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CSF3R T618-MUTATED CHRONIC NEUTROPHILIC LEUKEMIA: A RARE CASE SUCCESSFULLY TREATED WITH RUXOLITINIB
Author(s):
Valeria Calafiore
,
Valeria Calafiore
Affiliations:
Division of Hematology, A.O. “Policlinico-Vittorio Emanuele”, University of Catania, Via Citelli 6, 95124 Catania, Italy,Catania,Italy
Marina Parisi
,
Marina Parisi
Affiliations:
Division of Hematology, A.O. “Policlinico-Vittorio Emanuele”, University of Catania, Via Citelli 6, 95124 Catania, Italy,Catania,Italy
Valentina Zammit
,
Valentina Zammit
Affiliations:
Division of Hematology, A.O. “Policlinico-Vittorio Emanuele”, University of Catania, Via Citelli 6, 95124 Catania, Italy,Catania,Italy
Enrica Martino
,
Enrica Martino
Affiliations:
Division of Hematology, A.O. “Policlinico-Vittorio Emanuele”, University of Catania, Via Citelli 6, 95124 Catania, Italy,Catania,Italy
Maria Cristina Pirosa
,
Maria Cristina Pirosa
Affiliations:
Division of Hematology, A.O. “Policlinico-Vittorio Emanuele”, University of Catania, Via Citelli 6, 95124 Catania, Italy,Catania,Italy
Antonio Spitaleri
,
Antonio Spitaleri
Affiliations:
Division of Hematology, A.O. “Policlinico-Vittorio Emanuele”, University of Catania, Via Citelli 6, 95124 Catania, Italy,Catania,Italy
Fabio Stagno
,
Fabio Stagno
Affiliations:
Division of Hematology, A.O. “Policlinico-Vittorio Emanuele”, University of Catania, Via Citelli 6, 95124 Catania, Italy,Catania,Italy
Concetta Conticello
,
Concetta Conticello
Affiliations:
Division of Hematology, A.O. “Policlinico-Vittorio Emanuele”, University of Catania, Via Citelli 6, 95124 Catania, Italy,Catania,Italy
Francesco Di Raimondo
Francesco Di Raimondo
Affiliations:
Division of Hematology, A.O. “Policlinico-Vittorio Emanuele”, University of Catania, Via Citelli 6, 95124 Catania, Italy,Catania,Italy
(Abstract release date: 05/18/17) EHA Library. conticello C. 05/18/17; 182777; PB2063
Concetta conticello
Concetta conticello
Contributions
PDF Abstract
Abstract

Abstract: PB2063

Type: Publication Only

Background

Chronic neutrophilic leukemia (CNL) is a rare BCR-ABL1–negative myeloproliferative neoplasm (MPN) with only 200 patients reported to date according to the WHO criteria. These cases are characterized by a high number of mature neutrophils in peripheral blood (PB), a hypercellular bone marrow due to neutrophilic granulocyte proliferation and hepatosplenomegaly. None standard of care exist for CNL; most patients are palliated with hydroxyurea, interferons, splenic radiation or splenectomy.
In the past years CNL has been often confused with chronic myeloid leukemia (CML), atypical CML (aCML) or chronic myelomonocytic leukemia (CMML), however, this diagnosis has been more defined since the oncogenic mutations in the granulocyte colony-stimulating 3 factor receptor (CSF3R) gene were identified in approximately 83 % of WHO-defined CNL patients.
CSF3R T618I mutation is now considered as a highly specific molecular marker for CNL that is sensitive to in vitro and in vivo inhibition by currently approved protein kinase inhibitors.

Aims
here we report a case of a 76-years old man with diagnosis of chronic neutrophilic leukemia, according to WHO criteria, successfully treated with ruxolitinib.

Methods

On May 2015 a 76 aged male patient presented at our Institution with fatigue, night sweats, neutrophilic leukocytosis (neutrophils 42.080/mmc, immature granulocytes <5%), and symptomatic splenomegaly (277x127x200 mm). Marrow biopsy was hypercellular (100%) with myeloid hyperplasia, mild myeloid dysplasia and profound erythropoietic hypoplasia; reticulin fibrosis was minimally present. Molecular profiling demonstrated no mutations of JAK2 or CALR and polymerase chain reaction (PCR) studies for t(9; 22) and BCR-ABL fusion, was negative.
The patient was initially treated with hydroxyurea with a provisional diagnosis of prefibrotic phase of primary myelofibrosis (PMF), but symptoms worsened and the therapy was interrupted after 9 months for progressive anemia (Hb 9,9 gr/dl) and thrombocytopenia (82.000/mmc); meanwhile polymerase chain reaction (PCR) studies revealed the presence of CSF3R T618I mutation, suggesting diagnosis of CNL. By taking into account the activity of ruxolitinib in overt PMF, we decided to start this drug. The initial dose was 5 mg twice daily with a gradual increase in the dose to 20 mg twice daily when platelet count became normal.

Results
on a follow-up of 6 months after initiation of ruxolitinib therapy, symptoms resolved, hemoglobin and platelet levels improved (PLT 186.000/mmc), leukocytosis persisted (WBC 24.600/mmc), and the patient achieved a dramatic reduction in spleen size (209x119x74 mm).

Conclusion
Current data suggest that constitutively active JAK-STAT signaling plays a central role in the pathogenesis of BCR-ABL1 –negative myeloproliferative neoplasms (MPNs); our experience suggests that ruxolitinib use in CNL patients can induce partial responses by improving marrow function (normalization of hemoglobin and platelets count), splenomegaly and symptoms.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Ruxolitinib, Myeloproliferative disorder

Abstract: PB2063

Type: Publication Only

Background

Chronic neutrophilic leukemia (CNL) is a rare BCR-ABL1–negative myeloproliferative neoplasm (MPN) with only 200 patients reported to date according to the WHO criteria. These cases are characterized by a high number of mature neutrophils in peripheral blood (PB), a hypercellular bone marrow due to neutrophilic granulocyte proliferation and hepatosplenomegaly. None standard of care exist for CNL; most patients are palliated with hydroxyurea, interferons, splenic radiation or splenectomy.
In the past years CNL has been often confused with chronic myeloid leukemia (CML), atypical CML (aCML) or chronic myelomonocytic leukemia (CMML), however, this diagnosis has been more defined since the oncogenic mutations in the granulocyte colony-stimulating 3 factor receptor (CSF3R) gene were identified in approximately 83 % of WHO-defined CNL patients.
CSF3R T618I mutation is now considered as a highly specific molecular marker for CNL that is sensitive to in vitro and in vivo inhibition by currently approved protein kinase inhibitors.

Aims
here we report a case of a 76-years old man with diagnosis of chronic neutrophilic leukemia, according to WHO criteria, successfully treated with ruxolitinib.

Methods

On May 2015 a 76 aged male patient presented at our Institution with fatigue, night sweats, neutrophilic leukocytosis (neutrophils 42.080/mmc, immature granulocytes <5%), and symptomatic splenomegaly (277x127x200 mm). Marrow biopsy was hypercellular (100%) with myeloid hyperplasia, mild myeloid dysplasia and profound erythropoietic hypoplasia; reticulin fibrosis was minimally present. Molecular profiling demonstrated no mutations of JAK2 or CALR and polymerase chain reaction (PCR) studies for t(9; 22) and BCR-ABL fusion, was negative.
The patient was initially treated with hydroxyurea with a provisional diagnosis of prefibrotic phase of primary myelofibrosis (PMF), but symptoms worsened and the therapy was interrupted after 9 months for progressive anemia (Hb 9,9 gr/dl) and thrombocytopenia (82.000/mmc); meanwhile polymerase chain reaction (PCR) studies revealed the presence of CSF3R T618I mutation, suggesting diagnosis of CNL. By taking into account the activity of ruxolitinib in overt PMF, we decided to start this drug. The initial dose was 5 mg twice daily with a gradual increase in the dose to 20 mg twice daily when platelet count became normal.

Results
on a follow-up of 6 months after initiation of ruxolitinib therapy, symptoms resolved, hemoglobin and platelet levels improved (PLT 186.000/mmc), leukocytosis persisted (WBC 24.600/mmc), and the patient achieved a dramatic reduction in spleen size (209x119x74 mm).

Conclusion
Current data suggest that constitutively active JAK-STAT signaling plays a central role in the pathogenesis of BCR-ABL1 –negative myeloproliferative neoplasms (MPNs); our experience suggests that ruxolitinib use in CNL patients can induce partial responses by improving marrow function (normalization of hemoglobin and platelets count), splenomegaly and symptoms.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Ruxolitinib, Myeloproliferative disorder

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