Contributions
Abstract: PB1946
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm which commonly manifests with neutrophilic leukocytosis in a chronic phase of the disease. We have experienced two young female CML with more than 3,000 x 109/L platelet count without significant leukocytosis. Although their clinical features suggested essential thrombocythemia (ET), they were diagnosed as CML due to the presence of Philadelphia (Ph) chromosome. Our cases together with other cases in the literature indicated that CML with remarkable thrombocytosis without significant leukocytosis (CML-IT) may have some common clinical characteristics.
Aims
We attempted to define common clinical characteristics in CML-IT, comparing with typical CML and ET.
Methods
We reviewed the literature to compile and summarize reported cases of CML-IT. We defined marked thrombocytosis as a platelet count more than 1,000 x 109/L, and normal or slightly elevated white blood cell (WBC) count as a WBC count less than 12.0 x 109/L. Clinical data of ET patients with remarkable thrombocytosis without significant leukocytosis in our hospital was also collected and compared with those of CML-IT.
Results
Our CML-IT cases were both in their mid-thirties at diagnosis. Basophils were increased, but immature myeloid cells were not detected in PB. Their von Willebrand factor ristocetin cofactors were below 30%. JAK2 V617F, CALR exon 9, and MPL exon 10 mutation analyses were performed and confirmed to be unmutated. Their bone marrow histology exhibited marked megakaryocytic hyperplasia, and most of megakaryocytes were small and hypolobulated or unilobulated. These features were dissimilar to bone marrow histopathological findings in ET. Although Sokal score was high in both of them, deep molecular response was obtained within 2 years with tyrosine kinase inhibitor (TKI) treatment. We found 26 cases of CML-IT in the literatures and analyzed total 28 cases of CML-IT including our two cases. Most of them were female (3 males and 25 females), and the median age was 43 years old. Neutrophil alkaline phosphatase (NAP) score was decreased in chronic phase CML in general, but it was normal or increased in all 12 CML-IT. Immature myeloid cells were not detected in peripheral blood (PB) in 18 out of 20 CML-IT as opposed to those in typical CML. G-banding karyotype of bone marrow cells showed that Ph clone was below 19/20 in 10 cases out of 12 CML-IT. 8 cases were treated with TKI, and 7 out of 8 cases obtained complete cytogenetic response at 3 months. 25 cases of ET with the similar laboratory data with CML-IT cohort were found in our hospital. This ET cohort included 11 males and 14 females. Mutational analyses revealed 16 cases with CALR mutation, 4 cases with JAK2 V617F mutation, and 1 case with MPL S505N mutation. As was the case with CML-IT, severe splenomegaly and immature myeloid cells in PB were not seen in this ET cohort. However, basophilia beyond the upper limits of normal range was not detected in ET cohort. NAP score was low in all of tested cases. These two clinical findings were different from clinical characters observed in patients with CML-IT.
Conclusion
Our cases together with other cases in the literature suggest that there is a subgroup of CML which exhibits hematologic findings similar to those in ET. Although they might be misdiagnosed as ET, laboratory findings with normal or high NAP score and basophilia may be useful to differentiate between CML-IT and ET. Further studies are warranted to better understand the clinical characteristics and molecular mechanism of CML-IT.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Essential Thrombocytemia, Thrombocytosis
Abstract: PB1946
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm which commonly manifests with neutrophilic leukocytosis in a chronic phase of the disease. We have experienced two young female CML with more than 3,000 x 109/L platelet count without significant leukocytosis. Although their clinical features suggested essential thrombocythemia (ET), they were diagnosed as CML due to the presence of Philadelphia (Ph) chromosome. Our cases together with other cases in the literature indicated that CML with remarkable thrombocytosis without significant leukocytosis (CML-IT) may have some common clinical characteristics.
Aims
We attempted to define common clinical characteristics in CML-IT, comparing with typical CML and ET.
Methods
We reviewed the literature to compile and summarize reported cases of CML-IT. We defined marked thrombocytosis as a platelet count more than 1,000 x 109/L, and normal or slightly elevated white blood cell (WBC) count as a WBC count less than 12.0 x 109/L. Clinical data of ET patients with remarkable thrombocytosis without significant leukocytosis in our hospital was also collected and compared with those of CML-IT.
Results
Our CML-IT cases were both in their mid-thirties at diagnosis. Basophils were increased, but immature myeloid cells were not detected in PB. Their von Willebrand factor ristocetin cofactors were below 30%. JAK2 V617F, CALR exon 9, and MPL exon 10 mutation analyses were performed and confirmed to be unmutated. Their bone marrow histology exhibited marked megakaryocytic hyperplasia, and most of megakaryocytes were small and hypolobulated or unilobulated. These features were dissimilar to bone marrow histopathological findings in ET. Although Sokal score was high in both of them, deep molecular response was obtained within 2 years with tyrosine kinase inhibitor (TKI) treatment. We found 26 cases of CML-IT in the literatures and analyzed total 28 cases of CML-IT including our two cases. Most of them were female (3 males and 25 females), and the median age was 43 years old. Neutrophil alkaline phosphatase (NAP) score was decreased in chronic phase CML in general, but it was normal or increased in all 12 CML-IT. Immature myeloid cells were not detected in peripheral blood (PB) in 18 out of 20 CML-IT as opposed to those in typical CML. G-banding karyotype of bone marrow cells showed that Ph clone was below 19/20 in 10 cases out of 12 CML-IT. 8 cases were treated with TKI, and 7 out of 8 cases obtained complete cytogenetic response at 3 months. 25 cases of ET with the similar laboratory data with CML-IT cohort were found in our hospital. This ET cohort included 11 males and 14 females. Mutational analyses revealed 16 cases with CALR mutation, 4 cases with JAK2 V617F mutation, and 1 case with MPL S505N mutation. As was the case with CML-IT, severe splenomegaly and immature myeloid cells in PB were not seen in this ET cohort. However, basophilia beyond the upper limits of normal range was not detected in ET cohort. NAP score was low in all of tested cases. These two clinical findings were different from clinical characters observed in patients with CML-IT.
Conclusion
Our cases together with other cases in the literature suggest that there is a subgroup of CML which exhibits hematologic findings similar to those in ET. Although they might be misdiagnosed as ET, laboratory findings with normal or high NAP score and basophilia may be useful to differentiate between CML-IT and ET. Further studies are warranted to better understand the clinical characteristics and molecular mechanism of CML-IT.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Essential Thrombocytemia, Thrombocytosis