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)

Two patients with the Wiskott-Aldrich syndrome had complete donor lymphoid and hematopoietic engraftment after successful allogeneic bone-marrow transplantation. One patient had had only a temporary donor T-lymphocyte graft after a previous transplantation, for which he had been prepared with cytarabine and cyclophosphamide; the patient's own T lymphocytes returned six months later. A repeat transplant, for which the patient was prepared with anti-human thymocyte serum, total-body irradiation and procarbazine, resulted in complete donor engraftment. The second patient underwent a successful transplantation after similar preparation, except that procarbazine was omitted. At 11 and five months after transplantation both had normal hematopoiesis and no evidence of graft-versus-host disease. This treatment of the Wiskott-Aldrich syndrome may be a model for the correction of other genetically determined immune and hematologic bone-marrow disorders.
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PMID:Complete correction of the Wiskott-Aldrich syndrome by allogeneic bone-marrow transplantation. 34 89

Unrelated donor marrow transplantation was undertaken in eight infants with severe combined immunodeficiency (SCID) and two children each with Wiskott-Aldrich syndrome (WAS) and Chediak-Higashi syndrome (CHS) who did not have histocompatible siblings. Donors for three patients were phenotypically matched at all HLA-A, B, Dr, and Dw loci, whereas nine donors were mismatched from the recipients at one of the HLA-A or B loci but phenotypically identical at evaluable D loci. All but one patient received conditioning chemotherapy and/or radiotherapy before infusion of donor marrow, which was not T-cell depleted. Prophylaxis for graft-versus-host disease (GVHD) consisted of methotrexate and prednisone combined with either cyclosporine A (six patients), antithymocyte globulin (five patients), or anti-CD5 ricin A chain immunotoxin (one patient). All patients engrafted with donor cells, and only 4 of 12 experienced any GVHD (1 of 8 SCID, 1 of 2 WAS, 2 of 2 CHS). Two children who developed grade II and two who developed grade III GVHD were successfully treated and all are now alive, off immuno-suppressive therapy, with no evidence of chronic GVHD greater than 18 months after transplant. Ten patients are alive with excellent immunoreconstitution greater than or equal to 1 year to greater than or equal to 3 years after transplant; actuarial survival is predicted to be 83% with a median follow-up of 2 years. Two children with SCID succumbed to pre-existing opportunistic infection early posttransplant. We conclude that closely matched unrelated donor bone marrow transplantation can correct congenital immunodeficiencies including variants of SCID, WAS, and CHS, with an acceptably low incidence of transplant-related complications, principally GVHD.
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PMID:Unrelated donor bone marrow transplantation for correction of lethal congenital immunodeficiencies. 161 Oct 94

Since 1979, a total of 17 patients with Wiskott-Aldrich syndrome have undergone allogeneic bone marrow transplantation at Memorial Sloan-Kettering Cancer Center. Eleven patients received marrow from either human leukocyte antigen (HLA) genotypically identical siblings (nine patients) or an HLA phenotypically identical parent (two patients). Six patients received marrow grafts from HLA-disparate parents. Cytoreduction was accomplished with busulfan and cyclophosphamide for the HLA-identical recipients and total-body irradiation followed by high-dose cytarabine therapy in the mismatched recipients. All 11 recipients of HLA-identical marrow had successful grafts, and 10 of 11 are alive and well 28 to 145 months after transplantation. One patient died 10 months after transplantation of chronic graft-versus-host disease and interstitial pneumonitis caused by cytomegalovirus. Only one of the six mismatched graft recipients survives, 52+ months after transplantation; the other patients have died of extensive chronic graft-versus-host disease (one patient), lymphoma (three patients), or progressive pancytopenia accompanying Candida sepsis (one patient). Thus bone marrow transplantation represents the treatment of choice in patients with Wiskott-Aldrich syndrome who have an HLA-identical donor. However, our approach for patients lacking a histocompatible family donor requires modifications to overcome allogeneic resistance and decrease the posttransplantation immunoincompetence in these patients.
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PMID:Marrow transplantation from human leukocyte antigen-identical or haploidentical donors for correction of Wiskott-Aldrich syndrome. 196 Jun 5

Forty-six infants and children suffering from either inherited immunodeficiency disorders (Wiskott-Aldrich syndrome, functional T-cell immunodeficiency with or without HLA class II expression deficiency), malignant osteopetrosis, or Fanconi's anemia received HLA-nonidentical bone marrow transplantation (BMT) from related donors. Bone marrow was T-cell depleted to reduce the risk of graft-versus-host disease (GVHD). To prevent graft failure, a mouse monoclonal antibody specific for the CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule was infused into the patients. Eleven patients received five infusions of 0.1 mg/kg every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg daily from day -3 to +6. The overall sustained engraftment rate was 72% instead of 26.1% in a historical control group of 24 patients similarly treated except for the infusion of the anti-LFA-1 antibody. No late rejection occurred. The T-cell depletion method (E-rosetting or Campath IM plus complement) resulted in different rate of engraftment (83.3% v 57.9%, respectively, P = .05). Engraftment rate was slightly but not significantly influenced by the degree of HLA incompatibility between donor and recipient. Acute GVHD of grade II or more occurred in 35.5% of the patients and the rate of chronic GVHD was 12.9%. The overall actuarial survival rate with a functional graft is 47.3% with a mean follow-up of 28.0 months for patients with immunodeficiency and osteopetrosis, while none of the four patients with Fanconi's anemia survived. The development of full T-cell functions took on the average 6 months and of full B-cell functions 10 months. Significant infectious problems developed in the majority of the patients during the posttransplant course. Epstein-Barr virus-induced B-cell proliferative syndromes were observed in seven patients, six of whom had Wiskott-Aldrich syndrome. Correction of immunodeficiency was comparable in terms of kinetics and quality with that observed in patients with severe combined immunodeficiency undergoing HLA-nonidentical BMT. Correction of osteopetrosis appears not to be different from what has been observed after HLA-identical BMT. The in vivo use of an anti-CD11a-LFA-1 antibody as an additional immunosuppressive therapy in HLA-nonidentical BMT may thus promote engraftment and survival with correction of the primary disease in a significant number of patients with life-threatening immunodeficiency and osteopetrosis, but not with Fanconi's anemia.
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PMID:Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report. 198 91

Clinicopathologic records and neuropathologic tissues of 109 patients who underwent necropsy after treatment with bone marrow transplantation (BMT) were examined. Underlying disorders included leukemia (70), aplastic anemia (25), solid tumors (7), lymphoma (5), Hodgkin's disease (1) and Wiskott-Aldrich syndrome (1). There were 34 females and 75 males, ranging in age from 2 to 56 years. Survival after transplantation averaged 3.6 months. The most common findings were cerebrovascular lesions (29), including hematomas, hemorrhagic necrosis, and infarcts. Central nervous system infections comprised the next most common finding, including 10 fungal and four bacterial infections. A recurrence of underlying malignancy for which transplant had been performed occurred in five patients. Leukoencephalopathy of varying severity was found in eight patients, half of whom had received intrathecal chemotherapy and/or cranial radiation. Patients with systemic graft-versus-host disease had a variety of nonspecific neuropathologic findings in the nervous system; however, nearly half (44%) showed no detectable changes. Other nonspecific alterations included hypoxic/ischemic changes, vascular siderocalcinosis, and neuroaxonal spheroids (associated with hemorrhage or necrosis). These findings provide a guide as to likely causes of a neurologic syndrome in a patient who has undergone BMT, and can be compared with neuropathologic findings in other forms of immunosuppression.
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PMID:Neuropathologic findings after bone marrow transplantation: an autopsy study. 219 Sep 10

Four patients with Wiskott-Aldrich syndrome received bone marrow transplants (BMT) using monoclonal antibody T cell-depleted HLA-haploidentical marrow from a family member donor. The patients did not receive a significantly larger inoculum of mature T cells than other recipients of T cell-depleted marrow transplants. All four patients achieved quick engraftment, and three of the four patients are alive and well today. The three living patients have all had a complete return of normal T-cell and B-cell function. Infectious complications in the surviving patients were minimal; however, all three experienced some degree of graft-versus-host disease (GVHD). Two of these three patients received GVHD prophylaxis. The patient not receiving GVHD prophylaxis experienced severe GVHD and had a difficult posttransplant course. The patient who did not survive was chronically ill before BMT, whereas the other patients were in relatively good health at the time of BMT. Since the majority of individuals with this disease lack a matched bone marrow donor, our results using partially matched donors suggest that a greater number of patients can be successfully treated for Wiskott-Aldrich syndrome and that outcome is related to control of GVHD and state of health before BMT. Marrow transplantation should be offered earlier in the disease course before the onset of major infectious problems.
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PMID:Monoclonal antibody T-cell-depleted HLA-haploidentical bone marrow transplantation for Wiskott-Aldrich syndrome. 230 55

Seven patients with immunodeficiencies (Wiskott-Aldrich syndrome, combined immunodeficiency, and osteopetrosis) were given a mouse monoclonal antibody against the alpha subunit of human leucocyte functional antigen (HLFA-1; CD18) to facilitate the engraftment of mismatched haploidentical related-donor bone marrow. Other conditioning included busulphan, cyclophosphamide, and antilymphocyte globulin. To prevent graft-versus-host disease the bone-marrow T cells were depleted with sheep erythrocyte rosetting and cyclosporin therapy was given. HLFA-1 antibody injections were well tolerated without side-effects except slight, transient fever (38-40 degrees) after the first injection. Engraftment was rapid in all seven patients. The regenerating leucocytes were of donor origin in all cases, and two patients have a mixed chimera. Two patients died from infections. The others are alive and well 60-395 days after transplantation. In a historical control group given the same treatment without anti-HLFA-1 infusion, only one of seven transplants partially engrafted; only two patients remain alive with autologous reconstitution but with uncorrected immunodeficiency.
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PMID:Prevention of graft failure by an anti-HLFA-1 monoclonal antibody in HLA-mismatched bone-marrow transplantation. 287 23

The factors that impact upon successful bone marrow transplantation leading to immunologic reconstitution in severe combined immune deficiency (SCID). Wiskott-Aldrich syndrome, and in other lethal congenital immunodeficiencies are reviewed. Evidence is presented that graft-versus-host disease (GVHD) can be abrogated by the depletion of T cells, even from histoincompatible marrow grafts. However, graft resistance or restricted immune reconstitution has been observed with significant frequency. The bases for T cell reconstitution and limitations in B cell humoral immune recovery in the postgrafting period are reviewed, together with emerging evidence that pretransplant cytoreduction might obviate some of these problems.
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PMID:Evaluation of HLA-haplotype disparate parental marrow grafts depleted of T lymphocytes by differential agglutination with a soybean lectin and E-rosette depletion for the treatment of severe combined immunodeficiency. 353 40

IgE levels were determined before and serially after allogeneic bone marrow transplantation (BMT) in 12 patients. Six patients had aplastic anemia, four leukemia, and one each Wiskott-Aldrich syndrome and infantile agranulocytosis. IgE levels increased sharply (7- to 2,000-fold) in 10 of the 12 as early as 14 days after BMT. They all returned to baseline levels by 60 days. In six of these patients, the rise accompanied clinical and biochemical evidence of acute graft-versus-host disease (GVHD). All of the patients who received rabbit antihuman thymocytic serum (ATS) in preparation for transplantation and were tested for IgE antirabbit serum antibody by radioallergosorbent test (RAST) (n = 6) developed a strongly positive RAST which paralleled their total IgE levels. These high IgE levels detected during the period of acute GVHD may be a manifestation of a transient lack of suppressor T cell activity.
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PMID:Increased serum immunoglobulin E levels following allogeneic bone marrow transplantation. 699 85

Two males of 3 and 3 1/2 years of age with the Wiskott-Aldrich syndrome who underwent bone marrow transplantation from an HLA compatible brother following conditioning treatment with busulphan and cyclophosphamide are described. In both patients the taking of the graft was proven by study of blood subgroups and correction of the immunodeficiency, normalization of platelet number and function and disappearance of cutaneous eczema were seen. At 3 and 1 year respectively of the transplantation the patients showed no evidence of graft versus host disease and no severe infections or hemorrhagic episodes have seen.
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PMID:[Allogenic bone marrow transplantation in Wiskott-Aldrich syndrome]. 774 1


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