Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Induction of cutaneous graft-versus-host disease by administration of cyclosporine to patients undergoing autologous bone marrow transplantation for acute myeloid leukemia. 145 Apr 23

The pathophysiology and clinical features of TA-GVHD are reviewed. Engrafted donor derived lymphocytes in TA-GVHD mainly target the immune system, i.e. myeloid and lymphoid as a result of recognition of "foreign" recipient transplantation antigens. The pathophysiology of acute GVHD has been described as a "cytokine storm" at the barrier of the immunobiological defence in the skin, liver, and intestine. TA-GVHD is mostly an acute syndrome, and predominantly associated with a pan-cytopenia, severe immunosuppression, a skin eruption, hepatitis, and gastrointestinal dysfunction, clinically manifested nausea, vomiting and diarrhea. The overall risk of TA-GVHD is unknown and is probably higher than the approximately 300-350 cases reported in the literature. TA-GVHD is often unrecognized in the setting of complex medical situations, where target organs are already dysfunctional. Furthermore, incomplete manifestations of the triad of GVHD may be present, or the syndrome may be mild or atypical. Finally, the potential diagnosis may be missed. We present an atypical case of fatal TA-GVHD in an immunocompetent diabetic patient after CABG operation, showing leukocytosis throughout the clinical course.
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PMID:[Clinicopathological features of transfusion-associated graft-versus-host disease]. 930 Dec 85