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Koen Van Besien

Publications and source records attributed to Koen Van Besien.

9 recordsLinked to original sources
PubMed2006

The evolving role of autologous and allogeneic stem cell transplantation in follicular lymphoma.

Treatment options for follicular lymphoma have expanded dramatically. The most important relate to the introduction of monoclonal antibodies and the completion of important studies regarding autologous and allogeneic transplantation. The EBMTR-sponsored "CUP Trial" (conventional Chemotherapy, Unpurged autograft, Purged autograft), demonstrated that for patients under age 60 years with recurrent chemotherapy-sensitive disease, autologous stem cell transplantation (ASCT) provides a survival benefit over conventional therapy. Three randomized studies demonstrated that consolidation with autologous transplantation in first remission leads to improvement in progression free survival and perhaps in overall survival, but possibly with an increased risk for secondary MDS. Novel approaches involve the incorporation of rituximab as an in-vivo purging agent or as post-transplant therapy, and the use of radiolabelled monoclonals in the conditioning regimens. Allogeneic stem cell transplantation (alloSCT) has become a more effective option but continues to have a high TRM. Reduced-intensity alloSCT procedures now are being performed at an increasing rate and may have advantages in particular situations. A CIBMTR analysis unfortunately did not show a major advantage in terms of TRM or EFS to non-myeloablative transplantation. Performance status and disease sensitivity remain the major predictors of outcome for allogeneic transplantation.

Bone Marrow Purging↗
PubMed2006

Order of patient entry influences outcome for metastatic renal cell cancer after non-myeloablative allogeneic stem cell transplantation.

Allogeneic transplantation for renal cell carcinoma has shown encouraging preliminary results. We reviewed the published literature to evaluate the impact of patient selection. Most studies did not include information on prognostic factors. We used patient entry rank within individual studies as a novel surrogate for patient selection, motivated by our own experience of an apparent impact of entry rank. One hundred patients were identified from nine studies. Twenty-six per cent of patients demonstrated either a partial or complete response. Median overall survival was 12.3 months. Grade 2-4 acute graft-versus-host disease correlated with an increased likelihood of response (odds ratio: 5.4, 95% confidence interval: 1.6-18.1, P = 0.006) but not survival. Earlier patient entry rank on each trial was associated with a higher probability of response (P = 0.004) and superior survival (P = 0.004). Patient entry rank served as a powerful prognostic factor, suggesting bias in patient selection that evolved over the course of the study. Further studies are warranted to determine the influence of order of patient entry in other early clinical trial settings.

Acute Disease↗
PubMed2005

Simultaneous generation of CD8+ and CD4+ melanoma-reactive T cells by retroviral-mediated transfer of a single T-cell receptor.

Adoptive immunotherapy of cancer requires the generation of large numbers of tumor antigen-reactive T cells for transfer into cancer patients. Genes encoding tumor antigen-specific T-cell receptors can be introduced into primary human T cells by retroviral mediated gene transfer as a potential method of providing any patient with a source of autologous tumor-reactive T cells. A T-cell receptor-specific for a class I MHC (HLA-A2)-restricted epitope of the melanoma antigen tyrosinase was isolated from a CD4(+) tumor-infiltrating lymphocyte (TIL 1383I) and introduced into normal human peripheral blood lymphocytes by retroviral transduction. T-cell receptor-transduced T cells secreted various cytokines when cocultured with tyrosinase peptide-loaded antigen-presenting cells as well as melanoma cells in an HLA-A2-restricted manner, and could also lyse target cells. Furthermore, T-cell clones isolated from these cultures showed both CD8(+) and CD4(+) transduced T cells could recognize HLA-A2(+) melanoma cells, giving us the possibility of engineering class I MHC-restricted effector and T helper cells against melanoma. The ability to confer class I MHC-restricted tumor cell recognition to CD4(+) T cells makes the TIL 1383I TCR an attractive candidate for T-cell receptor gene transfer-based immunotherapy.

CD4-Positive T-Lymphocytes↗
PubMed2005

Autologous and allogeneic stem cell transplantation in follicular lymphoma.

Follicular non-Hodgkin's lymphomas (NHL) usually present in advanced stage and although frequently are chemotherapy-sensitive remain incurable using conventional approaches. Treatment options are evolving rapidly and now include targeted therapies such as monoclonal antibodies. Recent studies, including the EBMTR-sponsored "CUP Trial" (conventional Chemotherapy, Unpurged autograft, Purged autograft), demonstrate that for patients under age 60 years with recurrent chemotherapy-sensitive disease, autologous stem cell transplantation (ASCT) provides a survival benefit over conventional therapy. Allogeneic stem cell transplantation (alloSCT) has become a more effective option. Although incorporation of TBI into the preparative regimen may increase treatment-related mortality (TRM), relapses appear to be reduced compared to a chemotherapy-alone regimen. Reduced-intensity alloSCT procedures now are being performed at an increasing rate, in part due to a lower risk for TRM. Until more data are available, however, reduced-intensity alloSCT should be considered only in cases where myeloablative conditioning is contra-indicated. There are no clear means for choosing ASCT versus alloSCT, a decision influenced by amount of residual tumor, disease-responsiveness, degree of marrow involvement and extent of prior chemotherapy. ASCT or alloSCT in first remission remains an investigational procedure. Future considerations include incorporation of novel preparative regimens, in vitro purging techinques, anti-lymphoma vaccines, post-transplant immunotherapy and ex vivo-manipulated donor lymphocyte infusions.

Clinical Trials as Topic↗
PubMed2004

Phase II study of autologous transplantation with interleukin-2-incubated peripheral blood stem cells and posttransplantation interleukin-2 in relapsed or refractory non-Hodgkin lymphoma.

Previous work suggested that interleukin (IL)-2 can be used for eradicating residual disease in autologous grafts and for preventing recurrence. We report a phase II study of autologous peripheral blood stem cell transplantation with in vitro IL-2 incubation of peripheral blood stem cells and posttransplantation IL-2 in patients with recurrent or refractory non-Hodgkin lymphoma. Salvage chemotherapy consisted of ifosfamide and etoposide. Responding patients underwent autologous peripheral blood stem cell transplantation. IL-2-incubated stem cells were infused on day 0. IL-2 1 mIU/m2 was given from day 1 until day 28. Four monthly maintenance cycles of IL-2 4 mIU/m2 subcutaneously twice daily days 1 to 5 and days 8 to 11 were administered thereafter. Eighty-four evaluable patients were enrolled, and 60 proceeded to transplantation, of which 56 received IL-2-incubated stem cells. The average received dose of posttransplantation IL-2 was 30% to 50% of planned. Only 42 patients received maintenance IL-2. The average received maintenance dose of IL-2 was also approximately 30% of planned. Most dose reductions were due to toxicity or patient refusal. Three-year survival and progression-free survival for all registered patients were 43% (95% confidence interval [CI], 33%-53%) and 31% (95% CI, 21%-41%), respectively. For the 60 patients undergoing transplantation, they were 59% (95% CI, 46%-72%) and 44% (95% CI, 31%-57%), respectively. There was no relation between the dose of IL-2 received and outcome. Survival and disease-free survival of the study group were similar to those of a previous study cohort that received unmanipulated stem cells and no systemic IL-2. Administration of IL-2-incubated peripheral blood stem cells and intensive posttransplantation IL-2 was associated with considerable but rapidly reversible toxicity. No effect on long-term outcome was observed.

Adult↗
PubMed2004

Low-grade lymphoma.

Folicular lymphoma (FL), the second most common subtype of non-Hodgkin lymphoma, shows considerable heterogeneity in its clinical behavior, representative of a biology that appears increasingly complex and diverse. As our knowledge of the molecular basis of FL increases, we strive for an integration between the bench and clinic that yields treatments based on our scientific understanding and biomarkers that allow us to prescribe treatment rationally. In Section I, Dr. Randy Gascoyne describes the histologic, cytogenetic and biologic features of FL that underlie its clinical variability. Key aspects of the pathologic diagnosis of FL that have particular relevance to the clinician are highlighted. A proposed model for follicular lymphomagenesis and diffuse large B cell lymphoma transformation has emerged and continues to evolve as the molecular story unfolds. A biologic basis for clinical outcome in FL also appears to be forthcoming. In Section II, Dr. Jane Winter addresses the complex process of selecting among the many treatment options for patients with FL. Previously a simple matter of deciding between oral or intravenous alkylators, clinicians and patients must now struggle to choose among vastly different approaches ranging from "watch and wait" to stem cell transplantation. The introduction of rituximab and radioimmunoconjugates is changing the treatment paradigm, but the optimal approach to integrating these and other new agents remains to be determined. At every decision point, the best approach is always a clinical trial. In Section III, Dr. Koen Van Besien provides a well-documented update on outcomes associated with autologous and allogeneic stem cell transplantation for FL. The results of trials of autologous stem cell transplantation in first remission and recent data supporting a role for graft purging are discussed. Based on the premise that a graft-versus-lymphoma effect is operative in FL, reduced-intensity allogeneic transplantation is the preferred approach in many cases, and recently reported results are summarized. Criteria for patient selection and the optimal role of transplantation in the overall therapeutic plan for the patient with FL are presented.

Antineoplastic Agents↗
PubMed2002

A comparison of allogeneic and autologous bone marrow transplantation for lymphoblastic lymphoma.

Lymphoblastic lymphoma (LBL) is a rare, clinically aggressive neoplasm of the young that frequently involves the bone marrow (BM) and/or central nervous system. Because LBL is similar to acute lymphoblastic leukemia, some centers prefer allogeneic hematopoietic stem cell (SC) transplantation to autologous SC transplantation. We retrospectively analyzed outcomes for patients who underwent autologous (auto, n = 128) or HLA-identical sibling (allo, n = 76) SC transplantations from 1989 to 1998 and were reported to International Bone Marrow Transplant Registry (IBMTR) or Autologous Blood and Marrow Transplant Registry (ABMTR). Allo stem cell transplant (SCT) recipients had higher treatment-related mortality (TRM) at 6 months (18% versus 3%, P =.002), and this disadvantage persisted at 1 and 5 years. Early relapse rates after alloSC transplantation and autoSC transplantation were similar, but significantly lower relapse rates were observed in alloSCT recipients at 1 and 5 years (32% versus 46%, P =.05; and 34% versus 56%, P =.004, respectively). No differences were noted in lymphoma-free survival rates between alloSC transplantations and autoSC transplantations (5-year rates 36% versus 39%, P =.82). AutoSCT recipients had higher overall survival at 6 months (75% versus 59%, P =.01), but survival did not significantly differ between the 2 groups at 1 and 5 years (60% versus 49%, P =.09; 44% versus 39%, P =.47, respectively). Multivariate analyses to account for confounding factors confirmed these results. Independent of SCT type, BM involvement at the time of transplantation and disease status more advanced than first complete remission were associated with inferior outcomes. In summary, alloSC transplantation for LBL is associated with fewer relapses than with autoSC transplantation, but higher TRM offsets any potential survival benefit.

Adolescent↗
PubMed2002

Cutting edge: activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia.

Myelosuppressive cytokines, in particular IFN-gamma and TNF-alpha, play an important role in the pathogenesis of idiopathic aplastic anemia in humans. It is unknown whether these negative regulators of hemopoiesis suppress stem cells by activating a common signaling cascade or via distinct nonoverlapping pathways. In this study, we provide evidence that a common element in signaling for IFN-gamma and TNF-alpha in human hemopoietic progenitors is the p38/MapKapK-2 signaling cascade. Our studies indicate that pharmacological inhibition of p38 reverses the suppressive effects of IFN-gamma and TNF-alpha on normal human bone marrow-derived erythroid and myeloid progenitors. Most importantly, inhibition of p38 strongly enhances hemopoietic progenitor colony formation from aplastic anemia bone marrows in vitro. Thus, p38 appears to play a critical role in the pathogenesis of aplastic anemia, suggesting that selective pharmacological inhibitors of this kinase may prove useful in the treatment of aplastic anemia and other cytokine-mediated bone marrow failure syndromes.

Anemia, Aplastic↗