Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with advanced hematological malignancies ineligible for conventional myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) due to advanced age or medical contraindications were enrolled in multi-center study to investigate the safety and efficacy of nonmyeloablative HSCT using a 2 Gy total body irradi ation (TBI)-based regimen. A total of 192 patients (median age 55) were treated with HLA-matched sibling peripheral blood stem cell (PBSC) grafts, and 63 patients (median age 53) received a 10 of 10 HLA-antigen matched unrelated donor (URD) HSCT (PBSC graft, n = 48; marrow graft, n = 15). Diagnoses included multiple myeloma (n = 61), myelodysplastic syndrome (n = 55), chronic myeloid leukemia (n = 31), non-Hodgkin lymphoma (n = 31), acute myeloid leukemia (n = 28), chronic lymphocytic leukemia (n = 24), Hodgkin Disease (n = 14). The conditioning regimen was fludarabine 30 mg/m2/d x 3 days and 2 Gy TBI. Ninety-five related HSCT patients received 2 Gy TBI without fludarabine. Postgrafting immunosuppression was combined mycophenolate mofetil an cyclosporine. Transplants were well tolerated with a median of 0 days of hospitalization in the first 60 days for eligible patients. For related HSCT recipients, median follow-up was 289 (100-1,188) days. Nonfatal graft rejection occurred in 6.8%. Of those with sustained engraftment, graft-versus-host disease (GVHD) occurred in 49% (33% grade II, 11% grade III, 5% grade IV). Day-100 non-relapse mortality was 6%. Overall, 59% (114/192) of patients were alive. The relapse/disease progression mortality was 18%, and non-relapse mortality was 22%. The projecte 2-year survival and progression-free survival were 50% and 40%. For the URD HSCT recipients, median follow-up was 190 (100-468) days. Graft rejection occurred in 27% (17/63) of patients, mostly in recipients of marrow grafts (9/15). Acute GVHD occurred in 63% (50% grade II, 13% grade III) of 46 engrafted patients. Chronic GVHD requiring therapy occurred in 50% of patients. Of the 63 URD HSCT patients, 54% were alive, 37% in CR, 3% PR, and 14% with disease progression or relapse. Related and unrelated nonmyeloablative HSCT is feasible and potentially curative in patients with advanced hematological malignancies who have no other treatment options.
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PMID:Related and unrelated nonmyeloablative hematopoietic stem cell transplantation for malignant diseases. 1243 Aug 51

The concept of utilizing enhanced immunosuppression rather than myeloablative cytotoxic conditioning has allowed the engraftment of allogeneic stem cells from related and unrelated donors with lower early transplant-related mortality (TRM) and morbidity. This approach shifts tumor eradication to the graft-vs-host immune response directed against minor histocompatibility antigens expressed on tumor cells. This is not without risk, as the long-term effects of graft-versus-host disease (GVHD), it's treatment, or resulting complications and immunodeficiency may be life threatening. However, this approach does allow the application of a potentially curative procedure to elderly or medically infirm patients who would not tolerate high-dose conditioning regimens. Section I, by Dr. Sandmaier, describes the current use of nonmyeloablative regimens and matched related or unrelated donors for the treatment of patients with CLL, CML, acute leukemia, MDS, lymphoma, and myeloma. In Section II, Dr. Maloney discusses the use of cytoreductive autologous followed by planned non-myeloablative allografts as treatment for patients with myeloma or NHL. This tandem transplant approach has a lower TRM than conventional high dose allografting. The nonmyeloablative allograft may allow the graft-versus-tumor (GVT) immune response to eradicate the minimal residual disease that causes nearly all patients with low-grade NHL or myeloma to relapse following autologous transplantation. In Section III, Dr. Mackinnon discusses the risks and benefits of T cell depletion strategies to prevent acute GVHD, while retaining GVT activity by planned donor lymphocyte infusions. Finally, in Section IV, Dr. Shizuru discusses the relationship between GVHD and GVT activity. Future studies, employing a greater understanding of these issues and the separation of GVHD from GVT activity by immunization or T cell cloning, may allow nonmyeloablative allogeneic transplantation to be safer and more effective.
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PMID:Non-myeloablative transplantation. 1244 34

We studied in 30 patients with progressive or relapsing chronic lymphocytic leukemia (CLL) if hematopoietic stem cell transplantation (HSCT) after conditioning with fludarabine, busulfan and ATG is effective and if treatment related mortality can be reduced compared to myeloablative conditioning regimens. Patients had 15 matched related and 15 matched unrelated donors. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine alone or a combination with "short course" methotrexate or mycophenolate mofetil. The median follow-up is 24 months. At last follow up 11 patients were in complete and 13 in partial remission. Six patients had stable or progressive disease. Late complete remissions occurred up to one year after transplantation and the number of patients with CR is still increasing. Four patients died due to treatment related complications resulting in a probability of treatment-related mortality of 15% (CI 95%, 1% to 29%) at 2 years. The probability of overall survival and progression free survival at two years was 79% and 61%, respectively. In conclusion, HSCT after reduced conditioning may lower the treatment-related toxicity and has the capacity to induce complete remissions.
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PMID:Reduced non-relapse mortality after reduced intensity conditioning in advanced chronic lymphocytic leukemia. 1261 Oct 75

Allogeneic stem cell transplantation (SCT) using reduced-intensity conditioning (RIC) has potential to be a promising treatment of aggressive chronic lymphocytic leukemia (CLL). Since available clinical data obtained with this novel approach are very limited, we have performed a survey on this issue. Data of 77 patients were collected from 29 European Group for Blood and Marrow Transplantation centers. Median age was 54 (30-66) years, and the median number of previous chemotherapy regimens was 3 (0-8). HLA-identical sibling donors were used in 81% of the cases. Moderate conditioning regimens (mainly low-dose total body irradiation (TBI) or fludarabine-cyclophosphamide combinations) were administered to 56% of the patients, whereas the remainder received more intense conditioning consisting of fludarabine-busulfan or high-dose melphalan combinations. In 40% of the patients, in vivo T-cell depletion (TCD) with anti-thymocyte globulin or CAMPATH-1H was part of the conditioning regimen. Cumulative treatment-related mortality (TRM) was 18% (95% CI 9; 27) after 12 months. Complete chimerism as well as best response was not achieved immediately post-transplant but took a median of 3 months to develop. The 2-year probability of relapse was 31% (95% CI 18; 44), with no event occurring later than 12 months post transplant in the absence of TCD. With one exception, relapses were not observed after onset of chronic graft-versus-host disease. Event-free and overall survival at 24 months were 56% (95% CI 43; 69) and 72% (95% CI 61; 83), respectively. The median follow-up was 18 (1-44) months. Donor lymphocyte infusions or secondary transplants were performed in 19 patients with insufficient disease control and/or incomplete donor chimerism post-transplant, leading to a response in seven patients (37%). Preliminary multivariate analysis identified less than PR at transplant (hazard ratio (HR) 3.5; P&<0.01) and alternative donor (HR 3.1; P=0.02) as significant risk factors for relapse, whereas number of previous regimens >2 (HR 5.4; P=0.03), TBI (HR 2.5; P=0.05), and alternative donor (HR 2.3; P=0.08) were risk factors for survival. We conclude that RIC might favorably influence the outcome after allogeneic SCT for CLL by reducing TRM while preserving graft-versus leukemia activity.
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PMID:Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning. 1275 Jun 95

Hematological malignancies in Jehovah's Witnesses are often difficult to cure since these patients deny transfusions. By a retrospective analysis, we report the possibility of treating some tumors, mostly hematological, with either autologous or allogeneic bone marrow transplantation (BMT) without blood support. Eight patients were evaluated, including lymphoma (two patients), acute lymphoblastic (one patient) and myeloblastic (one patient) leukemia, chronic lymphocytic leukemia (one patient), refractory anemia with blasts in transformation (one patient), chronic myeloid leukemia (one patient) and metastatic breast cancer (one patient). All patients experienced a severe cytopenia with no major side effects or life-threatening complications. We had four deaths: three from relapse and progression of the disease (at 5, 8 and 15 months after the stem cell infusion), and one from acute intestinal GVHD (at 2 months after the stem cell infusion). Four patients are in complete clinical remission (at 8, 10, 16 and 26 months after the stem cell infusion), and this was related to the disease outcome. We conclude that autologous and allogeneic BMT are feasible without the support of transfusions. We believe that this should be performed as soon as possible in the course of the disease.
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PMID:Myeloablative therapy and bone marrow transplantation in Jehovah's Witnesses with malignancies: single center experience. 1290 Jul 81

A CD8 murine monoclonal antibody-coated high-density microparticle (HDM) has been developed, which allows for the rapid depletion of CD8+ T cells from apheresis products by gravity sedimentation. We conducted a study to determine the efficacy and safety of CD8 depletion of donor lymphocyte infusions (DLI) to treat relapse after stem cell transplantation using the Eligix CD8-HDM Cell Separation System. Patients were targeted to receive 3 x 10(7) CD4+ T cells/kg. Nine patients were enrolled, three with CML, three myeloma, two CLL, and one NHL. A median of 1 x 10(10) mononuclear cells were obtained by apheresis and processed. The median depletion of CD8+ cells was 99.3% (97.8->99.5%). CD8 depletion was highly specific, with a median recovery of CD4+ cells of 75%. A median of 2.9 x 10(7) CD4+ cells/kg was infused. No infusional toxicity was noted. All CML patients achieved a complete molecular remission. A CLL patient demonstrated a complete response. One patient developed GVHD (grade II acute GVHD and subsequently chronic GVHD). The CD8-HDM Cell Separation System appears to be highly selective and effective in depleting CD8+ T cells from DLI apheresis products, and CD8-depleted DLI is capable of mediating a graft-versus-leukemia effect while minimizing GVHD.
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PMID:CD8+ cell depletion of donor lymphocyte infusions using cd8 monoclonal antibody-coated high-density microparticles (CD8-HDM) after allogeneic hematopoietic stem cell transplantation: a pilot study. 1513 87

The aim of this study was to investigate if graft-versus-leukemia (GVL) activity conferred by allogeneic stem cell transplantation (allo-SCT) is effective in chronic lymphocytic leukemia (CLL) with unmutated V(H) gene status. The kinetics of residual disease (MRD) were measured by quantitative allele-specific immunoglobulin heavy chain (IgH) polymerase chain reaction (PCR) in 9 patients after nonmyeloablative allo-SCT for unmutated CLL. Despite an only modest decrease in the early posttransplantation phase, MRD became undetectable in 7 of 9 patients (78%) from day +100 onwards subsequent to chronic graft-versus-host disease or donor lymphocyte infusions. With a median follow-up of 25 months (range, 14-37 months), these 7 patients remain in continuous clinical and molecular remission. In contrast, PCR negativity was achieved in only 6 of 26 control patients (23%) after autologous SCT for unmutated CLL and it was not durable. Taken together, this study shows for the first time that GVL-mediated immunotherapy might be effective in CLL with unmutated V(H).
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PMID:Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR. 1520 68

We report the preliminary results of 12 patients with advanced stage chronic lymphocytic leukemia (CLL) transplanted following reduced intensity conditioning (RIC. With a median of 22 months of follow-up, 9 patients are alive and 3 have died of progressive disease, graft-versus-host disease (GVHD) or toxic hepatitis. Acute grade I-III GVHD occurred in 33% of patients and chronic GVHD in 50%. Eight of the 12 patients achieved a complete remission (CR) and 2 patients a partial remission (PR). Donor lymphocyte infusion was effective in 6 patients. Event-free survival, progression-free survival and non-relapse mortality at 3 years were 68%, 42% and 16%, respectively. Our results show successful immunomodulation and reduction in tumor burden in high risk CLL.
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PMID:Reduced intensity conditioning allogeneic transplant for advanced chronic lymphocytic leukemia. 1525 53

We report the outcomes after reduced-intensity conditioning allogeneic stem cell transplantation (RIT) for non-Hodgkin lymphoma (NHL) in 88 patients (low-grade NHL [LG-NHL], n = 41; high-grade NHL [HG-NHL], n = 37; mantle cell lymphoma [MCL], n = 10). Thirty-seven patients had previously received autografts, and 21 were in complete remission (CR) at transplantation. Conditioning therapy consisted of alemtuzumab, fludarabine, and melphalan. Sixty-five patients received peripheral blood stem cells (PBSCs) from HLA-identical siblings, and 23 received bone marrow (BM) from matched unrelated donors. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporin A. Grade III-IV acute GVHD developed in 4 patients, and chronic GVHD developed in 6 patients. With a median follow-up of 36 months (range, 18-60 months), the actuarial overall survival (OS) rates at 3 years were 34% for HG-NHL, 60% for MCL, and 73% for LG-NHL (P < .001). The 100-day and 3-year transplant-related mortality (TRM) rates for patients with LG-NHL were 2% and 11%, respectively, and were better (P = .01) than they were for patients with HG-NHL (27% and 38%, respectively). The actuarial current progression-free survival (PFS) rate at 3 years, including the rate for patients who achieved remission after donor lymphocyte infusion (DLI) for progression, was 65% for LG-NHL, 50% for MCL, and 34% for HG-NHL (P = .002). Twenty-one patients underwent DLI for matched related donor (MD)-persistent disease or relapse, and 15 underwent DLI for mixed hematopoietic chimerism. Patients who experienced relapses of LG-NHL and chronic lymphocytic leukemia (CLL) achieved excellent PFS with extremely low TRM and GVHD, even when matched related donors were unavailable.
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PMID:Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. 1530 95

Alemtuzumab is a humanized therapeutic monoclonal antibody (MAb) that recognizes the CD52 antigen, expressed on normal and neoplastic lymphocytes, monocytes, and natural killer cells. In 2001, alemtuzumab was approved in the US and Europe to treat B-cell chronic lymphocytic leukemia (CLL) that had been treated previously with alkylating agents and was refractory to fludarabine. In heavily pretreated patients this MAb is able to produce response rates of about 40%, and in symptomatic, previously untreated patients response rates of more than 80% can be achieved. Alemtuzumab can also be used in patients with CLL as a preparative regimen for stem cell transplantation (SCT) and to prevent graft versus host disease. Moreover its in vivo use before or after SCT may also potentially result in depletion of residual leukemia cells, especially in the autologous setting. Adverse events associated with alemtuzumab include acute first-dose reaction, hematologic toxicity, and infectious complications. Usually they are predictable, manageable, and acceptable in the context of CLL. However, in a significant percentage of patients, cytomegalovirus reactivation occurs during alemtuzumab therapy, and routine weekly monitoring with the polymerase chain reaction methodology is indicated. Moreover, antiviral and antibacterial prophylaxis is mandatory.
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PMID:Alemtuzumab in the treatment of chronic lymphocytic leukemia. 1569 Dec 13


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