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Unrelated Donor Bone Marrow Transplantation for Chronic Myelogenous Leukemia: A Decision Analysis

Stephanie J. Lee, MD, MPH; Karen M. Kuntz, ScD; Mary M. Horowitz, MD, MS; Philip B. McGlave, MD; John M. Goldman, DM; Kathleen A. Sobocinski, MS; Janet Hegland, BS; Craig Kollman, PhD; Susan K. Parsons, MD, MRP; Milton C. Weinstein, PhD; Jane C. Weeks, MD, MS; and Joseph H. Antin, MD
[+] Article and Author Information

From Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard School of Public Health, Boston, Massachusetts; University of Minnesota and the National Marrow Donor Program, Minneapolis, Minnesota; Royal Postgraduate Medical School, London, United Kingdom; and the International Bone Marrow Transplant Registry, Milwaukee, Wisconsin. Acknowledgments: The authors thank the patients, donors, transplant centers, and staff who participate in the International Bone Marrow Transplant Registry and the National Marrow Donor Program. Grant Support: Dr. Lee was supported in part by a Health Services Research Fellowship from the Agency for Health Care Policy and Research. The International Bone Marrow Transplant Registry is supported by Public Health Service Grant P01-CA-40053 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung, and Blood Institute; Contract CP-21161 from the National Cancer Institute of the U.S. Department of Health and Human Services; and grants from Alpha Therapeutic Corporation; Amgen, Inc.; Anonymous; Astra Pharmaceutical; Baxter Healthcare Corp.; Bayer Corp.; Biogen; Blue Cross and Blue Shield Association; Lynde and Harry Bradley Foundation; Bristol-Myers Squibb Co.; Frank G. Brotz Family Foundation; CellPro, Inc.; Centeon; Center for Advanced Studies in Leukemia; Chimeric Therapies, Inc., Charles E. Culpeper Foundation; Eleanor Naylor Dana Charitable Trust; Eppley Foundation for Research; Genentech, Inc.; Glaxo Wellcome Co.; Hoechst Marion Roussel, Inc.; Immunex Corp.; Janssen Pharmaceutica; Kettering Family Foundation; Kirin Brewery Co.; Robert J. Kleberg, Jr., and Helen C. Kleberg Foundation; Herbert H. Kohl Charities, Inc.; Eli Lilly Co. Foundation; Nada and Herbert P. Mahler Charities; Milstein Family Foundation; Milwaukee Foundation/Elsa Schoeneich Research Fund; Samuel Roberts Noble Foundation; Ortho Biotech Corp.; John Oster Family Foundation; Elsa U. Pardee Foundation; Jane and Lloyd Pettit Foundation; Alirio Pfiffer Bone Marrow Transplant Support Association; Pfizer, Inc.; Pharmacia and Upjohn; RGK Foundation; Sandoz Pharmaceuticals; Schering-Plough International; Walter Schroeder Foundation; Searle; Stackner Family Foundation; Starr Foundation; Joan and Jack Stein Charities; and Wyeth-Ayerst Laboratories. Requests for Reprints: Stephanie Lee, MD, MPH, Center for Outcomes and Policy Research, Dana-Farber Cancer Institute, 454 Brookline Avenue, Suite 23, Boston, MA 02115. Current Author Addresses: Drs. Lee and Weeks: Center for Outcomes and Policy Research, Dana-Farber Cancer Institute, 454 Brookline Avenue, Suite 23, Boston, MA 02115.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1997;127(12):1080-1088. doi:10.7326/0003-4819-127-12-199712150-00005
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Background: Chronic myelogenous leukemia (CML) is an indolent but ultimately fatal disease. Because the natural history of CML varies and quality of life with CML may be excellent until shortly before death, deciding whether and when to pursue unrelated donor bone marrow transplantation is often difficult.

Objective: To compare early transplantation, delayed transplantation, and no transplantation for patients with chronic-phase CML on the basis of discounted, quality-adjusted life expectancy.

Design: A Markov model comparing different strategies was constructed. This model considers patient age, quality of life, risk aversion, and the competing risks for CML progression and transplant toxicity.

Setting: Therapeutic decision at the time of diagnosis of CML.

Patients: The base case is a 35-year-old patient with intermediate-prognosis CML. Younger and older patients with better and worse prognoses are also evaluated.

Intervention: Early transplantation, delayed transplantation, and no transplantation.

Measurements: Quality-adjusted, discounted life expectancy.

Results: For patients with newly diagnosed CML, transplantation within the first year provides the greatest quality-adjusted expected survival, although this benefit decreases with increasing patient age. For a 35-year-old patient with intermediate-prognosis CML, transplantation within the first year results in 5.3 more discounted, quality-adjusted years of life expectancy than does no transplantation. This finding is robust even with varying baseline assumptions.

Conclusions: These results support the use of early unrelated donor bone marrow transplantation for most patients with CML.

Figures

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Figure 1.
Structure of the Markov model.

All patients are initially in the Alive (chronic-phase CML) state. With each 6-month cycle, they can move to a different state or remain in the same state, as indicated by the arrows. BMT = bone marrow transplantation; CML = chronic myelogenous leukemia; GVHD = graft-versus-host disease.

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Figure 2.
Composite survival curves showing the effects of progression of chronic myelogenous leukemia (CML) and transplantation-related mortality for a 35-year-old patient with intermediate-prognosis CML under different scenarios.

The number of patients providing data in the transplanted cohorts at 1, 3, and 5 years after bone marrow transplantation (BMT) was 34, 11, and 3, respectively, for transplantation within the first year after diagnosis; 54, 23, and 5, respectively, for transplantation 1 to 2 years after diagnosis; 15, 5, and 1, respectively, for transplantation 2 to 3 years after diagnosis; and 24, 13, and 4, respectively, for transplantation more than 3 years after diagnosis. Survival for patients with CML who did not have transplantation was estimated from published data. Dashed lines indicate extrapolation beyond the data.

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Figure 3.
Comparison of immediate bone marrow transplantation (BMT) and no transplantation for a 35-year-old patient with best-, intermediate-, or worst-prognosis chronic myelogenous leukemia.

Net benefit is expressed as the difference in discounted, quality-adjusted years of life expectancy between cohorts with and without transplantation as a function of time from diagnosis.

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Figure 4.
Effect of varying assumptions about the incidence of chronic graft-versus-host disease (GVHD) and quality of life (utilities) after transplantation.

Early bone marrow transplantation (BMT) is better for combinations of utilities represented by the area at the upper right; no transplantation is better for combinations of utilities in the area at the lower left. The dotted line represents the threshold for a 59% incidence of chronic graft-versus-host disease; the dashed line represents the threshold for a 90% incidence of chronic graft-versus-host disease. The X indicates baseline assumptions (utility after transplantation without chronic graft-versus-host disease, 0.979; utility with chronic graft-versus-host disease, 0.9).

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