Methotrexate therapy for complex graft rejection in pediatric heart transplant recipients. The Pediatric Heart Transplant Team--Loma Linda.
BACKGROUND
We retrospectively reviewed all pediatric heart transplant recipients at Loma Linda University Medical Center between January 1990 and September 1993 to evaluate the efficacy and safety of methotrexate when it is used for the treatment of graft rejection.


METHODS
Twenty-eight of 156 patients (18%) received methotrexate therapy. The dose used for recurrent rejection was 10 mg/m2/week given every 12 hours for three doses. Rejection history, complete blood counts, liver function tests, and infectious complications were reviewed.


RESULTS
Eighteen patients were treated for recurrent rejection. Methotrexate was begun at a median of 115 days (13 to 1093 days). Older patients were more likely to receive methotrexate (p < 0.01). Efficacy was assessed as rejection episodes (mean +/- standard deviation) occurring in the 2 months before methotrexate administration compared with the 2 months after methotrexate administration and fell from 2.0 +/- 0.2 to 0.6 +/- 0.2 episodes (p < 0.001). The rejection rate (rejections per patient-month) fell in treated patients to a rate similar to patients who did not receive methotrexate. Two patients (11%) died while receiving methotrexate. An additional nine patients were treated for acute rejection with hemodynamic compromise, and one was treated for graft-versus-host disease. The incidence of significant infections was 50% (but no deaths were due to infection) during methotrexate therapy in all patients treated (n = 28). The minimum white blood cell count in the first month of methotrexate therapy occurred at 2 weeks (median of 2700 to 3500 x 10(6) cells/L). Only one patient had elevated transaminase levels.


CONCLUSIONS
Methotrexate is an effective and safe adjunct in the management of chronic pediatric cardiac graft rejection.
Chinnock
R
R
Department of Pediatrics, Loma Linda University Children's Hospital, Calif. 92350, USA.
Emery
J
J
Larsen
R
R
Baum
M
M
Janner
D
D
Razzouk
A
A
Gundry
S
S
Nehlsen-Cannarella
S
S
Bailey
L
L
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology; D006330:Heart Defects, Congenital / Q000276:immunology / Q000601:surgery*; D016027:Heart Transplantation / Q000276:immunology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D007958:Leukocyte Count / Q000187:drug effects; D008111:Liver Function Tests; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D008727:Methotrexate