title: Leukemia and myelodysplastic syndrome in granulomatosis with polyangiitis: subtypes, clinical characteristics, and outcome.
abstract: OBJECTIVE
  Previous studies have shown that patients with granulomatosis with polyangiitis (GPA) have an increased risk of hematological malignancies, especially leukemia. Our aim was to assess clinical characteristics and treatment of patients with GPA complicated by hematological malignancies with focus on leukemia and to describe these malignancies in more detail.
  
  
  METHODS
  From the Swedish population-based patient register, all individuals with a diagnosis of GPA from 1964-2012 were identified (n = 3224). Through linkage with the Swedish Cancer Register, we searched for all cases of leukemia [International Classification of Diseases (ICD) 7: 204-207 and corresponding codes ICD 8-10] registered after the first discharge listing GPA. The GPA diagnosis was evaluated using the European Medical Association classification algorithm. To confirm the hematological malignancy, all diagnostic bone marrow samples were reclassified. Clinical data of both the GPA and hematological malignancy were collected from medical files.
  
  
  RESULTS
  Twenty-one cases were identified, all of myeloid origin, including 9 with myelodysplastic syndrome developing to acute myeloid leukemia (MDS-AML), 7 AML, 3 MDS, and 2 chronic myeloid leukemia. The median time from GPA diagnosis to hematological malignancy was 8 years (range 5-21). All patients had severe generalized GPA and had received high doses of cyclophosphamide (CYC; median cumulative dose 96.5 g). Cytopenia occurred in 76% of the patients prior to the hematological malignancy.
  
  
  CONCLUSIONS
  The findings emphasize the longterm risk of leukemia and MDS in CYC-treated, severely ill patients with GPA. Cytopenia during the course of GPA may be a warning sign and warrants a liberal attitude toward bone marrow examination.
authors: From the Department of Medical Sciences, Section of Rheumatology, and Department of Medical Sciences, Section of Hematology, and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Clinical Epidemiology Unit, and Rheumatology Unit, Department of Medicine, Solna; Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.A. Knight, MD, PhD; K. Hjorton, MD; E. Baecklund, Assistant Professor; C. Backlin, PhD, Department of Medical Sciences, Section of Rheumatology; C. Sundström, Professor, Department of Immunology, Genetics and Pathology; M. Höglund, Assistant Professor, Department of Medical Sciences, Section of Hematology, Uppsala University; K.E. Smedby, MD, PhD, Clinical Epidemiology Unit, Department of Medicine, and Karolinska Institutet, Karolinska University Hospital; J. Askling, Professor, Clinical Epidemiology Unit, Rheumatology Unit, Department of Medicine, and Karolinska Institutet at Karolinska University Hospital. ann.knight@akademiska.se.
authors: Ann
authors: A
authors: Knight
authors: From the Department of Medical Sciences, Section of Rheumatology, and Department of Medical Sciences, Section of Hematology, and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Clinical Epidemiology Unit, and Rheumatology Unit, Department of Medicine, Solna; Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.A. Knight, MD, PhD; K. Hjorton, MD; E. Baecklund, Assistant Professor; C. Backlin, PhD, Department of Medical Sciences, Section of Rheumatology; C. Sundström, Professor, Department of Immunology, Genetics and Pathology; M. Höglund, Assistant Professor, Department of Medical Sciences, Section of Hematology, Uppsala University; K.E. Smedby, MD, PhD, Clinical Epidemiology Unit, Department of Medicine, and Karolinska Institutet, Karolinska University Hospital; J. Askling, Professor, Clinical Epidemiology Unit, Rheumatology Unit, Department of Medicine, and Karolinska Institutet at Karolinska University Hospital.
authors: Karin
authors: K
authors: Hjorton
authors: From the Department of Medical Sciences, Section of Rheumatology, and Department of Medical Sciences, Section of Hematology, and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Clinical Epidemiology Unit, and Rheumatology Unit, Department of Medicine, Solna; Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.A. Knight, MD, PhD; K. Hjorton, MD; E. Baecklund, Assistant Professor; C. Backlin, PhD, Department of Medical Sciences, Section of Rheumatology; C. Sundström, Professor, Department of Immunology, Genetics and Pathology; M. Höglund, Assistant Professor, Department of Medical Sciences, Section of Hematology, Uppsala University; K.E. Smedby, MD, PhD, Clinical Epidemiology Unit, Department of Medicine, and Karolinska Institutet, Karolinska University Hospital; J. Askling, Professor, Clinical Epidemiology Unit, Rheumatology Unit, Department of Medicine, and Karolinska Institutet at Karolinska University Hospital.
authors: Christer
authors: C
authors: Sundström
authors: From the Department of Medical Sciences, Section of Rheumatology, and Department of Medical Sciences, Section of Hematology, and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Clinical Epidemiology Unit, and Rheumatology Unit, Department of Medicine, Solna; Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.A. Knight, MD, PhD; K. Hjorton, MD; E. Baecklund, Assistant Professor; C. Backlin, PhD, Department of Medical Sciences, Section of Rheumatology; C. Sundström, Professor, Department of Immunology, Genetics and Pathology; M. Höglund, Assistant Professor, Department of Medical Sciences, Section of Hematology, Uppsala University; K.E. Smedby, MD, PhD, Clinical Epidemiology Unit, Department of Medicine, and Karolinska Institutet, Karolinska University Hospital; J. Askling, Professor, Clinical Epidemiology Unit, Rheumatology Unit, Department of Medicine, and Karolinska Institutet at Karolinska University Hospital.
authors: Martin
authors: M
authors: Höglund
authors: From the Department of Medical Sciences, Section of Rheumatology, and Department of Medical Sciences, Section of Hematology, and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Clinical Epidemiology Unit, and Rheumatology Unit, Department of Medicine, Solna; Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.A. Knight, MD, PhD; K. Hjorton, MD; E. Baecklund, Assistant Professor; C. Backlin, PhD, Department of Medical Sciences, Section of Rheumatology; C. Sundström, Professor, Department of Immunology, Genetics and Pathology; M. Höglund, Assistant Professor, Department of Medical Sciences, Section of Hematology, Uppsala University; K.E. Smedby, MD, PhD, Clinical Epidemiology Unit, Department of Medicine, and Karolinska Institutet, Karolinska University Hospital; J. Askling, Professor, Clinical Epidemiology Unit, Rheumatology Unit, Department of Medicine, and Karolinska Institutet at Karolinska University Hospital.
authors: Carin
authors: C
authors: Backlin
authors: From the Department of Medical Sciences, Section of Rheumatology, and Department of Medical Sciences, Section of Hematology, and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Clinical Epidemiology Unit, and Rheumatology Unit, Department of Medicine, Solna; Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.A. Knight, MD, PhD; K. Hjorton, MD; E. Baecklund, Assistant Professor; C. Backlin, PhD, Department of Medical Sciences, Section of Rheumatology; C. Sundström, Professor, Department of Immunology, Genetics and Pathology; M. Höglund, Assistant Professor, Department of Medical Sciences, Section of Hematology, Uppsala University; K.E. Smedby, MD, PhD, Clinical Epidemiology Unit, Department of Medicine, and Karolinska Institutet, Karolinska University Hospital; J. Askling, Professor, Clinical Epidemiology Unit, Rheumatology Unit, Department of Medicine, and Karolinska Institutet at Karolinska University Hospital.
authors: Karin E
authors: KE
authors: Smedby
authors: From the Department of Medical Sciences, Section of Rheumatology, and Department of Medical Sciences, Section of Hematology, and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Clinical Epidemiology Unit, and Rheumatology Unit, Department of Medicine, Solna; Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.A. Knight, MD, PhD; K. Hjorton, MD; E. Baecklund, Assistant Professor; C. Backlin, PhD, Department of Medical Sciences, Section of Rheumatology; C. Sundström, Professor, Department of Immunology, Genetics and Pathology; M. Höglund, Assistant Professor, Department of Medical Sciences, Section of Hematology, Uppsala University; K.E. Smedby, MD, PhD, Clinical Epidemiology Unit, Department of Medicine, and Karolinska Institutet, Karolinska University Hospital; J. Askling, Professor, Clinical Epidemiology Unit, Rheumatology Unit, Department of Medicine, and Karolinska Institutet at Karolinska University Hospital.
authors: Johan
authors: J
authors: Askling
authors: From the Department of Medical Sciences, Section of Rheumatology, and Department of Medical Sciences, Section of Hematology, and Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala; Clinical Epidemiology Unit, and Rheumatology Unit, Department of Medicine, Solna; Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.A. Knight, MD, PhD; K. Hjorton, MD; E. Baecklund, Assistant Professor; C. Backlin, PhD, Department of Medical Sciences, Section of Rheumatology; C. Sundström, Professor, Department of Immunology, Genetics and Pathology; M. Höglund, Assistant Professor, Department of Medical Sciences, Section of Hematology, Uppsala University; K.E. Smedby, MD, PhD, Clinical Epidemiology Unit, Department of Medicine, and Karolinska Institutet, Karolinska University Hospital; J. Askling, Professor, Clinical Epidemiology Unit, Rheumatology Unit, Department of Medicine, and Karolinska Institutet at Karolinska University Hospital.
authors: Eva
authors: E
authors: Baecklund
mesh_terms: D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007938:Leukemia / Q000150:complications / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000175:diagnosis*; D012042:Registries; D013548:Sweden
chemical_list: D003520:Cyclophosphamide
keywords: CYCLOPHOSPHAMIDE; GRANULOMATOSIS WITH POLYANGIITIS; HEMATOLOGICAL MALIGNANCY; LEUKEMIA; MYELODYSPLASTIC SYNDROME