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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-06-1672.
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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4367-4371
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Prognostic implications of declining plasma gelsolin levels after
allogeneic stem cell transplantation
Mark J. DiNubile,
Thomas P. Stossel,
Olof C. Ljunghusen,
James L. M. Ferrara, and
Joseph H. Antin
From the Divisions of Infectious Diseases,
Hematology-Oncology, and Experimental Medicine, Departments of
Medicine, Cooper Health System, University of Medicine and Dentistry of
New Jersey/Robert Wood Johnson Medical School, Camden, NJ; and the
Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard
Medical School, Boston, MA.
The idiopathic pneumonia syndrome (IPS) represents a common and
often fatal complication of hematopoietic stem cell transplantation (HSCT). Gelsolin is a highly conserved actin-binding protein normally present in plasma that may serve a basic physiological role in limiting
acute lung injury of diverse etiologies. We hypothesized that depletion
of circulating gelsolin following HSCT might play a permissive role
in the pathogenesis of IPS. Plasma gelsolin levels were measured by
immunoblotting in frozen samples obtained weekly from 24 patients
undergoing allogeneic HSCT. Patients with and without IPS were similar
with respect to age, diagnosis, histocompatibility differences between
donor and recipient, and conditioning regimen. Mean gelsolin levels in
the 9 patients with rapidly fatal IPS were significantly lower than
those in patients without this complication by week 3 after HSCT
(101 ± 61 mg/L versus 221 ± 54 mg/L; P = .0002).
Seven (88%) of the 8 patients with gelsolin levels of less than 100 mg/L in the first month after HSCT died from IPS within 3 months;
conversely, gelsolin levels fell to less than 100 mg/L in 7 (78%) of the 9 patients who died from IPS within 3 months of HSCT
(P = .0007). These findings suggest that gelsolin levels
shortly after allogeneic HSCT can predict the later development of
fatal IPS. Gelsolin replacement in selected transplant patients may
offer a novel strategy to prevent or reverse IPS.
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