Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Animal models of bone marrow transplantation (BMT) allow evaluation of new experimental treatment strategies. One potential strategy involves the treatment of donor marrow with ultra-violet B light to allow transplantation across histocompatibility boundaries without an increase in graft rejection or graft-versus-host disease. A major requirement for a new experimental protocol, particularly if it involves manipulation of the donor marrow, is that the manipulated marrow gives rise to long-term multilineage engraftment. DNA based methodologies are now routinely used by many centres to evaluate engraftment and degree of chimaerism post-BMT in humans. We report the adaptation of this methodology to the serial study of engraftment in rodents. Conditions have been defined which allow analysis of serial tail vein samples using PCR of short tandem repeat sequences (STR-PCR). These markers have been used to evaluate the contribution of ultraviolet B treated marrow to engraftment following BMT in rodents without compromising the health of the animals under study. Chimaerism data from sequential tail vein samples and bone marrow from selected sacrificed animals showed excellent correlation, thus confirming the validity of this approach in analysing haemopoietic tissue. Thus the use of this assay may facilitate experimental studies in animal BMT.
 ...
PMID:PCR amplification of short tandem repeat sequences allows serial studies of chimaerism/engraftment following BMT in rodents. 864 Jan 77

Chronic myeloid leukaemia (CML) can be treated successfully with allogeneic bone marrow transplantation (BMT) leading to long-term disease-free survival. Leukemia relapse, however, remains a significant clinical problem. Relapse following BMT presumably results from the expansion of small numbers of recipient leukaemic cells which have survived the conditioning therapy. In order to define patients who are at a high risk of leukaemia relapse, a variety of techniques have been employed to detect persistence of host haemopoiesis (mixed chimaerism, MC) or residual leukaemia (minimal residual disease, MRD). However, the precise relationship between the detection of MC and MRD post-BMT is unknown. We have investigated chimaerism and MRD status in 22 patients who were in clinical and haematological remission post-allogeneic BMT for chronic phase CML. Chimaerism was assessed using short tandem repeat PCR (STR-PCR) while BCR-ABL mRNA detection using reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect the presence of MRD. Seventeen patients received unmanipulated marrow (non-TCD) while in five patients a T cell-depleted transplant (TCD) was performed as additional GVHD prophylaxis. Chimaerism was evaluated in 18 patients (14 non-TCD, four TCD). Mixed chimaerism was an uncommon finding in recipients of unmanipulated BMT (21%) when compared to TCD BMT (100%). No evidence of MRD, as identified using the BCR-ABL mRNA RT-PCR assay, was detected in those patients who were donor chimaeras. Early and transient MC and MRD was detected in four patients (two non-TCD, two TCD) who have subsequently converted to a donor profile. One patient has stable low-level MC but remains MRD negative 4 years post-BMT. Late MC and MRD was observed in two patients who relapsed >6 years after TCD BMT for CML. We conclude that mixed chimaerism is a rare event in recipients of unmanipulated BMT and that donor chimaerism as detected by STR-PCR assay is consistent with disease-free survival and identifies patients with a low risk of leukaemic relapse post-BMT for CML.
 ...
PMID:Persistent donor chimaerism is consistent with disease-free survival following BMT for chronic myeloid leukaemia. 925 92

Instead of donor T cell depletion, we used CTLA4 and TJU103 (a small organic compound believed to block CD4 binding to MHC II molecule of APC) to block donor T lymphocyte activation in vitro before infusion, and mycophenolate mofetil to control the activity of lymphocytes of the recipient. We successfully treated a patient with an HLA-mismatched graft without donor T cell depletion. Mixed chimerism was observed 30 days and 60 days after transplantation. STR-PCR showed that 28% and 62% of blood mononuclear cells (MNC) were donor derived at day +30 and day +60, respectively. Mixed chimerism converted into full donor chimerism, when 99.7% of the MNC in the recipient were donor derived after three courses of DLI. A powerful GVL effect related to mixed chimerism was observed. No acute GVHD occurred, only grade II chronic GVHD occurred 6 months after transplant. Based on this case, we suggest that: (1) stable mixed chimerism can be intentionally established across HLA barriers without donor T cell depletion; (2) mixed chimerism can be converted into full donor chimerism by DLI; (3) mixed chimerism induced with this approach can be associated with a very powerful GVL effect, and these may be enhanced by DLI, without severe GVHD.
 ...
PMID:Mixed chimera converted into full donor chimera with powerful graft-versus-leukemia effects but no graft-versus-host disease after non T cell-depleted HLA-mismatched peripheral blood stem cell transplantation. 1103 76

Using red cell phenotyping (RCP) and/or cytogenetics (CYT) we identified 19 patients with persisting mixed chimerism (MC) among 231 patients transplanted with partially T cell-depleted stem cell grafts from HLA-identical siblings. Persisting MC is defined as MC for more than 2 years in patients without any evidence of relapse. Median leukemia-free survival in these patients was 150 (range, 50-218) months. Diagnoses were ALL (n= 10); AML (n = 2); CML (n = 2); NHL (n = 2); MDS (n= 1); MM (n = 1) and SAA (n = 1). Purpose of this study was the long-term follow-up of MC and definition of patterns of chimerism in the various subsets of PBMCs and granulocytes. Using a PCR-STR technique CD3(+)/CD4(+) (T4 lymphocytes), CD3(+)/CD8(+) (T8 lymphocytes), CD45(+)/CD19(+) (B lymphocytes), CD45(+)/CD14(+) (monocytes), CD45(+)/CD15(+) (granulocytes) and CD3(-)/CD56(+) (NK-cells) were analyzed. The majority of patients with persisting MC were conditioned with a less intensive conditioning regimen and had little GVHD. Sequential monitoring of the chimerism resulted in a group of patients (n = 7) with very slow transient mixed chimerism that resulted in complete DC after median 7 years. Another nine patients had a relatively high percentage of persisting autologous cells for a median of 12 years and in three patients we observed a stable low percentage of autologous cells. Only two out of 19 patients (AML-CR1, CML-CP1) relapsed during follow-up. Both patients had a relatively high percentage of autologous cells. Chimerism in granulocytes and PBMC subsets was analyzed at a median of 8 years after SCT in nine patients. In five patients mixed chimerism simultaneously detected by RCP and CYT was associated with MC in all subsets. Within each individual patient the percentages of donor and recipient cells were very different between the different subsets. Two CML-CP1 patients were mixed chimera in only two subsets and in one patient these subsets represented pending relapse. In another two patients mixed chimerism with a very low number of autologous red cells was not found in the PBMCs because of the different sensitivity level of the RCP and the PCR-STR technique. We conclude that in patients with persisting mixed chimerism after partially T cell-depleted SCT a remarkable number of patients had lymphoid malignancies, the majority of the patients were conditioned with less intensive conditioning regimens and the mixed chimerism was not correlated with relapse. Chimerism in granulocytes and PBMC subsets did show great intra-individual differences in the subsets and these data correlated well with RCP and CYT data with the exception of the NK cells.
 ...
PMID:Long-term follow-up of persisting mixed chimerism after partially T cell-depleted allogeneic stem cell transplantation. 1184 Feb 58

The need of quantitation of chimerism is increasing as mini-transplantation has been on trial and they are possibly become the mixed chimeras. FISH method using XY chromosome as a marker is effective in heterosexual transplantation, And STR-PCR method is effective in homosexual transplantation. There is wide range in strength of pre-conditioning in Mini-transplantation; almost all stronger pre-conditioning with fludarabine end up in completely donor-type, and the pre-conditioning with ATG, TBL, L-PAM, M-Pred, 40% became mixed chimera but they all became completely donor type with DLI. There is a report that there are less GVHD with mixed chimera. To decide which pre-conditioning to use, we need to examine the rate of the relapse.
 ...
PMID:[Chimerism in allogeneic mini-transplantation]. 1451 18

To explore the hematopoietic reconstitution and transplantation-related complications of two units of unrelated umbilical cord blood combined transplantation for the treatment of adult hematologic malignancies, one adult patient with chronic myelogenous leukemia received two units of unrelated umbilical cord blood combined transplantation. The conditioning regimen was busulfan and cyclophosphamide (Bu-Cy). GVHD prophylaxis regimen consisted of mycophenolate mofetil (MMF), cyclosporine A (CsA) and methotrexate (MTX). The patient received total nucleated cells 4.63 x 10(7)/kg with CD34+ cells 8.34 x 10(5)/kg. Engraftment was documented by the analysis of short tandem repeat with polymerase chain reaction (STR-PCR). The results showed that the STR-PCR analysis for peripheral blood at day 31, 46 and 71 after transplantation suggested that one of two units of cord blood were completely engrafted. The ANC > 0.5 x 10(9)/L in the patient occurred at day 23, blood platelet counts > 20 x 10(9)/L at day 33 and > 50 x 10(9)/L at day 47. The Philadelphia chromosome and bcr/abl fusion gene of the patient also turned to negative after engraftment. Acute GVHD grade II occurred at day 13 and cured after treatment. It is concluded that umbilical cord blood can be used in adult hematopoietic stem cell transplantation. Two or more units umbilical cord blood combined transplantation might be the way to solve the problem of the low counts of nucleated cells when be used for adult.
 ...
PMID:[Treatment of one case of adult chronic myelogenous leukemia by two units of unrelated umbilical cord blood transplantation]. 1457 47

The main goal of post-transplantation monitoring in hematopoietic stem cell transplantation (HSCT) is to predict negative events, such as disease relapse, graft rejection and graft-versus-host disease, in order to intervene with appropriate therapy. In this context, chimerism analysis is an important method in monitoring post HSCT outcome. Mixed chimerism (MC) is mainly evaluated to define engraftment and relapse. Detection of MC is a prerequisite in both myeloablative and nonmyeloablative HSCT, in order to assess the graft status and decide later therapeutic strategies such as donor lymphocyte infusion. In this review, we discuss various techniques including erythrocyte phenotyping, cytogenetic analysis, fluorescent in situ hybridization, restriction fragment length polymorphism, STR/VNTR analysis and real-time quantitative PCR, along with the various methods used to detect minimal residual disease (MRD) in different diseases such as chronic myeloid leukemia, acute myelomonocytic leukemia or acute lymphoblastic leukemia. The review mainly highlights the optimal methodological approach, which needs to be informative, sensitive and quantitatively accurate for MC detection. Future of post HSCT graft monitoring lies in the selection of the most accurate and sensitive technique to determine both MC and MRD. Such an approach would be helpful in not only determining relapse or rejection, but also in ascertaining various responses to different treatment modalities.
 ...
PMID:Significance of chimerism in hematopoietic stem cell transplantation: new variations on an old theme. 1515 63

Polymyositis usually occurred along with other manifestations of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) had been reported. However, polymyositis with a sole manifestation of acute GVHD following donor lymphocyte infusion (DLI) is rare. We reported a 45-yr-old man of acute lymphoid leukemia post-allogeneic HSCT 6 months developed acute polymyositis after DLI. He did not develop any symptoms, signs of acute or chronic GVHD following allogeneic HSCT, despite withdraw of immuosuppresive agents, cyclosporin A (CsA). As the DNA-STR of bone marrow analysis showed mixed chimerism, he received the DLI for remission on May 16, 2002. Acute polymyositis developed following DLI 22 d later. The clinical presentation of polymyositis is compatible with a manifestation of acute GVHD following DLI. It also responds to the treatment of steroid and CsA.
 ...
PMID:Acute polymyositis after donor lymphocyte infusion. 1565 9

Achievement of complete donor hematopoietic chimerism (CC) is the goal of allogeneic stem cell transplantation (allo-SCT). Persistence of recipient hematopoiesis augments the risk of relapse, which is one of the main reasons for mortality after allo-SCT. Another main reason for morbidity and mortality is severe extensive chronic graft-versus-host disease (cGvHD). We examined chimerism in peripheral blood of 54 allogeneic stem cell recipients using multiplex STR-PCR method and compared it with the timing and severity of cGvHD. In total, 25 patients achieved early CC (by day 100 post transplant) at a median time of 60 days. In total, 21 of them developed extensive cGvHD. In those patients CC uniformly preceded emergence of cGvHD by a mean of 85 days. A total of 26 patients obtained late CC at a median time of 270 days post transplant. Of this group, only eight patients developed extensive disease. Development of cGvHD in those patients preceded achievement of CC in 10 of 13 cases by a mean of 100 days. The difference between early and late CC groups as to the frequency of the extensive cGvHD was statistically significant (P<0.001). Also, there was a significant correlation of the time of CC and time between CC and cGvHD. Additionally, patients with early CC developed significantly more severe cGvHD measured by the need of three-drug treatment to control the disease (P<0.005). It can be concluded that achievement of early complete donor hematopoietic chimerism in peripheral blood is strongly predictive of severe extensive GvHD.
 ...
PMID:Early complete donor hematopoietic chimerism in peripheral blood indicates the risk of extensive graft-versus-host disease. 1582 66

A 34-year-old female was referred to our hospital for the evaluation of atypical lymphocytosis. Leukocyte count at diagnosis was 17,900/microl with 58% atypical lymphocytes having a convoluted nucleus and prominent nucleoli. Because the leukocyte count increased to 43,600/microl, the patient was treated with 2'deoxycoformycin followed by CHOP combination chemotherapy. However, both treatments failed to achieve remission. We planned an allogeneic bone marrow transplantation from an HLA-matched unrelated donor. The patient was treated with Ara-C and etoposide before conditioning to decrease the high leukemia burden. After administration of total body irradiation (12 Gy in six fractions) and cyclophosphamide (total dose of 120 mg/kg) unmanipulated marrow cells were infused. Under prevention of GVHD by CsA and short-term MTX, leukocyte engraft was prompt at day 16, and acute GVHD grade II was observed. Because 9.4% of residual recipient type T-cells was seen with STR analysis on day 22, we decreased the dose of Cs'A. After the occurrence of mild acute GVHD, the residual T-cell number decreased. The patient is still in complete remission for up to 22 months after BMT. We conclude that allogeneic SCT is effective for the treatment of T-PLL.
 ...
PMID:[Allogeneic bone marrow transplantation for chemotherapy-resistant T-prolymphocytic leukemia]. 1644 Jul 47


1 2 Next >>