title: Methotrexate-induced pancytopenia: a case series of 46 patients.
abstract: OBJECTIVE
  Methotrexate (MTX) has the potential to cause serious adverse reactions and even mortality. We analyzed the predisposing factors and outcome in patients with MTX-induced pancytopenia admitted into our unit from 1996 to 2015.
  
  
  METHODS
  Patients were identified by departmental database search. Pancytopenia was defined as white blood cell count (WBC) < 3500 cells/mm3, hemoglobin (Hb) < 11 g/dL and platelet count < 150 000 cells/mm3. Severe pancytopenia was defined as WBC < 2000 cells/mm3, Hb < 10 g/dL and platelet count < 50 000 cells/mm3.
  
  
  RESULTS
  Forty-six patients were included in the study (female = 35). Twenty-four had been under the care of either primary care physicians or orthopedic surgeons and presented to us with pancytopenia. Sixteen patients had severe pancytopenia. Disease distribution was as follows: rheumatoid arthritis 33, psoriasis eight, systemic sclerosis two and others three. The median dose of MTX was 10 mg/week and median duration of treatment was 11 months. The median cumulative dose was 750 mg. Symptoms at presentation included: oral mucositis (n = 37); fever (n = 24); diarrhea (n = 12), bleeding gums (n = 5) and purpura (n = 3). The potential risk factors were: hypoalbuminemia (n = 23), renal insufficiency (n = 14), dosing errors (n = 13) and non-supplementation of folates (n = 7). Thirteen patients died. WBC at admission was found to determine survival (P < 0.05).
  
  
  CONCLUSIONS
  In patients on MTX, oral mucositis and fever can herald pancytopenia. MTX-induced pancytopenia is associated with high mortality. WBC at admission is the most important prognostic factor. There is need for increased awareness among physicians to minimize prescribing errors. A national guideline on monitoring of patients on MTX is desirable.
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Sajal
authors.initials: S
authors.lastname: Ajmani
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Preet Singh
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Shiva
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Abhra
authors.initials: A
authors.lastname: Chowdhury
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Amita
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Able
authors.initials: A
authors.lastname: Lawrence
authors.affiliation: Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Ramnath
authors.initials: R
authors.lastname: Misra
authors.affiliation: Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Mishra
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Agarwal
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D016208:Databases, Factual; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D010198:Pancytopenia / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality; D010976:Platelet Count; D011565:Psoriasis / Q000175:diagnosis / Q000188:drug therapy*; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D006454:Hemoglobins; D008727:Methotrexate
keywords: drug induced pancytopenia; methotrexate; methotrexate toxicity