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)

We report the case of a patient with fatal obstructive lung disease after an HLA-haploidentical sibling cord blood transplant (CBT), with severe acute GVHD. A 2-year-old girl developed expiratory air trapping gradually with acute and chronic GVHD after CBT for the treatment of ALL. Anti-CMV and immunosuppressive therapy were ineffective, and the patient died of progressive respiratory acidosis. Necropsy of the lung revealed severe bronchiolitis obliterans with cytomegalic inclusion cells in the granulation tissues of the bronchiolitis. Thus, immunologic and GVHD problems can occur even in CBT.
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PMID:Fatal obstructive lung disease after haploidentical sibling cord blood transplantation. 961 88

Mitoxantrone (Mito) is presently used in an increasing number of malignancies including leukemias, breast carcinomas and solid tumors. With it has come increased incidence of post remission cytopenias and delayed engraftment following autologous bone marrow transplantation (ABMT). We evaluated engraftment in 18 patients who underwent allogeneic BMT (allo-BMT) following a preparative regimen that included high dose Mito (60 mg m2). Sixteen patients with malignant disease (AML 10, ALL 3, CML 2, MDS 1) and two with non-malignant disease (SCID 1, osteopetrosis 1) underwent non-T cell depleted allo-BMT. Fourteen patients with malignancies were transplanted at an advanced stage of disease while only two patients were standard risk patients. Of the 18 patients, 12 were females and six males, with a median age of 30.5 (0.3-48) years. Nine patients, (breast cancer 3, malignant lymphoma 4 and AML 2), who underwent ABMT following preparative regimens with comparable doses of Mito, served as controls. Engraftment following allo-BMT was normal and not statistically different from engraftment following ABMT. Five patients, who underwent allo-BMT, developed >grade II acute graft versus host disease (GVHD) and two developed chronic GVHD. After a median follow up of 28 (6-42) months, five patients are alive (one with disease). In summary, engraftment following high dose Mito and allo-BMT is not statistically different from engraftment following ABMT. Controlled studies with a larger group of standard risk patients are needed to elucidate the role of Mito in conditioning regimens pre-BMT.
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PMID:Engraftment following mitoxantrone (Mito) based conditioning for allogeneic bone marrow transplantation (allo-BMT). 961 12

Donor-derived CD4+ T cells may play a role in the development of graft-versus-host disease (GVHD) and graft-versus-leukemia reaction after allogeneic bone marrow transplantation (BMT). Therefore, we evaluated the effect of CD4+ T-cell depletion on GVHD and graft-versus-leukemia reaction after HLA-matched BMT. CD4 depletion was performed using anti-CD4 monoclonal antibodies and immunomagnetic beads, initially in small-scale experiments on bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood apheresis products. The result was elimination of the CD4+ T cells from both sources (0% and 2+/-1.4% CD4+ cells, respectively). Subsequently, we used this technique for large-scale negative selection of CD4+ T cells from bone marrow grafts of four consenting leukemic patients in relapse (ALL-3, ANLL-1) (M-3, F-1). The large-scale CD4+ T-cell depletion resulted in >98% (n=4) elimination of CD4+ cells. The resulting population included 17.7+/-4.6% CD3+ T cells, 8.9+/-2.5% CD8+ T cells, 0.1+/-0.1% CD16+ natural killer cells, and 2.3+/-3.2% CD34+ hematopoietic progenitor cells. Patients were transplanted with 2.84+/-1.31 x 10(8) viable cells/kg. They received cyclosporine starting on day -1 as GVHD prophylaxis. Engraftment was fast with a white blood cell count of >1 x 10(9)/L on day 13.2+/-0.5, an absolute neutrophil count of >0.5 x 10(9)/L on day 13.8+/-0.5, and a platelet count of >25 x 10(9)/L on day 26.5+/-6.8. Immunological reconstitution was normal, and peripheral blood phenotyping 3 weeks after BMT disclosed 49.0+/-5.0% CD3, 14.3+/-12.4% CD4, and 59.5+/-7.8% CD8 T cells in addition to 17.0+/-3.0% CD16+ and 9.0+/-3.0% CD56 natural killer cells. Three out of four patients developed very early grade IV GVHD beginning on day 12 (10-13) and died 2-4 months after BMT. One patient is alive and well with a follow-up of 36 months. We conclude that selective CD4 T-cell depletion does not prevent GVHD.
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PMID:Selective CD4+ T-cell depletion does not prevent graft-versus-host disease. 967 38

In this retrospective study, 23 recipients of peripheral blood progenitor cells (PBPC) were compared to 23 recipients of bone marrow (BM). The donors were 12 HLA-A-B-DR identical siblings and 11 HLA-A-B-DR identical unrelated donors in the PBPC and BM groups, respectively. Diagnoses in the PBPC group were CML seven, AML, nine, ALL three, lymphoma one, myeloma two and aspartylglucosaminuria (AGU) one. The median age was 40 (5-55) years. The BM group was matched for diagnosis, age, conditioning therapy, GVHD prophylaxis and G-CSF treatment after BMT. A higher number of MNC (P<0.001), CD34+ (P = 0.05), CD3+ (P<0.001) and CD56+ (P<0.001) cells in the graft, a reduced number of platelet transfusions (P = 0.03) and a significant hastening of neutrophil and platelet recovery were seen in the PBPC group compared to the BM group. In logistic regression analysis, the following factors were important for engraftment of ANC >0.5 x 10(9)/l: peripheral blood progenitor cell transplantation (PBPCT) (P = 0.003) and mononuclear cells (MNC) > or =2.5 x 10(8)/kg recipient in the graft (above median) (P = 0.009) in univariate analysis. For recovery of platelets >30 x 10(9)/l: PBPCT (P = 0.03) and HLA-identical sibling donors (P = 0.05) were significant in multivariate analysis. A trend towards a lower incidence of bacteremia was seen in the PBPC group, ie 22 vs 48% (P = 0.06) in the BM group. GVHD, TRM and survival did not differ between the two groups.
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PMID:Faster neutrophil and platelet engraftment, but no differences in acute GVHD or survival, using peripheral blood stem cells from related and unrelated donors, compared to bone marrow. 970 19

Over the past decade, allogeneic cord blood transplantation (CBT) has been widely used for treating patients with malignant disorders. However, the reported low incidence of GVHD observed after allogeneic CBT might be a major drawback in leukemic recipients and at present it is not clear whether CBT really predisposes patients to an increased risk of leukemia relapse. In order to further elucidate the role of CBT in children with hematological malignancies, 54 patients with ALL or AML given either a related (31 cases) or an unrelated (23 cases) CBT in 25 centers participating in the Eurocord Registry were analyzed. Overall survival of related and unrelated CBT recipients was substantially similar, the most important factor influencing patients' outcome being disease state at time of transplantation. In fact, due to a markedly increased relapse rate, poor-risk children (ie patients transplanted in more advanced disease) experienced a significantly worse EFS than those given CBT in a more favorable disease phase (ie CR1 or CR2). These data confirm that allogeneic CBT from either a related or an unrelated donor is a feasible procedure able to cure a significant proportion of children with acute leukemia, especially if transplanted in a favorable phase of disease.
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PMID:Cord blood transplantation for children with acute leukemia. Eurocord Transplant Group. 971 98

Outcome of allogeneic BMT for childhood ALL performed at a national centre was evaluated for the period between 1985 and 1996. Sixty-seven patients representing all Danish children and adolescents (1-19 years) transplanted for ALL, were evaluated. Patients transplanted with a family donor (n = 51) had a 3-year probability of leukaemia-free survival (P-LFS) of 56% (95% confidence limits 41-69%) and patients receiving marrow from a matched unrelated donor (MUD) (n = 16) had a 3-year P-LFS of 67% (34-86%) (P = 0.38). Relapse was responsible for 48% of the deaths and occurred with increasing frequency among children transplanted with marrow from HLA-identical siblings. Patients transplanted with family donors from 1985-1989 had P-LFS of 72% (54-84%) compared to patients transplanted after 1990 who revealed a significantly reduced P-LFS of 28% (10-49%, P = 0.01). Furthermore, the risk of relapse was increased (65% (24-88%)) (P = 0.02) in the later period. In contrast, patients transplanted with marrow from a MUD (1990-1996) had a lower risk of relapse (11%, 5-20%) (P = 0.002) but a comparable risk of transplant-related mortality. Children who experience relapse after modern, intensive treatment for ALL may have an increased propensity for relapse even after BMT. Therefore, when performing BMT for childhood ALL, there may be a benefit in overall survival from the increased graft-versus-leukaemia effect that follows less intensive GVHD prophylaxis or transplantation with a MUD.
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PMID:Outcome of acute lymphoblastic leukaemia in Danish children after allogeneic bone marrow transplantation. Superior survival following transplantation with matched unrelated donor grafts. 972 66

Donor lymphocyte infusions (DLI) are an effective treatment of leukemia relapse after allogeneic bone marrow transplantation. Undesired side-effects are the development of graft-versus-host disease (GVHD) and the occurrence of pancytopenia in some patients. In a pilot study, we investigated if unmanipulated G-CSF-mobilized peripheral blood stem cells which naturally contain large numbers of T lymphocytes (D-PBSC/LI) would be equally effective or even superior than DLI in generating a graft-versus-leukemia reaction (GVL) but could mitigate or prevent the development of pancytopenia. We treated 12 patients with CML chronic phase (n = 5), CML blast crisis (n = 2), AML (n = 2), ALL (n = 1), CLL (n = 1) and multiple myeloma (n = 1). In five patients with acute leukemia or CML blast crisis D-PBSC/LI followed intensive chemotherapy (group A), in seven patients D-PBSC/LI were given without any prior chemotherapy (group B). In group A two patients were evaluable for hematologic toxicity. Leukopenia <1000/microl lasted for 10 and 19 days, and thrombocytopenia <20,000/microl for 11 and 13 days, respectively. In group B leukopenia <1000/microl and thrombocytopenia <20,000/microl was observed in only one patient. Moderate cytopenia developed in four of five evaluable patients. A complete remission could be achieved in all seven patients with CML who all developed acute and/or chronic GVHD. None of the remaining five patients achieved a complete remission despite acute and/or chronic GVHD in two of them. Four patients died from disease progression, one patient from a secondary lymphoma, and one patient as a result of uncontrolled GVHD. In conclusion, D-PBSC/LI is effective in inducing GVL reaction but it does not prevent pancytopenia in each case. It remains unclear if it mitigates the incidence and severity of pancytopenia.
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PMID:Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation. 975 47

Human minor histocompatibility antigens (mHags) play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). As most mHags are not leukemia specific but are also expressed by normal tissues, antileukemia reactivity is often associated with life-threatening graft-versus-host disease (GVHD). Here, we describe a novel mHag, HB-1, that elicits donor-derived CTL reactivity in a B cell acute lymphoblastic leukemia (B-ALL) patient treated by HLA-matched BMT. We identified the gene encoding the antigenic peptide recognized by HB-1-specific CTLs. Interestingly, expression of the HB-1 gene was only observed in B-ALL cells and Epstein-Barr virus-transformed B cells. The HB-1 gene-encoded peptide EEKRGSLHVW is recognized by the CTL in association with HLA-B44. Further analysis reveals that a polymorphism in the HB-1 gene generates a single amino acid exchange from His to Tyr at position 8 within this peptide. This amino acid substitution is critical for recognition by HB-1-specific CTLs. The restricted expression of the polymorphic HB-1 Ag by B-ALL cells and the ability to generate HB-1-specific CTLs in vitro using peptide-loaded dendritic cells offer novel opportunities to specifically target the immune system against B-ALL without the risk of evoking GVHD.
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PMID:A human minor histocompatibility antigen specific for B cell acute lymphoblastic leukemia. 989 12

Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.
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PMID:Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: a pilot study. 1045 58

Between February 1993 and November 1997, 62 patients with severe aplastic anaemia (SAA), acute myeloid (AML), acute lymphoid (ALL), or chronic myeloid leukaemia (CML) as well as two patients with NHL underwent allogeneic marrow transplantation (BMT) from HLA-identical or one-antigen mismatched sibling or unrelated donors. Patients received preparative regimens according to the baseline disease. Patients with SAA were conditioned with ATG/Cy (2 cases) and TAI/Cy (3 cases), AML, ALL and NHL with TBI/Cy (21 cases including two retransplantations) and CML with Mitobronitol/Ara-C/Cy except two patients conditioned traditionally with Bu/Cy. For GVHD prevention, patients received cyclosporin-A (CsA) with short course methotheraxe according to the Seattle protocol. Significantly better overall survival rates were associated with the Mitobronitol (DBM)/Ara-C/Cy conditioning regarded the patients as a whole. Autologous stem cell transplantation (bone marrow and/or peripheral blood) were performed in ten cases including 2 AML, 4 non-Hodgkin's lymphoma (NHL), 3 Hodgkin's disease (HD) and 1 patient with multiple myeloma (MM). Patients with AML and two patients with NHL were conditioned with TBI/Cy and the others with BEAM combined chemotherapy. Eight out of ten patients are leukaemia- or lymphoma-free survivors. One patient relapsed having conventional chemotherapy and interferon maintenance therapy. One patient died in a rapid relapse five months post-BMT.
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PMID:Haemopoietic cell transplantation activity and results: a single institution experience. 991 38


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