Predicting Survival of BMT Patients without GVHD at Day 100

LETTER TO THE EDITOR

Use of Screening Studies to Predict Survival Among Patients Who Do Not Have Chronic Graft-Versus-Host Disease at Day 100 After Bone Marrow Transplantation

Biology of Blood and Marrow Transplantation 7:239-240
© 2001 American Society for Blood and Marrow Transplantation

A variety of screening tests have been used to predict the development of chronic graft-versus-host disease (GVHD) in patients who survive the first 4 months after a bone marrow transplantation [1,2]. We have analyzed additional follow-up data from a previously published study [1] of chronic GVHD outcome to determine whether tests can predict overall survival among patients who had no clinical manifestations of chronic GVHD at the time of the screening studies and no recurrent malignancy. The screening studies were interpreted between days 71 and 115 (median, day 90). The study cohort consisted of 241 patients who received methotrexate and cyclosporine for GVHD prophylaxis. First, a Cox regression base model was constructed with high-versus low-risk categories for pretransplantation diagnosis, total body irradiation (TBI) dose (>1200 cGy TBI versus <1200 cGy TBI versus no TBI), age (>40 years versus <40 years), and donor relationship/histocompatibility type (unrelated or HLA-mismatched related donor versus HLA-matched relative) as shown in Table 1.

We then determined whether screening test results contributed any additional information to the multivariable model after taking into account the factors shown in Table 1. In this analysis, an abnormal Schirmer's test result, an elevated alkaline phosphatase level, and a low platelet count were correlated with an increased risk of mortality (Table 2).

The association of a positive Schirmer's test with increased mortality could be a reflection of illnesses other than GVHD. Medications, gonadal failure, and radiation can cause ocular sicca. This complication has been reported in 20% of autologous transplant recipients and in 47% of allogeneic transplant recipients [3]. Similarly, an elevated alkaline phosphatase level often indicates liver dysfunction and could represent drug toxicity, infection, or other complications.

A previous study [4] showed that thrombocytopenia was associated with an increased risk of mortality among patients with extensive clinical chronic GVHD. Our current results suggest that thrombocytopenia is associated with an increased risk of mortality after BMT even without extensive clinical chronic GVHD. Thrombocytopenia could reflect an undiagnosed viral infection or another serious systemic illness.

Conversely, perhaps all of these tests are associated with an increased mortality because they represent an ongoing undetected chronic GVHD that is associated with an immune deficiency. This immune deficiency could predispose patients to fatal infections. The positive test results could be associated with undetected chronic GVHD in combination with other factors. Study of a larger cohort and analysis of the causes of death might yield further insights that could explain the higher mortality associated with thrombocytopenia, an elevated alkaline phosphatase level, and an abnormal Schirmer's test in this study population.

John L.Wagner, Mary E.D.Flowers, Gary Longton,
Rainer Storb, Paul Martin

Clinical Research Division and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Department of Medicine, University of Washington School of Medicine, Seattle, Washington

REFERENCES

1. Wagner JL,Flowers MED,Longton G,et al.The development of chronic graft-versus-host disease:an analysis of screening studies and the impact of corticosteroid use at 100 days after transplantation.Bone Marrow Transplant.1998;22:139-146.

2. Loughran TP,Sullivan K,Morton T,et al.Value of day 100 screening studies for predicitng the development of chronic graft-versus-host disease after allogeneic bone marrow transplantation. Blood.1990;76:228-234.

3. Holmes JA,Livesy SJ,Bedwell AE,et al.Antibody analysis in chronic graft-versus-host disease. Bone Marrow Transplant.1989;4:529-531.

4. First LR,Smith BR,Lipton J,et al.Isolated thrombocytopenia after allogeneic bone marrow transplant and chronic thrombocytopenic syndromes. Blood.1985;65:368-374.

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