Myelodysplastic Syndromes Following Therapy with Purine Analogues Therapy Related Myeloid Neoplasms?
M Kluk, C Toomey, E Hochberg, R Hasserjian. Massachusetts General Hospital, Boston, MA
Background: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) may occur as complications of chemotherapy and/or radiation therapy (XRT) and are classified as therapy-related AML or MDS (t-AML/MDS). These neoplasms typically follow alkylating agent or topoisomerase II inhibitor therapy, exhibit characteristic cytogenetic findings, and have a very poor prognosis. It is unclear if purine analogues (fludarabine, cladrabine, and pentostatin) also can cause AML or MDS, as the features of myeloid neoplasms occurring after such therapies have not been well-characterized.
Design: We searched the pathology files from one institution over a four-year period (2004-2008) for bone marrow samples taken from patients who had been treated with purine analogues and that were diagnostic of AML or MDS (PA-AML/MDS); cases treated with any additional chemotherapeutic agents or XRT were excluded. These cases were compared to a control group of 16 cases of AML or MDS arising in patients who had been treated with alkylating agents (ALK-AML/MDS).
Results: We identified 5 cases of PA-AML/MDS that occurred in two men and three women with a median age of 74; over the same time period, 54 cases of t-AML/MDS were diagnosed. All patients had been treated with fludarabine (3 patients) or fludarabine and rituximab (2 patients) for chronic lymphocytic leukemia (4 patients) or marginal zone lymphoma (1 patient). Compared to the control group of ALK-AML/MDS cases, the PA-AML/MDS cases occurred with a shorter latency, were less likely to show complex karyotypes, and had a longer median survival (although the latter finding did not reach statistical significance). These data are shown in Table 1.
Comparison of AML/MDS cases occurring after purine analogue therapy (PA-AML/MDS) or alkylating agent therapy (ALK-AML/MDS)
|PA-AML/MDS (n=5)||ALK-AML/MDS (n=16)||P|
|Presented as AML||0/5||6/16||NS|
|Latency in years, median (range)||1 (0.5-3)||3 (0.5-20)||0.015|
|Survival in months, median||16||4||0.13|
Conclusions: AML or MDS occurring after purine analogue therapy is rare, comprising <10% of all t-AML/MDS cases diagnosed during the same time period. Although purine analogues are included among agents that can cause t-AML/MDS in the 2008 WHO Classification of Myeloid Neoplasms, the cytogenetics and short latency of these cases suggest a pathogenesis distinct from t-AML/MDS caused by alkylating agents. PA-AML/MDS patients also appear to have superior survival to typical t-AML/MDS.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 189, Wednesday Afternoon