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)

The AML1/ETO fusion transcript is expressed in virtually all patients with t(8;21) (q22;q22) acute myeloid leukemia (AML). The fusion transcript can be detected by reverse transcription-polymerase chain reaction (RT-PCR) in most of these patients in long-term complete remission (CR) following conventional chemotherapy or autologous bone marrow transplantation (BMT). However, AML1/ETO expression has not been analyzed in a series of patients following allogeneic BMT. We examined CR bone marrow (BM) samples and, in some cases, blood samples from 10 patients with t(8;21) leukemia who underwent allogeneic BMT in either first or second remission or first or second relapse. A variety of myeloablative regimens were used. Eight patients received non-T-cell depleted BM from matched sibling donors, one patient received a T-cell depleted haploidentical BM, and one patient received a non-T-cell depleted BM from a matched unrelated donor (MUD). Five patients developed acute and/ or chronic graft versus host disease (GVHD). The furthest time points analyzed for the AML1/ETO transcript in the 10 patients in CR following allogeneic BMT ranged from 7.5 to 83.0 months. Sufficient RNA was extracted from the most recent BM or BM and blood samples from nine patients to assay for presence or absence of the AML1/ETO fusion transcript by RT-PCR. The fusion transcript was detected by RT-PCR in all nine of these patient samples; eight were positive in BM and one was negative in BM, but positive in blood. The fusion transcript could not be detected in a BM sample from the tenth patient obtained 7.5 months after BMT, but the amount of RNA available was suboptimal. Hematopoietic chimerism could be demonstrated in sorted CD34+ BM cells from two of four patient CR BM samples with RT-PCR evidence of the fusion transcript. Additionally, in one of the two cases with chimerism, we demonstrated an abnormal clonal population of recipient cells in the CR BM sample by fluorescence in situ hybridization. One patient died of complications from GVHD, while the other nine patients remain alive without evidence of relapse, with a median follow-up time of 27 (range, 7.5 to 87) months post-BMT. These data suggest that allogeneic BMT, like conventional chemotherapy and autologous BMT, is not sufficient to eradicate cells expressing AML1/ETO, and that a positive RT-PCR for the fusion transcript post allogeneic BMT is compatible with continued CR.
 ...
PMID:Persistence of the AML1/ETO fusion transcript in patients treated with allogeneic bone marrow transplantation for t(8;21) leukemia. 937 7

Expression of AML1/ETO mRNA was observed in bone marrow cells from 49 untreated leukemic patients, and continuously detected during different periods after chemotherapy (12 cases) or bone marrow transplantation (8 cases). The results showed that AML1/ETO mRNA could be expressed in cells from AML-M(2), AML-M(4) and MDS-RAEB-T patients. The positive expression changed into negative at different duration in patients who achieved complete remission either by chemotherapy (9 cases), allogeneic bone marrow transplantation (5 cases) and autologous peripheral blood stem cell transplantation (1 case), and they were sustained in complete remission status. In chemotherapeutic group, patients whose AML1/ETO expression turning from negative (2 cases) or faint positive (1 case) to positive relapsed later. Two patients treated with Allo-BMT showed continuously positive results and died of GVHD and relapse, respectively. These observations suggest that AML1/ETO chimeric mRNA could disappeared after chemotherapy or bone marrow transplantation. The patients have a great probability to relapse if the results of RT-PCR are continuously positive or change from negative to positive. Regular detection is necessary for leukemic patients.
 ...
PMID:[Follow up Detection of AML/ETO Fushion Transcripts after Chemotherapy or Bone Marrow Transplantation in Leukemia Patients] 1257 21

To examine relapse, survival and transplant-related complications in relationship to disease- and pre-treatment-related characteristics, we evaluated 132 children, who consecutively received an allogeneic HLA-identical SCT for acute leukaemia in our centre: ALL in first remission (n=24), ALL in second remission (n=53) and AML in first remission (n=55). The source of the stem cells was bone marrow in all but three cases. Most patients (89%) were pre-treated with cyclophosphamide and an age-related dose of TBI. Initially, GVHD prophylaxis consisted of long-course MTX only (n=24), later short-course MTX and CsA (n=102) was given. All patients were nursed in strictly protective isolation and received total gut decontamination to suppress their potentially pathogenic enteric microflora. The 5-year probability of overall survival was 63, 53 and 74% for ALL1, ALL2 and AML1, respectively (median follow-up: 10.6 years). The overall transplant-related mortality was 6%. The incidence of acute GVHD was 17%; 6% was grades II-IV. A higher total biologically effective TBI dose (BED) resulted in a decreased relapse frequency (P=0.034) and increased overall survival. AML patients with acute GVHD got no relapse (P=0.02); this was not the case in ALL patients. Fractionated TBI regimens with higher BED should be evaluated in prospective studies.
 ...
PMID:HLA-identical haematopoietic stem cell transplantation for acute leukaemia in children: less relapse with higher biologically effective dose of TBI. 1757 15

We herein present a case of pediatric therapy-related myelodysplastic syndrome (t-MDS) with complex karyotype who was treated with azacitidine (AZA) for AML1-EVI1 fusion transcript as minimal residual disease after allogeneic hematopoietic stem cell transplantation (HSCT). The patient was started on AZA 41 days after the HSCT without having achieved complete remission. After 9 cycles of AZA, the AML1-EVI1 fusion transcript disappeared, and there was no manifestation of graft versus host disease during AZA treatment. Preemptive AZA treatment for minimal residual disease has an acceptable safety profile and appears to be an effective strategy for preventing or substantially delaying hematological relapse in pediatric patients with high-risk myelodysplastic syndrome after HSCT.
...
PMID:Azacitidine in the treatment of pediatric therapy-related myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation. 2460 72