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Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens.

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. corey_cutler@dfci.harvard.edu

    , , , , , , , , , , ,

    Source

    MeSH

    Adult
    Cohort Studies
    Drug Evaluation
    Female
    Graft vs Host Disease
    Hematopoietic Stem Cell Transplantation
    Humans
    Length of Stay
    Male
    Methotrexate
    Middle Aged
    Mouth Mucosa
    Premedication
    Retrospective Studies
    Sirolimus
    Stomatitis
    Tacrolimus
    Transplantation, Homologous
    Treatment Outcome

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15846292

    Citation

    Cutler, Corey, et al. "Mucositis After Allogeneic Hematopoietic Stem Cell Transplantation: a Cohort Study of Methotrexate- and Non-methotrexate-containing Graft-versus-host Disease Prophylaxis Regimens." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 11, no. 5, 2005, pp. 383-8.
    Cutler C, Li S, Kim HT, et al. Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens. Biol Blood Marrow Transplant. 2005;11(5):383-8.
    Cutler, C., Li, S., Kim, H. T., Laglenne, P., Szeto, K. C., Hoffmeister, L., ... Antin, J. H. (2005). Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 11(5), pp. 383-8.
    Cutler C, et al. Mucositis After Allogeneic Hematopoietic Stem Cell Transplantation: a Cohort Study of Methotrexate- and Non-methotrexate-containing Graft-versus-host Disease Prophylaxis Regimens. Biol Blood Marrow Transplant. 2005;11(5):383-8. PubMed PMID: 15846292.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens. AU - Cutler,Corey, AU - Li,Shuli, AU - Kim,Haesook T, AU - Laglenne,Patricia, AU - Szeto,Kwok Chuen, AU - Hoffmeister,Laura, AU - Harrison,M Joel, AU - Ho,Vincent, AU - Alyea,Edwin, AU - Lee,Stephanie J, AU - Soiffer,Robert, AU - Sonis,Stephen, AU - Antin,Joseph H, PY - 2005/4/23/pubmed PY - 2005/9/24/medline PY - 2005/4/23/entrez SP - 383 EP - 8 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 11 IS - 5 N2 - 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. SN - 1083-8791 UR - https://www.unboundmedicine.com/medline/citation/15846292/Mucositis_after_allogeneic_hematopoietic_stem_cell_transplantation:_a_cohort_study_of_methotrexate__and_non_methotrexate_containing_graft_versus_host_disease_prophylaxis_regimens_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083879105001540 DB - PRIME DP - Unbound Medicine ER -