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Induction of cutaneous graft-versus-host disease by administration of
cyclosporine to patients undergoing autologous bone marrow transplantation
for acute myeloid leukemia [see comments]
AM Yeager, GB Vogelsang, RJ Jones, ER Farmer, V Altomonte, AD Hess and GW Santos
Oncology Center, Johns Hopkins University School of Medicine, Baltimore,
MD.
Cutaneous graft-versus-host disease (GVHD) has been reported after
administration of cyclosporine (CSP) after autologous bone marrow
transplantation (ABMT) with unpurged marrow in patients with lymphoma. To
determine whether GVHD can be induced after ABMT with chemopurged marrow in
acute myeloid leukemia (AML), we administered intravenous CSP for 28 days
(beginning on the day of ABMT) to 19 patients with AML (12 in first
remission [CR1], six in CR2, and one in CR3) who received busulfan (16
mg/kg) and cyclophosphamide (200 mg/kg) and ABMT with 4-
hydroperoxycyclophosphamide (4HC)-treated marrow. In this dose- escalation
trial, CSP daily doses were 1 mg/kg in seven patients, 2.5 mg/kg in eight
patients, or 3.75 mg/kg in four patients. Skin biopsies were obtained
weekly after ABMT or on appearance of rash and were graded for GVH changes.
Overall, 15 of 19 patients (79%) had cutaneous histopathologic grade 2 GVHD
at a median of 33 days (range, 14 to 49) after ABMT; in 10, cutaneous
manifestations were present at time of positive biopsy. The frequency, time
to onset, and duration of GVHD were similar among the three CSP dosage
groups. No patients had hepatic or gastrointestinal dysfunction
attributable to GVHD or required specific therapy for GVHD. Positive
biopsies for GVHD were seen in seven of eight patients who received
full-course, full-dose CSP and 8 of 11 patients who had CSP discontinued or
dosage reduced because of renal insufficiency. Three patients (one with
positive biopsy) died with ABMT-related complications. Seven patients (four
CR1, three CR2) relapsed with AML at a median of 411 days (range, 178 to
549) after ABMT; six of seven had positive biopsies for cutaneous GVHD.
Nine patients (seven CR1, one CR2, and one CR3) are alive without relapse
at a median of 501+ days (range, 252+ to 811+) after ABMT; eight of nine
had cutaneous GVHD. Short-course CSP can induce autologous GVHD in
recipients of chemopurged marrow autografts for AML, but randomized
prospective trials are needed to determine whether this immunologic
reaction is associated with alterations in leukemic relapse rate and
disease-free survival after ABMT in AML.
Volume 79,
Issue 11,
pp. 3031-3035,
06/01/1992
Copyright © 1992 by The American Society of Hematology
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