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A case of chronic neutrophilic leukemia successfully treated with pegylated interferon alpha-2a.

Yassin MA, Kohla S, Al-Sabbagh A, Soliman AT, Yousif A, Moustafa A, Battah AA, Nashwan A, Al-Dewik N - Clin Med Insights Case Rep (2015)

Bottom Line: A woman in her 40s who was incidentally found to have leukocytosis was referred to the hematology service at the National Center for Cancer Care and Research for evaluation.Peripheral blood and flow cytometry did not show any evidence of lymphoproliferative disorder or myeloblasts.To the best of our knowledge, this is the first case of CNL reported among the Arab population.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Bone Marrow Transplant, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar.

ABSTRACT
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) that represents a diagnostic dilemma for both clinicians and pathologists. Because this disease entity is very rare, and because its diagnosis is by exclusion, it is important for clinical hematologists and hematopathologists to be familiar with CNL when approaching patients with MPNs and persistent neutrophilia. A woman in her 40s who was incidentally found to have leukocytosis was referred to the hematology service at the National Center for Cancer Care and Research for evaluation. Complete blood count revealed hyperleukocytosis with predominant neutrophilia. Peripheral blood and flow cytometry did not show any evidence of lymphoproliferative disorder or myeloblasts. Bone marrow aspirate and biopsy revealed a hypercellular marrow with myeloid hyperplasia. Cytogenetics revealed normal karyotype. Tests for both Janus kinase mutation JAK2 V617F and rearrangement of the genes BCR-ABL1, platelet-derived growth factor receptor-α (PDGFRα), PDGFRβ, and fibroblast growth factor receptor-1 (FGFR1) were negative. Thereafter, the diagnosis of CNL was reached. She was treated with pegylated interferon alpha-2a, with very good hematological response. To the best of our knowledge, this is the first case of CNL reported among the Arab population.

No MeSH data available.


Related in: MedlinePlus

(A) Bone marrow aspirate smear demonstrates myeloid hyperplasia (elevated myeloid: erythroid ratio = 7.5: 1) (40×, Wright-Giemsa). (B) Neutrophil proliferation from myelocyte to segmented forms without dysplasia (50×, Wright-Giemsa).
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f1-ccrep-8-2015-033: (A) Bone marrow aspirate smear demonstrates myeloid hyperplasia (elevated myeloid: erythroid ratio = 7.5: 1) (40×, Wright-Giemsa). (B) Neutrophil proliferation from myelocyte to segmented forms without dysplasia (50×, Wright-Giemsa).

Mentions: A woman in her 40s was incidentally found to have leuko-cytosis. She was referred to the Hematology service at the National Center for Cancer Care and Research for evaluation. Her clinical examination was unremarkable and there was no hepatosplenomegaly. Most notable among the first set of studies was an abnormal white blood cell (WBC) count of 40.9 × 103/μL (reference range: 4.0- to 11.0 × 103/μL). The differential count revealed 95% bands/segmented neutrophils, 4% lymphocytes, and 1% monocytes, eosinophils, and baso-phils. Hemoglobin (Hb) level was 10.1 g/dL and platelet count was normal. Her peripheral blood smear revealed neutrophilic leukocytosis with increased toxic granulation. Neutrophil precursors were <1%, with occasional myelocytes noted on scanning. No circulating myeloblasts or neutrophil dysplasia was noted. The bone marrow aspirate was hypercellular with myeloid hyperplasia, with a predominance of mature neutrophils and no relative increase in blast count (blasts = 1%). Toxic granulations were seen in neutrophils (Fig. 1A and B). The myeloid: erythroid ratio was 7.5: 1. The erythroid series was sparsely represented but did not show any morphologic abnormalities. The majority of megakaryocytes were normal in size and morphology, with only minor hypolobulation on a subset of cells (Fig. 2A and B). No increase in eosinophils, basophils, plasma cells, or mast cells was observed. Sea blue histiocytes were not seen. Stainable iron was markedly reduced without any ringed sideroblasts. Significant dysplasia was not present in any of the cell lineages. The bone marrow core biopsy was hypercellular for age, with a cellularity estimated at 75%–85% with neutrophilic proliferation and adequate megakaryocytes (Fig. 3A). There was no increase in myeloblasts, eosinophils, basophils, or mast cells. Only minimal focal reticulin fibrosis was noted in some regions. Immunohistochemical staining performed on the core biopsy showed predominance of myeloperoxidase-positive myeloid cells, without any increase in cluster of differentiation-34 (CD34)-positive cells (Fig. 3B). The conventional marrow karyotype was 46, XX, with no abnormalities noted. A t(9;22) translocation was not identified by either polymerase chain reaction or fluorescence in-situ hybridization methods. Mutation analyses for Janus kinase-2 (JAK2) and PDGFRα/PDGFRβ were similarly negative. The mutation analysis for the colony-stimulating factor-3 receptor gene (CSF3R) was performed by bidirectional sequencing method. The mutation hot spots exon 14 and exon 17 of this gene were analyzed. This assay has a typical sensitivity of 10%–15% for detecting mutated CSF3R DNA. CSF3R was studied and the result was negative; similarly, FGFR1 was investigated and the result was negative. Computerized scans of the chest, abdomen, and pelvis were negative for lymphadenopathy or hepatosplenomegaly. Positron emission tomography–computed tomography (PET/CT) scans were negative. Blood, urine, stool, and sputum cultures were done repeatedly, as well as sputum cultures for acid-fast bacilli, Mycobacterium tuberculosis, and Brucella, with sustained negative results. The diagnosis of CNL was thereafter reached. The patient was treated with pegylated interferon alpha-2a (Pegasys®), as per Yassin et al.2 This therapy comprised the following protocol2: 50 μg once weekly for 2 weeks, then 135 μg once weekly for 6 weeks, and finally 135 μg every 2 weeks.


A case of chronic neutrophilic leukemia successfully treated with pegylated interferon alpha-2a.

Yassin MA, Kohla S, Al-Sabbagh A, Soliman AT, Yousif A, Moustafa A, Battah AA, Nashwan A, Al-Dewik N - Clin Med Insights Case Rep (2015)

(A) Bone marrow aspirate smear demonstrates myeloid hyperplasia (elevated myeloid: erythroid ratio = 7.5: 1) (40×, Wright-Giemsa). (B) Neutrophil proliferation from myelocyte to segmented forms without dysplasia (50×, Wright-Giemsa).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4403902&req=5

f1-ccrep-8-2015-033: (A) Bone marrow aspirate smear demonstrates myeloid hyperplasia (elevated myeloid: erythroid ratio = 7.5: 1) (40×, Wright-Giemsa). (B) Neutrophil proliferation from myelocyte to segmented forms without dysplasia (50×, Wright-Giemsa).
Mentions: A woman in her 40s was incidentally found to have leuko-cytosis. She was referred to the Hematology service at the National Center for Cancer Care and Research for evaluation. Her clinical examination was unremarkable and there was no hepatosplenomegaly. Most notable among the first set of studies was an abnormal white blood cell (WBC) count of 40.9 × 103/μL (reference range: 4.0- to 11.0 × 103/μL). The differential count revealed 95% bands/segmented neutrophils, 4% lymphocytes, and 1% monocytes, eosinophils, and baso-phils. Hemoglobin (Hb) level was 10.1 g/dL and platelet count was normal. Her peripheral blood smear revealed neutrophilic leukocytosis with increased toxic granulation. Neutrophil precursors were <1%, with occasional myelocytes noted on scanning. No circulating myeloblasts or neutrophil dysplasia was noted. The bone marrow aspirate was hypercellular with myeloid hyperplasia, with a predominance of mature neutrophils and no relative increase in blast count (blasts = 1%). Toxic granulations were seen in neutrophils (Fig. 1A and B). The myeloid: erythroid ratio was 7.5: 1. The erythroid series was sparsely represented but did not show any morphologic abnormalities. The majority of megakaryocytes were normal in size and morphology, with only minor hypolobulation on a subset of cells (Fig. 2A and B). No increase in eosinophils, basophils, plasma cells, or mast cells was observed. Sea blue histiocytes were not seen. Stainable iron was markedly reduced without any ringed sideroblasts. Significant dysplasia was not present in any of the cell lineages. The bone marrow core biopsy was hypercellular for age, with a cellularity estimated at 75%–85% with neutrophilic proliferation and adequate megakaryocytes (Fig. 3A). There was no increase in myeloblasts, eosinophils, basophils, or mast cells. Only minimal focal reticulin fibrosis was noted in some regions. Immunohistochemical staining performed on the core biopsy showed predominance of myeloperoxidase-positive myeloid cells, without any increase in cluster of differentiation-34 (CD34)-positive cells (Fig. 3B). The conventional marrow karyotype was 46, XX, with no abnormalities noted. A t(9;22) translocation was not identified by either polymerase chain reaction or fluorescence in-situ hybridization methods. Mutation analyses for Janus kinase-2 (JAK2) and PDGFRα/PDGFRβ were similarly negative. The mutation analysis for the colony-stimulating factor-3 receptor gene (CSF3R) was performed by bidirectional sequencing method. The mutation hot spots exon 14 and exon 17 of this gene were analyzed. This assay has a typical sensitivity of 10%–15% for detecting mutated CSF3R DNA. CSF3R was studied and the result was negative; similarly, FGFR1 was investigated and the result was negative. Computerized scans of the chest, abdomen, and pelvis were negative for lymphadenopathy or hepatosplenomegaly. Positron emission tomography–computed tomography (PET/CT) scans were negative. Blood, urine, stool, and sputum cultures were done repeatedly, as well as sputum cultures for acid-fast bacilli, Mycobacterium tuberculosis, and Brucella, with sustained negative results. The diagnosis of CNL was thereafter reached. The patient was treated with pegylated interferon alpha-2a (Pegasys®), as per Yassin et al.2 This therapy comprised the following protocol2: 50 μg once weekly for 2 weeks, then 135 μg once weekly for 6 weeks, and finally 135 μg every 2 weeks.

Bottom Line: A woman in her 40s who was incidentally found to have leukocytosis was referred to the hematology service at the National Center for Cancer Care and Research for evaluation.Peripheral blood and flow cytometry did not show any evidence of lymphoproliferative disorder or myeloblasts.To the best of our knowledge, this is the first case of CNL reported among the Arab population.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Bone Marrow Transplant, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar.

ABSTRACT
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) that represents a diagnostic dilemma for both clinicians and pathologists. Because this disease entity is very rare, and because its diagnosis is by exclusion, it is important for clinical hematologists and hematopathologists to be familiar with CNL when approaching patients with MPNs and persistent neutrophilia. A woman in her 40s who was incidentally found to have leukocytosis was referred to the hematology service at the National Center for Cancer Care and Research for evaluation. Complete blood count revealed hyperleukocytosis with predominant neutrophilia. Peripheral blood and flow cytometry did not show any evidence of lymphoproliferative disorder or myeloblasts. Bone marrow aspirate and biopsy revealed a hypercellular marrow with myeloid hyperplasia. Cytogenetics revealed normal karyotype. Tests for both Janus kinase mutation JAK2 V617F and rearrangement of the genes BCR-ABL1, platelet-derived growth factor receptor-α (PDGFRα), PDGFRβ, and fibroblast growth factor receptor-1 (FGFR1) were negative. Thereafter, the diagnosis of CNL was reached. She was treated with pegylated interferon alpha-2a, with very good hematological response. To the best of our knowledge, this is the first case of CNL reported among the Arab population.

No MeSH data available.


Related in: MedlinePlus