Submitting Author: Sander, Birgitta, MD, PhD
Institution: Karolinska Institutet and Karolinska University Hospital Huddinge
Session: AML secondary to myeloproliferative neoplasms and other types of disease progression in MPN

Male, age 82, with marked leukocytosis, 200 x 10e9/L. Diagnostic bone marrow in July 2007 showed a morphology suggesting CML in accelerated phase with 11% blasts. FISH analysis for BCR-ABL1 was positive in 99% of cells.

leevec treatement was initiated but after 6 weeks the dose was withdrawn for a month due to thrombocytopenia. Thereafter low dose treatment with Glivec was initiated. 5 months after the initial diagnosis increasing leukocytes (78*10(9)/L) and blasts in peripheral blood. A new bone marrow was sampled in early January 2008 and showed CML in accelerated phase with 7% blasts and marked increase in basophils (30%) and eosinophils (21%).

MC1325 is the initial biopsy and clot from July 2007. It is fixed in 4% formalin. The bone marrow shows maximal cellularity due to granulocytic proliferation, increased fibrosis, small megakaryocytes and focal blast aggregates. In smears from bone marrow granulocytopoiesis dominates, blasts are 11%. In blood there is leukoerythroblastosis with marked dominance of the granulocytis series and increased number of blasts.

MC82 (formalin-fixed) is the relapse bone marrow clot from January 2008. The material is rather sparse due to fibrosis, there is maximal cellularity, increase of immature cells. In the bone marrow smears blasts are 7% but importantly there is a marked increase in basophils (30%). There is also blast increase and marked increase of basophils and eosinophils in the blood.

Flow cytometry of the bone marrow was done at diagnosis and relapse. It confirmed increase of precursors positive for CD34 and/or CD117. Basophils (dim positive for CD45, positive for CD117, CD123, CC13, CD33 and negative for HLA-DR) constituted 4,2% of total cells at diagnosis and 31,2% at relapse.

In flow cytometry the patterns of CD45 expression and light scatter properties of basophils and myeloblasts are similar which could lead to false over-estimation of the number of myeloblasts. They may also share immune phenotypic markers such as CD117, CD33 and CD13. However, basophils are characterized by being CD34 negative and often express CD123 bright.

FISH for BCR-ABL1 was positive in 99% of cells at diagnosis.

Increased number of basophil granulocytes at relapse. This was confirmed by flow cytometry. Useful markers for discriminating myeloid blasts and basophils by multiparameter flow cytometry is discussed. Further reading on this issue see for instance:

Han X. et al. Arch Pathol. Lab. Med. Vol. 132 page 813-819

Toba K. et al. Cytometry Vol 35. page 249-259

It could be discussed whether this case represents a basophilic transformation of CML or whether the increased number of basophils should be considered to represent accelerated phase.

Chronic myelogenous leukemia, BCR-ABL1 positive, accelerated phase (marked basophilia)

Case 140