scholarly journals Allogeneic Peripheral Blood Stem-Cell Compared With Bone Marrow Transplantation in the Management of Hematologic Malignancies: An Individual Patient Data Meta-Analysis of Nine Randomized Trials

2005 ◽  
Vol 23 (22) ◽  
pp. 5074-5087 ◽  
Keyword(s):  
Late Stage ◽  
Randomized Trials ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Free Survival ◽  
Stage Disease ◽  
Disease Free

Purpose Considerable uncertainty exists regarding relative effects of allogeneic peripheral blood stem cells transplantation (PBSCT) versus bone marrow transplantation (BMT) on outcomes of patients with hematologic malignancies. Patients and Methods To provide the totality of research evidence related to the effects of PBSCT versus BMT, we conducted an individual-patient data meta-analysis using data from nine randomized trials enrolling 1,111 adult patients. Results Compared with BMT, PBSCT led to faster neutrophil (odds ratio [OR] = 0.31; 95% CI, 0.25 to 0.38; P < .00001) and platelet engraftment (OR = 0.52; 95% CI, 0.44 to 0.61; P < .00001). PBSCT was associated with a significant increase in the development of grade 3-4 acute graft-versus-host disease (GVHD; OR = 1.39; 95% CI, 1.03 to 1.88) and extensive (47% v 31% at 3 years; OR = 1.89; 95% CI, 1.47 to 2.42; P < .000001) and overall chronic GVHD (68% v 52% at 3 years; OR = 1.92; 95% CI, 1.47 to 2.49; P < .000001), but not grade 2-4 acute GVHD (54% v 53%; P = .49). PBSCT was associated with a decrease in relapse (21% v 27% at 3 years; OR = 0.71; 95% CI, 0.54 to 0.93; P = .01) in both late-stage–(33% v 51% at 3 years; OR = 0.59; 95% CI, 0.38 to 0.93; P = .02) and early-stage–disease patients (16% v 20% at 3 years; OR = 0.69; 95% CI, 0.49 to 0.98; P = .04). Nonrelapse mortality was not different between groups. Overall and disease-free survival were only statistically significantly improved in patients with late-stage disease (overall survival: 46% v 31% at 3 years; OR = 0.64; 95% CI, 0.46 to 0.90; P = .01; disease-free survival: 41% v 27% at 3 years; OR = 0.63 95% CI, 0.45 to 0.87; P = .01). Conclusion PBSCT is associated with a decreased relapse rate in hematologic malignancies and improvement in overall and disease-free survival in patients with late-stage disease. PBSCT is also associated with a significant risk of extensive chronic GVHD.

Chronic Graft Versus Host Disease and Pretransplant Disease Status Predict Outcomes in Patients with Hematologic Malignancies Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5090-5090
Author(s):  
Megha A. Shah ◽  
Mounzer Agha ◽  
Markus Mapara ◽  
Kate Lenhart ◽  
Anastasios Raptis
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Disease Status ◽  
Hematologic Malignancies ◽  
Free Survival ◽  
Effective Treatment Modality ◽  
Disease Free ◽  
Reduced Intensity

Abstract Reduced intensity stem cell transplantation (SCT) is an effective treatment modality for patients with hematologic malignancies who are not candidates for conventional myeloablative SCT. We conducted a retrospective review of all patients with hematologic malignancies receiving a reduced intensity allogeneic SCT from July 2002 to July 2007. Data pertaining to patient demographics, engraftment, disease status pre and post transplant, graft versus host disease (GVHD), and HLA matching was analyzed to identify factors significantly affecting the clinical outcome. Seventy three patients, with a median age of 55 (range of 19–70) and with the diagnoses of ALL (n=8), AML (n=30), CLL (n=3), CML (n=1), Hodgkin’s (n=7), non-Hodgkin’s (n=7), MDS (n=11), and MM (n=6) underwent a reduced intensity SCT using a fludarabine based conditioning regimen. Thirty nine (53%) received unrelated donor grafts and 34 (47%) received sibling donor grafts. Fifty six patients (77%) received fully matched grafts whereas 17 patients (23%) had an antigen or allele mismatch. Acute GVHD grade II-IV was observed in 27 of the 73 patients and chronic GVHD was seen in 18 of the 48 patients who could be evaluated. Seventeen patients developed transplant related fatal complications and 30 patients died from disease progression or relapse. Median time to neutrophil recovery was 15 days (range of 9–41 days) and median time to platelet recovery was 18 days (range of 9–42 days). Graft failure was observed in 6 of the 73 patients. Median overall survival and disease free survival for all patients was 7.7 and 6.6 months respectively. Median overall survival for patients with persistent disease or in remission at the time of the SCT was 5.6 and 21.8 months (p= 0.01) while that for disease free survival was 5.7 and 8.4 months (p=0.06). Median overall survival with and without chronic GVHD was 25.6 and 9.4 months (p <0.0001) while median disease free survival was 18.2 and 6.0 months (p< 0.0001). Patients with limited chronic GVHD have not yet reached median overall survival while the median disease free survival was 18.4 months. Those with no or extensive chronic GVHD had medians of 9.4 and 9.2 months for overall survival and 6.0 and 9.2 months for disease free survival (p= 0.004 and p=0.02). The source of the stem cells as well as the administration of allele or single antigen mismatch grafts did not affect the outcome. Reduced intensity SCT is an effective treatment modality in patients with hematologic malignancies, though it is most effective in patients who are in remission at the time of transplant and should be offered in this setting. Patients with limited chronic GVHD had a better outcome suggesting the presence of potent anti-tumor activity of the donor immune competent cells without the detrimental effects in clinical outcome caused by extensive chronic GVHD.

Individual patient data-based meta-analysis assessing pre-operative chemotherapy in resectable oesophageal carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4512-4512 ◽  
Author(s):  
P. G. Thirion ◽  
S. Michiels ◽  
A. Le Maître ◽  
J. Tierney
Keyword(s):  
Preoperative Chemotherapy ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Oesophageal Carcinoma ◽  
Patient Data ◽  
Complete Resection ◽  
Resection Rate ◽  
Free Survival ◽  
Disease Free

4512 Background: Optimal management of operable localised oesophageal carcinoma remains to be determined. The debate is fuelled by some positive individual trials showing a benefit of preoperative chemotherapy (CT+S) or preoperative chemo-radiotherapy (CRT+S) over surgery alone (S). Our group has initiated an individual patient data-based meta-analysis to quantify the potential benefit of CT+S over S. Methods: The methodology used for trial identification and data analysis has been previously reported. The primary endpoint was overall survival (OS). The secondary endpoints were disease-free-survival (DFS) analyzed with a 6 months landmark method, tumour resectability (complete resection rate) and post-operative mortality. The logrank-test, stratified by trial, and hazard ratio (HR) were used for comparison. Subgroup analyses by age, sex, performance status, and histologic type were prospectively planned. Results: Twelve eligible randomized trials (2,284 patients) were identified. Individual patient data from 9 trials (2,102 patients) with a median follow-up of 5.3 years were available for the OS analysis. There was a statistically significant OS benefit in favour of CT+S (HR=0.87, 95% CI 0.79–0.95, p=0.003) translating into a 5-year absolute OS increase of 4% (from 16 to 20%). Based on 7 trials (1,849 patients), the HR for DFS was 0.82 (95% CI 0.74–0.91, p=0.001) in favour of CT+S, representing a 5-year absolute DFS benefit of 4% (from 6 to 10%). The complete resection rate across 8 trials (1,933 patients) was significantly greater in the CT+S arm (67%) compared to the S arm (62%) (OR=0.81, 95% CI 0.67–0.98, p=0.03). No difference was seen in postoperative death (6.7%). No interaction between treatment effect and patients characteristics was seen. Conclusions: Individual patient data-based meta-analysis represents the highest level of evidence and this study shows a small but significant overall and disease-free survival benefit in favour of preoperative chemotherapy over surgery alone. Unrestricted grants from LNCC and Sanofi-Aventis. No significant financial relationships to disclose.

Risk Factors for Graft-versus-Host Disease (GVHD) Following Myeloablative HLA-Identical Sibling Transplantation with Allogeneic Peripheral Blood Stem Cells (PBSC): An Analysis of 546 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3318-3318
Author(s):  
Mohamad Mohty ◽  
Keyword(s):  
Risk Factors ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Individual Patient Data ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Factors Associated ◽  
Disease Free

G-CSF-mobilized PBSCs are increasingly used in allogeneic transplantation. In comparison to bone marrow (BM), PBSCs have been shown to allow faster engraftment, but also can lead to more chronic GVHD. Our current knowledge of risk factors for GVHD is based primarily on historical analyses performed using BM as the stem cell source. This analysis sought to identify potential risk factors predicting for the development of acute and chronic GVHD after related HLA-identical PBSC transplantation (PBSCT). We analyzed the outcome of 546 patients who were part of an international database bringing together individual-patient data from nine randomized trials. Median age of recipients was 39 years. 180 (33%) patients had acute myeloid leukemia (AML), 237 (43%) had chronic myeloid leukemia (CML) and 129 patients had other hematological malignancies. 398 (73%) patients had standard risk disease at time of PBSCT and 218 (41%) patients received TBI-based myeloablative conditioning. 312 (57%) patients received short-course methotrexate (days 1, 3, 6) as GVHD prophylaxis, while 234 (43%) received long-course methotrexate (days 1, 3, 6, 11). 190 (35%) patients received G-CSF post-transplant. An ANC of >500/μL was reached at a median of 16 (range, 8–50) days. Platelet recovery occurred at a median of 15 (range, 5–376) days. The incidence of grades II-IV acute GVHD was 44% (95%CI, 40–48%), while the incidence of extensive chronic GVHD was 40% (95%CI, 36%–44%). In a Cox multivariate analysis, the incidence of acute GVHD was significantly associated with age (P=0.001; RR=1.60 for age >40; 95%CI, 1.2–2.1), and TBI-based conditioning (P=0.0009; RR=1.7; 95%CI, 1.2–2.2). The main risk factors associated with an increased risk of extensive chronic GVHD in a Cox multivariate analysis were grade II-IV acute GVHD and a female donor (P=0.009; RR=1.5; 95%CI, 1.1–2.0; and P<0.0001; RR=2.2; 95%CI, 1.6–2.9 respectively). At a median follow-up of 35 months, disease-free survival (DFS) was significantly higher in patients with extensive chronic GVHD compared to patients without extensive chronic GVHD (P=0.03). G-CSF post-transplant (P=0.0027; RR=1.9; 95%CI, 1.2–2.9), disease status at transplant ((P<0.0001; RR=2.9 for advanced diseases; 95%CI, 1.9–4.3), and a diagnosis of acute leukemia (AML or ALL; P<0.0001; RR=3.5; 95%CI, 2.2–5.6) were the major factors associated with worsened disease-free-survival. In conclusion, although the use of PBSCs is associated with more frequent and clinically more severe chronic GVHD, this large-scale analysis based on individual-patient data demonstrates that some risk factors for GVHD after PBSCT are qualitatively comparable to those observed with BM-derived stem cells and might be determinant for the ultimate outcome. Most importantly, extensive chronic GVHD is associated with significantly improved DFS, while the use of G-CSF post-transplant might be detrimental.

Efficacy of Oral Adjuvant Therapy After Resection of Colorectal Cancer: 5-Year Results From Three Randomized Trials

2004 ◽  
Vol 22 (3) ◽  
pp. 484-492 ◽  
Author(s):  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Therapy ◽  
Oral Therapy ◽  
Randomized Trials ◽  
Early Stage ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Oral Fluoropyrimidines ◽  
Disease Free

Purpose Adjuvant therapy of colorectal cancer with oral fluorinated pyrimidines is attractive because of its ease of administration and good tolerability. The purpose of this meta-analysis is to assess the survival and disease-free survival benefits of treating patients after surgical resection of a primary colorectal tumor with oral fluoropyrimidines for 1 year. Patients and Methods This meta-analysis was performed on individual data from three randomized trials conducted by the Japanese Foundation for Multidisciplinary Treatment for Cancer involving a total of 5,233 patients with stages I to III colorectal cancer. Results The overall hazard ratio in favor of oral therapy was 0.89 for survival (95% CI, 0.80 to 0.99; P = .04), and 0.85 for disease-free survival (95% CI, 0.77 to 0.93; P < .001). Thus oral therapy reduced the risk of death by 11% and the risk of recurrence or death by 15%. There was no significant heterogeneity between trials, nor did the benefit of oral therapy depend on tumor stage (I, II, or III), tumor site (rectum or colon), patient age, or patient sex. Conclusion Oral fluoropyrimidines improve disease-free survival and survival of patients after resection of early-stage colorectal cancer. These observations support the use of these agents alone after resection of early-stage disease, as well as further testing of oral agents in combination with new drugs that have recently shown antitumor activity in advanced colorectal cancer.

scholarly journals Acute graft-versus-host disease prophylaxis with methotrexate and cyclosporine after busulfan and cyclophosphamide in patients with hematologic malignancies

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 849-855 ◽  
Author(s):  
A von Bueltzingsloewen ◽  
R Belanger ◽  
C Perreault ◽  
Y Bonny ◽  
DC Roy ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Low Risk ◽  
Free Survival ◽  
Graft Versus Host ◽  
Disease Free ◽  
Acute Graft

The combination of two powerful immunosuppressive agents, methotrexate (MTX) and cyclosporine (CSP), has resulted in a significant decrease in the morbidity and mortality after allogeneic bone marrow transplantation (BMT). However, the additive toxicities from ablative preparative regimens may lead to suboptimal use of this combined immunoprophylaxis. We evaluated the efficacy and feasibility of administering MTX/CSP with busulfan (4 mg/kg/d for 4 days) and cyclophosphamide (50 mg/kg/d for 4 days) (BuCy4) in 101 consecutive patients with hematologic malignancies categorized into high- and low- risk groups receiving HLA-matched marrow grafts. Postgrafting immunosuppression consisted of MTX short course (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11) and intravenous CSP (1.5 mg/kg every 12 hours). Eighty-three patients (82.1%) received 100% of MTX calculated dose and 87 (86.1%) achieved a CSP therapeutic level (250 to 600 ng/mL) within a median of 16 days. Seventy-three patients (72.2%) received optimal immunosuppressive therapy comprising a full MTX course and achieving CSP therapeutic concentrations. The Kaplan-Meier estimated incidence of grade II to IV acute graft-versus-host disease (GVHD) was 9.2% for all patients and 5.5% in patients receiving optimal GVHD prophylaxis. Eighty-nine patients (88.2%) survived > or = 100 days posttransplant and 43 (48.3%) developed chronic GVHD, the majority of which were de novo (31 of 43). The estimated incidence of relapse was 28.9% for all patients and 14.8% in the low-risk group, with a median follow-up of 24.5 months. High-risk features and the absence of chronic GVHD were significantly associated with relapse (P = .002 and .036, respectively) in multivariate analyses. Projected disease-free survival at 2 years was 52.3% for all patients and 65.2% in low-risk patients. Disease-free survival was significantly improved in optimally treated patients (P = .03) due to a lower incidence of early deaths from acute GVHD and infectious episodes. In conclusion, optimal delivery of MTX/CSP in association with BuCy4 resulted in a near complete abrogation of acute GVHD in HLA-matched transplants and a significantly improved disease-free survival.

scholarly journals Acute graft-versus-host disease prophylaxis with methotrexate and cyclosporine after busulfan and cyclophosphamide in patients with hematologic malignancies

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 849-855
Author(s):  
A von Bueltzingsloewen ◽  
R Belanger ◽  
C Perreault ◽  
Y Bonny ◽  
DC Roy ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Low Risk ◽  
Free Survival ◽  
Graft Versus Host ◽  
Disease Free ◽  
Acute Graft

Abstract The combination of two powerful immunosuppressive agents, methotrexate (MTX) and cyclosporine (CSP), has resulted in a significant decrease in the morbidity and mortality after allogeneic bone marrow transplantation (BMT). However, the additive toxicities from ablative preparative regimens may lead to suboptimal use of this combined immunoprophylaxis. We evaluated the efficacy and feasibility of administering MTX/CSP with busulfan (4 mg/kg/d for 4 days) and cyclophosphamide (50 mg/kg/d for 4 days) (BuCy4) in 101 consecutive patients with hematologic malignancies categorized into high- and low- risk groups receiving HLA-matched marrow grafts. Postgrafting immunosuppression consisted of MTX short course (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11) and intravenous CSP (1.5 mg/kg every 12 hours). Eighty-three patients (82.1%) received 100% of MTX calculated dose and 87 (86.1%) achieved a CSP therapeutic level (250 to 600 ng/mL) within a median of 16 days. Seventy-three patients (72.2%) received optimal immunosuppressive therapy comprising a full MTX course and achieving CSP therapeutic concentrations. The Kaplan-Meier estimated incidence of grade II to IV acute graft-versus-host disease (GVHD) was 9.2% for all patients and 5.5% in patients receiving optimal GVHD prophylaxis. Eighty-nine patients (88.2%) survived > or = 100 days posttransplant and 43 (48.3%) developed chronic GVHD, the majority of which were de novo (31 of 43). The estimated incidence of relapse was 28.9% for all patients and 14.8% in the low-risk group, with a median follow-up of 24.5 months. High-risk features and the absence of chronic GVHD were significantly associated with relapse (P = .002 and .036, respectively) in multivariate analyses. Projected disease-free survival at 2 years was 52.3% for all patients and 65.2% in low-risk patients. Disease-free survival was significantly improved in optimally treated patients (P = .03) due to a lower incidence of early deaths from acute GVHD and infectious episodes. In conclusion, optimal delivery of MTX/CSP in association with BuCy4 resulted in a near complete abrogation of acute GVHD in HLA-matched transplants and a significantly improved disease-free survival.

scholarly journals P22 Are Elderly Patients at Increased Perioperative Morbidity and Mortality from Oesophagectomy for Oesophageal Cancer? A Systematic Mapping Review and Meta-Analysis

BJS Open ◽  
2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Rohan R Gujjuri ◽  
Muhammed Elhadi ◽  
Hamza Umar ◽  
Manjunath S Subramanya ◽  
Richard P T Evans ◽  
...  
Keyword(s):  
Elderly Population ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
The Elderly ◽  
Pulmonary Complications ◽  
Cardiac Complications ◽  
Anastomotic Leaks ◽  
Free Survival ◽  
Younger Patients ◽  
Disease Free

Abstract Introduction Oesophagectomy is being increasingly performed in an ageing population that is observing a concomitant growth in the life expectancy. However, the risks are poorly quantified, and this study aims to review current evidence to further quantify the postoperative of oesophagectomy in the elderly population compared to younger patients. Methods A systematic electronic search was conducted for studies reporting oesophagectomy in the elderly population. Meta-analysis was performed using random-effects modelling to compute odds ratios (OR) and 95% confidence intervals (CI). Primary outcome was overall complications and secondary outcomes included anastomotic leaks, cardiac complications, pulmonary complications, overall and disease-free survival. Meta-regression was performed to identify study-, hospital- and patient-level factors confounding study findings. Results This review included 37 eligible studies involving 61,723 patients. Increasing age was significantly associated with increased rates of overall complications (OR: 1.67, CI 95%: 1.42 – 1.97), cardiac complications (OR: 1.62, CI 95%: 1.10 – 2.40), pulmonary complications (OR: 1.44, CI 95%: 1.11 – 1.87) and decreased 5-year overall survival (OR: 1.36, CI 95%: 1.11 – 1.66) and 5-year disease-free survival (OR: 1.66, CI 95%: 1.40 – 1.97). Rates of anastomotic leaks showed no difference between elderly and younger patients (OR: 1.06, CI 95%: 0.71 – 1.59). Conclusion Postoperative outcomes such as overall complications, 5-year overall survival and disease-free survival appear to significantly worse in all age cut-offs in this meta-analysis. Sarcopenia and frailty act as better predictors of postoperative outcomes than chronological age. This study confirms the preconceived suspicions of increased risks in elderly patients following oesophagectomy and will aid future pre-operative counselling and informed consent.

scholarly journals Prognostic Value of C-Reactive Protein-to-Albumin Ratio in Head and Neck Cancer: A Meta-Analysis

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 403
Author(s):  
Chih-Wei Luan ◽  
Hsin-Yi Yang ◽  
Yao-Te Tsai ◽  
Meng-Chiao Hsieh ◽  
Hsin-Hsu Chou ◽  
...  
Keyword(s):  
Head And Neck ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Head And Neck Cancers ◽  
C Reactive Protein ◽  
Free Survival ◽  
Albumin Ratio ◽  
Reactive Protein ◽  
Distant Metastasis Free Survival ◽  
Disease Free

The C-reactive protein-to-albumin ratio is a proven prognostic predictor of nasopharyngeal carcinoma. However, the role of the C-reactive protein-to-albumin ratio in other head and neck cancers remains unclear. This meta-analysis explored the prognostic value of the C-reactive protein-to-albumin ratio in head and neck cancers. A systematic search was conducted. Outcomes of interest included overall survival, disease-free survival, and distant metastasis–free survival. The hazard ratio with 95% confidence interval was pooled using a random-effects model. A total of 11 publications from the literature were included, allowing for the analysis of 7080 participants. Data pooling demonstrated that pretreatment C-reactive protein-to-albumin ratio had a hazard ratio of 1.88 (95% CI: 1.49−2.37, p < 0.001) for predicting overall survival, 1.91 (95% CI: 1.18−3.08, p = 0.002) for disease-free survival, and 1.46 (95% CI: 1.08−1.96, p = 0.001) for distant metastasis–free survival. Subgroup analysis showed that the C-reactive protein-to-albumin ratio is a significant prognostic marker for various head and neck cancers. An elevated pretreatment C-reactive protein-to-albumin ratio predicts a worse prognosis for patients with head and neck cancers. Therefore, the C-reactive protein-to-albumin ratio could serve as a potential prognostic biomarker facilitating treatment stratification.

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