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)

We investigated the graft-versus-myeloma effect (GVM) after allogeneic bone marrow transplantation (allo-BMT). Three patients with refractory multiple myeloma (MM) underwent related allo-BMT. Two of the patients showed disappearance of serum M protein 4 and 5 months after transplantation, respectively. One of them has remained in complete remission for more than 22 months after allo-BMT, with accompanying chronic GVHD. Two patients with relapse and disease progression after allo-BMT underwent donor lymphocyte infusion (DLI). Although one patient did not respond to DLI, the other developed acute GVHD after 4 weeks and achieved a 75% reduction in serum M protein. DLI did not produce severe acute GVHD or myelosuppression. These findings suggest the presence of a GVM effect. DLI may be an effective therapy for patients with MM who have relapsed after allo-BMT. Furthermore, non-myeloablative stem cell transplantation (mini-transplantation) for refractory MM should be investigated further as a potentially curative option.
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PMID:[Allogeneic bone marrow transplantation for refractory multiple myeloma: presence of a graft-versus-myeloma effect]. 1150 27

This study investigated the use of a nonablative conditioning regimen to decrease toxicity and achieve engraftment of an allogeneic blood stem cell transplant, allowing a graft-versus-malignancy effect to occur. All patients had follicular or small cell lymphocytic lymphoma after relapse from a prior response to conventional chemotherapy. Patients received a preparative regimen of fludarabine (25 mg/m(2) given daily for 5 days or 30 mg/m(2) daily for 3 days) and intravenous cyclophosphamide (1 g/m(2) given daily for 2 days or 750 mg/m(2) daily for 3 days). Nine patients received rituximab in addition to the chemotherapy. Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Twenty patients were studied; their median age was 51 years. Twelve were in complete remission (CR) at transplantation. All patients achieved engraftment of donor cells. The median number of days with severe neutropenia was 6. Only 2 patients required more than one platelet transfusion. The cumulative incidence of acute grade II to IV GVHD was 20%. Only one patient developed acute GVHD of greater than grade II. All patients achieved CR. None have had a relapse of disease, with a median follow-up period of 21 months. The actuarial probability of being alive and in remission at 2 years was 84% (95% confidence interval, 57%-94%). Nonablative chemotherapy with fludarabine/cyclophosphamide followed by allogeneic stem cell transplantation is a promising therapy for indolent lymphoma with minimal toxicity and myelosuppression. Further studies are warranted to compare nonablative allogeneic hematopoietic transplantation with alternative treatment strategies.
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PMID:Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. 1173 62

Donor lymphocyte infusion (DLI) can produce durable remissions in patients with chronic myelogenous leukemia (CML) who have a relapse after an allogeneic stem cell transplantation. However, the best modality to administer DLI is still unclear. The effect of the initial cell dose (ICD; ie, mononuclear cells x 10(8)/kg received in the first instance) on outcome was retrospectively analyzed in 298 of 344 patients treated with DLI at 51 centers. Patients were classified into 3 groups according to the ICD: 98 in group A (<or= 0.20), 107 in group B (0.21-2.0), and 93 in group C (> 2.0). Additional infusions were given to 62%, 20%, and 5% of patients in groups A, B, and C, respectively. A lower ICD was associated with less graft-versus-host disease (GVHD; A, 26%; B, 53%; C, 62%; P <.001), less myelosuppression (A, 10%; B, 23%; C, 24%; P =.01), and similar response rate (A, 78%; B, 73%; C, 70%; P =.48). Nonadjusted estimates of 3-year survival, failure-free survival, and DLI-related mortality were 84%, 66%, and 5% respectively, in group A; 63%, 57%, and 20% in group B; and 58%, 45%, and 22% in group C. Outcome analysis was adjusted for patient age, donor type, sex of donor, sex mismatch, disease phase at transplantation, T-cell depletion, interval from transplantation to DLI, GVHD prior to relapse, relapse type, and date of DLI. After adjustment, lower ICD was associated with less GVHD, less myelosuppression, same response rate, better survival, better failure-free survival, and less DLI-related mortality. Our results suggest that the first DLI dose should not exceed 0.2 x 10(8) mononuclear cells/kg.
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PMID:Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. 1209 28

Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic stem cell transplantation (SCT) received imatinib mesylate (400-1000 mg/d). Disease was in chronic phase in 5 patients, accelerated in 15, and blastic in 8 (7 medullary, 1 extramedullary); median time from transplantation to relapse was 9 months (range, 1-137 months). Thirteen patients had undergone salvage donor lymphocyte infusion (DLI) (median time from DLI to imatinib mesylate therapy, 4 months [range, 2-39 months]). The overall response rate was 79% (22 of 28 patients); the complete hematologic response (CHR) rate was 74% (17 of 23 patients), and the cytogenetic response rate was 58% (15 of 26 patients; complete response in 9 [35%] patients). CHR rates were 100% for chronic phase, 83% for accelerated phase, and 43% for blastic phase. The patient with extramedullary blastic disease achieved complete response. Cytogenetic response rates were 63% (12 of 19 patients) for chronic or accelerated phases (complete cytogenetic response in 8) and 43% for blastic phase (3 of 7 patients). At median follow-up of 15 months, 19 patients were alive, 9 with no evidence of disease. The 1-year estimated survival rate was 74%. Five patients had recurrence of grade 3 (3 patients) or grades 1 to 2 (2 patients) graft-versus-host disease (GVHD). Severe granulocytopenia developed in 43% of patients and thrombocytopenia in 27%; both conditions reversed with dose adjustments of imatinib mesylate. We conclude that imatinib mesylate effectively controlled CML that recurred after allogeneic SCT, but it was associated with side effects including myelosuppression and recurrence of severe GVHD.
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PMID:Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. 1252 95

Graft rejection and graft-versus-host disease are major problems in mismatched marrow transplants along with toxicity from standard myeloablative host treatments. We have established a tolerization model, using 1 Gy irradiation, which reduces stem cell capacity to < 10% of control while causing minimal myelosuppression, donor antigen pre-exposure (spleen cells), CD40-ligand antibody blockade and high levels of marrow (40 x 106 cells), which allows for stable long-term multilineage engraftment in H2-mismatched murine marrow transplants. We now show that the establishment of 'microchimaerism' (0.5-3.8%) sets the stage for macrochimaerism, with subsequent marrow infusions in H2-mismatched mice with CD40-ligand blockade only. Neither irradiation nor spleen cell exposure were necessary. When 40 x 106 bone marrow cells were infused on weeks 0, 12, 14 and 16, blood engraftment was about seven times the single 40 x 106 control. When marrow cells were given on weeks 0, 3, 4, 5 and 6, engraftment at 24 weeks post transplant was 17.9 +/- 1.2%, compared with 2.7 +/- 0.8% for the single 40 x 106 control (P = 0.009). We have shown stable, long-term multilineage chimaerism and established that the schedule of marrow administration, not the total cell dose, is critical for tolerization. This approach indicates that microchimaerism can tolerize for subsequent marrow infusions and produce macrochimaerism. This strategy could be applied in clinical human transplants.
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PMID:H2-mismatched transplantation with repetitive cell infusions and CD40 ligand antibody infusions without myeloablation. 1235 20

We describe a 51-year-old woman with recurrent follicular lymphoma from the age of 47 despite chemo-radio therapy, who subsequently underwent nonmyeloablative stem cell transplantation with conditioning consisting of fludarabine and low-dose total body irradiation (2 Gy). Myelosuppression was very mild, so the patient required no transfusions. Chimerism analysis from peripheral blood showed that T-cell mixed chimerism continued over 12 months after stem cell transplantation (the percentage of recipient T-cells was approximately 20%). Despite this, the lymphadenopathy disappeared, and the patient developed grade II acute GVHD (graft versus host disease). It has been considered that the establishment of full donor chimerism is required to induce GVHD and GVM (graft versus malignancy) effects. In this case, however, an allo-response was observed despite the persistence of T-cell mixed chimerism.
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PMID:[Persistent T-cell mixed chimerism in a case of malignant lymphoma after nonmyeloablative allogeneic peripheral blood stem cell transplantation]. 1250 89

Human herpesvirus (HHV)-6 and HHV-7 loads were evaluated retrospectively in peripheral blood mononuclear cells (PBMC) from 78 recipients of stem cell transplantation (SCT) by real-time polymerase chain reaction. The median HHV-6 load in patients was 1357 genome equivalent copies (EqCop)/10(6) PBMC but was below the quantitation threshold in 31 immunocompetent individuals, which strongly suggests that HHV-6 reactivation occurred after SCT. The HHV-6 load was higher in patients with delayed neutrophil engraftment (P=.002) or severe graft-versus-host disease (P=.009). Moreover, the occurrence of at least 1 HHV-6-related manifestation (fever, cutaneous rash, pneumonitis, or partial myelosuppression) was statistically associated with a concomitant virus load >10(3) EqCop/10(6) PBMC (P=.007). Conversely, HHV-7 reactivation was not favored, because median HHV-7 loads were similar in patients and healthy control subjects (1053 vs. 1216 EqCop/10(6) PBMC). The kinetics of Roseolovirus loads during the posttransplantation period suggested that HHV-7 may act as a cofactor of HHV-6 reactivation.
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PMID:Human herpesvirus (HHV)-6 and HHV-7: two closely related viruses with different infection profiles in stem cell transplantation recipients. 1255 42

Five cases of systemic Nocardia infection were diagnosed among 301 allogeneic bone marrow transplant recipients. A sixth case included in this report received her transplant at another institution. The cumulative annual incidence rate of this infection was 1.75%. All patients had been treated previously for acute graft-versus-host disease (GVHD). At the time of diagnosis of systemic Nocardia infection, a median of 198 (range 148-1121) days after transplantation, all patients had extensive chronic GVHD and were taking 2 to 3 immunosuppressive medications. Prior to diagnosis of Nocardia infection patients had experienced multiple opportunistic infections, including infections with Mycobacterium avium-intracellulare, Pneumocystis carinii, and cytomegalovirus antigenemia. Treatment with trimethoprim-sulfamethoxazole (TMP-SMX), ceftriaxone, or carbapenem antibiotics resulted in a median survival of 219 days from the time of diagnosis and an actuarial 1-year survival of 40%. All patients who received more than 2 weeks of therapy were cured of their infections. Notably, 5/6 patients in this cohort were unable to take TMP-SMX because of myelosuppression. In comparison with randomly selected control patients, the use of pentamidine for prevention of P. carinii infection was associated with a marginal increase in the risk of Nocardia infection. We postulate that the use of TMP-SMX may be of benefit in the prophylaxis of infections other than P. carinii in patients with chronic GVHD.
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PMID:Systemic nocardiosis following allogeneic bone marrow transplantation. 1279 Oct 70

Hematopoietic stem cell transplantation may be used to induce a graft-versus-tumor effect against a range of malignancies. Pretransplantation conditioning regimens vary considerably in their degree of myelosuppression and immunosuppression, which may result in marked differences in the rate of T-cell engraftment and, as a consequence, the onset and severity of graft-versus-host disease (GVHD). We have examined the development of T-cell chimerism and the onset of GVHD following fludarabine and melphalan conditioning in 39 patients undergoing stem cell allografts from matched-sibling donors. Cyclosporin and short-course methotrexate were used as GVHD prophylaxis. Fatal regimen-related toxicity occurred in 4 patients. Rapid T-cell engraftment was found in all but 1 of the patients assessed, with more than 90% donor T-cell chimerism at 1 month posttransplantation. Of the evaluable patients, 43% developed grade 2-4 acute GVHD and 87% developed chronic GVHD (70% extensive). Overall, the combination of fludarabine and melphalan is intensely immunosuppressive, leads to rapid T-cell engraftment and results in substantial toxicity and GVHD, particularly in heavily pretreated patients.
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PMID:Graft-versus-host disease, donor chimerism, and organ toxicity in stem cell transplantation after conditioning with fludarabine and melphalan. 1286 57

The aim of reduced-intensity allogeneic stem cell transplantation is to exploit the graft-versus-tumor effect and reduce the toxicity associated with traditional ablative preparative regimens. Reduced-intensity regimens often use a purine analog with chemotherapeutic agents or low-dose total body irradiation. Postgrafting immunosuppression is variable and often consists of cyclosporine or tacrolimus plus methotrexate or mycophenolate mofetil. Regimen-related toxicity may be reduced using this approach, with a reduction in early mortality. Acute and chronic graft-versus-host disease continue to be problematic and are the primary causes of treatment-related mortality. The degree of myelosuppression is dependent on the regimen and the postgrafting immunosuppression. Myelosuppression is modest after 200 cGy of total body irradiation (with or without fludarabine), but it is more significant after regimens that use a purine analog with robust doses of chemotherapy. Stable mixed or full donor chimerism occurs with most regimens and graft rejection is more common in recipients of unrelated grafts. Reduced-intensity regimens are active in most hematologic malignancies and in some solid tumors, although the data in solid tumors are limited. Data suggest that rapidly growing malignancies require a more intensive regimen than indolent malignancies or those in remission. Reduced-intensity approaches have an appeal for nonmalignant diseases treated by allotransplantation. No prospective randomized trials have compared reduced-intensity approaches with conventional allotransplant preparation or postgrafting immunosuppression after reduced-intensity allografting. However, the strategy holds great promise and offers the possibility of curative therapy for patients who are ineligible for an ablative transplant.
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PMID:Reduced-intensity allogeneic stem cell transplantation. 1290 24


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