title: Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model.
abstract: Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Grazziutti
authors.forename: L
authors.initials: L
authors.lastname: Dong
authors.forename: M H
authors.initials: MH
authors.lastname: Miceli
authors.forename: S G
authors.initials: SG
authors.lastname: Krishna
authors.forename: E
authors.initials: E
authors.lastname: Kiwan
authors.forename: N
authors.initials: N
authors.lastname: Syed
authors.forename: A
authors.initials: A
authors.lastname: Fassas
authors.forename: F
authors.initials: F
authors.lastname: van Rhee
authors.forename: H
authors.initials: H
authors.lastname: Klaus
authors.forename: B
authors.initials: B
authors.lastname: Barlogie
authors.forename: E J
authors.initials: EJ
authors.lastname: Anaissie
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005949:Glucose Oxidase / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000150:complications; D007784:Lactoperoxidase / Q000627:therapeutic use; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D008962:Models, Theoretical; D009101:Multiple Myeloma / Q000188:drug therapy*; D009113:Muramidase / Q000627:therapeutic use; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013280:Stomatitis / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014182:Transplantation, Autologous / Q000009:adverse effects
chemical_list: C111669:Biotene; D004338:Drug Combinations; D019653:Myeloablative Agonists; D005949:Glucose Oxidase; D007784:Lactoperoxidase; D009113:Muramidase; D008558:Melphalan