Pure erythroid leukemia evolving from a therapy‐related myelodysplastic syndrome secondary to treatment for chronic lymphocytic leukemia

Abstract

A 75-year-old male carried a diagnosis of chronic lymphocytic leukemia (CLL) for many years for which he received several courses of chemotherapy, in succession cladribine, cyclophosphamide, vincristine, and prednisone, and fludarabine and cyclophosphamide. Approximately 14 years after his CLL diagnosis, he developed progressive and refractory thrombocytopenia which did not respond to anti-CLL therapy. A bone marrow biopsy was performed and was markedly hypercellular and left shifted. There were several lymphoid aggregates consistent with CLL, but comprising only about 20% of the marrow cellularity. The hypercellular areas of hematopoiesis contained increased small, dysplastic megakaryocytes, and increased blasts (Image 1A), confirmed by CD34 immunohistochemistry (Image 1B). Cytogenetics revealed a t(7;14)(p11.2;q32) abnormality in five of 20 metaphases. Overall, these pathologic features were consistent with a therapy-related myelodysplastic syndrome. He was treated with 5-azacitidine, and a repeat bone marrow biopsy after two cycles of therapy revealed a decrease in the number of CD341 blasts, indicating a modest response. Five months after his diagnosis of therapy-related myeloid neoplasm, due to worsening pancytopenia and persistent fevers, he underwent a bone marrow biopsy, which revealed evolution to pure erythroid leukemia (PEL) (Image 1C,D), with primitive, glycophorin positive erythroid blasts present in cohesive sheets (Image 1E) that were CD34-negative and comprised 80% of the cellularity. Also, present were aggregates of persistent PAX5-positive CLL cells

Pure Erythroid Leukemia in a Sickle Cell Patient Treated with Hydroxyurea

“…This is only the third case of PEL reported in the literature associated with the use of hydroxyurea. PEL has also been reported with other therapies [18, 19]. While there is no known clear etiology for the development of this rare and aggressive disease, complex genetic abnormalities seen in these cases may suggest therapy-related cause and the use of hydroxyurea or other anti-metabolites may be responsible for these changes.…”

The Diagnostic Challenge of Therapy-Related Pure Erythroid Leukemia Arising in the Setting of Multiple Myeloma

“…The majority of the reported cases were classified as AML with myelodysplasia-related changes either because they evolved from a previous Myelodysplastic Syndrome (MDS), or because they had cytogenetic abnormalities frequently associated with MDS. It is uncommon for PEL to occur as a therapy-related Myeloid Neoplasm (t-MN); PEL as a t-MN has been described in patients previously treated for precursor B-lymphoblastic leukemia [5], chronic lymphocytic leukemia [6], solid tumors [7], and myeloma [8]. The rarity of PEL coupled with the lack of erythroid-lineage-specific markers, frequent occurrence of early myeloid antigens on erythroid precursors, and an undifferentiated morphology makes distinction from minimally differentiated AML (M0) challenging.…”

Pure erythroid leukemia in advanced breast cancer

“…PEL is defined by the presence of immature erythroblasts, which should comprise at least 80% of the BM cells, with no evidence of a significant myeloblastic component [2, 3, 4]. PEL accounts for about 10-20% of all acute erythroid leukemias (AEL) and less than 1% of all AML cases [2], and it has been very rarely reported as a therapy-related AML [5, 6, 7, 8]. Moreover, its occurrence has never been reported after exposure to chemotherapy and radiation for breast cancer.…”