Retrospective survival analysis and cost-effectiveness evaluation of second allogeneic bone marrow transplantation in patients with acute leukemia

Abstract

Summary:The therapeutic options for patients with acute leukemia who relapse after the initial transplant include second bone marrow transplantation (2BMT) and conventional chemotherapy (CC). In this work, we conducted an analysis of published survival data and we evaluated the cost-effectiveness of 2BMT in comparison with CC. We retrieved survival information on 167 patients treated with 2BMT and 299 patients treated with CC. Survival figures were derived from individual patient data and were compared between 2BMT and CC. The mean lifetime survival (MLS) was estimated for each of the two patient cohorts using standard techniques of survival-curve extrapolation. The cost data of patients given 2BMT or CC were estimated from published data. Our analysis of individual survival data showed that 2BMT improved survival at levels of statistical significance (survival gain = 19.6 months per patient). Using an incremental cost of $90 000 per patient, the costeffectiveness ratio of 2BMT in comparison with CC was calculated as $52 215 discounted dollars per discounted life year gained. Our results indicate that, in patients with acute leukemia who relapse after their first transplant, 2BMT significantly prolongs survival in comparison with CC and seems to have an acceptable cost-effectiveness profile. Keywords: acute leukemia; second bone marrow transplantation; cost-effectiveness analysisIn patients with acute leukemia who have received an allogeneic bone marrow transplant, relapse implies a grim prognosis. To improve survival in these patients, a second allogeneic bone marrow transplant (2BMT) has been proposed as a more effective salvage intervention than conventional chemotherapy. [1][2][3][4][5][6][7][8] Six open uncontrolled studies [1][2][3][4][5][6] have thus far assessed the impact of 2BMT on survival, whereas at least two large-scale uncontrolled studies reported survival information for patients treated with a first allogeneic transplant and with conventional chemotherapy after relapse. In our work, seven of these studies [1][2][3][4][5]7,8 were utilized to conduct a retrospective survival analysis and to evaluate the cost-effectiveness ratio of 2BMT in comparison with conventional chemotherapy. Methods Study designOur study was aimed at evaluating survival and cost of the two following therapeutic options for patients with acute leukemia who relapse after the first allogeneic transplant: (1) 2BMT; (2) standard salvage chemotherapy.Our analysis consisted of three sequential phases: (1) literature search (from January 1985 to June 1998) of the clinical trials that evaluated survival for these two therapeutic options; (2) survival analysis with meta-analytic pooling of the results from the trials and with statistical testing; (3) cost-effectiveness analysis.Our survival meta-analysis was conducted through the following procedure (Model 1): firstly, the individual survival data were retrieved from the patient cohorts enrolled in the various studies; then, the survival difference between 2BMT vs conventional chemot...

Event-free survival and cost-effectiveness in adult acute lymphoblastic leukaemia in first remission treated with allogeneic transplantation

“…In particular, the data of individual survivals were derived either from the original raw data provided by the trial's authors or from the information contained in the original survival graphs. A number of survival meta-analyses have already been published, [10][11][12][13][14][15][16][17] in which approximated methods have been used to reconstruct individual survival times from published information (such as the Kaplan-Meier graphs, the text of the article, the tables showing patients at risk at various follow-up times and so on). Formal methods have also been reported wherein a computer program is used to analyse KaplanMeier graphs to estimate the time distribution of the events and of the terminations of the follow-up.…”

“…Cost-minimization analysis is appropriate for comparing equi-effective treatments, whereas cost-effectiveness analysis is indicated when there is a significant difference in clinical effectiveness. 11 Our study utilized a cost-effectiveness analysis because allogeneic transplantation proved to be significantly more effective than the reference treatments. Our cost-effectiveness analysis was designed to determine the incremental cost-effectiveness ratio, that is the ratio of incremental cost and incremental effectiveness (where incremental cost is the lifetime cost difference per patient between allogeneic transplantation and standard chemotherapy or autologous transplantation and incremental effectiveness is the lifetime survival difference per patient between the two treatments).…”

Second hematopoietic stem cell transplantation for the treatment of graft failure, graft rejection or relapse after allogeneic transplantation

“…91 Data were derived from patients with acute leukemia who failed a first allogeneic HSC transplant. Patients from five second HSC transplant series (n = 167) and two non-transplant series (n = 299) were analyzed with outcome derived using survival extrapolation.…”

Survival in patients with intermediate or high grade non-Hodgkin’s lymphoma: meta-analysis of randomized studies comparing third generation regimens with CHOP

“…This approximated method for constructing individual survival times has often been used in previous retrospective overviews and in meta-analyses of survival data (Fine et al, 1993;Messori et al, 1994;Bardelli et al, 1995;Trallori et al, 1995;Ferradina et al, 1997;Messori et al, 1999aMessori et al, , 1999b. The computer programme implementing this method has been recently published (Messori et al, 2000).…”