Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently published data show an extremely poor survival of infants with AML and HLXB9/ETV6 rearrangement which is the fusion, resulting from the translocation t(7;12)(q36;p13). None of the patients reported survived a period of 3 years, including four patients who have received allogeneic hematopoietic stem cell transplantation (HSCT). Herein, we report the clinical course of an 8-month-old patient with acute myeloid leukemia, M2 subtype and with a HLXB9/TEL rearrangement. The patient received a haploidentical HSCT in relapse situation without any prior re-induction. The patient became MRD-negative over a period of 53 days after HSCT. This case reinforces the potential benefit of a graft-versus-leukemia effect in the haploidentical setting even in chemoresistant myeloid leukemias with poor-prognosis molecular features.
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PMID:Graft versus leukemia effect after haploidentical HSCT in a MLL-negative infant AML with HLXB9/ETV6 rearrangement. 1796 Jun 38

Acute promyelocytic leukemia (APL) is the most curable subtype of acute myeloid leukemia. Second complete remission (CR2) can be easily achieved with several therapeutic options even after relapse. However, the optimal strategy to treat APL in CR2 is still controversial. We retrospectively compared the outcome of autologous (auto) and allogeneic (allo) hematopoietic stem cell transplantation (HSCT) for patients with APL in CR2 or CR3. Fifteen patients received auto and 13 received allo HSCT between 1999 and 2004 at eight hospitals belonging to the Nagoya Blood and Marrow Transplantation Group. Four-year disease-free survival (DFS) and overall survival (OS) for autografted patients were 68.9 and 75.8%, whereas those for allografted patients were 46.2 (P = 0.350) and 46.2% (P = 0.185), respectively. Three autografted patients and one allografted patient relapsed, and one autografted patient and five allografted patients died without leukemia relapse. Among 14 autografted patients who were evaluated for MRD with molecular analysis, relapse occurred in one with positive MRD (n = 2) and two with negative MRD (n = 12). These data suggest that auto HSCT is very effective for APL in CR2 or CR3, and may be preferable to allo HSCT for a portion of patients. Prospective studies are required to define the role of auto HSCT in the treatment of relapsed APL.
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PMID:Hematopoietic stem cell transplantation for acute promyelocytic leukemia in second or third complete remission: a retrospective analysis in the Nagoya Blood and Marrow Transplantation Group. 1830 63

The ALL IC-BFM 2002 protocol was created as an alternative to the MRD-based AIEOP-BFM ALL 2000 study, to integrate early response criteria into risk-group stratification in countries not performing routine PCR-based MRD testing. ALL IC stratification comprises the response to prednisone, bone marrow (BM) morphology at days 15 and 33, age, WBC and BCR/ABL or MLL/AF4 presence. Here, we compared this stratification to the MRD-based criteria using MRD evaluation in 163 patients from four ALL IC member countries at days 8, 15 and 33 and week 12. MRD negativity at day 33 was associated with an age of 1-5 years, WBC<20,000 microl(-1), non-T immunophenotype, good prednisone response and non-M3 morphology at day 15. There were no significant associations with gender or hyperdiploidy in the study group, or with TEL/AML1 fusion within BCP-ALL. Patients with M1/2 BM at day 8 tended to be MRD negative at week 12. Patients stratified into the standard-risk group had a better response than intermediate-risk group patients. However, 34% of them were MRD positive at day 33 and/or week 12. Our findings revealed that morphology-based ALL IC risk-group stratification allows the identification of most MRD high-risk patients, but fails to discriminate the MRD low-risk group assigned to therapy reduction.
Leukemia 2008 May
PMID:Minimal residual disease (MRD) analysis in the non-MRD-based ALL IC-BFM 2002 protocol for childhood ALL: is it possible to avoid MRD testing? 1830 63

The aim of this study was to evaluate the significance of id4 gene promotor methylation detection in NHL patients. MS-PCR method was used to detect the status of id4 gene methylation in health donors and newly diagnosed NHL patients. The results indicated that the id4 gene was unmethylated in bone marrow samples from health donors. Among 18 newly diagnosed NHL patients, including one NHL patient with bone marrow cells involved, 4 patients were found in id4 gene methylation by MS-PCR. The 14 patients with id4 gene unmethylation were in their stable status and no bone marrow involvement were found by bone marrow biopsy during the 8-month follow-up. During the follow-up, the patient with both bone marrow involvement and id4 gene methylation turned to leukemia, in 2 out of the 3 patients with id4 gene methylation but without bone marrow involvement at diagnosis, the bone marrow involvement was found at last. It is concluded that the id4 gene methylation may be an indicator for MRD in NHL patients without bone marrow involvement.
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PMID:[Significance of id4 gene promoter methylation detection in lymphoma]. 1842 57

The use of DLI can change chimerism and prevent rejection and relapse. However, the prerequisite for a successful use of this powerful and potentially harmful tool is a minimal burden with resting leukemia or in the case of nonmalignant disease autologous cells. Therefore, a monitoring of the hematopoietic chimerism and of the post-transplant MRD is recommended with a narrow (best: weekly) time schedule. Also, using low and increasing numbers of DLI, a GvHD can be avoided or even minimized.
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PMID:Delayed lymphocyte infusion in children given SCT. 1854 38

This study purposed to investigate the correlation of expression level of e2a-pbx1 (immunoglobulin enhancer binding factor-Pre-B leukemia) with clinical characteristics and early response to treatment in children patients with acute lymphoblastic leukemia (ALL). The expression level of e2a-pbx1 at primary diagnosis in 45 children with ALL, and on day 33 after induction of remission in 23 children with ALL were detected by real-time quantitative polymerase chain reaction (RQ-PCR). The corelation of e2a-pbx1 expression level at primary diagnosis, MRD level with clinical characteristics and early response to treatment were all observed and explored. The expression level of e2a-pbx1 and clinical characteristics at primary diagnosis were compared between MRD negative and MRD positive patients. The results showed that the expression level of e2a-pbx1 was correlated with the blast percentage in peripheral blood at primary diagnosis. The MRD level at day 33 after induction of remission in 23 children were not related to the expression level of e2a-pbx1 at primary diagnosis and the clinical characteristics. The expression level of e2a-pbx1 at primary diagnosis in MRD positive patients was higher than that in MRD negative patients, while their age was significantly lower than that of patients with MRD negative. The blast percentage in peripheral blood at diagnosis of patients with presenting leukocyte count < 25 x 10(9)/L was significantly lower than that of patients with presenting leukocyte count >or= 25 x 10(9)/L, while the platelet count was higher. It is concluded that the expression level of e2a-pbx1 at primary diagnosis indicates the load of tumor in patients. In patients whose MRD were positive, the expression level of e2a-pbx1 at primary diagnosis is high and their age is young. The platelet count is low in the patients with high load of tumor at primary diagnosis.
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PMID:[Correlation of E2a-pbx1 expression level with clinical characteristics and early response to treatment in children with acute lymphoblastic leukemia]. 1854 31

Wilm's tumor gene WT1, which has an oncogenic function, is expressed in various kinds of hematological malignancies and solid cancers. WT1 antibodies at higher titers and WT1-specific cytotoxic T lymphocytes (CTLs) at higher frequencies were detected in cancer patients than in healthy donors, indicating that WT1 protein was immunogenic. Furthermore, WT1-specific immune responses are considered to be involved with Graft versus Leukemia effect in the context of hematopoietic stem cell transplantation. These findings provided us with the rationale for cancer immunotherapy targeting WT1. Clinical trials of WT1 peptide vaccination for cancer patients were started, and WT1 vaccination-driven immunological responses and clinical responses, including reduction of leukemic cells, reduction of M-protein amount in myeloma, and shrinkage of solid cancer, were observed. Further enhancement of efficacy of WT1 peptide vaccine can be expected by co-administration of WT1-specific helper peptide or anti-cancer chemotherapy agent. WT1 peptide vaccination in the setting of MRD (minimal residual disease) may prolong "progression-free survival time", or decrease "relapse rate".
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PMID:[Cancer antigen WT1-targeting treatment for the malignancies]. 1897 21

PCR retains a pivotal role in making accessible marker nucleic acid sequences for ready analysis in cancer diagnosis. For certain cancers such as acute lymphoblastic leukaemia, the application of quantitative procedures to assess and subsequently direct therapy has given rise to the slowly maturing field of MRD (minimal residual disease) management. Although excellent protocols exist for performing these analyses, akin to all PCR procedures the limit of detection can vary markedly between laboratories. The present paper is an overview that describes how the analytical field relating to miniaturization is likely to identify the missing link that integrates sample processing with downstream PCR, analysis and eventual therapy. Miniaturized devices are suited to the multi-parallelized handling of defined numbers of cells, and PCR-based microfluidic procedures have become reasonably established. The integration of sample processing and PCR in microfluidic devices is beginning to offer reproducible quantitative data that relate the number of biomarker nucleic acids to the defined analysed cell or cells for meaningful clinical assessment. The application of MRD may, through integrated miniaturized PCR, become more reliable and routine with additional applications in defining disease threshold levels for other cancer types. These enabling integrated platforms may facilitate biomarker measurements to predict the response and outcome, which are also of current interest for personalized medical care.
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PMID:Miniaturized PCR systems for cancer diagnosis. 1929 Aug 74

The goal of this study was to analyze results and to determine factors affecting outcome of HLA-matched hematopoetic stem cells transplantation (MRD-HSCT) for patients with acute leukemia transplanted in first complete remission in Eastern European countries. Six hundred forty HSCT were performed between 1990 and 2006 for adults with acute myeloid (n = 459) and lymphoblastic (n = 181) leukemia. Two-year leukemia-free survival (LFS), nonrelapse mortality (NRM), and relapse incidence were 58 +/- 2%, 19 +/- 2%, and 23 +/- 2%, respectively. The cumulative incidence of NRM decreased from 22 +/- 2% for patients treated between 1990 and 2002 to 15 +/- 3% for transplantations performed between 2003 and 2006 (p = 0.02), despite increasing recipient age. In a multivariate analysis, time of HSCT affected both NRM and LFS. Among other prognostic factors, the use of TBI decreased relapse incidence and increased the LFS rate. We conclude that results of MRD-HSCT for acute leukemia in Eastern Europe improved over time as a consequence of decreased NRM. The use of TBI containing regimens appears advantagous.
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PMID:Outcome of HLA-matched related allogeneic hematopoietic stem cell transplantation for patients with acute leukemia in first complete remission treated in Eastern European centers. Better results in recent years. 1930 Oct 5

Monitoring patients with multiple myeloma during and after treatment for the presence of residual myeloma cells (minimal residual disease - MRD) has been shown to give a major insight into the effectiveness of treatment. It has been reported that Wilms' tumor gene (WT1) expression levels measured by real-time quantitative polymerase chain reaction was useful as an indicator of minimal residual disease in leukemia and myelodysplastic syndrome. The aim of this study was to measure levels of WT1 expression, in order to find a possible association between the expression of this gene and multiple myeloma at diagnosis. If an association was found, the WT1 gene could be evaluated as an MRD marker by comparison with other prognostic factors. We investigated peripheral blood WT1 expression level measured by real-time light cycler quantitative polymerase chain reaction in 50 newly diagnosed multiple myeloma patients. The normal WT1 gene copy number was found to be <23/microl cDNA and all patients with myeloma were found to have normal WT1-mRNA levels. On this basis WT1 expression analyses is unlikely to be a useful genetic marker for routine clinical use in multiple myeloma patients at diagnosis.
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PMID:Expression of WT1 gene in multiple myeloma patients at diagnosis: is WT1 gene expression a useful marker in multiple myeloma? 2013 61


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