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)

A 21-year-old male patient with non-Hodgkin's lymphoma (diffuse large T-cell type, clinical stage IV) received allogeneic bone marrow transplantation (BMT) from a partially HLA-mismatched unrelated donor in July 1998 and achieved complete remission. Thereafter, he suffered from chronic graft-versus-host disease (GVHD) and was continuously administered immunosuppressive drugs for a long time. Two years after the BMT, he complained of severe pain in the right knee, which was swollen, and was diagnosed as having pneumococcal purulent genual arthritis. He underwent arthroscopic synovectomy and was administered systemic and intra-articular antibiotics, leading to a gradual improvement. Streptococcal infections are often seen in patients in the late phase after allogeneic BMT because of immunodeficiency associated with chronic GVHD and hyposplenism. Most streptococcal infections are respiratory tract infections and septicemia, and there have been very few reports on cases of purulent genual arthritis. Administration of prophylactic antibiotics and control of chronic GVHD, which is a risk factor of pneumococcal infection, seem to be important to prevent purulent genual arthritis.
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PMID:Pneumococcal purulent genual arthritis after allogeneic bone marrow transplantation. 1202 38

Graft-versus-host disease (GVHD) is rare in the autologous setting. We describe a non-Hodgkin's lymphoma case developing acute GVHD after autologous peripheral blood stem cell transplantation following several lines of chemotherapy inclusive of fludarabine. At day +33, he complained of fever, diffused erythematous papulosis with ulceration of skin lesions. A punch biopsy indicated a grade III GVHD. A dose escalation of corticosteroids, cyclosporin-A and photoapheresis induced a transient response. He developed positivity to CMV and systemic aspergillosis. He died at day +185 in haematological complete remission, despite infection-oriented treatment. In spite of the use of prophylactic immunosuppressive drugs, between 50% and 70% of patients given HLA-identical marrow graft develop acute graft-versus-host disease (GVHD) that, in turn, significantly increases the risk of transplant-related mortality. Autologous BMT has been shown to be an effective procedure in several malignancies, persistently becoming a first-line choice in treating patients affected with lymphoproliferative disorders, specially non-Hodgkin's lymphoma (NHL). Although GVHD is a very rare event in the autologous setting (AuGVHD), a consistent number of reports dealing with GVHD-like phenomena has emerged, especially in breast cancer patients. More often, AuGVHD has been induced by the use of immunosuppressive agents, such as cyclosporin-A (CSA), in attempt to evoke a graft-versus-tumor (GVT) effect. However, AuGVHD is mild and self-limited phenomenon. We report the case of a NHL patient who developed unresponsive GVHD after autologous peripheral blood stem cell transplantation (PBSCT). Because of the immunosuppressive therapies, he developed systemic aspergillosis. He died in haematological complete remission despite infection-oriented treatment.
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PMID:Systemic aspergillosis in a patient with non-Hodgkin's lymphoma developing acute graft-versus-host disease after autologous peripheral blood stem cell transplantation. 1209 Nov 38

We present a 60-year-old patient with primary refractory non-Hodgkin's lymphoma and a 58-year-old patient with multiple myeloma with relapse after first autologous stem cell transplantation (ASCT), who underwent ASCT followed by allogeneic stem cell transplantation (alloSCT) with reduced intensity conditioning consisting of fludarabine and a single dose of total body irradiation. For graft-versus-host disease prophylaxis cyclosporine and mycophenolate mofetyl were given. Complete donor chimaerism was observed on d 28 after SCT. Both patients achieved sustained complete haematological and molecular remission of the immunoglobulin kappa light chain (Igkappa) rearrangement and are alive and well 17 and 16 months after SCT respectively.
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PMID:Continuous complete clinical and molecular remission in two patients with refractory lymphoid malignancies after autografting followed by allogeneic stem cell transplantation with reduced intensity conditioning. 1210 Jan 37

Intravenous busulfan (i.v. BU) has demonstrated safety when administered at 0.8 mg/kg per dose i.v. every 6 hours x 16 doses. We evaluated the safety and pharmacokinetics (PK) of giving the same total daily i.v. BU dose (3.2 mg/kg) either divided as a twice-daily infusion or as a single infusion to patients undergoing hematopoietic stem cell transplantation (HSCT). Twelve patients with hematologic malignant disease were treated; 7 patients had non-Hodgkin's lymphoma, 4 patients had acute myeloid leukemia, and 1 patient had chronic myelogenous leukemia. The first cohort (group A) received, on the basis of actual body weight, i.v. BU at 1.6 mg/kg per dose over 4 hours every 12 hours for 4 days (day -7 to day -4). The second cohort (group B) received 3.2 mg/kg per dose of i.v. BU (same total dose as group A) as a single infusion over 4 hours daily for 4 days. In both groups the i.v. BU was followed by cyclophosphamide 60 mg/kg daily for 2 days (day -3 and day -2). Blood specimens were collected on the first, fifth, and seventh doses for group A and on the first and fourth doses for group B to determine the disposition of i.v. BU. Peripheral blood stem cells (autologous in 7 cases and HLA-matched allogeneic in 5 cases) were given 2 days after completion of cyclophosphamide administration (day 0), and granulocyte colony-stimulating factor 5 microg/kg was started on the same day. GVHD prophylaxis consisted of tacrolimus plus methotrexate for recipients of allogeneic stem cells. One patient developed presumed fungal pneumonia and died of multisystem organ dysfunction on day +21 before hematologic reconstitution could be evaluated. Another was reported to have sudden death of undetermined cause at home on day 40. The remaining patients had engraftment (absolute neutrophil count >500/microL) at a median of 11 days and sustained platelet counts >20,000/microL at a median of 14 days. Significant regimen-related toxicity (grade III-IV) was limited to hepatic toxicity (2 cases) catheter infection (2 cases), epistaxis (3 cases), diarrhea (1 case), anorexia (1 case), mucositis (1 case), hyperglycemia (1 case), pneumonia (1 case), and sepsis (1). In group B there was 1 case of mild venoocclusive disease, which resolved without sequelae. No central nervous system or pulmonary toxicity was noted. Pharmacokinetic parameters, including clearance, half-life, maximum concentration, and area under the curve, demonstrated that the first dose profile was highly predictive of later dose PK profiles. No accumulation of the drug was noted. The change in dosing schedule did not increase toxicity or end-organ damage despite higher plasma concentration-times. Although further study for long-term efficacy is warranted, i.v. BU can be given safely with reproducible results on a twice-daily divided or single-daily dosing schedule to patients undergoing HSCT.
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PMID:Evaluation of safety and pharmacokinetics of administering intravenous busulfan in a twice-daily or daily schedule to patients with advanced hematologic malignant disease undergoing stem cell transplantation. 1237 50

Basiliximab, a chimeric interleukin-2 receptor (IL-2-R) antagonist, was evaluated in 17 patients with steroid-refractory acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT). Patients were transplanted from a related (n = 6) or unrelated (n = 11) HLA-identical donor because of acute lymphoblastic leukemia (n = 4), acute myeloid leukemia (n = 3), chronic myeloid leukemia (n = 7), myelodysplastic syndrome (n = 1), non-Hodgkin's lymphoma (n = 1), and multiple myeloma (n = 1). Basiliximab was given at a dose of 2 x 20 mg on 2 consecutive days after steroid-refractory acute GVHD had developed. Basiliximab was repeated on day 8 in cases of persistent GVHD. A median of four basiliximab infusions (range 1-12) were given to these patients. None had infusion-associated or cytokine-related side-effects after basiliximab. Twelve of 17 patients (71%) responded to basiliximab, 9/17 (53%) had a complete response (CR) of acute GVHD and 3/17 (18%) had a partial response (PR). Five of 17 patients (29%) did not respond. Chronic GVHD developed in 8/13 evaluable patients and only 2/8 had responded to basiliximab before. Five of 13 evaluable patients have no signs of chronic GVHD and all five had a CR or PR after basiliximab. This is the first report on the safety of basiliximab in patients with steroid-refractory acute GVHD. Our data suggest that basiliximab is effective in a substantial proportion of these patients.
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PMID:Basiliximab is well tolerated and effective in the treatment of steroid-refractory acute graft-versus-host disease after allogeneic stem cell transplantation. 1247 83

A patient with low-grade non-Hodgkin's lymphoma (NHL) who relapsed shortly after an allogeneic bone marrow transplant (BMT) is reported. The patient was treated with interleukin 2 (IL-2), which resulted in a flare-up of graft-versus-host disease followed by disease control, with disappearance of peripheral lymphadenopathy. Sequential bone marrow testing showed the disappearance of bone marrow involvement with disease but occurrence of T-cell aggregates post IL-2 that were identified as polyclonal by molecular methods. The patient remains in complete remission 37 months following allogeneic BMT.
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PMID:Complete remission of tumour with interleukin 2 therapy in a patient with non-Hodgkin's lymphoma post allogeneic bone marrow transplant associated with polyclonal T-cell bone marrow lymphocytosis. 1258 Sep 72

Post-transplant lymphoproliferative disorder (PTLD) represents a spectrum of Epstein-Barr virus-related (EBV) clinical diseases, from a benign mononucleosis-like illness to a fulminant non-Hodgkin's lymphoma. In the setting of hematopoietic stem cell transplantation, PTLD is an often-fatal complication occurring relatively early after transplant. Risk factors for the development of PTLD are well established, and include HLA-mismatching, T-cell depletion, and the use of antilymphocyte antibodies as conditioning or treatment of graft-versus-host disease. Early recognition of PTLD is particularly important in the SCT setting, because PTLD in these patients tends to be rapidly progressive. Familiarity with the clinical features of PTLD and a heightened level of suspicion are critical for making the diagnosis. Surveillance techniques with EBV antibody titers and/or polymerase chain reaction (PCR) may have a role in some high-risk settings. Immune-based therapies such as monoclonal anti-B-cell antibodies, interferon-alpha, and EBV-specific donor T cells, either as treatment for PTLD or as prophylaxis in high-risk patients, represent promising new directions in the treatment of this disease.
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PMID:Post-transplant lymphoproliferative disorder: a review. 1262 74

High-dose therapy with stem-cell transplantation is a potentially curative therapy for younger patients with relapsed aggressive non-Hodgkin's lymphoma (NHL) and is also under investigation in relapsed indolent NHL. There are, however, risks associated with this treatment strategy. Autologous stem-cell transplantation (ASCT) continues to be associated with a high risk of relapse, while graft-versus-host disease is a major limiting factor with allogeneic stem-cell transplantation. The presence of minimal residual disease (MRD) in the harvested, re-infused stem cells, or remaining in the patient following chemotherapy, is associated with relapse after ASCT. As a result, monitoring and eradicating MRD has become a major focus of many studies in NHL. Rearrangement and overexpression of the bcl-1 and bcl-2 genes are the hallmarks of mantle-cell and follicular lymphoma, respectively, and evidence suggests that they are promising surrogate markers of MRD. Polymerase chain reaction analysis is a sensitive methodology used to monitor the status of occult lymphoma cells bearing these genetic aberrations, and results from trials of ASCT have shown that clearance of bcl-1/JH- and bcl-2/JH-positive cells following treatment is associated with a significant improvement in outcome. Rituximab, the anti-CD20 monoclonal antibody, is increasingly used for in vivo purging and can effectively eradicate bcl-1/JH- and bcl-2-positive cells. If the encouraging preliminary results with rituximab are maintained with a longer follow-up, this agent could play a pivotal role in improving outcome after stem-cell transplantation in NHL.
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PMID:Stem-cell transplantation in non-Hodgkin's lymphoma: improving outcome. 1271 May 89

Donor lymphocyte infusions (DLI) are used to treat relapsed haematological diseases after allogeneic stem cell transplantation (SCT). We treated seven patients with DLI for indolent non-Hodgkin's lymphoma relapsed after SCT. In available blood and bone marrow samples, lymphoma cells were analysed by real-time quantitative polymerase chain reaction of t(14;18)-positive cells in follicular lymphoma, and by immunophenotyping in small lymphocytic lymphoma. Before DLI, three patients were treated with chemo- and/or radiotherapy, and one with rituximab. Evaluable responses to pre-DLI therapy were stable disease in one and partial remission (PR) in two patients. Six patients responded to DLI (complete remission (CR) in four and PR in two). After DLI, acute graft-versus-host disease (GVHD) occurred in 3/6 patients, classified as grade 2, whereas only limited chronic GVHD was seen (n=5). The four continuous CR are lasting for median 65+ (43-89) months. In the remaining patient, not responding to DLI, progressive disease was seen later on; chemotherapy followed by another DLI resulted in CR. In three cases, clinical responses to DLI could be substantiated by molecular or immunophenotypic analysis of lymphoma cells. We conclude that DLI is effective for treatment of indolent lymphoma relapsing after SCT.
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PMID:Graft-versus-lymphoma effect of donor lymphocyte infusion in indolent lymphomas relapsed after allogeneic stem cell transplantation. 1464 70

High-dose chemotherapy and allogeneic stem cell transplantation is a potentially curative therapy for younger patients with non-Hodgkin's lymphoma (NHL). The benefits of this therapy, however, are largely offset by the high rate of treatment-related mortality, exceeding 40% in many studies. Risks increase with comorbidities, advanced age, histocompatibility, and disease-related prognostic factors. Given the potential efficacy of graft-versus-malignancy effects against many lymphoid malignancies, we evaluated an alternative strategy utilizing less toxic, nonmyeloablative conditioning regimens to allow engraftment of donor cells, and then exploit the graft-versus-lymphoma (GVL) effects of allogeneic transplantation as the primary therapy. This strategy involved fludarabine-based preparative regimens +/- high-dose rituximab, graft-versus-host disease (GVHD) prophylaxis for 6 months, and donor lymphocyte infusion (DLI) only for progressive or nonresponding disease. Results from these trials confirm the full potential on nonmyeloablative transplantation for patients with NHL.
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PMID:Nonmyeloablative stem cell transplantation for lymphoma. 1497 Sep 33


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