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

A 9-year-old boy was admitted with the diagnosis of myelodysplastic syndrome (FAB RAEB in T). The patient was treated with busulfan and cyclophosphamide and transplanted with bone marrow cells from an HLA identical sister. Cyclosporin A (CyA) and short term methotrexate (MTX) was given for prophylaxis against graft versus host disease (GvHD). The serum potassium value was observed to increase to 6.3 mEq/l during the period of CyA therapy. The serum potassium value returned to 4 mEq/l when CyA treatment was decreased to a serum concentration of less than 50 ng/ml (FPIA). On day 90 post transplantation the patient was diagnosed as relapsed. The patient was preconditioned with cyclophosphamide and total body irradiation and a second bone marrow transplantation was performed using cells from the same donor. He was treated again with CyA and short term MTX for the prevention of GvHD. Once again the patient became hyperkalemic with 6.8 mEq/l. The serum creatinine level was 0.9 mg/dl, the GFR was 52.1 ml/min, FEK was 7.1%. Pseudohypoaldosteronism or hyporeninemic hypoaldosteronism was suspected. To investigate this possibility a renin/aldosterone stimulation test was performed. We speculate that an idiosyncratic response to CyA resulted in pseudohypoaldosteronism and produced a defect in potassium secretion.
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PMID:[Hyperkalemia in a cyclosporine A-treated allogeneic bone marrow transplant recipient]. 154 16

A 36-year-old man was diagnosed as having RAEB in 1986, and required blood transfusion regularly because of severe anemia. He received the first bone marrow transplantation following total-body irradiation and etoposide infusion in October 1987. He was found to be relapsed into RAEB on 106th day after BMT. And the second BMT was planned. According to the conditioning regimen of Tutschka, et al, we administrated busulfan and cyclophosphamide before re-transplantation. On 26th day after BMT, the WBC count exceeded 1,000/microliters and anemia was improved, while thrombocytopenia persisted until 50th day. Normal hematopoiesis in the bone marrow was confirmed on the 29th day. No severe side effect except for a little fevering and bleeding was found during the clinical course. Unfortunately he died of pneumonia following graft versus host disease on the 166th day after re-BMT. This new conditioning regimen is considered to be a choice for the high risk patients on re-transplantation.
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PMID:[Bone marrow re-transplantation following a busulfan and cyclophosphamide regimen]. 221 94

A 49-year-old man with myelodysplastic syndrome (MDS, RAEB in T) who relapsed following allogeneic bone marrow transplantation (allo BMT) was treated with infusions of donor buffy coat leukocytes. He sustained hematologic and cytogenetic remission, but severe graft-versus-host disease (GVHD) developed for which cyclosporin A and prednisolone were required. This therapeutic approach appears to be valuable for relapsed MDS following allo BMT as well as for chronic myelogenous leukemia (CML).
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PMID:Donor buffy coat infusions for a patient with myelodysplastic syndrome who relapsed following allogeneic bone marrow transplantation. 853 26

Between December 1981 and March 1994, 24 patients with a myelodysplastic syndrome (MDS) underwent allogeneic bone marrow transplantation (BMT) for RA with trilineage dysplasia (n = 4), CMML (n = 1), RAEB (n = 4), RAEBt (n = 9) and AML following MDS (n = 6). Fifteen patients (two RAEB, seven RAEBt and six sAML) received chemotherapy before BMT resulting in complete remission in 10 patients (six RAEBt and four sAML) at the time of BMT. Sixteen marrow donors were genotypically HLA-identical siblings. Remaining donors were other family members (five) or unrelated donors (three). The status of the underlying disease at the time of conditioning was the major factor determining long-term survival. The disease-freed survival of RA patients and patients presenting with RAEB, RAEBt and AML but transplanted in complete remission, was respectively 50 and 60%. On the contrary, none of the nine high-risk MDS patients transplanted with persistent disease, survived. Outcome after transplantation with alternative donors was inferior with one long-term survivor, mainly related to the high incidence of severe acute GVHD and its accompanying infectious complications. Six patients relapsed resulting in an actuarial probability of relapse of 28%. Twelve patients died of transplant-related complications leading to a non-relapse mortality at 5 years of 50%. At present eight patients are alive and disease-free 20 to 132 months post-transplantation resulting in an actuarial 5-year disease-free survival of 40.7%. Our results suggest that allogeneic bone marrow transplantation is a feasible treatment option for patients with MDS. However, improvement in GVHD prophylaxis and supportive care to reduce transplant-treated mortality and improved relapse prevention are imperative.
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PMID:Treatment of patients with myelodysplastic syndromes with allogeneic bone marrow transplantation from genotypically HLA-identical sibling and alternative donors. 873 92

Umbilical cord blood (CB) has been widely used for related and unrelated transplants in pediatric patients. We present the case of an adult with secondary AML who received an unrelated, one-antigen mismatched CB transplant due to the lack of a matched donor. The patient was a 26-year-old female (35 kg/bw) who had received an autologous bone marrow transplant for Hodgkin's disease in April 1994 and, 6 months later, developed secondary MDS (RAEB, 46, XX, -7, +mar), which slowly evolved into acute myelogenous leukemia. In May 1995, she was transplanted with a 165 ml CB unit containing a total of 1.6 x 10(9) nucleated cells, 11 x 10(6) CD34+ cells and 7.2 x 10(5) CFU-GM. GVHD prophylaxis consisted of standard CsA and methotrexate. Myeloid engraftment occurred on day +28 (PMN > 500) and full donor chimerism was confirmed twice (on days +33 and +56) by means of cytogenetics and DNA microsatellite analysis. Erythroid and megakaryocytic engraftment was documented by immunohistochemical analysis of a bone marrow biopsy on day +40, showing the presence of erythroblastic islands and isolated CD61+ immature cells. The patient did not develop GVHD but died on day +56 from idiopathic interstitial pneumonia and multiorgan failure. To our knowledge, this is one of the first case reports of unrelated mismatched CB transplantation in an adult.
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PMID:Unrelated mismatched cord blood transplantation in an adult with secondary AML. 886 67

A 36-year-old woman with RAEB-t and severe bone marrow fibrosis undergoing autologous BMT, developed a histologically documented GVHD-like skin rash. Thereafter, autoimmune thyroiditis, autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia and a lupus anti-coagulant (LAC) were diagnosed. The patient is still alive, symptom-free and in first complete remission (CR); however, all of the autoantibodies are still detectable, with the exception being the anti-erythrocyte antibody. The most outstanding feature of the present case is the polymorphism of the autoimmune events, in the absence of a coexisting systemic autoimmune disease. This patient has achieved long-term disease-free survival (DFS) in first CR despite high-risk MDS and the repeated immunosuppressant therapy required because of the complications described above; a GVL reaction somewhat similar to the autoimmune events may have contributed towards maintaining disease control.
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PMID:Multiple autoimmune events after autologous bone marrow transplantation. 915 54

Allogeneic bone marrow transplantation (BMT) offers a potential cure for younger patients with myelodysplastic syndromes (MDS) or secondary acute myeloid leukemia (sAML). More than 600 patients from 50 European centers have now been reported to the European Group for Blood and Marrow Transplantation (EBMT). We retrospectively analyzed 131 patients reported to the Chronic Leukemia Working Party of the EBMT who underwent BMT from HLA-identical siblings without prior remission induction chemotherapy. At the time of BMT 46 patients had refractory anemia (RA) or RA with ringed sideroblasts, 67 patients had more advanced MDS subtypes and 18 patients had progressed to sAML. The 5-year disease-free (DFS) and overall survival (OS) for the entire group of patients was 34 and 41%, respectively. Fifty patients died from transplant-related complications, most commonly graft-versus-host disease and/or infections. Relapse occurred in 28 patients between 1 and 33 months after BMT, resulting in an actuarial probability of relapse of 39% at 5 years. DFS and OS were dependent on pretransplant bone marrow blast counts. Patients with RA/RARS, RAEB, RAEB/T and sAML had a 5-year DFS of 52, 34, 19 and 26%, respectively. The 5-year OS for the respective patient groups was 57, 42, 24 and 28%. In a multivariate analysis, younger age, shorter disease duration, and absence of excess of blasts were associated with improved outcome. From these data we conclude that patients with myelodysplasia who have appropriate marrow donors, especially those aged less than 40 years and those with low medullary blast cell count should be treated with BMT as the primary treatment early in the course of their disease. Transplantation early after establishing the diagnosis of MDS may improve prognosis due to a lower treatment-related mortality and a lower relapse risk.
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PMID:Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. 948 48

The Chronic Leukemia Working Party of the EBMT has collected data on 118 patients of median age 24 years (range 0.3 to 53 years) who underwent an allogeneic bone marrow transplantation from unrelated donors for treatment of MDS or secondary AML (RA/RARS, n = 24; RAEB, n = 26; RAEB-t, n = 34; CMML, n = 12; sAML, n = 22) between 1986 and 1996. The data were reported by 49 EBMT centers. Thirty-four of 118 patients are alive, relapse was the cause of death in 19 of 84 patients and the remaining patients died of transplant-related mortality. For the whole group the actuarial probability of survival at 2 years is 28%, disease-free survival 28%, relapse risk 35% and transplant-related mortality is 58%. The transplant-related mortality is significantly influenced by the age of the recipient (<18 years 40%, 18-35 years 61%, >35 years 81%). The relapse rate after BMT is influenced by FAB classification of the disease at BMT. Patients with a low blast count (RA, RAEB) have a lower probability of relapse (13%, 15%) compared to patients with RAEB-t or sAML (29%, 45%). Furthermore, we found evidence of a graft-versus-leukemia effect in MDS/sAML. Patients with acute GVHD, grade II-IV, had a probability of relapse of 26% vs 42% in patients with no acute GVHD or grade I only. Allogeneic transplantation with an HLA-matched, unrelated donor may be offered to younger patients (age <35 years) with poor risk myelodysplasia or secondary AML.
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PMID:Unrelated bone marrow transplantation in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: an EBMT survey. European Blood and Marrow Transplantation Group. 967 54

Donor leukocyte infusions (DLI) from the original marrow donor have been shown to induce remission in patients with relapse after BMT. We analyzed factors that were associated with remission. Twenty-six patients with a relapse after T cell depleted BMT received DLI. The following pre-DLI factors were analyzed: sex and age of the patients and donors, GVHD after BMT, indication for DLI, percentage of donor T lymphocytes in the patient at the time of DLI, interval between relapse and DLI, and number of T lymphocytes infused. Remission was achieved in 11 of 15 patients (73%) treated for relapsed CML and in one of 11 patients (9%) treated for relapsed AML, ALL or RAEB-t (P = .002). Two of 13 patients (15%) with < or =40% of T lymphocytes from donor origin attained remission compared with 10 of 13 patients (77%) with >40% (P = .002). Two of 13 patients (15%) with an interval of < or =18 months between BMT and first DLI entered remission compared with 10 of 13 patients (77%) with an interval of >18 months (P = .002). Multivariate analysis demonstrated that indication for DLI (CML versus AML/ALL and RAEB-t) and the percentage T lymphocytes from donor origin (< or =40 versus >40) were significantly correlated with remission (P = .03). The occurrence of GVHD post DLI was highly associated with achievement of remission (P = .0001). DLI res ults in remission in a high percentage of patients with relapsed CML after BMT. The percentage of T lymphocytes from donor origin still present in the patient at the time of DLI is highly correlated with achievement of remission.
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PMID:In relapsed patients after lymphocyte depleted bone marrow transplantation the percentage of donor T lymphocytes correlates well with the outcome of donor leukocyte infusion. 1003 29

Six children with myelodysplastic syndrome underwent allogeneic bone marrow transplantation (BMT) from their HLA-identical siblings. Ages ranged from six to 16 years. French-American British (FAB) diagnosis was refractory anemia with excess blasts (RAEB) in three, RAEB in transformation (RAEB-t) in one and chronic myelomonocytic leukemia (CMML) in two cases. Two patients had progressed to leukemia before BMT. All patients received busulfan and cyclophosphamide as a conditioning regimen. Antithymocyte globulin (ATG) was administered to two of them due to the multiple transfusion history. Graft versus host disease (GvHD) prophylaxis consisted of cyclosporine-methotrexate. Engraftment was documented in all patients except one who underwent a second infusion of bone marrow cells. She died in the early post-transplant period with pancytopenia and veno-occlusive disease of the liver. Two patients died from disease recurrence. Three patients are alive > 12 months post-transplant, two are in remission and one just relapsed at +16 months and is now being prepared for a second bone marrow transplant. The only significant factor for favorable outcome was short duration between diagnosis to transplant in the two patients in remission.
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PMID:Allogeneic bone marrow transplantation for children with myelodysplastic syndrome. 1110 16


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