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)

Forty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5-96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1-8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GCHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survival of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure.
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PMID:Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle. 1 59

Between 1971 and 1990, nine patients ranging in age from 14-38 years received marrow transplants for paroxysmal nocturnal hemoglobinuria (PNH). Six were transplanted for aplastic complications of PNH. Four of these were from HLA-identical siblings, and the patients were conditioned with cyclophosphamide. One graft was form a syngeneic twin without conditioning, and one from a two HLA-antigen nonidentical father after conditioning with cyclophosphamide and total body irradiation. Three of the four recipients of allogeneic marrow developed acute and two chronic graft-versus-host disease (GVHD). Five of six transplanted for severe aplastic anemia are long-term survivors with follow-up ranging from more than 6.2 to more than 19.1 years. The HLA nonidentical transplant recipient experienced graft rejection and died of a pulmonary hemorrhage. Three patients were transplanted for nonaplastic complications of PNH consisting of life threatening recurrent thromboses or refractory hemolysis. Two of these patients received marrow grafts from HLA-identical siblings after conditioning with busulfan and cyclophosphamide. They are surviving with normal hemograms greater than 2.2 and greater than 2.5 years and had mild chronic GVHD which resolved, although one has biochemical evidence of PNH in 15% of the red cells. One received a syngeneic marrow graft without conditioning but reverted to PNH. He is alive greater than 8.6 years after transplantation. Marrow transplantation for aplastic complications of PNH is successful, well tolerated, and compatible with long-term survival when an HLA-identical sibling or a syngeneic donor is available. For patients without aplasia, one must weigh the complications of transplantation with the life threatening nature of thrombotic episodes and hemolysis.
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PMID:Marrow transplantation for paroxysmal nocturnal hemoglobinuria. 155 57

Survival of patients with aplastic anemia after immunosuppressive therapy with ATG/ALG ranges from 35% to 60%. However, long-term follow-up on these patients has indicated a high frequency of hematologic complications, including PNH, myelodysplasia, ANL, and recurrent aplasia. In contrast to immunosuppressive therapy, allogeneic marrow transplantation results in cure of aplasia. Problems initially limiting the success of HLA-matched allogeneic marrow transplants included graft rejection and complications associated with acute and chronic GVHD. Infusion of donor buffy coat cells along with marrow or alternatively more intensive immunosuppressive regimens containing irradiation have substantially decreased the risk of rejection. However, buffy coat infusion increases the incidence of chronic GVHD and irradiation treatment adds to toxicity of the conditioning regimen as well as producing long-term complications. The incidence and severity of acute GVHD have been significantly decreased by the use of MTX/CSP as GVHD prophylaxis; however, this regimen has had no impact on the incidence of chronic GVHD. Long-term survival in multiply transfused patients after HLA-identical marrow transplantation is on the order of 60% to 70%; survival in untransfused patients approximates 80%. Patients less than age 18 transplanted on protocols currently active in Seattle have greater than 90% survival. Further increases in survival must come from improvement in preventing and treating chronic GVHD. Patients diagnosed with aplastic anemia should have rapid HLA typing performed to identify possible marrow donors. Transfusions from prospective marrow donors should be avoided and the patient referred to a major treatment center. We continue to recommend allogeneic marrow transplantation for patients with severe aplastic anemia who are less than 40 years old and who have HLA-identical related donors. Immunosuppressive therapy should be tried first in patients without HLA-matched donors and for patients over the age of 40. HLA-mismatched marrow transplantation and use of unrelated marrow donors for severe aplastic anemia remain areas of active research.
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PMID:Treatment of aplastic anemia. 219 14

Of 145 patients with severe aplastic anemia (SAA) treated in Basel from 1976 to 1987, 34 underwent bone marrow transplantation (BMT) and 111 received ALG therapy. We have analyzed the incidence of late complications in both groups of patients. 34 patients treated with ALG developed a hematological complication, 10 a myelodysplastic syndrome (MDS) and 18 paroxysmal nocturnal hemoglobinuria (PNH) associated with clinical symptoms in 12. Two patients had both MDS and PNH. Eight suffered relapse of SAA. After BMT neither of these complications occurred. Most of the non-hematological problems were associated with therapy. In the ALG group androgens were responsible for impotence and gynecomastia in men, deep voice in women and liver tumors in 4 patients. Four other patients developed aseptic necrosis of the hip and one carcinoma of the breast. The most severe late complication after BMT was chronic graft-versus-host disease (GvHD), occurring in patients still receiving methotrexate for prophylaxis of GvHD.
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PMID:[Late complications in patients with aplastic anemia]. 305 87

Four patients with paroxysmal nocturnal hemoglobinuria and severe marrow aplasia were given marrow grafts either from allogeneic human-leukocyte-antigen-identical siblings (three patients) or from a syngeneic donor (one patient). The patients with allogeneic grafts were conditioned with regimens that included cyclophosphamide and had sustained and complete marrow engraftment; subsequent tests were negative for paroxysmal nocturnal hemoglobinuria. One patient developed chronic graft-versus-host disease that resolved over 4 years. The patient receiving a syngeneic graft received marrow infusion without preceding immunosuppression. He had prompt engraftment, and hematologic variables returned to normal. A Ham's test done at 3 years was negative, but a complement lysis sensitivity test done 10 years after grafting was positive; the patient, however, remains asymptomatic. All four patients are alive and well 4, 9, 10, and 12 years after transplantation. Paroxysmal nocturnal hemoglobinuria apparently can be treated successfully by allogeneic or syngeneic marrow transplantation without subsequent maintenance therapy.
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PMID:Long-term survival after marrow transplantation for paroxysmal nocturnal hemoglobinuria with aplastic anemia. 637 2

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder characterized by pancytopenia and a hypocellular marrow. Drugs, chemical exposure, radiation, and viruses are implicated as etiologic agents, although the majority of community-acquired SAA is idiopathic. Regardless of the inciting event, most cases of SAA result from immune-mediated destruction of bone marrow progenitor cells, which spares pluripotent hematopoietic stem cells. SAA is treated by either allogeneic bone marrow transplantation (BMT) or immunosuppressive therapy. BMT restores normal hematopoiesis and cures the disease in 60% to 80% cases, with the major causes of failure being graft rejection and graft-versus-host disease. Most patients treated with immunosuppressive therapy recover hematopoiesis sufficiently to not require transfusions and are free of infection, although in many, recovery is incomplete. Moreover, up to 50% of SAA patients successfully treated with immunosuppressive therapy relapse or develop a secondary clonal disorder, such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, or leukemia. High-dose cyclophosphamide without BMT is capable of restoring normal hematopoiesis with little or no risk of relapse or secondary clonal disorders. A number of effective treatment options for the treatment of SAA are now available. The optimal approach for definitive management of SAA continues to evolve.
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PMID:Biology and management of acquired severe aplastic anemia. 955 29

Hematopoietic stem-cell transplantation (HSCT) is an effective mode of therapy in pediatrics for the treatment of both malignant and non-malignant disorders. We compared the course of children transplanted with unrelated umbilical cord blood (UCB) to those transplanted with allogeneic sibling bone marrow (BM) for bone marrow failure syndromes. Thirteen patients with a median age of 6.3 years were transplanted for the following diseases between April 1992 and November 1997: myelodysplastic syndromes, aplastic anemia, Diamond-Blackfan anemia, myelofibrosis, paroxysmal nocturnal hemoglobinuria, osteopetrosis and dyskeratosis congenita. The stem cell source was BM in ten patients and UCB in three. We retrospectively examined the conditioning regimens, stem cell source and dose, days to engraftment, survival and complication rate to see whether there was a significant advantage in using one source over the other. The median time to an absolute neutrophil count > 500 per microL was 25 days for UCB patients and 16 days for BM patients. The median time to a platelet count > 20,000 per microL was 55 days for UCB patients and 22 days for BM patients. The 100-day mortality was 66% in UCB patients and 20% in BM patients. The overall mortality rates were 66% and 40%, respectively. Three patients died prior to engraftment. Seven patients (54%) were still alive as of May 1999 with a median follow-up of 1574 days post-transplant. The patients transplanted with BM had faster engraftment and lower rates of graft-versus-host disease, 100-day mortality and overall mortality. HLA-matched sibling BM is preferred as a source but transplantation using unrelated UCB is still an option in treating pediatric bone marrow failure syndromes.
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PMID:Hematopoietic stem-cell transplantation using unrelated cord-blood versus matched sibling marrow in pediatric bone marrow failure syndrome: one center's experience. 1056 77

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disease of hematopoiesis due to a mutation in the PIG-A gene. Affected patients may demonstrate hemolysis or venous thrombosis, and may develop MDS or aplastic anemia. Successful results may be obtained after conditioning and transplantation from syngeneic or genotypically matched sibling donors. Experience with transplantation from matched unrelated donors (MUD) is limited to eight patients, with only one survivor. We report three patients who underwent successful MUD BMT for PNH. All three patients had severe aplastic anemia (SAA) and PNH at the time of BMT. Unrelated donors were six-antigen HLA-matched (n = 2) or HLA-A mismatched (n = 1). Conditioning consisted of cytarabine, cyclophosphamide, TBI, and ATG. Grafts were T cell-depleted by anti-CD6/CD8 antibodies + complement. Further GVHD prophylaxis consisted of cyclosporine. Patients received 0.7-1.1 x 10(8) nucleated cells/kg and 1.1-2.1 x 10(6) CD34(+) cells/kg. Neutrophil engraftment occurred at 16-21 days. One patient developed grade 1 acute GVHD. Although all three patients experienced significant transplant-related complications, they ultimately resolved and all patients are alive and well 30-62 months after BMT. T cell-depleted MUD BMT is an effective treatment option for PNH-related MDS and SAA.
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PMID:Successful unrelated donor bone marrow transplantation for paroxysmal nocturnal hemoglobinuria. 1131 87

Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of the hematopoietic stem cell in which intravascular hemolysis is due to an intrinsic defect in the membrane of red cells that makes them increasingly susceptible to lysis by complement. The phenotypic hallmark of PNH cells is an absence or marked deficiency of GPI-anchored proteins such as CD 59+, CD 55+ and others which normally protect cells from the action of complement. PHN is closely associated with aplastic anemia. Some degree of bone marrow failure is always present. Management of PNH is complicated by a highly variable clinical picture and course. Some patients have severe anemia aggravated by hemolytic crises and associated thromboses. Bone marrow failure is accompanied with frequent infections and hemorrhagic manifestations due to thrombocytopenia. With the exception of marrow transplantation, no definite therapy is available. In the exceptional circumstance in which the patient has a syngeneic twin, bone marrow transplantation is the most appropriate therapy for severe PNH because of absence of graft-versus-host disease. In general syngeneic transplantation without preconditioning has been unsuccessful because abnormal hematopoiesis returns. Allogeneic bone marrow transplantation has been used, but the transplant-associated morbidity and mortality are high due mainly to the fatal graft-versus-host disease and severe posttransplant marrow failure. Use of an unrelated donor transplant has to be considered as contraindicated. PNH is associated with striking predisposition to intravascular thrombosis which often involves the portal system or the brain. Fatal thromboses account for about 40-50% of all deaths in patients with PNH. The etiology of the thrombophilia in PNH is not fully clarified. Anticoagulation or thrombolytic therapy is required for treatment of venous thrombosis, the latter vena cava. Prophylactic anticoagulation in patients without contraindications such as severe thrombocytopenia seems to be justified. However, whether such therapy may be efficacious in reducing the incidence of thromboses or affect survival is conjectural. PNH patients have varying degree of platelet activation and some authors suggest that antiplatelet therapy might be efficacious in reducing the incidence and severity of venous thrombosis in PNH. Pregnancy is hazardous. Female patients should avoid the use of oral contraceptives. Pregnant patients require combined care of an experienced hematologist and obstetrician specialized in the management of high-risk pregnancies.
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PMID:[Treatment of paroxysmal nocturnal hemoglobinuria (PNH)]. 1182 54

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of haematopoietic stem cells associated with a somatic mutation in the phosphatidylinositol glycan complementation class A (PIG-A) gene. The only curative option is an allogeneic stem cell transplant (SCT), although treatment is hazardous. A 46-year-old male patient with PNH and obvious signs of severe, progressive haemolysis was transplanted in July 2002 with highly purified CD34 T-cell depleted peripheral blood stem cells from his HLA-identical brother. Prior to transplantation, the PNH was resistant to immunosuppressive therapy. The patient received 6.1 x 10(6)/kg bodyweight CD34-positive cells with a proportion of CD3-positive cells of 0.81 x 10(4)/kg bodyweight. After engraftment, 12 days post transplant (neutrophils>1.0/nl) the patient's physical condition steadily improved and parameters of haemolysis decreased. No glycophosphatidylinositol-deficient cells in peripheral blood could be detected by flow cytometry 40 and 100 days after transplant. We conclude that PNH may be cured by allogeneic CD34-enriched SCT from a sibling donor attempting to avoid acute GVHD and to reduce cumulative organ toxicity by using this transplantation modality.
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PMID:Allogeneic CD34-enriched peripheral blood stem cell transplantation in a patient with paroxysmal nocturnal haemoglobinuria. 1295 38


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