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Douglas W. Blayney - One of the best experts on this subject based on the ideXlab platform.
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Lymphoma after solid organ transplantation risk response to therapy and survival at a transplantation center
Journal of Clinical Oncology, 2009Co-Authors: Jason S Knight, Alexander Tsodikov, Diane M Cibrik, Charles W Ross, Mark S Kaminski, Douglas W. BlayneyAbstract:Purpose We studied the incidence, risk factors, treatment, and outcomes of post-transplantation lymphoproliferative disorder (PTLD) that occurred at the University of Michigan since 1964. Patients and Methods We identified 7,040 patients who received solid organ transplantation (SOT) and post-transplantation immunosuppressive therapy. Seventy-eight patients developed PTLD. Results Diffuse large B-cell Lymphoma (n = 43), polymorphic PTLD (n = 10), Hodgkin's Lymphoma (n = 7), Burkitts Lymphoma (n = 6), plasmacytoma (n = 5), and mucosa-associated lymphoid tissue Lymphoma (n = 3) were all over-represented in the SOT population compared with a population sample from the Surveillance, Epidemiology, and End Results (SEER) database; follicular Lymphoma (n = 0) was underrepresented. Negative pretransplantation Epstein-Barr virus (EBV) serology was a risk factor for PTLD. Available histologic analysis of tumor tissue showed that 75% were CD20 positive and that 62% were EBV positive; EBV-positive tumors occurred soo...
Andrew Mcmillan - One of the best experts on this subject based on the ideXlab platform.
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successful salvage of refractory Burkitts Lymphoma using maximum intensity of the da epoch r regimen a case report
Blood, 2017Co-Authors: Andrew Mcmillan, Sarah Hartley, Catherine Loughran, Mark Bishton, Eleanor James, Catherine Griffiths, Faith Richardson, Christopher P FoxAbstract:Burkitt Lymphoma (BL) that is refractory to frontline intensive therapy is generally associated with a dismal outcome. We report a case where this prognosis has apparently been overcome with an intensified variation of the DA EPOCH-R schedule. Wilson and coworkers have developed this infusional schedule with dose modification and it has been reported to achieve excellent outcomes in the first line therapy of BL. A 56 year old male presented with rapid onset superior vena cava obstruction that caused an intensive care admission at the time of diagnosis. Staging showed stage 2 with neck disease, near complete SVC obstruction and a 6 x 5 x 5cm superior mediastinal mass. Therapy was commenced with R CODOX-M / R IVAC with an initial symptomatic improvement but by the time of recovery from course 2, the symptoms of respiratory distress were recurring in the left neck where partial acute respiratory obstruction occurred. No significant improvement in the neck mass was seen on repeat CT and urgent radiotherapy (R/T) was given to relieve symptoms. Persistent active disease was then confirmed by CT /PET scanning in the left neck (SUV 10.8), an exemplar image of this scan is shown in Figure. The patient was counselled as to the dire prognosis but was unwilling to accept that further intensive treatment was unlikely be successful and requested further chemotherapy. In the light the intensity of the treatment already delivered a novel strategy was conceived and agreed. Second line treatment was given with the DA EPOCH -R schedule but escalated to dose level 6 from the start of second line therapy. The rationale for this was that the dose intensity needed to be higher than that of the failed front line regimen. Dose limiting mucositis was encountered and the etoposide was reduced to 65% of dose level 6, other drugs remained at dose level 6. By cycle 5, the doxorubicin dose was capped at a total cumulative dose of 450 mg/m2 so as to not exceed a safe cardiac dose. The chemotherapy doses delivered were Etoposide 125 ( 80 from cycle 2) mg/ m2 /day , Vincristine 0.4 mg/ m2/day, Doxorubicin 25 mg/ m2/day (cycle1-4), Cyclophosphamide 1900 mg/ m2 day 5 and rituximab 375 mg/ m2. 5 cycles were delivered in total. The total cumulative hospital inpatient stay during treatment was 58 days. End of treatment PET showed a complete response which has now been maintained for 12 months. Two attempts at stem cell mobilisation failed, despite the use of plerixifor, so a consolidation autologous stem cell transplant was not pursued. End of treatment radiotherapy to sites of initial disease was implemented after end of treatment restaging. This is a single case but we believe a good outcome has been achieved in an otherwise near hopeless situation and may provide a useful insight into improving salvage therapy of BL. We believe the strategy of using DA EPOCH R starting at maximum intensity from the start of therapy has not been previously reported. We also acknowledge the courage and stoicism of our patient whose determination to persist with therapy was exceptional. He remains in remission, has an ECOG status of 0 and has returned to work. Disclosures McMillan: Roche: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: travel sponsorship. Bishton: Roche: Other: Travel Sponsorship. Fox: Roche: Consultancy, Honoraria, Other: Travel Sponsorship, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Travel Sponsorship, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel Sponsorship, Speakers Bureau.
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rituximab and codox m ivac without stem cell transplantation for poor risk diffuse large b cell Lymphoma ipi3 5 and Burkitts Lymphoma is feasible and gives a high response rate preliminary results of a phase 2 uk national cancer research institute tr
Blood, 2013Co-Authors: Andrew Mcmillan, Kirit M Ardeshna, Jo Gambell, Andrew Jack, Amy A Kirkwood, Anthony Laurie, Silvia Montoto, Shankaranarayana Paneesha, Simon Rule, Russell PatmoreAbstract:Introduction R-CHOP is the standard of care for patients with diffuse large B cell Lymphoma (DLBCL) however poor risk patients (IPI 3-5) still have an inadequate outcome. Neither first remission high dose chemotherapy and peripheral blood stem cell transplantation (HDC+PBSCT) nor selection of cases for intensification by interim PET scanning have demonstrated a proven benefit. In the case of Burkitts Lymphoma (BL) there is a paucity of data on the addition of Rituximab to the CODOX-M and IVAC regimen. Patients and Methods 113 patients with DLBCL and 37 with BL were recruited from 53 UK sites between May 2008 and April 2013. Median age was 49 years (18-65). For DLBCL patients IPI scores were 3 – 72 ( 64%), 4 -40 (35%) and 5 – 1 (1%). All patients received the modified CODOX-M and IVAC regimen including all CNS directed therapy( Mead et al Ann Oncol. 2002 Aug;13(8):1264-74) and 8 doses of rituximab. The primary end point of the study was Progression Free survival (PFS) and secondary endpoints included toxicity and CR rate. Results The main toxicities reported were neutropenia ( 89% grade 3 or 4), thrombocytopenia (84.2% grade 3 or 4), infection 61.6% grade 3 or 4 and mucositis (30.1% grade 3 or 4). 4 patients were excluded from toxicity assessment as they did not start therapy after registration. There were 8 treatment related deaths observed (infection with neutropenia (5), GI haemorrhage (1), acute cerebral haemorrhage (1) and bowel perforation (1) ). 78 patients with DLBCL and 31 with BL have completed all therapy ( 78.5 % of patients with available data) with an overall response rate of 92 % for DLBCl and 94% for BL. In patients who completed all therapy CR was achieved in 34 (44%), CR (u) in 8 (10%) and PR in 30 (38%) for DLBCL patients and CR was achieved in 21 (68%), CR (u) in 6 (19%) and PR in 2 (6%) in BL patients. 3 patients ( 2 DLBCL and 1 BL) who progressed during therapy have been included in the response analysis. End of treatment PET scanning was not obligatory. 80 patients with DLBCL and 30 patients with BL remain alive and without progression at a median follow up of 18.6 and 19.3 months respectively. Conclusion The R-CODOX-M -R-IVAC regimen can be delivered to patients with poor risk DLBCL in a multicentre setting. High rates of haematological toxicity and consequent infection are inevitable with treatment of this intensity but appear acceptable when compared with other treatments such as HDC+PBSCT. Response rates are encouraging in view of the very poor risk IPI profile of the patients included in this study. Burkitts Lymphoma patients also achieved an excellent response rate with no apparent additional toxicity attributable to the addition of rituximab to the regimen. We currently plan the first analysis for the primary endpoint of PFS in 2015. The Trial was supported by Leukaemia and Lymphoma Research (LLR). Disclosures: McMillan:Roche: Consultancy, Honoraria; Amgen: Research Funding. Off Label Use: Rituximab usage in Burkitts Lymphoma. Ardeshna:Roche: Honoraria, Research Funding. Jack:Roche/Genentech: Research Funding. Patmore:Roche: Consultancy, Honoraria. Pettengell:Roche: Honoraria; Amgen: Honoraria. Linch:Roche: Honoraria, Research Funding.
Russell Patmore - One of the best experts on this subject based on the ideXlab platform.
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rituximab and codox m ivac without stem cell transplantation for poor risk diffuse large b cell Lymphoma ipi3 5 and Burkitts Lymphoma is feasible and gives a high response rate preliminary results of a phase 2 uk national cancer research institute tr
Blood, 2013Co-Authors: Andrew Mcmillan, Kirit M Ardeshna, Jo Gambell, Andrew Jack, Amy A Kirkwood, Anthony Laurie, Silvia Montoto, Shankaranarayana Paneesha, Simon Rule, Russell PatmoreAbstract:Introduction R-CHOP is the standard of care for patients with diffuse large B cell Lymphoma (DLBCL) however poor risk patients (IPI 3-5) still have an inadequate outcome. Neither first remission high dose chemotherapy and peripheral blood stem cell transplantation (HDC+PBSCT) nor selection of cases for intensification by interim PET scanning have demonstrated a proven benefit. In the case of Burkitts Lymphoma (BL) there is a paucity of data on the addition of Rituximab to the CODOX-M and IVAC regimen. Patients and Methods 113 patients with DLBCL and 37 with BL were recruited from 53 UK sites between May 2008 and April 2013. Median age was 49 years (18-65). For DLBCL patients IPI scores were 3 – 72 ( 64%), 4 -40 (35%) and 5 – 1 (1%). All patients received the modified CODOX-M and IVAC regimen including all CNS directed therapy( Mead et al Ann Oncol. 2002 Aug;13(8):1264-74) and 8 doses of rituximab. The primary end point of the study was Progression Free survival (PFS) and secondary endpoints included toxicity and CR rate. Results The main toxicities reported were neutropenia ( 89% grade 3 or 4), thrombocytopenia (84.2% grade 3 or 4), infection 61.6% grade 3 or 4 and mucositis (30.1% grade 3 or 4). 4 patients were excluded from toxicity assessment as they did not start therapy after registration. There were 8 treatment related deaths observed (infection with neutropenia (5), GI haemorrhage (1), acute cerebral haemorrhage (1) and bowel perforation (1) ). 78 patients with DLBCL and 31 with BL have completed all therapy ( 78.5 % of patients with available data) with an overall response rate of 92 % for DLBCl and 94% for BL. In patients who completed all therapy CR was achieved in 34 (44%), CR (u) in 8 (10%) and PR in 30 (38%) for DLBCL patients and CR was achieved in 21 (68%), CR (u) in 6 (19%) and PR in 2 (6%) in BL patients. 3 patients ( 2 DLBCL and 1 BL) who progressed during therapy have been included in the response analysis. End of treatment PET scanning was not obligatory. 80 patients with DLBCL and 30 patients with BL remain alive and without progression at a median follow up of 18.6 and 19.3 months respectively. Conclusion The R-CODOX-M -R-IVAC regimen can be delivered to patients with poor risk DLBCL in a multicentre setting. High rates of haematological toxicity and consequent infection are inevitable with treatment of this intensity but appear acceptable when compared with other treatments such as HDC+PBSCT. Response rates are encouraging in view of the very poor risk IPI profile of the patients included in this study. Burkitts Lymphoma patients also achieved an excellent response rate with no apparent additional toxicity attributable to the addition of rituximab to the regimen. We currently plan the first analysis for the primary endpoint of PFS in 2015. The Trial was supported by Leukaemia and Lymphoma Research (LLR). Disclosures: McMillan:Roche: Consultancy, Honoraria; Amgen: Research Funding. Off Label Use: Rituximab usage in Burkitts Lymphoma. Ardeshna:Roche: Honoraria, Research Funding. Jack:Roche/Genentech: Research Funding. Patmore:Roche: Consultancy, Honoraria. Pettengell:Roche: Honoraria; Amgen: Honoraria. Linch:Roche: Honoraria, Research Funding.
Jason S Knight - One of the best experts on this subject based on the ideXlab platform.
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Lymphoma after solid organ transplantation risk response to therapy and survival at a transplantation center
Journal of Clinical Oncology, 2009Co-Authors: Jason S Knight, Alexander Tsodikov, Diane M Cibrik, Charles W Ross, Mark S Kaminski, Douglas W. BlayneyAbstract:Purpose We studied the incidence, risk factors, treatment, and outcomes of post-transplantation lymphoproliferative disorder (PTLD) that occurred at the University of Michigan since 1964. Patients and Methods We identified 7,040 patients who received solid organ transplantation (SOT) and post-transplantation immunosuppressive therapy. Seventy-eight patients developed PTLD. Results Diffuse large B-cell Lymphoma (n = 43), polymorphic PTLD (n = 10), Hodgkin's Lymphoma (n = 7), Burkitts Lymphoma (n = 6), plasmacytoma (n = 5), and mucosa-associated lymphoid tissue Lymphoma (n = 3) were all over-represented in the SOT population compared with a population sample from the Surveillance, Epidemiology, and End Results (SEER) database; follicular Lymphoma (n = 0) was underrepresented. Negative pretransplantation Epstein-Barr virus (EBV) serology was a risk factor for PTLD. Available histologic analysis of tumor tissue showed that 75% were CD20 positive and that 62% were EBV positive; EBV-positive tumors occurred soo...
Toyoro Osato - One of the best experts on this subject based on the ideXlab platform.
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high irradiation sensitivity of epstein barr virus ebv in lymphoblastoid cells from patients with ataxia telangiectasia and ebv genome positive Burkitts Lymphoma
International Journal of Oncology, 1993Co-Authors: Motohiko Okano, Yukio Sakiyama, Shuzo Matsumoto, Fumio Mizuno, Toyoro OsatoAbstract:Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines derived from the peripheral blood of patients with ataxia telangiectasia (AT) and EBV genome-positive Burkitt's Lymphoma (BL) were tested for expression of EBV-related lytic antigens by means of irradiation. We used 1 Gy in each experiment, according to the results of the P3HR-1 (derived from African BL) cell line. Significantly higher expression of early antigens (EA) and viral capsid antigen (VCA) was demonstrated in lymphoblastoid cell lines derived from both patients with AT and those with EBV genome-positive BL, as compared to those derived from healthy individuals. These results suggested that defective regulating mechanisms on B lymphocytes, responsible for EBV infection, may underlie for the pathogenesis of development of lymphoproliferative diseases both in patients with AT and EBV genome-positive BL.
