Daan Dierickx - Academia.edu (original) (raw)
Papers by Daan Dierickx
American Journal of Transplantation, 2013
We performed a multicenter, International analysis of solid organ transplant (SOT)-related primar... more We performed a multicenter, International analysis of solid organ transplant (SOT)-related primary central nervous system (PCNS) posttransplant lymphoproliferative disease (PTLD). Among 84 PCNS PTLD patients, median time of SOT-to-PTLD was 54 months, 79% had kidney SOT, histology was monomorphic in 83% and tumor was EBVþ in 94%. Further, 33% had deep brain involvement, 10% had CSF involvement, while none had ocular disease. Immunosuppression was reduced in 93%; additional first-line therapy included high-dose methotrexate (48%), high-dose cytarabine (33%), brain radiation (24%) and/or ritux-imab (44%). The overall response rate was 60%, while treatment-related mortality was 13%. With 42-month median follow-up, three-year progression-free survival (PFS) and overall survival (OS) were 32% and 43%, respectively. There was a trend on univariable analysis for improved PFS for patients who received rituximab and/or high-dose cytarabine. On multivariable Cox regression, poor performance status predicted inferior PFS (HR 2.61, 95% CI 1.32-5.17, p ¼ 0.006), while increased LDH portended inferior OS (HR 4.16, 95% CI 1.29-13.46, p ¼ 0.02). Moreover, lack of response to first-line therapy was the most dominant prognostic factor on multivariable analysis (HR 8.70, 95% CI 2.56-29.57, p ¼ 0.0005). Altogether, PCNS PTLD appears to represent a distinct clinicopathologic entity within the PTLD spectrum that is associated with renal SOT, occurs late, is monomorphic and retains EBV positivity.
Blood Advances, 2021
The low abundance of Hodgkin/Reed-Sternberg (HRS) cells in lymph node biopsies in classical Hodgk... more The low abundance of Hodgkin/Reed-Sternberg (HRS) cells in lymph node biopsies in classical Hodgkin lymphoma (cHL) complicates the analysis of somatic genetic alterations in HRS cells. As circulating cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA) from HRS cells, we prospectively collected cfDNA from 177 patients with newly diagnosed, mostly early-stage cHL in a monocentric study at Leuven, Belgium (n = 59) and the multicentric BREACH study by Lymphoma Study Association (n = 118). To catalog the patterns and frequencies of genomic copy number aberrations (CNAs), cfDNA was sequenced at low coverage (0.26×), and data were analyzed with ichorCNA to yield read depth-based copy number profiles and estimated clonal fractions in cfDNA. At diagnosis, the cfDNA concentration, estimated clonal fraction, and ctDNA concentration were significantly higher in cHL cases than controls. More than 90% of patients exhibited CNAs in cfDNA. The most frequent gains encompassed 2p16 (69%), 5p...
Cancer Immunology, Immunotherapy, 2021
Acta Clinica Belgica, 2020
We present the case of a 67-year-old woman who suffered recurrent episodes of angioedema of the f... more We present the case of a 67-year-old woman who suffered recurrent episodes of angioedema of the face and larynx. After thorough biochemical investigations, an acquired deficiency of C1-INH was suspected. To evaluate a potential underlying malignancy, a whole-body FDG-PET/CT was performed and showed solely a marked splenomegaly pointing towards a splenic marginal zone lymphoma, which was confirmed by pathological examination. With this case, we discuss the pathophysiology, diagnosis and management of recurrent acquired angioedema attacks as the first presentation of an underlying lymphoproliferative disease.
![Research paper thumbnail of Semi-Quantitative Characterization of Post-Transplant Lymphoproliferative Disorder Morphological Subtypes with [18F]FDG PET/CT](https://attachments.academia-assets.com/86971989/thumbnails/1.jpg)
](Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transp... more Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation classified according to the WHO as nondestructive, polymorphic, monomorphic, and classic Hodgkin Lymphoma subtypes. In this retrospective study, we investigated the potential of semi-quantitative 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET/computed tomography (CT)-based parameters to differentiate between the PTLD morphological subtypes. Methods: 96 patients with histopathologically confirmed PTLD and baseline [18F]FDG PET/CT between 2009 and 2019 were included. Extracted semi-quantitative measurements included: Maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean). Results: Median SUVs were highest for monomorphic PTLD followed by polymorphic and nondestructive subtypes. The median SUVpeak at the biopsy site was significantly higher in monomorphic PTLD (17.8, interquartile range (IQR):16) than in polymorphic subtypes (9.8, IQR:13.4) and nondestruc...
American Journal of Kidney Diseases, 2021
Post-transplant lymphoproliferative disorder (PTLD) is one of the most feared complications follo... more Post-transplant lymphoproliferative disorder (PTLD) is one of the most feared complications following kidney transplantation. Over a 10-year period, the risk of PTLD in kidney transplant recipients is 12-fold higher than in matched non-transplanted population. Given the number of kidney transplantations performed, kidney transplant recipients experiencing PTLD outnumber other organ transplant recipients who develop PTLD. EBV infection is one of the most important risk factors for PTLD, although 40% of PTLDs are not EBV-associated in contemporary series. The overall level of immunosuppression seems to be the most important driver of the increased occurrence of PTLD in solid organ transplant recipients. Reduction in immunosuppression is commonly accepted to prevent and treat PTLD. Although the cornerstone of PTLD treatment had been chemotherapy (typically CHOP), the availability of rituximab has changed the treatment landscape in the last two decades. The outcome of PTLD in KTR patients has clearly improved due to the introduction of more uniform treatment protocols, improved supportive care, increased awareness and use of positron emission tomography combined with computed tomography in both staging and response monitoring. In this review, we will focus on the most recent data on epidemiology, presentation, risk factors and management of PTLD in KTR.
Blood, 2008
Background: The addition of Rituximab to CHOP chemotherapy (R-CHOP) has significantly improved th... more Background: The addition of Rituximab to CHOP chemotherapy (R-CHOP) has significantly improved the overall survival of patients with diffuse large B cell lymphoma (DLBCL) by 10–15%. To evaluate the biological basis of survival for DLBCL, we profiled gene expression in biopsy samples from patients treated with R-CHOP. Methods: Whole genome Affymetrix U133 2.0 plus arrays were used to profile gene expression in pre-treatment biopsies from patients with de novo DLBCL who received CHOP (n=181) or R-CHOP (n=233). Samples were classified as germinal center B cell-like (GCB), activated B cell-like (ABC) or unclassified DLBCL. A multivariate gene expression-based survival predictor was created using CHOP cases as training and R-CHOP cases as validation set. Results: R-CHOP treated patients with GCB DLBCL had a more favorable survival than those with ABC DLBCL, with 3-year overall survival rates of 84% and 56%, respectively (p<0.001). A multivariate model created from 3 gene expression si...
Blood, 2007
Background. Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) may resp... more Background. Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) may respond to the chimeric anti-CD20 monoclonal antibody rituximab, even when refractory to conventional therapy. Aims. To collect data on Belgian patients given rituximab in the setting of ITP or AIHA in order to assess the response rate and the factors predictive for response in a multicenter study. Method. Belgian hematology centers were invited to fill a questionnaire specifying the major characteristics and quality of response of ITP and AIHA patients given rituximab. For ITP, complete response (CR) was defined as a platelet count >150,000/μL, and a partial response (PR) as a platelet count 50–100,000/μL. For AIHA, Response (R) was defined as a 2g increase of the hemoglobin concentration and achievement of transfusion independence. Results. All the patients were given rituximab after relapse or after failing at least one previous line of treatment. Except in 10 cases, rituximab was give...
Journal of Clinical Oncology, 2012
8030 Background: The prospective, multicenter international phase II PTLD-1 trial of sequential t... more 8030 Background: The prospective, multicenter international phase II PTLD-1 trial of sequential treatment (ST, 4 cycles of weekly rituximab followed by 4 cycles of CHOP-21 + G-CSF) in adult CD20-positive PTLD demonstrated excellent efficacy (90% overall response rate, ORR) and safety (11% treatment-related mortality, TRM). As the response to rituximab predicted overall survival (OS), the trial was amended in 2007 introducing risk-stratified sequential treatment (RSST) according to the response to rituximab (NCT00590447). Methods: Following rituximab on days 1, 8, 15 and 22, RSST consisted of 4 3-weekly courses of rituximab monotherapy for patients (pts) in complete remission (CR, low risk) while all others (high risk) received 4 cycles of R-CHOP-21 + G-CSF. Key exclusion criteria were CNS involvement, HIV infection, severe organ dysfunction not related to PTLD, and ECOG > 2. Primary endpoint was ORR. This is an analysis of the first 91 patients treated with RSST. Results: 79/91 p...
Blood, 2018
Background: Patients with MYC rearrangement positive large B cell lymphoma other than Burkitt lym... more Background: Patients with MYC rearrangement positive large B cell lymphoma other than Burkitt lymphoma (MYC+ LBCL), have a dismal prognosis following standard first line therapy with R-CHOP. Retrospective studies report complete remission rates < 50% and 2-year overall survival (OS) of approximately 35%. Lenalidomide is an immunomodulatory drug and is able to down-regulate MYC and its target genes and proteins in B cells that harbor a MYC rearrangement. We report data of a prospective phase II study evaluating the efficacy of lenalidomide in combination with R-CHOP (R2CHOP) in newly diagnosed MYC+ LBCL patients. Methods: A national screening program for MYC rearrangement by fluorescence in situ hybridization (FISH) was performed in newly diagnosed LBCL patients. Patients with a proven MYC rearrangement, ≥ 18 year, Ann Arbor stage II-IV, were offered participation in a single arm phase II study. Treatment consisted of 6 cycles R-CHOP21 plus lenalidomide 15 mg on day 1-14, followed...
Blood, 2014
Peripheral T-cell lymphoma - not otherwise specified (PTCL-NOS) is the largest, most common and v... more Peripheral T-cell lymphoma - not otherwise specified (PTCL-NOS) is the largest, most common and very heterogeneous category of PTCL. To date three PTCL variants have been described, including follicular variant (PTCL-F), a rare and poorly understood entity. Cytogenetically, PTCL-F is associated with a recurrent t(5;9)(q33;q22) resulting in the fusion of two protein tyrosine kinase (PTK) genes, ITK and SYK, showing constitutive activation of SYK. Transforming capacities of ITK-SYK were documented both in vitro and in vivo. Involvement of other PTK genes in the pathogenesis of PTCL-F has been postulated, but is thus far, not evidenced. We present cytogenetic, molecular and functional studies of two PTCL-F cases recently identified in our institution. The first case was characterized by complex chromosomal rearrangements involving several chromosomal regions harboring PTK genes. Extensive FISH analysis eventually identified FES involvement in t(15;16)(q26;q22). Further RNA-sequencing o...
Journal of Crohn's and Colitis, 2018
American Journal of Transplantation, 2013
We performed a multicenter, International analysis of solid organ transplant (SOT)-related primar... more We performed a multicenter, International analysis of solid organ transplant (SOT)-related primary central nervous system (PCNS) posttransplant lymphoproliferative disease (PTLD). Among 84 PCNS PTLD patients, median time of SOT-to-PTLD was 54 months, 79% had kidney SOT, histology was monomorphic in 83% and tumor was EBVþ in 94%. Further, 33% had deep brain involvement, 10% had CSF involvement, while none had ocular disease. Immunosuppression was reduced in 93%; additional first-line therapy included high-dose methotrexate (48%), high-dose cytarabine (33%), brain radiation (24%) and/or ritux-imab (44%). The overall response rate was 60%, while treatment-related mortality was 13%. With 42-month median follow-up, three-year progression-free survival (PFS) and overall survival (OS) were 32% and 43%, respectively. There was a trend on univariable analysis for improved PFS for patients who received rituximab and/or high-dose cytarabine. On multivariable Cox regression, poor performance status predicted inferior PFS (HR 2.61, 95% CI 1.32-5.17, p ¼ 0.006), while increased LDH portended inferior OS (HR 4.16, 95% CI 1.29-13.46, p ¼ 0.02). Moreover, lack of response to first-line therapy was the most dominant prognostic factor on multivariable analysis (HR 8.70, 95% CI 2.56-29.57, p ¼ 0.0005). Altogether, PCNS PTLD appears to represent a distinct clinicopathologic entity within the PTLD spectrum that is associated with renal SOT, occurs late, is monomorphic and retains EBV positivity.
Blood Advances, 2021
The low abundance of Hodgkin/Reed-Sternberg (HRS) cells in lymph node biopsies in classical Hodgk... more The low abundance of Hodgkin/Reed-Sternberg (HRS) cells in lymph node biopsies in classical Hodgkin lymphoma (cHL) complicates the analysis of somatic genetic alterations in HRS cells. As circulating cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA) from HRS cells, we prospectively collected cfDNA from 177 patients with newly diagnosed, mostly early-stage cHL in a monocentric study at Leuven, Belgium (n = 59) and the multicentric BREACH study by Lymphoma Study Association (n = 118). To catalog the patterns and frequencies of genomic copy number aberrations (CNAs), cfDNA was sequenced at low coverage (0.26×), and data were analyzed with ichorCNA to yield read depth-based copy number profiles and estimated clonal fractions in cfDNA. At diagnosis, the cfDNA concentration, estimated clonal fraction, and ctDNA concentration were significantly higher in cHL cases than controls. More than 90% of patients exhibited CNAs in cfDNA. The most frequent gains encompassed 2p16 (69%), 5p...
Cancer Immunology, Immunotherapy, 2021
Acta Clinica Belgica, 2020
We present the case of a 67-year-old woman who suffered recurrent episodes of angioedema of the f... more We present the case of a 67-year-old woman who suffered recurrent episodes of angioedema of the face and larynx. After thorough biochemical investigations, an acquired deficiency of C1-INH was suspected. To evaluate a potential underlying malignancy, a whole-body FDG-PET/CT was performed and showed solely a marked splenomegaly pointing towards a splenic marginal zone lymphoma, which was confirmed by pathological examination. With this case, we discuss the pathophysiology, diagnosis and management of recurrent acquired angioedema attacks as the first presentation of an underlying lymphoproliferative disease.
Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transp... more Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation classified according to the WHO as nondestructive, polymorphic, monomorphic, and classic Hodgkin Lymphoma subtypes. In this retrospective study, we investigated the potential of semi-quantitative 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET/computed tomography (CT)-based parameters to differentiate between the PTLD morphological subtypes. Methods: 96 patients with histopathologically confirmed PTLD and baseline [18F]FDG PET/CT between 2009 and 2019 were included. Extracted semi-quantitative measurements included: Maximum, peak, and mean standardized uptake value (SUVmax, SUVpeak, and SUVmean). Results: Median SUVs were highest for monomorphic PTLD followed by polymorphic and nondestructive subtypes. The median SUVpeak at the biopsy site was significantly higher in monomorphic PTLD (17.8, interquartile range (IQR):16) than in polymorphic subtypes (9.8, IQR:13.4) and nondestruc...
American Journal of Kidney Diseases, 2021
Post-transplant lymphoproliferative disorder (PTLD) is one of the most feared complications follo... more Post-transplant lymphoproliferative disorder (PTLD) is one of the most feared complications following kidney transplantation. Over a 10-year period, the risk of PTLD in kidney transplant recipients is 12-fold higher than in matched non-transplanted population. Given the number of kidney transplantations performed, kidney transplant recipients experiencing PTLD outnumber other organ transplant recipients who develop PTLD. EBV infection is one of the most important risk factors for PTLD, although 40% of PTLDs are not EBV-associated in contemporary series. The overall level of immunosuppression seems to be the most important driver of the increased occurrence of PTLD in solid organ transplant recipients. Reduction in immunosuppression is commonly accepted to prevent and treat PTLD. Although the cornerstone of PTLD treatment had been chemotherapy (typically CHOP), the availability of rituximab has changed the treatment landscape in the last two decades. The outcome of PTLD in KTR patients has clearly improved due to the introduction of more uniform treatment protocols, improved supportive care, increased awareness and use of positron emission tomography combined with computed tomography in both staging and response monitoring. In this review, we will focus on the most recent data on epidemiology, presentation, risk factors and management of PTLD in KTR.
Blood, 2008
Background: The addition of Rituximab to CHOP chemotherapy (R-CHOP) has significantly improved th... more Background: The addition of Rituximab to CHOP chemotherapy (R-CHOP) has significantly improved the overall survival of patients with diffuse large B cell lymphoma (DLBCL) by 10–15%. To evaluate the biological basis of survival for DLBCL, we profiled gene expression in biopsy samples from patients treated with R-CHOP. Methods: Whole genome Affymetrix U133 2.0 plus arrays were used to profile gene expression in pre-treatment biopsies from patients with de novo DLBCL who received CHOP (n=181) or R-CHOP (n=233). Samples were classified as germinal center B cell-like (GCB), activated B cell-like (ABC) or unclassified DLBCL. A multivariate gene expression-based survival predictor was created using CHOP cases as training and R-CHOP cases as validation set. Results: R-CHOP treated patients with GCB DLBCL had a more favorable survival than those with ABC DLBCL, with 3-year overall survival rates of 84% and 56%, respectively (p<0.001). A multivariate model created from 3 gene expression si...
Blood, 2007
Background. Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) may resp... more Background. Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) may respond to the chimeric anti-CD20 monoclonal antibody rituximab, even when refractory to conventional therapy. Aims. To collect data on Belgian patients given rituximab in the setting of ITP or AIHA in order to assess the response rate and the factors predictive for response in a multicenter study. Method. Belgian hematology centers were invited to fill a questionnaire specifying the major characteristics and quality of response of ITP and AIHA patients given rituximab. For ITP, complete response (CR) was defined as a platelet count >150,000/μL, and a partial response (PR) as a platelet count 50–100,000/μL. For AIHA, Response (R) was defined as a 2g increase of the hemoglobin concentration and achievement of transfusion independence. Results. All the patients were given rituximab after relapse or after failing at least one previous line of treatment. Except in 10 cases, rituximab was give...
Journal of Clinical Oncology, 2012
8030 Background: The prospective, multicenter international phase II PTLD-1 trial of sequential t... more 8030 Background: The prospective, multicenter international phase II PTLD-1 trial of sequential treatment (ST, 4 cycles of weekly rituximab followed by 4 cycles of CHOP-21 + G-CSF) in adult CD20-positive PTLD demonstrated excellent efficacy (90% overall response rate, ORR) and safety (11% treatment-related mortality, TRM). As the response to rituximab predicted overall survival (OS), the trial was amended in 2007 introducing risk-stratified sequential treatment (RSST) according to the response to rituximab (NCT00590447). Methods: Following rituximab on days 1, 8, 15 and 22, RSST consisted of 4 3-weekly courses of rituximab monotherapy for patients (pts) in complete remission (CR, low risk) while all others (high risk) received 4 cycles of R-CHOP-21 + G-CSF. Key exclusion criteria were CNS involvement, HIV infection, severe organ dysfunction not related to PTLD, and ECOG > 2. Primary endpoint was ORR. This is an analysis of the first 91 patients treated with RSST. Results: 79/91 p...
Blood, 2018
Background: Patients with MYC rearrangement positive large B cell lymphoma other than Burkitt lym... more Background: Patients with MYC rearrangement positive large B cell lymphoma other than Burkitt lymphoma (MYC+ LBCL), have a dismal prognosis following standard first line therapy with R-CHOP. Retrospective studies report complete remission rates < 50% and 2-year overall survival (OS) of approximately 35%. Lenalidomide is an immunomodulatory drug and is able to down-regulate MYC and its target genes and proteins in B cells that harbor a MYC rearrangement. We report data of a prospective phase II study evaluating the efficacy of lenalidomide in combination with R-CHOP (R2CHOP) in newly diagnosed MYC+ LBCL patients. Methods: A national screening program for MYC rearrangement by fluorescence in situ hybridization (FISH) was performed in newly diagnosed LBCL patients. Patients with a proven MYC rearrangement, ≥ 18 year, Ann Arbor stage II-IV, were offered participation in a single arm phase II study. Treatment consisted of 6 cycles R-CHOP21 plus lenalidomide 15 mg on day 1-14, followed...
Blood, 2014
Peripheral T-cell lymphoma - not otherwise specified (PTCL-NOS) is the largest, most common and v... more Peripheral T-cell lymphoma - not otherwise specified (PTCL-NOS) is the largest, most common and very heterogeneous category of PTCL. To date three PTCL variants have been described, including follicular variant (PTCL-F), a rare and poorly understood entity. Cytogenetically, PTCL-F is associated with a recurrent t(5;9)(q33;q22) resulting in the fusion of two protein tyrosine kinase (PTK) genes, ITK and SYK, showing constitutive activation of SYK. Transforming capacities of ITK-SYK were documented both in vitro and in vivo. Involvement of other PTK genes in the pathogenesis of PTCL-F has been postulated, but is thus far, not evidenced. We present cytogenetic, molecular and functional studies of two PTCL-F cases recently identified in our institution. The first case was characterized by complex chromosomal rearrangements involving several chromosomal regions harboring PTK genes. Extensive FISH analysis eventually identified FES involvement in t(15;16)(q26;q22). Further RNA-sequencing o...
Journal of Crohn's and Colitis, 2018