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Borko Jovanovic - One of the best experts on this subject based on the ideXlab platform.

  • multicenter analysis of 80 solid organ transplantation recipients with post transplantation Lymphoproliferative Disease outcomes and prognostic factors in the modern era
    Journal of Clinical Oncology, 2010
    Co-Authors: Andrew M Evens, Kevin A David, Irene Helenowski, Beverly P Nelson, Dixon B Kaufman, Sheetal Mehta Kircher, Alla Gimelfarb, Elise Hattersley, Lauren Mauro, Borko Jovanovic
    Abstract:

    Purpose Adult Post-Transplantation Lymphoproliferative Disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. Methods We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) –related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P < .0001) ...

  • multicenter analysis of 80 solid organ transplantation recipients with post transplantation Lymphoproliferative Disease outcomes and prognostic factors in the modern era
    Meeting of the American Society of Hematology, 2010
    Co-Authors: Andrew M Evens, Kevin A David, Irene Helenowski, Beverly P Nelson, Dixon B Kaufman, Sheetal Mehta Kircher, Alla Gimelfarb, Elise Hattersley, Lauren Mauro, Borko Jovanovic
    Abstract:

    Purpose Adult Post-Transplantation Lymphoproliferative Disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. Methods We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) -related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21 % (P < .0001) and 33% (P = .0001), respectively, without rituximab. Notably, of all relapses, only 9% (4 of 34 patients) occurred beyond 12 months from PTLD diagnosis. On multivariate regression analysis, three factors were associated with progression and survival: CNS involvement (PFS, 4.70; P = .01; OS, 3.61; P = .04), bone marrow involvement (PFS, 2.95; P = .03; OS, 3.14; P = .03), and hypoalbuminemia (PFS, 2.96; P = .05; OS, 3.64; P = .04). Furthermore, a survival model by multivariate CART analysis that was based on number of adverse factors present (ie, 0, 1, ≥ 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11 %, respectively (P < .0001). Conclusion This large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.

Gregory Carey - One of the best experts on this subject based on the ideXlab platform.

  • A 2-Year Follow-Up of Post-Transplantation Malignancy in Renal Allograft Recipients Receiving Muromonab-CD3 for Immunosuppressive Induction Therapy
    Drug Investigation, 1992
    Co-Authors: Thomas P. Haverty, Marilyn Sanders, Gregory Carey
    Abstract:

    Muromonab-CD3 (OKT3) has been shown to be effective in the prevention and treatment of acute allograft rejection. However, prolonged treatment and repeated courses may be associated with an increased incidence of Post-Transplantation malignancy. In cardiac transplant recipients, total doses in excess of 75mg have been implicated as a cause of Post-Transplantation Lymphoproliferative Disease (LPD). A retrospective review was conducted in renal transplant recipients to evaluate the impact of muromonab-CD3 on the development of Post-Transplantation malignancy based on the data from a randomised prospective multicentre study that compared the efficacy and tolerability of muromonab-CD3 as induction therapy with that of a conventional immunosuppressive regimen. Patients who experienced a rejection episode could be treated (or retreated) with either muromonab-CD3 or corticosteroids. Of the 215 patients studied, 29 received muromonab-CD3 at a dosage exceeding 75mg and none of these patients developed malignancies. However, 3 malignant tumours were noted in the initial 12-month Post-Transplantation period: 2 basal cell carcinomas in the muromonab-CD3 induction therapy group (both patients received only 70mg of muromonab-CD3) and 1 adenocarcinoma in the conventional induction group. During the 2-year follow-up period, there was no significant difference in the incidence of malignancy between the 2 groups, and no Post-Transplantation LPDs were observed. No malignancies were noted in 4 patients who received multiple courses of muromonab-CD3 for rejection therapy or in 21 patients who received muromonab-CD3 for both induction and rejection therapy. In conclusion, the data show that the use of muromonab-CD3 as either induction therapy and/or rejection therapy in renal allograft recipients was not independently associated with an increased incidence of Post-Transplantation malignancy.

  • A 2-Year Follow-Up of Post-Transplantation Malignancy in Renal Allograft Recipients Receiving Muromonab-CD3 for Immunosuppressive Induction Therapy
    Drug Investigation, 1992
    Co-Authors: Thomas P. Haverty, Marilyn K. Sanders, Gregory Carey
    Abstract:

    Muromonab-CD3 (OKT3) has been shown to be effective in the prevention and treatment of acute allograft rejection. However, prolonged treatment and repeated courses may be associated with an increased incidence of Post-Transplantation malignancy. In cardiac transplant recipients, total doses in excess of 75mg have been implicated as a cause of Post-Transplantation Lymphoproliferative Disease (LPD). A retrospective review was conducted in renal transplant recipients to evaluate the impact of muromonab-CD3 on the development of Post-Transplantation malignancy based on the data from a randomised prospective multicentre study that compared the efficacy and tolerability of muromonab-CD3 as induction therapy with that of a conventional immunosuppressive regimen. Patients who experienced a rejection episode could be treated (or retreated) with either muromonab-CD3 or corticosteroids.

Andrew M Evens - One of the best experts on this subject based on the ideXlab platform.

  • multicenter analysis of 80 solid organ transplantation recipients with post transplantation Lymphoproliferative Disease outcomes and prognostic factors in the modern era
    Journal of Clinical Oncology, 2010
    Co-Authors: Andrew M Evens, Kevin A David, Irene Helenowski, Beverly P Nelson, Dixon B Kaufman, Sheetal Mehta Kircher, Alla Gimelfarb, Elise Hattersley, Lauren Mauro, Borko Jovanovic
    Abstract:

    Purpose Adult Post-Transplantation Lymphoproliferative Disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. Methods We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) –related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P < .0001) ...

  • multicenter analysis of 80 solid organ transplantation recipients with post transplantation Lymphoproliferative Disease outcomes and prognostic factors in the modern era
    Meeting of the American Society of Hematology, 2010
    Co-Authors: Andrew M Evens, Kevin A David, Irene Helenowski, Beverly P Nelson, Dixon B Kaufman, Sheetal Mehta Kircher, Alla Gimelfarb, Elise Hattersley, Lauren Mauro, Borko Jovanovic
    Abstract:

    Purpose Adult Post-Transplantation Lymphoproliferative Disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. Methods We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) -related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21 % (P < .0001) and 33% (P = .0001), respectively, without rituximab. Notably, of all relapses, only 9% (4 of 34 patients) occurred beyond 12 months from PTLD diagnosis. On multivariate regression analysis, three factors were associated with progression and survival: CNS involvement (PFS, 4.70; P = .01; OS, 3.61; P = .04), bone marrow involvement (PFS, 2.95; P = .03; OS, 3.14; P = .03), and hypoalbuminemia (PFS, 2.96; P = .05; OS, 3.64; P = .04). Furthermore, a survival model by multivariate CART analysis that was based on number of adverse factors present (ie, 0, 1, ≥ 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11 %, respectively (P < .0001). Conclusion This large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.

Dorothy H. Crawford - One of the best experts on this subject based on the ideXlab platform.

  • Expansion in scid mice of Epstein-Barr virus-associated Post-Transplantation Lymphoproliferative Disease biopsy material.
    Journal of General Virology, 2002
    Co-Authors: Ingolfur Johannessen, Sunimali M. Perera, Alice Gallagher, Paul A. Hopwood, J. Alero Thomas, Dorothy H. Crawford
    Abstract:

    Post-transplant Lymphoproliferative Disease (PTLD) biopsy material is rarely available in adequate quantity for research. Therefore, the present study was designed to expand biopsy material in scid mice. Epstein–Barr virus (EBV)+ve PTLD samples from five transplant patients were established in scid mice. PCR analysis of immunoglobulin gene rearrangements demonstrated that four of the five biopsies (80%) gave rise to scid tumours which represented the original tumour cell clones. Immunophenotyping showed that these four biopsies (and all scid tumours) expressed all EBV latent genes and a B lymphoblast phenotype; ≤26% T cells were found in the biopsy material whereas scid tumours showed a paucity of T lymphocytes. RT–PCR analysis revealed expression of IL-2, -4, -6, -10 and IFN-γ in all tumour material, suggesting key roles for these factors in tumour growth. The results show that EBV+ve PTLD material can be expanded in scid mice giving rise to quantities of homogeneous malignant tissue sufficient for research studies.

  • Expansion in scid mice of Epstein-Barr virus-associated Post-Transplantation Lymphoproliferative Disease biopsy material.
    The Journal of general virology, 2002
    Co-Authors: Ingolfur Johannessen, Sunimali M. Perera, Alice Gallagher, Paul A. Hopwood, J. Alero Thomas, Dorothy H. Crawford
    Abstract:

    Post-transplant Lymphoproliferative Disease (PTLD) biopsy material is rarely available in adequate quantity for research. Therefore, the present study was designed to expand biopsy material in scid mice. Epstein-Barr virus (EBV)+ve PTLD samples from five transplant patients were established in scid mice. PCR analysis of immunoglobulin gene rearrangements demonstrated that four of the five biopsies (80%) gave rise to scid tumours which represented the original tumour cell clones. Immunophenotyping showed that these four biopsies (and all scid tumours) expressed all EBV latent genes and a B lymphoblast phenotype;

Kevin A David - One of the best experts on this subject based on the ideXlab platform.

  • multicenter analysis of 80 solid organ transplantation recipients with post transplantation Lymphoproliferative Disease outcomes and prognostic factors in the modern era
    Journal of Clinical Oncology, 2010
    Co-Authors: Andrew M Evens, Kevin A David, Irene Helenowski, Beverly P Nelson, Dixon B Kaufman, Sheetal Mehta Kircher, Alla Gimelfarb, Elise Hattersley, Lauren Mauro, Borko Jovanovic
    Abstract:

    Purpose Adult Post-Transplantation Lymphoproliferative Disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. Methods We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) –related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P < .0001) ...

  • multicenter analysis of 80 solid organ transplantation recipients with post transplantation Lymphoproliferative Disease outcomes and prognostic factors in the modern era
    Meeting of the American Society of Hematology, 2010
    Co-Authors: Andrew M Evens, Kevin A David, Irene Helenowski, Beverly P Nelson, Dixon B Kaufman, Sheetal Mehta Kircher, Alla Gimelfarb, Elise Hattersley, Lauren Mauro, Borko Jovanovic
    Abstract:

    Purpose Adult Post-Transplantation Lymphoproliferative Disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. Methods We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) -related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21 % (P < .0001) and 33% (P = .0001), respectively, without rituximab. Notably, of all relapses, only 9% (4 of 34 patients) occurred beyond 12 months from PTLD diagnosis. On multivariate regression analysis, three factors were associated with progression and survival: CNS involvement (PFS, 4.70; P = .01; OS, 3.61; P = .04), bone marrow involvement (PFS, 2.95; P = .03; OS, 3.14; P = .03), and hypoalbuminemia (PFS, 2.96; P = .05; OS, 3.64; P = .04). Furthermore, a survival model by multivariate CART analysis that was based on number of adverse factors present (ie, 0, 1, ≥ 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11 %, respectively (P < .0001). Conclusion This large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.