CSF IGH REARRANGEMENT IN HIGH-RISK DLBCL PATIENTS TREATED WITH INTRATHECAL PROPHYLAXIS
(Abstract release date: 05/19/16)
EHA Library. Tisi M. 06/09/16; 134950; PB2050
Dr. Maria Chiara Tisi
Contributions
Contributions
Abstract
Abstract: PB2050
Type: Publication Only
Background
Central nervous system (CNS) involvement is one of the most serious and devastating complications for patients with diffuse large B-cell lymphoma (DLBCL). Patients with risk factors for secondary CNS localization as specific extranodal sites, bone marrow localization and high IPI score, are candidates for intrathecal prophylaxis. Cerebrospinal fluid (CSF) is routinely analyzed by cytology for the presence of lymphoma cells, while the role of the IgH rearrangement assay on CSF has not been studied in high-risk DLBCL patients treated with intrathecal prophylaxis.
Aims
To evaluate the incidence of IgH clonal rearrangement at diagnosis in high-risk DLBCL treated with intrathecal prophylaxis.
Methods
Patient population included 55 patients with aggressive B-cell lymphoma without CNS involvement, including 51 pts with DLBCL and 4 patients with unclassifiable lymphoma with intermediate features between DLBCL and Burkitt lymphoma. All patients were treated with R-CHOP-like regimens associated to intrathecal methotrexate prophylaxis given during the first 4 cycles of systemic therapy. Twenty-two patients were consolidated with ASCT. CSF samples at the first lumbar puncture were analyzed for IgH rearrangement. After CSF centrifugation, DNA was extracted through the EZ1 DNA Tissue Kit (Qiagen) using the BioRobot EZ1 (Qiagen). VH FR2-JH and VH FR3-JH rearrangement were amplified in two semi-nested PCRs by using the B-cell lymphoma kit-FL (Experteam), and analyzed by Gene Scanning on the ABI 3100 Genetic Analyzer (Applied Biosystem).
Results
A clonal IgH rearrangement in the liquor was detected in 16 of 55 patients (29 %), while it was polyclonal or absent in remaining 39 patients. In 4/55 (7 %) patients, the number of cells in the CSF was elevated. In the 4 patients with elevated CSF cells, IgH analysis showed a monoclonal band in 1 patient and a polyclonal rearrangement in 3 patients. The presence of clonal IgH rearrangement was associated with elevated (>40 mg/dl) protein levels in the liquor (p=0.001). In particular, only 3/30 (10%) patients with a normal CSF protein level showed a clonal IgH, while a clonal IgH rearrangement was present in 13/25 (60 %) patients with elevated CSF protein levels. No association was found between detection of clonal IgH in CSF and patient characteristics, as age, stage, bone marrow or extranodal involvement, LDH and international prognostic index IPI. Eight patients with clonal IgH on CSF were serially analyzed at sequential lumbar punctures: the clonal IgH peak disappeared in 7 patients and persisted only in one patient. Three patients developed CNS relapse (5.5 %), one of 16 patients with clonal IgH on CSF (6 %) and 2 of 39 patients with polyclonal IgH on CSF (5 %).
Conclusion
Clonal IgH rearrangements are frequently present in the CSF of high-risk DLBCL patients and tend to disappear during repeated CNS-directed prophylaxis. No association between detection of clonal IgH rearrangement and risk of CNS relapse was found in patients treated with intrathecal methotrexate.
Session topic: E-poster
Keyword(s): CNS, DLBCL, High risk, IgH rearrangment
Type: Publication Only
Background
Central nervous system (CNS) involvement is one of the most serious and devastating complications for patients with diffuse large B-cell lymphoma (DLBCL). Patients with risk factors for secondary CNS localization as specific extranodal sites, bone marrow localization and high IPI score, are candidates for intrathecal prophylaxis. Cerebrospinal fluid (CSF) is routinely analyzed by cytology for the presence of lymphoma cells, while the role of the IgH rearrangement assay on CSF has not been studied in high-risk DLBCL patients treated with intrathecal prophylaxis.
Aims
To evaluate the incidence of IgH clonal rearrangement at diagnosis in high-risk DLBCL treated with intrathecal prophylaxis.
Methods
Patient population included 55 patients with aggressive B-cell lymphoma without CNS involvement, including 51 pts with DLBCL and 4 patients with unclassifiable lymphoma with intermediate features between DLBCL and Burkitt lymphoma. All patients were treated with R-CHOP-like regimens associated to intrathecal methotrexate prophylaxis given during the first 4 cycles of systemic therapy. Twenty-two patients were consolidated with ASCT. CSF samples at the first lumbar puncture were analyzed for IgH rearrangement. After CSF centrifugation, DNA was extracted through the EZ1 DNA Tissue Kit (Qiagen) using the BioRobot EZ1 (Qiagen). VH FR2-JH and VH FR3-JH rearrangement were amplified in two semi-nested PCRs by using the B-cell lymphoma kit-FL (Experteam), and analyzed by Gene Scanning on the ABI 3100 Genetic Analyzer (Applied Biosystem).
Results
A clonal IgH rearrangement in the liquor was detected in 16 of 55 patients (29 %), while it was polyclonal or absent in remaining 39 patients. In 4/55 (7 %) patients, the number of cells in the CSF was elevated. In the 4 patients with elevated CSF cells, IgH analysis showed a monoclonal band in 1 patient and a polyclonal rearrangement in 3 patients. The presence of clonal IgH rearrangement was associated with elevated (>40 mg/dl) protein levels in the liquor (p=0.001). In particular, only 3/30 (10%) patients with a normal CSF protein level showed a clonal IgH, while a clonal IgH rearrangement was present in 13/25 (60 %) patients with elevated CSF protein levels. No association was found between detection of clonal IgH in CSF and patient characteristics, as age, stage, bone marrow or extranodal involvement, LDH and international prognostic index IPI. Eight patients with clonal IgH on CSF were serially analyzed at sequential lumbar punctures: the clonal IgH peak disappeared in 7 patients and persisted only in one patient. Three patients developed CNS relapse (5.5 %), one of 16 patients with clonal IgH on CSF (6 %) and 2 of 39 patients with polyclonal IgH on CSF (5 %).
Conclusion
Clonal IgH rearrangements are frequently present in the CSF of high-risk DLBCL patients and tend to disappear during repeated CNS-directed prophylaxis. No association between detection of clonal IgH rearrangement and risk of CNS relapse was found in patients treated with intrathecal methotrexate.
Session topic: E-poster
Keyword(s): CNS, DLBCL, High risk, IgH rearrangment
Abstract: PB2050
Type: Publication Only
Background
Central nervous system (CNS) involvement is one of the most serious and devastating complications for patients with diffuse large B-cell lymphoma (DLBCL). Patients with risk factors for secondary CNS localization as specific extranodal sites, bone marrow localization and high IPI score, are candidates for intrathecal prophylaxis. Cerebrospinal fluid (CSF) is routinely analyzed by cytology for the presence of lymphoma cells, while the role of the IgH rearrangement assay on CSF has not been studied in high-risk DLBCL patients treated with intrathecal prophylaxis.
Aims
To evaluate the incidence of IgH clonal rearrangement at diagnosis in high-risk DLBCL treated with intrathecal prophylaxis.
Methods
Patient population included 55 patients with aggressive B-cell lymphoma without CNS involvement, including 51 pts with DLBCL and 4 patients with unclassifiable lymphoma with intermediate features between DLBCL and Burkitt lymphoma. All patients were treated with R-CHOP-like regimens associated to intrathecal methotrexate prophylaxis given during the first 4 cycles of systemic therapy. Twenty-two patients were consolidated with ASCT. CSF samples at the first lumbar puncture were analyzed for IgH rearrangement. After CSF centrifugation, DNA was extracted through the EZ1 DNA Tissue Kit (Qiagen) using the BioRobot EZ1 (Qiagen). VH FR2-JH and VH FR3-JH rearrangement were amplified in two semi-nested PCRs by using the B-cell lymphoma kit-FL (Experteam), and analyzed by Gene Scanning on the ABI 3100 Genetic Analyzer (Applied Biosystem).
Results
A clonal IgH rearrangement in the liquor was detected in 16 of 55 patients (29 %), while it was polyclonal or absent in remaining 39 patients. In 4/55 (7 %) patients, the number of cells in the CSF was elevated. In the 4 patients with elevated CSF cells, IgH analysis showed a monoclonal band in 1 patient and a polyclonal rearrangement in 3 patients. The presence of clonal IgH rearrangement was associated with elevated (>40 mg/dl) protein levels in the liquor (p=0.001). In particular, only 3/30 (10%) patients with a normal CSF protein level showed a clonal IgH, while a clonal IgH rearrangement was present in 13/25 (60 %) patients with elevated CSF protein levels. No association was found between detection of clonal IgH in CSF and patient characteristics, as age, stage, bone marrow or extranodal involvement, LDH and international prognostic index IPI. Eight patients with clonal IgH on CSF were serially analyzed at sequential lumbar punctures: the clonal IgH peak disappeared in 7 patients and persisted only in one patient. Three patients developed CNS relapse (5.5 %), one of 16 patients with clonal IgH on CSF (6 %) and 2 of 39 patients with polyclonal IgH on CSF (5 %).
Conclusion
Clonal IgH rearrangements are frequently present in the CSF of high-risk DLBCL patients and tend to disappear during repeated CNS-directed prophylaxis. No association between detection of clonal IgH rearrangement and risk of CNS relapse was found in patients treated with intrathecal methotrexate.
Session topic: E-poster
Keyword(s): CNS, DLBCL, High risk, IgH rearrangment
Type: Publication Only
Background
Central nervous system (CNS) involvement is one of the most serious and devastating complications for patients with diffuse large B-cell lymphoma (DLBCL). Patients with risk factors for secondary CNS localization as specific extranodal sites, bone marrow localization and high IPI score, are candidates for intrathecal prophylaxis. Cerebrospinal fluid (CSF) is routinely analyzed by cytology for the presence of lymphoma cells, while the role of the IgH rearrangement assay on CSF has not been studied in high-risk DLBCL patients treated with intrathecal prophylaxis.
Aims
To evaluate the incidence of IgH clonal rearrangement at diagnosis in high-risk DLBCL treated with intrathecal prophylaxis.
Methods
Patient population included 55 patients with aggressive B-cell lymphoma without CNS involvement, including 51 pts with DLBCL and 4 patients with unclassifiable lymphoma with intermediate features between DLBCL and Burkitt lymphoma. All patients were treated with R-CHOP-like regimens associated to intrathecal methotrexate prophylaxis given during the first 4 cycles of systemic therapy. Twenty-two patients were consolidated with ASCT. CSF samples at the first lumbar puncture were analyzed for IgH rearrangement. After CSF centrifugation, DNA was extracted through the EZ1 DNA Tissue Kit (Qiagen) using the BioRobot EZ1 (Qiagen). VH FR2-JH and VH FR3-JH rearrangement were amplified in two semi-nested PCRs by using the B-cell lymphoma kit-FL (Experteam), and analyzed by Gene Scanning on the ABI 3100 Genetic Analyzer (Applied Biosystem).
Results
A clonal IgH rearrangement in the liquor was detected in 16 of 55 patients (29 %), while it was polyclonal or absent in remaining 39 patients. In 4/55 (7 %) patients, the number of cells in the CSF was elevated. In the 4 patients with elevated CSF cells, IgH analysis showed a monoclonal band in 1 patient and a polyclonal rearrangement in 3 patients. The presence of clonal IgH rearrangement was associated with elevated (>40 mg/dl) protein levels in the liquor (p=0.001). In particular, only 3/30 (10%) patients with a normal CSF protein level showed a clonal IgH, while a clonal IgH rearrangement was present in 13/25 (60 %) patients with elevated CSF protein levels. No association was found between detection of clonal IgH in CSF and patient characteristics, as age, stage, bone marrow or extranodal involvement, LDH and international prognostic index IPI. Eight patients with clonal IgH on CSF were serially analyzed at sequential lumbar punctures: the clonal IgH peak disappeared in 7 patients and persisted only in one patient. Three patients developed CNS relapse (5.5 %), one of 16 patients with clonal IgH on CSF (6 %) and 2 of 39 patients with polyclonal IgH on CSF (5 %).
Conclusion
Clonal IgH rearrangements are frequently present in the CSF of high-risk DLBCL patients and tend to disappear during repeated CNS-directed prophylaxis. No association between detection of clonal IgH rearrangement and risk of CNS relapse was found in patients treated with intrathecal methotrexate.
Session topic: E-poster
Keyword(s): CNS, DLBCL, High risk, IgH rearrangment
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