Influence of post-methotrexate folinic acid rescue on regimen-related toxicity and graft-versus-host disease after allogeneic bone marrow transplantation.
Thirty-two patients undergoing related-donor bone marrow transplantation (BMT) received cyclosporine (CSP) and methotrexate (MTX) with folinic acid rescue (FAR) as graft-versus-host disease (GVHD) prophylaxis. Fifty consecutive related-donor BMT patients given the CSP/MTX combination without FAR were utilized as historical controls. Patients receiving FAR experienced earlier engraftment, with absolute neutrophil count greater than 0.5 x 10(9)/l at a median of 17 days (vs 21 days in controls, p = 0.002). The day of last platelet transfusion was earlier in the FAR group (median of 14 days vs 17 days in controls, p = 0.01). Compared with the control group, patients receiving FAR had a lower incidence of grade II-IV stomatic (53% vs 78%, p = 0.04) and hepatic (25% vs 56%, p = 0.01) regimen-related toxicity. In the FAR group, 70% required total parenteral nutrition vs 92% of controls (p = 0.02). Broad-spectrum antibiotics were given to FAR patients for a median of 21 days (vs 23 days in controls, p = 0.09). The incidence of grade II-IV acute GVHD was similar in the FAR and control populations (45% and 35%, respectively, p = NS) as was the incidence of chronic GVHD (62% vs 55%, respectively, p = NS). Estimated event-free survival is 59% for FAR patients (median follow-up 64 weeks) and 58% for controls (median follow-up 109 weeks, p = NS). FAR reduces regimen-related toxicity in patients receiving CSP/MTX acute GVHD prophylaxis without significantly influencing GVHD incidence or event-free survival.
Nevill
T J
TJ
Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver, Canada.
Tirgan
M H
MH
Deeg
H J
HJ
Klingemann
H G
HG
Reece
D E
DE
Shepherd
J D
JD
Barnett
M J
MJ
Phillips
G L
GL
D000293:Adolescent; D000328:Adult; D001772:Blood Cell Count; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects; D009504:Neutrophils / Q000473:pathology; D011446:Prospective Studies; D016879:Salvage Therapy; D014184:Transplantation, Homologous
D002955:Leucovorin; D008727:Methotrexate