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Health and Functional Status of Long-Term Survivors of Bone Marrow Transplantation

Thomas Duell, MD; Maria Teresa van Lint, MD, PhD; Per Ljungman, MD, PhD; Andre Tichelli, MD, PhD; Gerard Socie, MD, PhD; Jane F. Apperley, MD, PhD; Melanie Weiss, MD; Amon Cohen, MD, PhD; Elke Nekolla, PhD; and Hans-Jochem Kolb, MD, PhD
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For the EBMT Working Party on Late Effects and EULEP Study Group on Late Effects Grant Support: In part by European Late Effect Project Group (EULEP) and Commission of European Community contract FI3P-CT920064f (for epidemiologic studies and tables). Requests for Reprints: Hans-Jochem Kolb, MD, PhD, Medizinische Klinik III, Knochenmarktransplantation, Klinikum Gro β hadern, Universitat Munchen, Marchioninistrasse 15, 81377 Munchen, Germany. Current Author Addresses: Dr. Duell: Center for Molecular Cytogenetics, Life Sciences Division, Lawrence Berkeley National Laboratory, MS 74-157, 1 Cyclotron Road, Berkeley, CA 94720.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;126(3):184-192. doi:10.7326/0003-4819-126-3-199702010-00002
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Background: Although many patients now survive the short-term complications of bone marrow transplantation for life-threatening hematologic disease, information on the health and activity of long-term survivors is sparse.

Objective: To evaluate the morbidity and mortality of patients surviving more than 5 years after allogeneic bone marrow transplantation.

Design: Retrospective, multicenter study.

Patients: 798 recipients of bone marrow transplants (477 adults, 321 children) from 43 European centers. Patients had received transplants before December 1985 and had survived at least 5 years. Patients had received allogeneic or syngeneic bone marrow for leukemia, lymphoma, inborn diseases of the hematopoietic and immune systems, and severe aplastic anemia.

Measurements: Survival, clinical performance according to Karnofsky score (in increments of 10%), and social reintegration were assessed as outcomes. Patient age and sex, primary disease and status at transplantation, histocompatibility of the donor, conditioning regimen, type of prophylaxis of graft-versus-host disease, and acute and chronic graft-versus-host disease were evaluated as variables.

Results: For the 55 5-year survivors, actuarial mortality was 8% at 10 years and 14% at 15 years. The leading causes of death were disease recurrence (21 patients), chronic graft-versus-host disease with complicating infections and lung disease (11 patients), secondary cancer (8 patients), and the acquired immunodeficiency syndrome (AIDS) (5 patients). When patients with recurrent disease were excluded, late death was associated with chronic graft-versus-host disease (P < 0.001), occurrence of secondary cancer (P < 0.001), male sex of the patient (P = 0.05), and female sex of the donor (P = 0.002). Clinical performance was normal (Karnofsky score, 100%) or minimally reduced (Karnofsky score, 90%) in 93% of patients; 89% of patients resumed full-time work or school. Reduced performance status and incomplete resumption of social activity were associated with chronic graft-versus-host disease, recurrent leukemia, AIDS, secondary cancer, organ dysfunction, and neurologic or psychological problems. Other risk factors for incomplete resumption of social activity were female sex (P = 0.002) and older age at transplantation (P = 0.001).

Conclusions: More than 5 years after bone marrow transplantation, most patients were in good health (93%) and had returned to full-time work or school (89%). Recurrence of the primary disease, secondary cancer, and chronic graft-versus-host disease and its sequelae remain problems for some patients.


Grahic Jump Location
Figure 1.
Mortality more than 5 years after bone marrow transplantation.

The curve marked by diagonal lines gives the number of observed patients as a function of time since treatment (person-years at risk). The step function with the hatched range of 95% Cls represents the probability of treatment failure before the specified time, with all observed deaths considered. The lower curve gives the expected mortality according to mortality rates of an age-adjusted normal population in western Europe. The mortality rate at 17 years was 21.6%; six patients were at risk at 17 years. The longest duration of observation was 19 years.

Grahic Jump Location




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