Submitting Author: Reichard, Kaaren Kemp, MD
Institution: Mayo Clinic Rochester
Additional authors:Drs. Rebecca McClure and Paul Kurtin, Mayo Clinic Rochester
Session: Therapy-related myeloid neoplasms

The patient is a 53 year-old male who presented seven years previously with acute promyelocytic leukemia. The patient is a 53 year-old male who presented with acute promyelocytic leukemia. PML-RARA was confirmed by both conventional cytogenetics and FISH. Cytogenetics revealed an isolated t(15;17)(q24;q21) without additional chromosomal abnormalities. He was treated with standard induction chemotherapy and ATRA, two cycles of consolidation and two years of routine maintenance chemotherapy. His cytogenetic and molecular studies revealed molecular remission.

Four years later, the patient presented for his routine follow-up and was found to have pancytopenia.

A bone marrow biopsy was performed.

Peripheral blood:

CBC: Hgb 8,7 g/dl, WBC 2.3 x 10^9 /L, Plt 61 x 10^9 /L

Differential count: neutrophils 30%, lymphocytes 57%, monocyte 7%, blasts 6%

Morphology: The red blood cells are moderately decreased in number with unremarkable cytology. The white blood cells are mildly decreased in number with a subset of neutrophils showing dysplastic changes (hypogranularity, hyposegmentation). Some monocytes show atypical chromatin but lack clear-cut features of promonocytes. Circulating blasts are present and are characterize by intermediate to large size, round nuclear contours, occasional nucleoli and a moderate amount of lightly basophilic cytoplasmi containing minimal granules. Features typical of acute promyelocytic leukemia are absent.

Bone marrow aspirate:

Differential count: neutrophils and bands 4%, metamyelocytes 1%, eosinophils and precursors 9%, blasts 57%, normoblasts 18%, lymphocytes 9%, plasma cells 2%.

Morphology: The predominant cell population is composed of blasts with cytologic features similar to that described for the peripheral blood smear. Granulocytic maturation is progressive but dysplastic. There is atypical eosinophil granulation. The erythroid series shows progressive maturation witha subset demonstrating dysplastic features. Megakaryocytes are increased and dysplastic showing a wide range of appearances including small, monolobated forms, occasional large hyperlobulated forms, abnormal chromatin condensation and forms with separate nuclear lobes.

Bone marrow biopsy: The bone marrow is mildly hypercellular (60%). The majority of cells, particularly evident within the interstitium and forming occasional small clusters, are consistent with blasts. Megakaryocytes are increased and distinctly abnormal. Erythroid precursors are present and show foci of pronormoblasts.

Flow cytometric analysis was performed on a portion of the bone marrow aspirate. An increased population of blasts (33%) was identified with the following immunophenotypic characteristics: CD13, CD33 (dim), CD15 (partial), CD117 (partial), CD34 (partial), HLA-DR, CD7 (dim).

Immunohistochemistry was not done.

43-45,XY,-3,del(5)(q31q35),-6,-7,-9, der(12)t(9;12)(q21.2;p13),+2-3r[17]/46,XY[3]

Molecular studies for PML/RARA mRNA analysis on the most recent bone marrow: Negative. No PML/RARA mRNA transcripts detected.

1) Therapy-related myeloid neoplasm arising after treatment for acute myeloid leukemia. We most often think of therapy-related myeloid neoplasms from the perspective of arising after treatment for a solid tumor, lymphoma and myeloma, not AML (even though we know that it occurs).

2) The treatment of acute myeloid leukemias, particularly those occuring in younger individuals and/or in the favorable prognostic groups, should be an ongoing area of investigation with the objective being to identify individuals/tumor types wherein the amount of cytotoxic chemotherapy needed to achieve a cure can be reduced. We know from studies in pediatric B-lymphoblastic leukemia/lymphoma therapy that less intensive therapeutic regimens retain a similar favorable outcome in patients with a certain profile and potentially avoid the downstream development of a therapy-related myeloid neoplasm.

Therapy-related acute myeloid leukemia

Therapy-related myeloid neoplasm, acute myeloid leukemia

Case 60