Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens.
Oral mucositis occurs in up to 75% of recipients of high-dose chemoradiotherapy conditioning regimens used for allogeneic hematopoietic stem cell transplantation (HSCT). As a result of mucositis, narcotic analgesia and total parenteral nutrition (TPN) are commonly required after HSCT. Methotrexate, an antiproliferative graft-versus-host disease (GVHD) prophylaxis agent, impairs mucosal regeneration and worsens and prolongs mucositis. We assessed the effect of substituting sirolimus for methotrexate as GVHD prophylaxis on outcomes associated with mucositis. Two patient cohorts undergoing allogeneic HLA-matched related donor peripheral blood stem cell transplantation with cyclophosphamide/total body irradiation conditioning were prospectively analyzed for mucositis severity and retrospectively reviewed for correlative outcomes. GVHD prophylaxis consisted of sirolimus/tacrolimus (ST) in the study group and tacrolimus/methotrexate (TM) in the control group. Thirty patients received ST and 24 patients received TM as GVHD prophylaxis between October 2000 and May 2003. Mild, moderate, and severe mucositis was noted in 37%, 57%, and 7% of the ST group and 8%, 42%, and 50% of the TM group (P = .0002). Less TPN was used in the ST group than the TM group (17% versus 43% of posttransplantation hospital days; P = .02). The total number of narcotic days was lower in the ST group in comparison with the TM group (median, 13.5 versus 17 days; P = .08). The time to first hospital discharge was shorter in the ST group compared with the TM group (median, 18 versus 22 days; P = .07). The substitution of sirolimus for methotrexate as GVHD prophylaxis is associated with a reduction in mucositis severity. As a result, TPN and narcotic use are reduced, and hospitalization duration is shortened. Less toxic GVHD prophylaxis regimens without methotrexate may have a significant effect on patient quality of life, patient outcomes, and economic outcomes associated with allogeneic stem cell transplantation.
Cutler
Corey
C
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. corey_cutler@dfci.harvard.edu
Li
Shuli
S
Kim
Haesook T
HT
Laglenne
Patricia
P
Szeto
Kwok Chuen
KC
Hoffmeister
Laura
L
Harrison
M Joel
MJ
Ho
Vincent
V
Alyea
Edwin
E
Lee
Stephanie J
SJ
Soiffer
Robert
R
Sonis
Stephen
S
Antin
Joseph H
JH
D000328:Adult; D015331:Cohort Studies; D004341:Drug Evaluation; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007902:Length of Stay; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009061:Mouth Mucosa; D011292:Premedication / Q000379:methods*; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use; D013280:Stomatitis / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D016559:Tacrolimus / Q000627:therapeutic use; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D020123:Sirolimus; D016559:Tacrolimus; D008727:Methotrexate