title: Factors Associated with Myelosuppression Related to Low-Dose Methotrexate Therapy for Inflammatory Rheumatic Diseases.
abstract: Severe myelosuppression is a serious concern in the management of rheumatic disease patients receiving methotrexate (MTX) therapy. This study was intended to explore factors associated with the development of MTX-related myelosuppression and its disease severity.
  
  
  
  We retrospectively examined a total of 40 cases of MTX-related myelosuppression that had been filed in the registries of participating rheumatology and hematology divisions. Data before onset were compared with those of 120 controls matched for age and sex. Cytopenia was graded according to the National Cancer Institute criteria for adverse events. Data before and at onset were compared between the severe and non-severe groups.
  
  
  
  Non-use of folic acid supplements, concurrent medications, and low renal function were significantly associated with the development of myelosuppression (p < 0.001, p < 0.001, and p = 0.002, respectively). In addition, significantly lower MTX dosages, higher blood cell counts, and lower hemoglobin levels were seen in the myelosuppression group (p < 0.001). No patients exhibited leukocytopenia, neutropenia, or thrombocytopenia in routine blood monitoring taken within the past month. One-fourth developed myelosuppression within the first two months (an early-onset period). Myelosuppression was severe in approximately 40% of patients. Hypoalbuminemia and non-use of folic acid supplements were significantly associated with the severity of pancytopenia (p = 0.001 and 0.008, respectively). Besides these two factors, early onset and the use of lower doses of MTX were significantly associated with the severity of neutropenia (p = 0.003, 0.007, 0.003, and 0.002, respectively).
  
  
  
  Myelosuppression can occur abruptly at any time during low-dose MTX therapy, but severe neutropenia is more likely to occur in the early-onset period of this therapy. Contrary to our expectations, disease severity was not dependent on MTX doses. Serum albumin levels and folic acid supplementation are the important factors affecting the severity of MTX-related pancytopenia and neutropenia.
authors.affiliation: Department of Rheumatology, Clinical Research Center for Rheumatic Diseases, NHO Kumamoto Saishunsou National Hospital, Kohshi, Kumamoto 861-1196, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Hematology, NHO National Kumamoto Medical Center, Kumamoto 860-0008, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hidaka
authors.affiliation: Department of Hematology, NHO National Kumamoto Medical Center, Kumamoto 860-0008, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kawakita
authors.affiliation: Institute of Rheumatology, Zenjinkai Shimin-no-Mori Hospital, Miyazaki 880-0122, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hidaka
authors.affiliation: Department of Hematology and Oncology, Kumamoto City Hospital, Kumamoto 862-8505, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuda
authors.affiliation: Yoshitama Clinic for Rheumatic Diseases, Kirishima, Kagoshima 899-5117, Japan.
authors.forename: Tamami
authors.initials: T
authors.lastname: Yoshitama
authors.affiliation: Clinical Research Center, NHO National Nagasaki Medical Center, Omura, Nagasaki 856-8652, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.affiliation: Rheumatic and Collagen Disease Center, Sasebo Chuo Hospital, Sasebo, Nagasaki 857-1195, Japan.
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Ueki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000097:blood / Q000209:etiology*; D006801:Humans; D034141:Hypoalbuminemia / Q000097:blood / Q000150:complications; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood / Q000209:etiology; D010198:Pancytopenia / Q000097:blood / Q000209:etiology; D012189:Retrospective Studies; D012216:Rheumatic Diseases / Q000188:drug therapy*; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D012709:Serum Albumin; D005492:Folic Acid; D008727:Methotrexate