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)

The immunology, pathophysiology, incidence, clinical manifestations, grading, and prevention of acute graft-versus-host disease (GVHD) are reviewed. GVHD occurs after allogeneic marrow transplantation when immunologically competent T lymphocytes in the donor marrow identify the host's antigens as foreign and attempt to reject host tissues. Acute GVHD occurs within three months after marrow transplantation and may affect the skin, gastrointestinal tract, liver, and immune system. Even with prophylactic immunosuppression, acute GVHD occurs in 20% to 80% of patients. Moderate to severe GVHD (grades II-IV) is a major cause of morbidity and mortality after allogeneic bone marrow transplantation. Conventional GVHD prophylaxis consists of immunosuppressives such as corticosteroids, methotrexate, and cyclosporine. Methotrexate and cyclosporine are equally effective in preventing GVHD. A combination of both drugs is better than either drug alone and results in an improved survival rate. The addition of corticosteroids to methotrexate, cyclosporine, or antithymocyte globulin is also more effective than single-drug therapy. Serial administration of intravenous immune globulin may contribute additional protection against acute GVHD. There is conflicting evidence concerning the prophylactic efficacy of pentoxifylline. Elimination of T lymphocytes from the donor marrow before transplantation has been associated with less GVHD but a higher incidence of graft failure. Total elimination of GVHD in patients with leukemia may cause loss of a graft-versus-leukemia effect, resulting in increased relapse rates and decreased long-term survival. Promising experimental prophylactic agents include thalidomide, zolimomab aritox, tacrolimus, antibodies to cytokines involved in the pathogenesis of GVHD, and monoclonal antibodies against cytokine receptors on T lymphocytes. Current research efforts are also directed toward eliminating GVHD without compromising the graft-versus-leukemia effect.
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PMID:Pharmacologic prophylaxis of acute graft-versus-host disease after allogeneic marrow transplantation. 825 55

The incidence of chronic GVHD, involved organs, and outcome were evaluated in 59 patients aged 15 years or more who survived for 2 months or more after HLA-matched bone marrow transplantation. The incidence of chronic GVHD was 65.3%. The incidence was not correlated with the age at the time of transplantation, underlying disease, or the method to prevent GVHD (group treated with MTX alone and CSP-treated group). Concerning the degree of organ involvement, the CSP-treated group more frequently showed slight involvement and, especially a significantly lower incidence of dryness of the eyeballs. According to organs, the oral cavity was most frequently involved (87%), followed in order by the liver (74%), skin (52%), and the eyes (30%). The oral cavity alone was involved in 6 patients, and the outcome was generally good. The outcome of multi-organ involvement of chronic GVHD was poor, and the major causes of death were interstitial pneumonia and sepsis. Even of patients who did not develop chronic GVHD, 25% showed dryness of the eyeballs and oral cavity. Biopsy and careful observation of the clinical course are needed for diagnosing GVHD.
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PMID:[Analysis of chronic graft-versus-host disease in patients after bone marrow transplantation from HLA-identical siblings]. 829 25

Fifteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 3/y) vaso-occlusive crises (VOC) associated with recurrent acute chest syndrome episodes (n = 10), osteitis (n = 3), osteonecrosis (n = 3), strokes (n = 3) or frequent massive deglobulisation (n = 2). Two children undergone splenectomy, two were chelated and two had an erythroid allo-immunization. Ethnic origins were from various countries in Africa (n = 11), North-Africa (n = 3) or West Indies (n = 1). At BMT, they were 2y 3m to 14y 9m old (mean: 8y 7m). Donors were AS (n = 11) or AA (n = 4). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n = 13) or 260 mg/kg (n = 2); BU: 14 mg/kg (n = 1), 16 mg/kg (n = 9), > 16 mg/kg (n = 5); one patient received also TLI and the last two anti-thymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n = 4) or CSA plus short-term MTX (n = 11). Median follow-up is 28 months (5 m to 53 m). All patients had an engraftment (d12 to d32) with a stable total chimerism in 10/14 patients. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (35 m follow-up) without any manifestation of SCD, with a high stable 22% Hb F level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of severe forms of sickle cell anemia with bone marrow allograft: French experience (15 cases). SFGM]. 833 53

One hundred and fifty children with AML in first remission were treated with allogeneic BMT in two sequential studies of the Childrens Cancer Group. The absence of differences in baseline variables justified comparison between the two studies. In the initial study (CCG-251), patients received GVDH prophylaxis with MTX alone (17 doses over 102 days). In an attempt to diminish the morbidity and mortality of acute GVDH, a second study (CCG-213) employed stronger GVHD prophylaxis with 6 months of CYA and short-course MTX (four doses over 11 days). Outcome was compared between these two non-randomized populations of children with AML transplanted in first remission. Augmented GVHD prophylaxis substantially diminished treatment-related mortality from 31% to 11% (p = 0.0033), but this effect was counterbalanced by an increase in the relapse risk from 22% to 35% (p = 0.29). Event-free survival at 2 years was 54% on CCG-251 and 59% on CCG-213 (p = 0.21). We observed a marginal diminution of relapse risk among patients with chronic GVHD compared with those without chronic GVHD (19% vs. 35%, respectively; p = 0.10). No anti-leukemic effect of acute GVHD was observed.
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PMID:Outcome of BMT during first complete remission of AML: a comparison of two sequential studies by the Children's Cancer Group. 837 37

Fourteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 4/y) vasoocclusive crises (VOC) and recurrent acute chest syndrome episodes (n:10), osteitis (n:3), osteonecrosis (n:3), strokes (n:3) or frequent massive deglobulisation (n:2). Two children undergone splenectomy, 2 were chelated and 2 had erythroid allo-immunization. Ethnic origins were from various countries in Africa (n:10), North-Africa (n:3) or West Indies (n:1). At BMT, they were 2y 3m to 14y 9m old (mean:8y 7m). Donors were AS (n:11) or AA (n:3). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n:12) or 260 mg/kg (n:2); BU:14 mg/kg (n:1), 16 mg/kg (n:9), > 16 mg/kg (n:4); 1 patient received also TLI and one other antithymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n:4) or CSA plus short-term MTX (n:10). Median follow-up was 23 months (8 m. to 48 m.). All patients had an engraftment (d13 to d32) with a stable total chimerism in 10/14 patients who are cured. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (28 m. follow-up) without any manifestation of SCD, with a high stable 22% Hb F level. One patient developed an aplastic anaemia 15 m after BMT: a second BMT was achieved 21 m after the first one with engraftment and total chimerism. Two patients have a relatively stable partial chimerism with still undergoing CSA therapy (11 m. and 23 m. follow-up).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation (BMT) in 14 children with severe sickle cell disease (SCD): the French experience. GEGMO. 837 51

Between January 1985 and March 1992, 48 patients with chronic phase CML underwent BMT from volunteer unrelated donors (MUD) serologically identical at HLA-A, B and DR loci. 19 patients received donor marrow ex vivo T-cell depleted (EX-TCD) with Campath monoclonal antibodies. 29 patients received unmanipulated donor marrow with CsA/MTX GVHD prophylaxis; 28 received additional intravenous antilymphocyte therapy from day +1 to +5 (IN-TCD). Overall 26 patients survive at median follow up of 362 days; actuarial survival at 3 years is 50%. 3 patients have sustained haematological relapse; actuarial leukaemia-free survival is 38%. There is no difference in overall survival between the EX-TCD and IN-TCD groups, but primary graft failure (n = 4) occurred only in the EX-TCD group, while GVHD (grade II or greater) occurred more frequently in the IN-TCD group (61% vs. 29%, p = 0.084). The optimum method for GVHD prophylaxis in MUD BMT remains uncertain.
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PMID:Matched unrelated donor bone marrow transplantation for chronic myeloid leukaemia in chronic phase: comparison of ex vivo and in vivo T-cell depletion. 844 31

Severe acute GVHD remains the main complication in unrelated donor BMT (UD-BMT). The previous encouraging reports on the use of anti-IL-2 receptor monoclonal Ab (33B31) for GVHD prophylaxis in genoidentical BMT led us to add this Ab to the standard GVHD prophylaxis regimen (MTX plus CsA). Sixty-four consecutive patients received 33B31, 20 mg on days 1 and 2, then 10 mg per day from day 3 to day 28 in association with CsA and MTX. They were compared with a historical control group of 89 patients who received conventional GVHD prophylaxis. The 33B31 was well tolerated. We did not find any statistical difference in terms of incidence and time of onset of severe GVHD, occurrence of chronic GVHD, engraftment, relapse or survival among the two groups. Immunization occurred but did not influence serum levels of 33B31. No correlation was found between the severity of GVHD and serum Ab levels. We conclude that other approaches for reducing acute GVHD should be developed to improve UD-BMT results.
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PMID:Use of an anti-interleukin-2 receptor monoclonal antibody for GVHD prophylaxis in unrelated donor BMT. 848 77

Use of the mother as mismatched marrow donor was assessed in 19 children with advanced leukemia. Patients were homogeneous for HLA incompatibility, age, donor, and conditioning regimen, and stage of disease. All received busulfan and cytoxan, combined with unmodified donor marrow, ALG given before and after transplant, and short MTX and cyclosporine as GVHD prophylaxis. Survival, LFS, and relapse respectively were 26, 26, and 33%. Incidence of overall and severe acute GVHD was 58 and 32%, respectively. Four patients had failure of engraftment, and two of these are alive with autologous reconstitution in complete remission. Probability of rejection was 21%. Results of haploidentical transplants were compared with those of children with advanced leukemia treated at the same institution, who received marrow from HLA-identical siblings. The probability of long-term leukemia-free survival was similar in the two groups. We thus propose using the mother as an alternative marrow donor in children with advanced leukemia.
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PMID:Haploidentical bone marrow transplantation from mother to child with advanced leukemia. 852 68

We describe the case of a 41-year-old female who underwent allogeneic blood cell transplantation with CD34(+)-enriched cells from an HLA-matched unrelated donor for AML in second CR. The conditioning regimen consisted of TBI (12 Gy), VP16 (1800 mg), cyclophosphamide (7200 mg), and ATG (7200 mg). GVHD prophylaxis consisted of CsA and a short course of MTX. Receiving G-CSF from day +1, engraftment occurred on day +19 after stem cell infusion. Starting on day +10, GVHD grade II (skin and liver) developed that responded to high-dose steroid therapy. The patient died on day +38 due to suspected cerebral aspergillus infection. This case demonstrates the feasibility of primary transplantation of CD34(+)-enriched allogeneic peripheral stem cells from a matched unrelated donor leading to engraftment of donor cells.
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PMID:Transplantation of allogeneic rhG-CSF mobilized peripheral CD34+ cells from an HLA-identical unrelated donor. 854 73

The number of patients undergoing BMT is rising steadily. The increase is due to a broadening of the indications for transplantation and an increase in the donor pool. There has been a progressive improvement in outcome particularly due to a fall in transplant-related mortality. Methotrexate and cyclosporin are the mainstay of graft versus host disease (GVHD) prophylaxis, but acute GVHD remains a major problem in the unrelated donor recipient. Infections remain an important cause of death and emphasise the crucial role of antimicrobial prophylaxis; death from Gram-negative sepsis has been significantly reduced by the use of prophylactic antibiotics. Fungal infections carry a high mortality, especially in allogenic transplant recipients. Fluconazole is used to protect patients in the neutropenic period and beyond in higher risk individuals. Viral infections, which may occur late, are emerging as a significant cause of morbidity and mortality in the allogeneic, particularly unrelated transplantation setting. A long term susceptibility to encapsulated bacteria suggests delayed immune reconstitution; revaccination policies are standard in most units. The longer term effects of transplantation are increasingly important with improving survival and include chronic GVHD, endocrine, cardiorespiratory and other systemic abnormalities. The increased risk of secondary malignancies is also of concern.
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PMID:Bone marrow transplantation: current situation, complications and prevention. 860 39


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