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)

Patients with Fanconi anemia (FA) commonly develop bone marrow failure, which may evolve to myelodysplasia or acute myeloid leukemia (AML). Treatment of these patients is complicated by their marked hypersensitivity to DNA cross-linking agents. In this report we describe the results of allogeneic unrelated donor bone marrow transplantation in seven FA patients, using a low-dose cyclophosphamide (40 mg/kg) and TBI (400-450 cGy) conditioning regimen. Two patients had bone marrow failure with normal chromosomes and no dysplasia prior to transplant. The remaining five had clonal chromosomal abnormalities. One patient had refractory anemia with excess blasts in transformation and two had early AML with 20 and 25% blasts, respectively. Two patients died early (before day 28) without hematological evidence of engraftment, one of veno-occlusive disease and one of infection (fungal). Four of the remaining five patients achieved sustained engraftment after the first marrow infusion; one patient had secondary graft failure requiring repeat marrow infusion but subsequently achieved engraftment. Of five evaluable patients, three had mild (grades I-II) acute GVHD and two had grade IV GVHD, which was fatal in both cases. Two of three evaluable surviving patients have chronic GVHD controlled with immunosuppression. Three patients survive 9 months to 3 years post-unrelated donor BMT: two who had early leukemia and one with severe aplasia at the time of transplant. These data indicate that unrelated donor BMT can be performed successfully in FA patients using cyclophosphamide 40 mg/kg and TBI 400 to 450 cGy, even after evolution to early leukemia. However, significant problems with both GVHD and engraftment remain. Future studies will evaluate the role of T cell depletion in improving the results of unrelated donor marrow transplantation in FA patients.
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PMID:Unrelated donor bone marrow transplantation for Fanconi anemia. 867 53

Blood conservation in infants and children has benefits even beyond those seen with the adult populations. For instance, acquired blood borne diseases such as cytomegalovirus not only cause illness but also can have deleterious effects on the growth and development of infants and children. Decreasing blood transfusions is especially important in preventing sensitization over a lifetime, which may require further transfusion and even organ transplantation. A less striking benefit, but one equally as significant, is decreasing the occurrence of graft-versus-host disease when blood conservation negates the need for multiple transfusions. The limitation of alternative transfusion practices in children and infants increases the benefits of blood conservation. Autologous blood donation may be an alternative to allogeneic transfusion in older children, but is not possible with neonates who may be born anemic and who experience a normal physiologic anemia during the first 2 months of life. Critical care nurses are instrumental in helping blood conservation by understanding blood salvaging techniques, including correct collection techniques, noninvasive monitoring, evaluation of diagnostic sample needs, and administration of erythrocyte-stimulating factors.
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PMID:Blood conservation in neonatal and pediatric populations. 871 85

A case of proliferation of CD68-positive macrophage-lineage cells in the bone marrow accompanied by severe thymic atrophy associated with graft-versus-host disease (GVHD) in a boy given allogeneic bone marrow transplantation (BMT) is reported. A 7-year-old boy was treated for posthepatitic severe aplastic anemia by BMT from his HLA-identical, mixed lymphocyte reaction-negative sister. After the transplantation his peripheral blood group converted to the donor type. However, the patient suffered from acute and chronic GVHD and slowly progressive anemia, and he died of multiple organ failure 21 months after BMT. At the autopsy diffuse and monotonous proliferation of CD68-positive macrophage-lineage cells was found to be replacing the blood-forming cells in the bone marrow. The thymus was almost empty of T lymphocytes, and remaining strands of extremely atrophic epithelial cells showed focal cystic change. Extramedullary hematopoiesis was found in the spleen. Analyses of microsatellite markers suggested the hematopoietic cells in the spleen to be of donor origin.
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PMID:Proliferation of macrophage-lineage cells in the bone marrow, severe thymic atrophy, and extramedullary hematopoiesis of possible donor origin in an autopsy case of post-transplantation graft-versus-host disease. 886 59

Eleven patients with Fanconi anemia (FA) underwent bone marrow transplantation (BMT) between March 1985 and May 1990 in a single institution. Ten patients received bone marrow from healthy full human leukocyte antigen (HLA) matched siblings and one patient from her father (one antigen mismatch). Ten patients were conditioned with cyclophosphamide (Cy) at a dose of 5 mg/kg per day for 4 days followed by total body irradiation (TBI) for a total of 600 cGy over 3 days. Six of the 11 patients are alive and have normal reconstitution of their bone marrow. Median follow-up was 72 months (range 42-84). Three of the 10 patients who received Cy and TBI (two HLA compatible, one antigen mismatch) had graft failure. Five patients developed at least grade III acute graft-versus-host disease (GVHD). The rates of graft failure and GVHD are, however, still significantly high. Modification of the conditioning regimen and GVHD prophylaxis is needed to improve the outcome.
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PMID:Bone marrow transplantation in patients with Fanconi anemia: experience with cyclophosphamide and total body irradiation conditioning regimen. 902 15

We report an 11-year old female with myelodysplastic (refractory anemia with excess of blasts) presentation of Fanconi anemia. After failure of initial chemotherapy with low doses of 6-mercaptopurine and prednisolone she underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched sibling. Busulfan 8 mg/kg and cyclophosphamide 40 mg/kg were used as conditioning. The post-transplant course was uneventful with fast trilineage engraftment and mild cutaneous acute GVHD. She is alive 17 months after BMT with full hematological reconstitution without evidence of MDS.
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PMID:Intermediate-dose busulfan and cyclophosphamide as a conditioning regimen for bone marrow transplantation in a case of Fanconi anemia in myelodysplastic transformation. 905 Dec 50

We report a case of oral squamous cell carcinoma (SCC) originating in the buccal mucosa of an 18-year-old female patient with chronic graft-versus-host disease (GVHD) 9 years after HLA-identical sibling bone marrow transplantation (BMT) for Fanconi anaemia (FA). The case highlights the problems of malignant change in FA and also the increased risk of second malignancy after BMT. The literature is reviewed with regard to previous cases and the possible aetiology of tumour formation. A high index of suspicion to any epithelial lesion in FA is appropriate so that early diagnosis may lead to improved prognosis.
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PMID:Oral squamous cell carcinoma after allogeneic bone marrow transplantation for Fanconi anaemia. 937 63

Fanconi anaemia (FA) is an accepted indication for treatment with allogeneic HLA-identical BMT. Most patients, however, lack a suitable HLA-identical donor. In our centre, six FA patients were transplanted with a matched unrelated donor. Due to hypersensitivity to DNA cross-linking agents, a low-dose cyclophosphamide (CY) and thoraco-abdominal irradiation (TAI) regimen is recommended for conditioning in FA. We added Ara-C upfront and anti-T cell antibodies to enhance engraftment and to prevent GVHD, in combination with T cell depletion in four out of six of the first transplants. One patient did not engraft. In three patients rejection was observed. In three of these four patients a second BMT, using full bone marrow grafts, resulted in successful engraftment. The other patient died before a second BMT could be performed. The incidence and severity of acute GVHD was low: only one patient with grade III acute GVHD was seen. Two out of four surviving patients suffered from chronic GVHD. Four patients survived (median survival time 43 months after BMT), three with good and one with acceptable quality of life. Two patients died, one patient due to adenoviral reactivation with multi-organ failure, and one due to sepsis complicated by ARDS. In conclusion, MUD BMT is feasible in FA patients with bone marrow failure in whom no HLA-identical sibling donor is available. In our study group, the major problem was graft rejection, despite the administration of a combination of graft enhancing anti-T cell antibodies. Multicentre studies are needed to determine a more intensive, but still tolerable, conditioning regimen.
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PMID:Unrelated donor bone marrow transplantation in Fanconi anaemia: the Leiden experience. 953 36

Pluripotent stem cells of hematopoiesis are included among CD34+ cells in the blood and bone marrow. After granulocyte-colony stimulating factor (G-CSF) mobilization, 1-2% of the mononuclear cells in the blood are CD34+ cells, which can be obtained by leukapheresis. We performed CD34+ progenitor cell transplantation in two children with severe aplastic anemia (SAA) who lacked HLA-matched donors. The donors were treated with G-CSF, 600 micrograms/body/day subcutaneously, for 4-5 days. CD34+ cell selection was performed from the apheresis concentrate with mouse anti-CD34 antibody 9C5 and magnet beads coated with sheep anti-mouse IgG1. After the transplantation, the patients received tacrolimus to prevent graft-versus-host disease (GVHD). G-CSF was given to both patients. A mean number of 4.96 x 10(6) CD34+ cells per kilogram of body weight were transplanted. The hematopoietic recovery after the CD34+ cell transplantation was rapid, except for platelets, and acute GVHD was less than or equal to grade I. Case 1, who demonstrated mixed chimerism, anemia and thrombocytopenia after the graft, received a second transplant with intensified preconditioning, and now sustains complete and stable hematopoiesis after a follow-up of 314 days posttransplant. Although Case 2 showed early rejection and received a second transplant, sustained engraftment was never achieved. However, the patient's own hematopoiesis appeared. For SAA patients who do not have HLA-matched donors, this type of approach seems to be a feasible and useful method. However, an intensified preconditioning regimen to overcome the high likelihood of rejection should be employed.
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PMID:CD34+ progenitor cell transplantation from two HLA-mismatched healthy fathers to two infants with severe aplastic anemia. 959 40

Recombinant human erythropoietin (rHu EPO) has been reported to accelerate early erythroid reconstitution after bone marrow transplantation (BMT). We conducted a pilot study on rHu EPO for late-onset anemia in 9 patients after allogeneic BMT. The patients achieved initial erythropoietic recovery (hemoglobin (Hb) range 9.1-13.4, mean 10.8 g/dl), but then developed transplant-related anemia (Hb range 6.3-9.7, mean 8.2 g/dl) more than 50 days after BMT. This type of anemia was related to graft-versus-host disease (GVHD), cytomegalovirus infection, and/or impaired EPO secretion. The patients received 3,000 or 12,000 U of rHu EPO subcutaneously three or seven times weekly. Hb levels increased by more than 2 g/dl in 6 of the 9 patients, but were unchanged in the 3 patients with severe GVHD. These findings suggest that in some cases rHu EPO is effective for the treatment of late-onset anemia after BMT.
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PMID:Recombinant human erythropoietin for late-onset anemia after allogeneic bone marrow transplantation. 963 79

In a multicentre trial involving 20 transplant centres from 10 countries haematopoietic stem cells were obtained either from the bone marrow of 33 sibling donors or from the peripheral blood of 33 such donors after administration of filgrastim (10 microg/kg/day). The haematopoietic stem cells were infused into their HLA-identical recipients suffering from acute leukaemias in remission or chronic myeloid leukaemia in chronic phase. PBPC donors tolerated filgrastim administration and leukapheresis well with the most frequent side-effects being musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT. Pain and haematoma at the harvest site and mild anaemia were the most frequent complaints of BM donors. Severe or life-threatening complications were not seen with any type of harvest procedure. Time to platelet recovery greater than 20 x 10(9)/l was 15 days (95% confidence interval (CI) 13-16 days) in the PBPCT group and 19 days (CI 16-25) in the BMT group. Time to neutrophil recovery greater than 0.5 x 10(9)/l was 14 days (CI 12-15 days) in the PBPCT group as compared to 15 days (CI 15-16 days) in the BMT group. The numbers of platelet transfusions administered to PBPCT and BMT patients were 12 (range: 1-28) and 10 (range: 3-39), respectively. Sixteen patients (48%) transplanted with bone marrow and 18 patients (54%) transplanted with PBPC developed acute GVHD of grades II-IV; acute GVHD of grades III or IV developed in six (18%) and seven (21%) patients, respectively. Kaplan-Meier plots for transplant-related mortality until day 100 and leukaemia-free survival at a median of 400 days after BMT or PBPCT showed no significant differences. Administration of filgrastim and leukapheresis in normal donors were feasible and well tolerated. The number of days with restricted activity and of nights spent in hospital was lower in donors of PBPC. Transplantation of PBPC to HLA-identical siblings with early leukaemia resulted in earlier platelet engraftment. The incidence of moderate to severe acute GVHD, transplant-related mortality, and leukaemia-free survival did not show striking differences. Further investigation of allogeneic PBPCT as a substitute for allogeneic BMT is warranted.
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PMID:Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: first results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation. 1045 58


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