Therapy related AML in a case of chronic lymphocytic leukemia

Abstract

In comparison to the general population, patients with chronic lymphocytic leukemia (CLL) are at a higher risk of developing secondary malignancies. Several factors may contribute to pathogenesis, including direct effects of chemotherapy and radiation as well as the reduction of immune surveillance. Factors influencing the increased risk include the increasing age of CLL patients, chronic antigenic stimulation, and immune impairment related to CLL or chemotherapy. Compared to patients with acute myeloid leukemia (AML) that developed from de novo, therapy-related AML (t-AML) has had a poorer outcome. The range of cytogenetic abnormalities in therapy-related AML is comparable to that in de novo AML, although these patients have a significantly higher frequency of unfavourable cytogenetics, such as a complex karyotype or a deletion or loss of chromosomes 5 and/or 7. Herein, we describe a case of therapy-related AML with monocytic differentiation and t(8;16) with a residual CLL population. The aim of the present case is to highlight rare occurrence of therapy related AML with t(8;16) in CLL after fluderabine based chemotherapy (FCR: fludarabine, cyclophosphamide, and rituximab). This case also highlights flowcytometric immunophenotyping as an ideal tool to characterize secondary AML along with the identification of minimal residual disease of CLL clone, which could have ignored at t-AML diagnosis. The pathogenesis of myeloid and lymphoid malignancies as well as their co-existence can be studied by focusing on such patients. Factors predisposing to the development of t-AML should be studied further, which would help in monitoring these patients more carefully.

Keywords: CLL; FISH; Therapy-related AML; flow cytometric immunophenotyping; real time PCR; t(8;16).

Figure 1

At initial diagnosis of CLL. A. Peripheral blood smear showing absolute lymphocytosis and presence of smudge cells (Leishman & Giemsa, 400×). B. FCMI showed CD19 positive abnormal lymphoid cells which were positive for CD5, CD23, CD38, kappa and negative for FCM 7 and lambda. C. FISH analysis showed positive for 17p deletion and negative for 6q, 8q, 11q and 13q deletion.

Figure 2

At diagnosis of therapy related AML. A. Peripheral blood smear (Leishman & Giemsa, 1000×). B. Bone marrow aspirate showing blasts and promonocytes (Leishman & Giemsa, 1000×). C. Karyotyping showed 46,XY, t(8;16)(p11.2;p13.3).

Figure 3

At diagnosis of therapy related AML. On FCMI (A), these blasts were positive for CD33, CD64, HLA-DR, CD123, CD4, CD11c (heterogenous), CD117 (dim), CD56 and negative for CD34, CD22, CD41a. (B) There is a residual abnormal lymphoid cell population constituting 1% of all nucleated cells which are CD19+CD5+CD23+ with FMC7 negative, CD22 (dim) and kappa restriction, corresponding to the diagnostic CLL clone.