Background Previous studies have suggested an increased risk of hematological malignancies in patients with granulomatous polyangiitis (GPA) (Wegener). In a Swedish study of GPA the risk for leukemia was 6-fold increased compared to the general population (1). In a Danish study the risk for acute myeloid leukemia (AML) was increased 19-fold in GPA patients who had received cyclophosphamide (2). Other information about leukemia in GPA is scarce.
Objectives To assess clinical characteristics of patients with GPA complicated by leukemia, including the distribution of different leukemia types.
Methods Patients with a listing of GPA and a hematological malignancy, respectively, were identified using the national Swedish Patient Register (hospitalization and non-primary care outpatient visits)1964-2007 for GPA followed by linkage with the Cancer Register 1990-2007 (n=81). Survey of the medical records verified the GPA diagnosis (EMEA consensus algorithm for classification of vasculitis) in 31 of the patients. Of these, the registered malignancy was leukemia in 18 and lymphoma in 13 of the patients. Clinical data was abstracted from the medical records for the 18 leukemia patients from onset of GPA until death or January 15th, 2012.
Results Thirteen (72%) patients were male. The median age at diagnosis of GPA was 59 years (25-69) and the median duration from GPA diagnosis to first hematological malignancy was 7 years (3-15).
All patients had been treated with alkylating agents for GPA. 17 of the 18 patients had received cyclophosphamide, two of them had also been treated with chlorambucil. One had been treated with chlorambucil only.
The median duration of cyclophosphamide (intravenous and/or oral) was 58 months (range 6-104) and the median cumulative dose was 111 grams (range 20-233).
The malignancies were all myeloid and consisted of myelodysplastic syndrome (MDS) (n=9), AML (n=5), chronic myelocytic leukemia (n=2), myelofibrosis (n=1), and chronic myelomonocytic leukemia (n=1). AML developed in 8 of the patients with MDS and in the patient with myelofibrosis.
MDS was typically diagnosed after a period of cytopenia suspected to be associated with GPA treatment. The median time between diagnosis of MDS and AML was in general short (months).
Overall survival after diagnosis of hematological malignancy was 7 months (0-58).
Conclusions All hematological malignancies in GPA were myeloid, 14 of the 18 patients were diagnosed with AML as first or secondary malignancy. Other inflammatory disorders, e.g. rheumatoid arthritis, have typically been associated with lymphoproliferative malignancies. All patients had been exposed to exceedingly high doses of alkylating agents, mainly cyclophosphamide, known to be carcinogenic, and an association with treatment and development of hematological malignancy in these patients seems plausible. These findings emphasize the need for long-term follow-up and awareness of signs of haematological malignancy in cyclophosphamide-treated GPA patients as well as the need for development of alternative treatments for GPA.
Knight A, et al. Int J Cancer 2002.
Faurschou M, et al. J Rheumatol 2008.
Disclosure of Interest None Declared
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