Contributions
Abstract: PB1886
Type: Publication Only
Background
Hairy cell leukemia(HCL) is a B cell lymphoproliferative disorder, presenting with splenomegaly, hepatomegaly and bone marrow infiltration. HCL accounts for %4,5 of non-Hodgkin lymphomas, more commonly seen in man. Diagnosis is based on the examination of peripheral blood smear, flow cytometry and the bone marrow aspiration-biopsy. Recently, B-RAFV600E mutation was demonstrated in %100 of Tiacci HCL case series.
Aims
Aim of our study is to investigate the frequency of B-RAFV600Emutation and other rare mutations of B-RAF (B-RAFG464E, B-RAFG466E, B-RAFG469V) and their relation with clinical data and treatment responses.
Methods
Charts of 13 patients diagnosed with HCL were analyzed retrospectively. Patients' clinical paremeters were evaluated. HCL variant type patients were excluded. Paraffin blocks of spleen or bone marrow tissues are obtained from the pathology archives. One thin section (10 micron) of bone marrow or three sections of spleen are cut and DNA extracted by spin column technique using DNA extraction kit. (QIAamp DNA FFPE Tissue Kit, Qiagen) After spectrophotometric measurement of DNA; common and uncommon mutations of B-RAF were investigated. (Qiagen PyroMark Q24 system, Therascreen BRAF Pyrokit 24, V1 (1/2) kit) Mutation and clinical data analysis were conducted using the SPSS 15.0 software. The study was approved by the local ethics board of Dokuz Eylul University.
Results
Male/female ratio was 9/4. Median age at diagnosis was 48(37-59). Median follow-up time was 59 (3-96) months. At the time of diagnosis, 46,2% (n=6) of patients were asymptomatic. All of the patients had splenomegaly (n=13), five patients had hepatomegaly and two had intraabdominal lymhadenopathy. Approximately half of the patients (%46,2) diagnosed with splenectomy. Only one patient was pancytopenic at diagnosis. Four patients were anemic (Hemoglobin<10 gr/dL), six were thrombocytopenic (Platelets<150000/µl). Leucopenia was seen in 84,6 % (n=11) of the patients. Monocytopenia commonly seen in HCL was detected in 61,5%. One of the patients was diagnosed and treated due to Mantle cell lymphoma (MCL) a year ago and found in remission for both MCL and HCL; one was diagnosed Kaposi carcoma just before the diagnosis of HCL and lost in follow-up. Twelve patients were hospitalized and treated with one cycle of cladribin (0,1 mg/kg/day IV for 7 days). One of these patients received SC IFNα at a dose of 4,5 mIU/day prior to cladribin therapy. Treatment responses could be evaluated in eleven patients and all of the patients gained CR. Survival analysis couldn’t be done because non of the patients had progressed or died. B-RAFV600E mutation was positive in 10(%76,9) patients. Three (%23,1) of the patients had B-RAF 464-469 codon mutations (One B-RAFG464E, one B-RAFG466E, one B-RAFG469E) Two patients were positive for both mutations. No relation could be determined between clinical findings and mutation state.
Conclusion
B-Raf mutations are variable and common mutations in HCL patients. B-RAFV600E mutation testing can be used as a supportive test for the diagnosis of HCL due to high incidence of mutation. Also it can be used as an indicator for patient selection that are appropriate for target therapies.
Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical
Keyword(s): Hairy cell leukemia
Abstract: PB1886
Type: Publication Only
Background
Hairy cell leukemia(HCL) is a B cell lymphoproliferative disorder, presenting with splenomegaly, hepatomegaly and bone marrow infiltration. HCL accounts for %4,5 of non-Hodgkin lymphomas, more commonly seen in man. Diagnosis is based on the examination of peripheral blood smear, flow cytometry and the bone marrow aspiration-biopsy. Recently, B-RAFV600E mutation was demonstrated in %100 of Tiacci HCL case series.
Aims
Aim of our study is to investigate the frequency of B-RAFV600Emutation and other rare mutations of B-RAF (B-RAFG464E, B-RAFG466E, B-RAFG469V) and their relation with clinical data and treatment responses.
Methods
Charts of 13 patients diagnosed with HCL were analyzed retrospectively. Patients' clinical paremeters were evaluated. HCL variant type patients were excluded. Paraffin blocks of spleen or bone marrow tissues are obtained from the pathology archives. One thin section (10 micron) of bone marrow or three sections of spleen are cut and DNA extracted by spin column technique using DNA extraction kit. (QIAamp DNA FFPE Tissue Kit, Qiagen) After spectrophotometric measurement of DNA; common and uncommon mutations of B-RAF were investigated. (Qiagen PyroMark Q24 system, Therascreen BRAF Pyrokit 24, V1 (1/2) kit) Mutation and clinical data analysis were conducted using the SPSS 15.0 software. The study was approved by the local ethics board of Dokuz Eylul University.
Results
Male/female ratio was 9/4. Median age at diagnosis was 48(37-59). Median follow-up time was 59 (3-96) months. At the time of diagnosis, 46,2% (n=6) of patients were asymptomatic. All of the patients had splenomegaly (n=13), five patients had hepatomegaly and two had intraabdominal lymhadenopathy. Approximately half of the patients (%46,2) diagnosed with splenectomy. Only one patient was pancytopenic at diagnosis. Four patients were anemic (Hemoglobin<10 gr/dL), six were thrombocytopenic (Platelets<150000/µl). Leucopenia was seen in 84,6 % (n=11) of the patients. Monocytopenia commonly seen in HCL was detected in 61,5%. One of the patients was diagnosed and treated due to Mantle cell lymphoma (MCL) a year ago and found in remission for both MCL and HCL; one was diagnosed Kaposi carcoma just before the diagnosis of HCL and lost in follow-up. Twelve patients were hospitalized and treated with one cycle of cladribin (0,1 mg/kg/day IV for 7 days). One of these patients received SC IFNα at a dose of 4,5 mIU/day prior to cladribin therapy. Treatment responses could be evaluated in eleven patients and all of the patients gained CR. Survival analysis couldn’t be done because non of the patients had progressed or died. B-RAFV600E mutation was positive in 10(%76,9) patients. Three (%23,1) of the patients had B-RAF 464-469 codon mutations (One B-RAFG464E, one B-RAFG466E, one B-RAFG469E) Two patients were positive for both mutations. No relation could be determined between clinical findings and mutation state.
Conclusion
B-Raf mutations are variable and common mutations in HCL patients. B-RAFV600E mutation testing can be used as a supportive test for the diagnosis of HCL due to high incidence of mutation. Also it can be used as an indicator for patient selection that are appropriate for target therapies.
Session topic: 19. Indolent Non-Hodgkin lymphoma - Clinical
Keyword(s): Hairy cell leukemia