexate for the prophylaxis of GVHD among people undergoing allo-HCT in this review. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data on outcomes from all studies and compared prior to data entry and analysis. We expressed results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes and hazard ratios (HR) and 95% CIs for time-to-event outcomes. We pooled the individual study effects using the random-effects model. Estimates lower than one indicate that mycophenolate mofetil was favored over methotrexate. MAIN RESULTS We included three trials enrolling 177 participants (174 participants analyzed). All participants in the trials by Keihl et al. and Bolwell et al. received cyclosporine while all participants enrolled in the trial by Perkins et al. received tacrolimus. However, the results did not differ by the type of calcineurin inhibitor employed (cyclosporine versus tacrolimus). There was no evidence for a difference between mycophenolate mofetil versus methotrexate for the outcomes of incidence of acute GVHD (RR 1.25; 95% CI 0.75 to 2.09; P value = 0.39, very low quality evidence), overall survival (HR 0.73; 95% CI 0.45 to 1.17; P value = 0.19, low-quality evidence), median days to neutrophil engraftment (HR 0.77; 95% CI 0.51 to 1.17; P value = 0.23, low-quality evidence), incidence of relapse (RR 0.84; 95% CI 0.52 to 1.38; P value = 0.50, low-quality evidence), non-relapse mortality (RR 1.21; 95% CI 0.62 to 2.36; P value = 0.57, low-quality evidence), and incidence of chronic GVHD (RR 0.92; 95% CI 0.65 to 1.30; P value = 0.62, low-quality evidence). There was low-quality evidence that mycophenolate mofetil compared with methotrexate improved platelet engraftment period (HR 0.87; 95% CI 0.81 to 0.93; P value < 0.0001, low-quality evidence). There was low-quality evidence that mycophenolate mofetil compared with methotrexate resulted in decreased incidence of severe mucositis (RR 0.48; 95% CI 0.32 to 0.73; P value = 0.0006, low-quality evidence), use of parenteral nutrition (RR 0.48; 95% CI 0.26 to 0.91; P value = 0.02, low-quality evidence), and medication for pain control (RR 0.76; 95% CI 0.63 to 0.91; P value = 0.002, low-quality evidence). Overall heterogeneity was not detected in the analysis except for the outcome of neutrophil engraftment. None of the included studies reported any outcomes related to quality of life. Overall quality of evidence was low. AUTHORS' CONCLUSIONS The use of mycophenolate mofetil compared with methotrexate for primary prevention of GVHD seems to be associated with a more favorable toxicity profile, without an apparent compromise on disease relapse, transplant-associated mortality, or overall survival. The effects on incidence of GVHD between people receiving mycophenolate mofetil compared with people receiving methotrexate were uncertain. There is a need for additional high-quality RCTs to determine the optimal GVHD prevention strategy. Future studies should take into account a comprehensive view of clinical benefit, including measures of morbidity, symptom burden, and healthcare resource utilization associated with interventions.