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)

21-year-old male was diagnosed as having acute lymphoblastic leukemia (ALL) in March 2001. Standard G-banding analysis revealed normal karyotype. He achieved complete remission after the first course of induction therapy and underwent allogeneic PBSCT in August 2001. However, leukemic cells appeared in the peripheral blood demonstrating complex chromosomal abnormalities with Philadelphia chromosome (Ph1) and expressing minor BCR/ABL transcripts. We thus retrospectively examined the bone marrow sample at presentation with both interphase FISH and RT-PCR methods. Surprisingly, almost all leukemic blasts at presentation turned out to possess the minor type of BCR/ABL fusion gene. In spite of the second allogeneic PBSCT, the patient died of pneumonia and graft-versus-host disease in the liver in September 2002. This case is rare in that cytogenetic analysis failed to detect Ph1 due to leukemic cells dormancy. The application of both FISH and RT-PCR studies would appear to be essential to avoid overlooking Ph1-positive ALL.
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PMID:[Philadelphia chromosome-positive acute lymphoblastic leukemia showing normal karyotype at presentation]. 1468 77

Graft rejection is a major cause of treatment failure after T-cell-depleted stem cell transplantation (TCD-SCT) and remains a therapeutic challenge. Donor leukocyte infusions (DLIs) have an efficient graft versus host effect, which has been successfully used to treat recipient relapses. We hypothesized that this effect could be exploited to counteract the host versus graft reactions responsible for graft rejection. We report two adult patients with haematological malignancies who underwent sex-mismatched TCD-SCT from HLA-identical sibling donors. Peripheral blood (PB) counts and bone marrow (BM) cellularity were studied on a serial basis. Sequential chimaerism and minimal residual disease analysis were performed by FISH on PB and BM samples as well as on leukocyte lineages (T and B lymphocytes and myeloid cells) purified from PB using immunomagnetic technology. Both patients were diagnosed with incipient graft rejection 2-3 months after engraftment, based on persistently decreasing PB counts and BM cellularity together with the observation of decreasing mixed chimaerism (increasing percentage of recipient cells), mostly in whole PB and T lymphocytes. Both patients were successfully treated with a single DLI (1 x 10(7) CD3+ cells/kg), thereafter achieving normal PB counts and BM cellularity as well as complete chimaerism. Interestingly, the only side effect observed was mild graft versus host disease that did not require treatment. In conclusion, provided that an early diagnosis is made, the graft versus host lymphohaemopoietic effect harboured by immunocompetent donor cells can be successfully used for the treatment of incipient graft rejection.
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PMID:Successful treatment of incipient graft rejection with donor leukocyte infusions, further proof of a graft versus host lymphohaemopoietic effect. 1506 92

Transfusion associated graft-versus-host disease (TA-GVHD) is a rare, dreadful complication of transfusion in immunocompromized and immunologically competent individuals. The diagnosis is often delayed, because of lack of awareness and the non-specific clinical features. We describe a rapid molecular cytogenetic analysis of FISH for the diagnosis of two cases of TA-GVHD with sex-mismatched donors. The use of FISH is a rapid and sensitive technique for the early diagnosis of TA-GVHD when the recipient and donor are of different gender.
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PMID:Rapid molecular cytogenetic diagnosis of transfusion associated graft-versus-host disease by fluorescent in situ hybridization (FISH). 1848 90

GVHD is a major complication in allogeneic SCT. Available GVHD models are mainly based on radiotherapy-conditioning and/or immune deficient mice. GVHD models based on chemotherapy-based regimens remain poorly studied, despite 50% of all transplantations being chemotherapy based. Our aim was to develop a GVHD model using chemotherapy as conditioning. Female BALB/c (H-2Kd) were conditioned with BU-CY and transplanted with 2 x 10(7) BM and 3 x 10(7) spleen cells from either C57BL/6 (H-2 Kb) mice (allogeneic setting) or from male BALB/c to serve as a control group for regimen-related toxicity and engraftment. GVHD manifestations and histopathological changes were evaluated. Chimerism and donor T cells presence in skin, intestine and liver were studied using FACS-, FISH analysis and immunohistochemistry. Allogeneic transplanted mice developed lethal GVHD starting from day+7 with both histological and clinical signs. Donor T cells accumulated in recipient skin and intestine with GVHD progression. BM-failure, apoptosis and T-lymphocyte infiltration into target organs were significantly higher in allogeneic when compared with the syngeneic group. No toxicity or GVHD signs were observed in the syngeneic setting. We report a mouse model of GVHD using BU-CY conditioning that represents the most common myeloablative-conditioning regimen in clinical SCT. This model can be utilized to study the role of conditioning on mechanisms underlying GVHD.
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PMID:GVHD after chemotherapy conditioning in allogeneic transplanted mice. 1882 Jul 12

The aim of this study was to explore the clinical effect and complications of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in hematologic malignancies through retrospective analysis of 75 patients (42 male, 33 female; aged from 13 to 72 years old) received allo-PBSCT from HLA matched (n=61) or haploidentical donors (n=14). 75 patients included 35 patients with chronic myeloid leukemia (CML), 30 patients with acute myeloid leukemia, 5 patients with severe aplastic anemia, 3 patients with acute lymphocytic leukemia, one patients with multiple myeloma and one patients with paroxysmal nocturnal hemoglobinuria. Conditioning regimens were (1) Cy/TBI or Bu/Cy; (2) Cy/TBI+Ara-C; (3) fludarabine+TBI/or (CTX+ATG). Minimal residual disease has been monitored regularly by PCR and FISH. Patients received cyclosporine A and methotrexate or ATG and anti-CD25 monoclonal antibody and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Relapsing patients after transplantation received DLI and/or chemotherapy. Patient with CML were treated with imatinib. The results showed that 74 patients had hematopoietic reconstitution, and eventually converted to full donor chimerism by FISH or PCR-STR. The median time for the initial hematopoietic reconstitution was 15 (5-25) days. 46 out of 75 patients were alive and median duration was 23 (2-61) months. Among 29 dead patients, 9 died of disease relapse, 7 died of III-IV grade of acute GVHD and 7 died of severe infection (2 patients developed interstitial pneumonia). 9 out of 14 patients received haploidentical transplantation were alive, and the time of event-free survival was 30 (6-53) months, the mean survival time of 5 died patients was 7 (2-17) months. 16 patients were infected by cytomegalovirus, 2 of them died of interstitial pneumonia. None of them suffered from veno-occlusive disease in the liver. It is concluded that allo-PBSCT is effective to treat refractory hematologic diseases, and DLI/or chemotherapy should be used in the patients relapsing after transplantation.
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PMID:[Allogeneic peripheral blood stem cell transplantation for 75 cases of hematologic malignancies]. 1909 38

Omenn's syndrome is a rare inherited variant of SCID. It is inevitably fatal, unless treated by bone marrow or stem cell transplantation. However, treatment-related complications and graft rejection are major obstacles to the success of transplantation. In this report, we describe an eight-month-old baby with Omenn's syndrome and disseminated BCGosis, who underwent allogenic BMT from his HLA-matched sister using anti-GVHD prophylaxis but without a conditioning regimen. Ten days after BMT, he developed acute GVHD involving the skin only (grade 1) with a flare of local BCGosis. Engraftment of 55% was demonstrated by FISH as early as the 11th day post-BMT. On day +48 post-BMT, he developed GVHD that was complicated by refractory pancytopenia, resistant to three doses of rituximab. Patient was re-transplanted (from the same donor) after receiving fludarabine and ATG, with successful engraftment and complete recovery from pancytopenia.
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PMID:Successful second bone marrow transplantation in Omenn's syndrome after bone marrow aplasia: a case report. 2110 10

Graft versus host disease (GVHD) following liver transplant occurs in 0.1-2% of patients and portends a poor prognosis. Affected organs include skin, the gastrointestinal tract and bone marrow. We present the case of a 61 year old female who developed skin rash and pancytopenia following sex-mismatched second liver transplant for autoimmune hepatitis. Initial skin biopsies revealed vacuolar interface change, keratinocyte necrosis and a mild mononuclear superficial perivascular infiltrate. The bone marrow was markedly hypocellular with scattered CD8 positive T lymphocytes. FISH analysis revealed chimerism with the presence of male donor cells in the skin and bone marrow biopsies. This case illustrates the diagnostic utility of FISH in detecting the presence of donor-derived cells in tissues affected by GVHD.
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PMID:The utility of fluorescence in situ hybridization (FISH) analysis in diagnosing graft versus host disease following orthotopic liver transplant. 2184 79

We present a case with sustained complete molecular response (CMR) after cessation of two months of imatinib mesylate (IM) treatment for chronic myelogenous leukemia (CML) relapsed after allogeneic stem cell transplantation (Allo-SCT). A 30-year-old previously healthy woman was seen in a clinic because of left abdominal discomfort. Splenomegaly and increased leukocytes with Philadelphia chromosome led to the diagnosis of CML in the accelerated phase. She received four months of IM treatment followed by allo-SCT from her HLA-matched sibling. She achieved and maintained CMR without developing acute GVHD for six months, when hematologic relapse occurred. While reducing the immunosuppressant, she received IM; however, it was discontinued two months later due to myelosuppression. Even after the termination of IM, the positivity of chimeric BCR-ABL gene detected by FISH analysis in peripheral blood continued to decrease. The molecular analysis of bone marrow one year after allo-PBSCT revealed CMR lasting for more than two years after cessation of IM. IM may possibly enhance the graft-versus-leukemia effects by reducing tumor burden in cases relapsed after allo-SCT.
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PMID:[Sustained complete molecular remission after cessation of imatinib mesylate treatment in a patient with relapsed chronic myelogenous leukemia after allogeneic stem cell transplantation]. 2245 May 81

There is increasing evidence suggesting that both angiogenesis and endothelial injury are involved in GVHD. To study the dynamics of angiogenesis, we examined 26 patients with AML who had undergone allogeneic haematopoietic SCT. All were in CR and had either acute GVHD (aGVHD) or chronic GVHD (cGVHD). We performed immunohistochemical studies of BM microvessel density (MVD) using Abs against vascular-endothelial (VE)-cadherin, CD34 and CD105, and expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2. At the time of diagnosis, the MVD in AML patients was higher than that in the normal controls, and the MVD decreased after induction chemotherapy. Patients with aGVHD had a significantly higher MVD than patients without aGVHD. Conversely, patients with cGVHD did not have a significantly different MVD. In previous aGVHD, we also found more VEGF+ megakaryocytes. XY FISH in sex-mismatched patients showed that the BM blood vessels consisted mainly of recipient endothelial cells. Taken together, these results suggest that new vessel formation and the VEGF/VEGFR system are involved in aGVHD.
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PMID:GVHD after allogeneic haematopoietic SCT for AML: angiogenesis, vascular endothelial growth factor and VEGF receptor expression in the BM. 2308 26


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