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)

Thrombotic microangiopathy (TMA) is an infrequent but serious complication of allogeneic transplantation. The success rate of plasma exchange (PE) reported in the treatment of this entity is a controversial subject. We report the outcome of 10 patients with TMA post-allogeneic transplantation after treatment with PE. Two out of the 10 patients have not responded, five had a partial response, but died of acute GVHD or interstitial pneumonitis, and three have responded and recovered. Our study suggests that there are different degrees of TMA severity. Only mild multifactorial cases with no severe hemolysis (LDH activity <1000 U/l) may be fully resolved with PE.
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PMID:Management of thrombotic microangiopathy following allogeneic transplantation: what is the role of plasma exchange? 928 45

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

A 44-year-old male with Ph+ chronic myeloid leukaemia (CML) underwent histoidentical allogeneic bone marrow transplantation 18 months after initial diagnosis. He received pretransplant conditioning with busulphan and cyclophosphamide (Bucy). GVHD prophylaxis consisted of methotrexate, cyclosporine (CsA) and methylprednisolone. On day +50, he developed a microangiopathic haemolytic anaemia with indirect bilirubinaemia, 10% fragmented red cells (FC) and an elevated LDH (1213 U/l: normal range 100-185 U/l). Clinical symptoms consisted of edema and hypertension. The patient was not febrile and had no neurological changes. A clinical diagnosis of severe (grade 4) multifactorial (acute GVHD, CMV infection and cyclosporine) BMT-TM was made. He responded following 19 plasma exchanges with replacement with fresh frozen plasma.
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PMID:Complete response in severe thrombotic microangiopathy post bone marrow transplantation (BMT-TM) after multiple plasmaphereses. 1084 37

A 36-year-old woman was referred to our hospital because of leukocytosis in June 2000, and was admitted to our hospital and diagnosed as having adult T-cell leukemia/lymphoma (ATL; acute type). Complete remission was achieved with eight courses of CHOP therapy, but ATL relapsed and she was readmitted to our hospital in September 2001. Laboratory examination showed elevated levels of serum LDH and soluble IL-2 receptor, and hypercalcemia. CT examinations showed swelling of the abdominal lymph nodes and hepatosplenomegaly. CHOP therapy improved the symptoms, but recrudescence soon occurred. After two courses of salvage therapy which resulted in no remission, the patient received an allogeneic peripheral blood stem cell transplant (allo-PBSCT) from her HLA-matched sibling donor after preconditioning with BU + CY in January 31, 2002. Cyclosporin A (CsA) and short-term MTX were used to prevent GVHD. Bone marrow engraftment was prompt and acute GVHD was not found. Two months later, recurrence was seen in the form of subcutaneous tumors, but the tumors spontaneously disappeared following CsA withdrawal. At the time of writing, eight months after the transplant, remission has been maintained. A graft-versus-leukemia (GVL) effect may have been the curative action in this case.
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PMID:[Cyclosporin A withdrawal causes spontaneous remission of recurrent subcutaneous tumors after allogeneic peripheral blood stem cell transplantation for adult T-cell leukemia/lymphoma]. 1269 82

A 10-year-old boy with acute lymphoblastic leukemia in second relapse received CD34+ purified allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-haploidentical father. The patient developed grade II acute GVHD and received high-dose methyl-prednisolone starting on day + 13 posttransplant. Renal dysfunction followed by massive gastrointestinal bleeding was observed from day + 14. The laboratory findings including elevated serum LDH, increased RBC fragmentation, higher level of thrombomodulin and undetectable haptoglobin corresponded with the diagnosis of thrombotic microangiopathy (TMA). In spite of various treatments, the patient died of multiple organ failure on day + 93. Post-mortem examination revealed systemic adenovirus infection without histological findings of TMA. Severe adenovirus infection may be confused with TMA, and should be distinguished by rapid virological assay.
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PMID:Fatal adenovirus infection indistinguishable from thrombotic microangiopathy after allogeneic CD34+ peripheral progenitor cell transplantation. 1595 1

We studied occurrence, risk factors and outcome of patients with transplant-associated microangiopathy (TAM) after allogeneic stem cell transplantation (HSCT). A total of 221 consecutive patients were transplanted between 1995 and 2002. TAM is defined as evidence of hemolysis and schistocytes in the first 100 days. Outcomes analyzed included TAM and overall survival. Of 221 patients, 68 had TAM. The cumulative incidence was 31 (25-38)% at 100 days. Patients with TAM had higher LDH, higher bilirubin, higher creatinine and more often neurologic symptoms. TAM was not associated with stem cell source, cyclosporine levels and was not more frequent in recent years. In multivariate analysis, risk factors for TAM included donor type, age, gender, ABO-incompatibility and acute graft-versus-host disease (aGvHD). In patients with TAM, 1-year survival was lower than in patients without TAM (27 +/- 18% for TAM with high schistocyte counts; 53 +/- 15% for TAM with low schistocyte counts; vs 78 +/- 7% in patients without TAM; P<0.0001). TAM was independently associated with mortality adjusting for donor type, age and aGvHD occurrence and severity. TAM is frequent after HSCT and is associated with mortality even after adjustment for aGvHD grade. Risk factors of TAM are similar to aGvHD. TAM may represent endothelial damage driven by donor-host interactions.
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PMID:Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants. 1618 83

A 17 years old female diagnosed with acute myeloid leukemia (AML)-M2 received an allogeneic haematopoietic stem cell transplant (HSCT) and was given graft versus host disease (GVHD) prophylaxis with methotrexate, cyclosporin-A (CsA) and methyl prednisolone. On day +42 post-transplant, she was diagnosed to have thrombotic thrombocytopenic purpura (TTP). Therapeutic plasma exchange (TPE) (40 ml/kg body mass) using fresh frozen plasma was performed on 8 consecutive days. The renal function, LDH levels, platelet count and peripheral smear findings improved but the neurological symptoms persisted even after TPE. Few reports are available in literature on the effectiveness of therapeutic plasma exchange (TPE) in post-bone marrow transplant (BMT) TTP. The good hematologic response achieved in this patient suggests that TPE could be life-saving and should be tried in every patient with post-BMT TTP.
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PMID:Plasma exchange for thrombotic thrombocytopenic purpura following hematopoietic stem cell transplantation. 1651 39

The study was aimed to establish a new method of preparation of human placenta factor (PF) and to determine its physic-chemical properties, as well as effects on lymphocytes in vitro. PF was prepared by ultrafiltration. The contents and molecular weight of all constitutions were determined by Bradford method and SDS-PAGE, respectively. Cyclosporin A (CsA) was served as positive control, normal saline (NS) was used as negative control. PHA-stimulated lymphocyte proliferation and mixed lymphocyte reaction (MLR) were detected with MTT assay. The expression of CD69 on T cells was analyzed by flow cytometry. Cytotoxicity of natural killer (NK) cells against K562 tumor cells was examined with LDH release assay. The results indicated that PF was determined to be a group of low molecular weight polypeptides, consisting of two major components whose molecular weight were 9.187 and 4.794 kD respectively. The contents of PF were 5.7 - 6.9 mg/g fresh placenta. PF had similar suppressive effects on PHA-stimulated lymphocyte proliferation and MLR in vitro as compared with CsA (P > 0.05). Both PF and CsA could downregulate the expression of CD69 on T cells which had been stimulated by PMA plus ionomycin (PF vs CsA, P > 0.05). The cytotoxicity of NK cells against K562 cells in PF group was slightly higher or equivalent as compared with that in NS group (P > 0.05), but the cytotoxicity in CsA group was much lower than that in NS group (P < 0.05). It is concluded that a new method of preparation of PF has been established. This study first demonstrates that PF has strong immunosuppressive effects on T cell in vitro, and suppresses T cell proliferation and activation induced by mitogen and alloantigen. This study indicats that PF has no any inhibitory effects, but even enhances the cytotoxicity of NK cells against K562 tumor cells. These results suggest that PF may have suppressive effects on graft-versus-host disease (GVHD) without diminishing graft-versus-tumor (GVT) effects. Therefore, PF may probably be an ideal and promising agent against GVHD.
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PMID:[Preparation of placenta factor and its immunoregulatory effects on lymphocytes in vitro]. 1760 67

This study was aimed to investigate the feasibility of low dose of fludarabine, cyclophosphamide combined with donor derived alloreactive NK cells as a new nonmyeloablative conditioning regimen in the haploidentical hematopoietic stem cell transplantation (haploidentical HSCT). F1 derived-NK cells were enriched with MACS magnetic separation system, in which the proportions of the Ly49C+ and Ly49A+ cells were detected by flow cytometry and the alloreactivity was measured by LDH method. The haploidentical HSCT models were constructed, and the myeloablativity in vivo, donor engraftment and the intensity of GVHD were compared between different myeloablative and nonmyeloablative conditioning regimens, including 9 Gy TBI, 6.5 Gy TBI, flu + cy, and flu + cy + allo-NK. The results showed that the flu + cy + allo-NK conditioning was nonmyeloablative, but the rate of donor chimerism after haploidentical HSCT was significantly higher as compared with other nonmyeloablative methods, which were (28.70 +/- 5.90)% in bone marrow and (46.40 +/- 5.00)% in spleen at day 21 post-transplantation. When compared with the flu + cy conditioning, the intensity of GVHD was slight in the flu + cy + allo-NK group, in which only a half of C57BL/6 recipients experienced weight loss, and no distinct pathological damages observed in the liver, intestine, kidney and skin samples. It is concluded donor derived-alloreactive NK cells can facilitate engraftment of the haploidentical hematopoietic stem cells and mitigate GVHD. The flu + cy + allo-NK conditioning provides a new method for those elder patients with high-risk solid tumor undergoing haploidentical-HSCT.
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PMID:[Application of low dose of fludarabine and cyclophosphamide combined with donor NK Cells as a non-myeloablative conditioning regimen for the haploidentical hematopoietic stem cell transplantation in mice]. 1795 81

Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare complication of hematopoietic stem cell transplantation (HSCT) with variable presentations. TA-TMA has often been described as a diagnosis of exclusion but a renal biopsy is rarely pursued to confirm the diagnosis, an essential step for our patient with renally limited TMA. We report a case report from the onconephrology clinic and review the literature associated with TA-TMA as it relates to diagnosis and treatment. A 45-year-old woman with acute myeloid leukemia and stage 3 chronic kidney disease underwent a matched unrelated donor allogenic HSCT. Postoperatively, she developed gastrointestinal graft versus host disease (GvHD) and was treated with tacrolimus, sirolimus, budesonide, and beclomethasone. Following discharge, she developed uncontrolled hypertension and required losartan, amlodipine, carvedilol, clonidine patch, and hydralazine as needed. On day 180 post-transplant, she developed lower extremity edema and acute kidney injury (AKI) with creatinine increasing to 2 mg/dL. On day 480 post-transplant, she developed worsening thrombocytopenia, anemia, new hematuria, left flank pain, and worsening renal function with creatinine peaking to 6 mg/dL. Peripheral smear revealed no schistocytes, lactate dehydrogenase of 265 mg/dL, and urinalysis with 100 mg/dL protein. ADAMTS 13 activity was normal (92%) and no inhibitor was detected. She became anuric and was started on hemodialysis. Renal biopsy revealed glomerular changes consistent with TA-TMA. During HSCT, systemic vascular endothelial injury triggers microangiopathic hemolytic anemia, platelet consumption, injury of glomerular endothelial cells and fibrin occluded renal capillaries. Thus, TA-TMA should be considered in HSCT patients with elevated LDH, proteinuria, hypertension, and AKI. However, a diagnosis is difficult to confirm without a renal biopsy. Treatment involves discontinuing potentially toxic agents such as calcineurin inhibitors and sirolimus, prescribing adequate antimicrobial treatment, and using renal replacement therapy if needed. A renal biopsy early in the course of disease not only confirms the diagnosis, but may limit the extent of disease.
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PMID:Thrombotic Microangiopathy With Granulomatosis Interstitial Nephritis in an Allogenic Bone Marrow Transplant Patient: A Case Report and Review of the Literature. 3230 Mar 93


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