[1563] Treatment-Related Myeloid Neoplasms Secondary to Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): A Clinicopathologic Study of 8 Cases

Maggie M Stoecker, Qin Huang, Elizabeth L Boswell, Endi Wang. Duke University Medical Center, Durham, NC; City of Hope Medical Center, Duarte, CA

Background: Therapy-related acute myeloid leukemia (t-AML) and myelodysplastic syndrome (t-MDS) following fludaribine-based therapies for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have been reported over the past decade. We describe our experience with t-AML and t-MDS in patients treated for CLL/SLL with a variety of therapeutic agents in 8 cases.
Design: Cases of t-AML and t-MDS in patients treated for CLL/SLL were identified in our diagnostic services. Clinical information and pathologic findings were retrospectively analyzed.
Results: 8 cases (age 34-80 years, median 58 years), including 5 t-MDS and 3 t-AML, were identified. Treatments included a combination of alkylating, antimetabolite, immunomodulatory, monoclonal antibody, tyrosine kinase inhibitor, and anti-inflammatory agents. Rituximab and fludarabine were used in 8/8 (100%) and 7/8 (88%) cases, respectively. In 1 case, only prednisone and rituximab were used. All cases had hypercellular marrows, and 7/8 (88%) had erythroid dysplasia. The median time to develop t-MDS/AML was 34 months (range 21-99).

Age/Sex CLL Therapy Type of Myeloid Neoplasm Latency (Months) Dysplasia CLL Persistence Cytogenetics Follow-up, Survival (Months)
34/MF,C,R,O,Cyt-MDS22EY (<1%)Normal14+
50/FF,C,Rt-MDS21EN46, X, inv(X)SCT, 26+
80/MF,C,Rt-AML39E, MyN45, XY, -715
64/MCh, F, C, Pe, R, A, L, Bt-AML99EY (<1%)Complex2
57/FCh, F, C, Rt-MDS29EY (45%)NDRichter transformation, 47
58/FF,C,R,Bt-MDS96MYNDTransformed to AML
58/MF,R,Dt-AML84E, M, MyY (5-10%)ComplexU
76/FR, Pt-MDS24E, MY (50%)ComplexU
F, fludarabine; C, cyclophosphamide; R, rituximab; B, bendamustine; D, dexamethasone; P, prednisone; Cy, cytarabine; O, oxaliplatin; Ch, chlorambucil; Pe, perifosine; A, alemtuzumab; L, lenalidomide; M, megakaryocyte; E, erythroid; My, myeloid; U, unknown; ND, not done; SCT, stem cell transplant

Conclusions: The majority of our patients exposed to multiple drugs including mutagenic agents. Longer latencies in AML implied a delayed identification of preceding MDS. Erythroid dysplasia was the most common morphologic deviation in our series, highlighting the importance of careful morphologic evaluation in cases of MDS without cytogenetic abnormality. Complex cytogenetic abnormalities in 50% of our cases, while consistent with therapy-related changes, may predict a poor prognosis in this population.
Category: Hematopathology

Wednesday, March 21, 2012 9:30 AM

Poster Session V # 228, Wednesday Morning


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