Prognosis In Acute Leukemia Patients Research Articles

Aberrant Expression of Small Nucleolar RNA SNORA63 and Its Clinical Significance in Patients with Acute Leukemia

To investigate the expression level of small nucleolar RNA (snoRNA) SNORA63 in bone marrow of patients with acute leukemia (AL) and its significance in the clinical diagnosis, treatment and prognosis of AL patients. Bone marrow samples of 53 newly diagnosed AL patients and 29 healthy subjects in the Affiliated Hospital of Guangdong Medical University from March 2018 to December 2021 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of SNORA63 in bone marrow mononuclear cells of the two groups. The median expression level of SNORA63 in AL patients was used as the boundary value to divide the patients into SNORA63 high and low expression groups, and the relationship between the expression level of SNORA63 and the clinical characteristics, clinical indicators and prognosis of AL patients was analyzed and discussed. The relative expression level of SNORA63 in AL patients was significantly lower than that in healthy control group [0.3018 (0.0244-1.2792) vs 1.0882 (0.2797-1.9889)] (P < 0.01). The expression level of SNORA63 in AL patients without remission after initial treatment was significantly lower than that in healthy controls and the patients who received complete remission (CR) (P < 0.01), while there was no statistical difference in the expression level of SNORA63 between AML and ALL groups (P >0.05). The abnormal low expression of SNORA63 was closely related to fever, hemorrage, poor prognosis, efficacy, platelets (PLT), lactate dehydrogenase (LDH), albumin (ALB), and molecular biological abnormalities of AL patients (P < 0.05), but not significantly correlated with sex, age, AL subtype, pallor, fatigue, extramedullary infiltration, white blood cell count (WBC), hemoglobin (HGB), C-reactive protein (CRP), procalcitonin (PCT), fibrinogen (FIB) or chromosome karyotype (P >0.05). Meanwhile, overall survival (OS) and event-free survival (EFS) of AL patients in SNORA63 high-expression group were significantly higher than those in SNORA63 low-expression group (P < 0.05). Univariate Cox regression analysis showed that SNORA63, molecular biological abnormalities, fever, PLT and LDH were the factors influencing OS and EFS in AL patients (P < 0.05). Multivariate Cox regression analysis indicated that fever, molecular biological abnormalities and LDH were independent factors associated with OS and EFS in AL patients (P < 0.05). SNORA63 is significantly down-expressed in AL patients, which is a molecular marker of great clinical value for disease monitoring and prognosis evaluation in AL patients.

Serum Stabilin1 as a Prognostic Marker in Adults Acute Leukemia Patients

Abstract Background STAB-1 (common lymphatic endothelial and vascular endothelial receptor) was found to be expressed on tumor lymphatic vessels in different malignancies and it is a bad prognostic marker. This study will assess the role of serum stabilin1 (STAB1) as a prognostic marker in adult patients with newly diagnosed acute leukemia and correlate it with the other well established prognostic markers. Acute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Aim of the Work To measure STAB1 expression in patients with AML and patients with ALL and assess its role as a prognostic factor with correlating it with other prognostic factors. Patients and Methods A case control study in Ain Shams University Hospitals, Clinical Haematology and Oncolgy division of Internal Medicine Department for one year on total 75 subjects divided into: 25 patients with newly diagnosed acute myeloid leukemia (AML), 25 patients with newly diagnosed acute lymphoblastic leukemia (ALL) and 25 age and sex matched healthy control subjects. The study population was recruited from Ain Shams University Hospitals, Clinical Haematology and Oncolgy division of Internal Medicine Department. Results There was no significant difference between cases of acute leukemia pts and control group as there was no statistically significant difference between control and patients group regarding sex, age, spleen size, liver size, LDH, CRP, uric acid and ESR of the studied subjects. Our study shows that as regard CBC; there was significant difference between the studied groups as regard leucocytic count, BUT Platelets, and hemoglobin was insignificant, which was also described in the study. Our study showed that there was high statistically significant difference between the acute leukemia patients and the healthy control group as regard sabilin1. Our study shows that the mean serum level of stabilin1 in the patients who didn’t respond to chemotherapy was higher than that of the patients that responded to chemotherapy. Conclusion There was high statistically significant difference between the studied groups as stabilin1. There was significant correlation between stabilin2 and chemotherapy response. Stabilin1 expression levels also identified a new subgroup at a higher risk for relapse and with a poor prognosis in acute leukemia patients. Stabilin 1 can be used as a prognostic factor in patients with acute leukemia.

Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios.

Background: Cell-free DNA (cfDNA) is a promising biomarker for disease prediction in many cancers, including acute leukemia (acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL]). This study investigated the role of cfDNA in predicting relapse or unfavorable outcomes in acute leukemia patients upon initial diagnosis. Methods: Paired peripheral blood samples of 25 patients with ALL and AML were compared at baseline and induction/follow-up and clinically correlated with clinicopathological and outcome variables according to the risk category. cfDNA was isolated using commercial cfDNA extraction kits. The probability of poor outcomes in high-risk groups and a cut-off value for risk stratification minimal residual disease (MRD) positivity and outcome prediction were derived. Results: Twenty-five patients diagnosed with AML and ALL were risk-stratified based on NCI risk stratification, and of these 25 patients, 4 patients were of standard risk (SR) and 1 patient was of intermediate risk (IR), while a majority of patients (80%) were of high risk (HR). Of these, four HR patients passed away. The ratio of cfDNA reduction at baseline and the end of induction was a strong predictor of poor outcomes in high-risk patients, regardless of the MRD status. A cfDNA ratio score of 2.6 or higher at diagnosis/remission predicted poor outcomes, with higher accuracy than conventional MRD detection by flow cytometry. Conclusion: A higher cfDNA ratio at diagnosis/remission or at baseline predicts poor outcomes in acute leukemia patients. This pilot study suggests that cfDNA ratio scoring may be a useful tool for predicting prognosis in acute leukemia patients, regardless of the MRD status.

Second Allogeneic Stem Cell Transplantation in Acute Leukemia with Post-Transplantation Relapse

Aim: It is known that the prognosis of acute leukemia patients who relapse after the first allogeneic stem cell transplantation (ASCT) is dismal. Our goal was to assess the value of a second allogeneic stem cell transplant in acute leukemia patients who experienced post-transplant recurrence.&#x0D; Material and Methods: We retrospectively reviewed data from 29 patients with relapsing acute leukemia who underwent a second ASCT. Nineteen patients with acute myeloid leukemia and ten patients with acute lymphoblastic leukemia were included in the study.&#x0D; Results: Ten AML patients and 10 ALL patients were included in the study. Most patients (62%) were in remission before the second transplantation. The median time between the first and second ASCT was 11.9 months (3.1-42 months). Complete remission (CR) was achieved after the second ASCT in 21 (72%) patients, and 11 (52%) patients relapsed after the second ASCT. During this analysis, six patients (21%) were alive and in remission. Relapse of the disease was the leading cause of mortality. After the second ASCT, overall survival (OS) was 6.34 months, and leukemia-free survival (LFS) was 13.8 months.&#x0D; Conclusion: For patients with acute leukemia who relapsed after the first ASCT, a second ASCT is a good option and can keep patients alive.

Establishment and validation of prognostic nomogram in acute leukemia with trisomy 8

ABSTRACTObjectiveThis study aims to construct a nomogram model for predicting poor prognosis in acute leukemia with trisomy 8.MethodsA retrospective analysis was conducted on 244 patients with primary acute leukemia with trisomy 8 who received treatment in our hospital, and they were randomly divided into the modeling group (122 cases, including 78 cases with good prognosis and 44 cases with poor prognosis) and the verification group (122 cases). R software was used to construct a nomogram model for predicting poor prognosis in acute leukemia with trisomy 8.ResultsThe results of multivariate analysis showed that age >51 years old, and white blood cell count ≤20 × 109/L were risk factors for poor prognosis in acute leukemia patients with trisomy 8 (P < 0.05), and chemotherapy + transplantation was a protective factor for poor prognosis in acute leukemia patients with trisomy 8 (P < 0.05). The nomogram for poor prognosis of acute leukemia patients with trisomy 8 was constructed using the above four risk predictors. The Hosmer-Lemeshow goodness of fit test was = 6.371, P = 0.497, and the area under the ROC curve was 0.817 (95%CI: 0.742-0.892). The slope of the calibration curve of external validation was close to 1, Hosmer-Lemeshow goodness of fit test was χ2 = 6.507, P = 0.448, and the area under the ROC curve was 0.834 (95%CI: 0.748-0.921).ConclusionThe nomogram model constructed in this study for predicting poor prognosis among acute leukemia patients with trisomy 8 demonstrates excellent discrimination and consistency.

International Collaborative Study to Compare the Prognosis for Acute Leukemia Patients Transplanted with Intensified Myeloablative Regimens

International Collaborative Study to Compare the Prognosis for Acute Leukemia Patients Transplanted with Intensified Myeloablative Regimens

Clinical characteristics and therapeutic effect of TP53 variant in patients with acute leukemia

To explore the clinical characteristics and prognostic values of TP53 gene variant in patients with acute leukemia(AL). The clinical data of 44 newly diagnosed AL patients with TP53 variant detected by next generation sequencing (NGS) were analyzed retrospectively. Targeted sequencing technique containing 108 leukemia-related genes was used for variant analysis, and conventional R-banding technique was used for karyotype analysis. The clinical features, cytogenetics, gene variant, curative effect and survival of AL patients with TP53 gene variant were analyzed. The median age of AML patients with TP53 gene variant (46 years) was higher than that of ALL patients (17.5 years), and the median number of bone marrow blasts (40.5%) was lower than the latter (89.2%), the differences were statistically significant (P< 0.01). A total of 28 cases of abnormal karyotype were detected, of which 25 cases were complex karyotype, 16 cases were monomeric karyotype, 14 cases had -17/17p-. The detection rates of TP53 in complex karyotype, monomeric karyotype and -17/17p- were 59.5%, 38.1% and 33.3%, respectively. Subgroup analysis showed that the detection rate of TP53 gene abnormalities in AML and ALL complex karyotypes was 73.1% and 40% respectively, the difference was statistically significant. A total of 41 TP53 gene variant types were found, and the median variant frequency was 43.58%. 75.6% variant was located in the DNA binding domain. The concomitant variant genes were mainly TET2 and IKZF1. Among 18 AML and 17 ALL patients who could be evaluated the curative effect, the CR rate of one course of treatment was 22.2% and 94.12% respectively, and the difference was statistically significant. The median RFS of 4 cases of AML with CR and 16 cases of ALL with CR were 174 and 246 days respectively, the difference was statistically insignificant. The median OS of AML and ALL was 20 and 375 days respectively, the difference was statistically significant. The TP53 gene variant is associated with the complex karyotype of AML, but has no significant effect on ALL. The variant site of TP53 gene was mainly distributed in the DNA binding domain. The remission rate of AML with TP53 gene variant was lower than that of ALL. The prognosis of AL patients with TP53 gene variant is poor, so allogeneic hematopoietic stem cell transplantation should be performed as soon as possible to prolong the survival of the patients.

Inhibition of acute leukemia with attenuated Salmonella typhimurium strain VNP20009

Acute leukemia is a common hematological malignancy. Despite recent promising progress, the prognosis of acute leukemia patients remains to be improved. New therapies are therefore still needed. Salmonella typhimurium has been shown to be highly effective as an anti-tumor agent in many solid cancer models, but it has not been applied in acute leukemia. Here, we report an attenuated Salmonella typhimurium strain, VNP20009, can induce apoptosis in multiple types of leukemia cells both in vivo and in vitro. Furthermore, VNP20009 significantly inhibited the proliferation of MLL-AF9-induced acute myeloid leukemia cells and prolonged the survival of the AML-carrying mice. VNP20009 restored the counts of white blood cell (WBC) and its five subsets in peripheral blood (PB) to near-physiological values, and elevated the levels of certain cytokines, such as tumor necrosis factor-α (TNF-α), leukemia inhibitory factor (LIF), interferon-γ (IFN-γ), chemokine C-X-C motif ligand-10 (CXCL-10) and C-C motif ligand-2 (CCL-2). Moreover, the ratio of immune cells, including natural killer cells (NKs), CD4+ Th1-type cells and CD8+ IFN-γ-producing effector T cells were highly upregulated in the AML mice treated with VNP20009. The results of the present study potentially provide an alternative therapeutic strategy for hematologic malignancies through boosting the innate and adaptive anti-tumor immunity.

Clinical Significance of Minimal Residual Disease Monitoring by Multi-parameter Flow Cytometry before Allogeneic Hematopoietic Stem Cell Transplantation for Prognosis of Acute Leukemia Patients

To investigate the clinical significance of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia. 81 cases of patients with AL treated with allo-HSCT in Department of Hematology, the First Affiliated Hospital of Chongqing Medical University form July 2015 to July 2018 was selected and retorspectively analyed. of which 79 patients were in CR and two patients were in non-CR. The CR group was further divided into two groups of MRD+ and MRD- based on the MRD level prior to HSCT. Among 81 patients, there were statistically significant differences in the three-year overall survival(OS) (CR 82.2%: NCR 0%), cumulative relapse incidence(RI) (CR 17.7%; NCR 100%) and leukemia-free survival rate(LFS) (CR 42.3%: NCR 0%) between CR and NCR group(P<0.05). Among 79 CR patients, MRD was negative in 30 patients while positive in 49 patients, there was significant differences in the three-year overall survival between MRD- and MRD+ group. The results of univariate analysis showed that the MRD+ group showed lower LFS compared with that of MRD- group （10.5% vs 36.2%）(P＜0.001，95%CI). MRD- patients shows longer LFS as compared with that of MRD+ patients, therefore, MRD monitoring by MFC before allo-HSCT is very important for the prognosis of the AL patients.

Clinical Significance of Minimal Residual Disease Monitoring by Multi-parameter Flow Cytometry before Allogeneic Hematopoietic Stem Cell Transplantation for Prognosis of Acute Leukemia Patients

To investigate the clinical significance of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia. 81 cases of patients with AL treated with allo-HSCT in Department of Hematology, the First Affiliated Hospital of Chongqing Medical University form July 2015 to July 2018 was selected and retorspectively analyed. of which 79 patients were in CR and two patients were in non-CR. The CR group was further divided into two groups of MRD+ and MRD- based on the MRD level prior to HSCT. Among 81 patients, there were statistically significant differences in the three-year overall survival(OS) (CR 82.2%: NCR 0%), cumulative relapse incidence(RI) (CR 17.7%; NCR 100%) and leukemia-free survival rate(LFS) (CR 42.3%: NCR 0%) between CR and NCR group(P<0.05). Among 79 CR patients, MRD was negative in 30 patients while positive in 49 patients, there was significant differences in the three-year overall survival between MRD- and MRD+ group. The results of univariate analysis showed that the MRD+ group showed lower LFS compared with that of MRD- group （10.5% vs 36.2%）(P＜0.001，95%CI). MRD- patients shows longer LFS as compared with that of MRD+ patients, therefore, MRD monitoring by MFC before allo-HSCT is very important for the prognosis of the AL patients.

Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients.

The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53% vs. 38%, P=0.002, 5-year OS) and multivariate (hazard ratio (HR)=0.63, confidence interval (CI) 95%=0.48–0.83, P=0.001) analyses. Further subgroup analysis demonstrated that the positive effect of HLA-E mismatch was significant and pronounced in advanced disease patients (n=120) (5-year OS: 50% vs. 18%, P=0.005; HR=0.40, CI 95%=0.22–0.72, P=0.002; results from univariate and multivariate analyses, respectively). The study herein is the first to report an association between HLA-E incompatibility and improved post–transplant prognosis in AL patients who have undergone matched unrelated HSCT. Combined NK and T cell HLA-E-mediated mechanisms may account for the better outcomes observed. Notwithstanding the necessity for in vitro and confirmational studies, our findings highlight the clinical relevance of HLA-E matching and strongly support prospective HLA-E screening upon donor selection for matched AL unrelated HSCTs.

Role of HOTAIR in the diagnosis and prognosis of acute leukemia.

HOX antisense intergenic RNA (HOTAIR), a long non-coding RNA, plays an important role in the development of many types of cancers. Its function in acute leukemia (AL), however, has not been examined. The present study investigated the role of HOTAIR and its downstream genes in AL, and determined whether it could act as a molecular marker for prediction of leukemia development and prognosis. Real-time quantitative PCR was used to examine the expression of each gene in the HOTAIR signaling pathway in AL patients. The relationship between expression of HOTAIR and downstream genes and AL prognosis was analyzed. Expression of HOTAIR in patients with acute monocytic leukemia (M5) was increased as compared to controls (P<0.05). Compared to patients with low HOTAIR expression, overall survival and event-free survival of patients with high HOTAIR expression was significantly reduced. In addition, the expression of downstream genes in the HOTAIR signaling pathway including EZH2, LSD1, DNMT3A and DNMT3B was significantly increased in AL patients, and showed a significant positive correlation with high expression of HOTAIR (P<0.05). In conclusion, HOTAIR was closely related with a poor prognosis in AL patients. It may be involved in the development of leukemia by mediating methylation of DNA and histones.

Clinical features and prognosis in MLL-AF10 positive acute leukemia

目的探讨MLL-AF10阳性急性白血病患者的临床特征及预后。方法回顾性分析6例MLL-AF10阳性急性白血病患者的临床资料，结合文献明确MLL-AF10阳性急性白血病患者的临床特征及预后。结果6例患者中男4例，女2例，中位年龄为19.5岁，其中5例患者以发热起病，4例患者起病时WBC <10×109/L，FAB分型M5 5例，M4 1例，初诊时MLL-AF10融合基因水平(实时定量PCR法)为0.23%~22.60%，4例患者均同时合并WT1基因突变，流式细胞术显示为髓系表达。5例可评估患者经常规化疗1个疗程均获得完全缓解，后均行异基因造血干细胞移植(allo-HSCT)。6例患者中2例复杂核型者死亡(1例死于诱导治疗期败血症，1例移植后未植入死亡)，5例移植患者中4例获得长期生存。结论MLL-AF10阳性急性白血病患者多为年轻男性，FAB分型以M5、M4居多，常以发热起病，初诊时白细胞计数低，起病时MLL-AF10融合基因水平低，常合并WT1基因突变，常规化疗具有较高的缓解率，但易复发，复杂核型者预后差，allo-HSCT有可能改善其预后。

Micronucleus Expression and Acute Leukemia Prognosis

The micronucleus frequency (MNF) in peripheral blood lymphocytes (PBL) is a biomarker of chromosomal damage and genome instability in human populations.The relationship of micronucleus frequency with prognosis of patients with acute leukemia is not clear. We therefore investigated MNF in mitogen-activated peripheral blood lymphocytes from patients with hematologic diseases and solid tumours. Patients included 50 with acute leukemia, 49 diagnosed with myelodysplastic syndrome (MDS), 54 with benign blood diseases, and 45 with solid tumours, examined with 50 healthy controls. The mean MNF was significantly higher in cases of hematologic diseases and solid tumor patients than in healthy controls (P<0.001). There was no evident difference between MNF in the acute leukemia (7.15 ± 2.18) and solid tumor groups (7.11 ± 1.47), but both were higher than in the MDS group (5.12 ± 1.29) and benign blood diseases group (3.08 ± 1.08). Taking 7.15%, the average MNF of the acute leukemia group as standard, and dividing 50 cases of acute leukemia patients into high MNF group (MNF ≥ 7.15%) and low MNF group (MNF<7.15%). The overall response (complete remission + partial remission) rates of the low MNF group were significantly higher than in the high MNF group (P=0.001). The high MNF group further showed lower overall survival rates than the low MNF group. MNF expression and progression-free survival seemed to have a opposite relationship, with a correlation coefficient of -0.702. These data indicate that MNF in peripheral blood lymphocytes is important for evaluation of prognosis of acute leukemia patients, and it can reflect progression of disease to a certain degree.

Outcome of Patients with Refractory Acute Leukemia Treated with a Third Induction Chemotherapy Regimen

Abstract 4305 BackgroundTreatment options are limited for refractory acute leukemia (AL) patients. Few data are available on the potential utility vs futility of a third course of induction chemotherapy. We have reviewed the characteristics and outcome of 35 patients treated with a third intensive induction course for refractory AL at our institution and other centers affiliated to the Quebec Leukemia Cell Bank (BCLQ). Methods and patientsAdult AL patients who never achieved complete remission (CR) or who relapsed within 6 months after 2 consecutive induction courses and who received a third line intensive induction course between 2000 and 2010 were included in this study. Clinical, laboratory and treatment data were collected from hospital and/or BCLQ files. Outcomes were measured after the third induction course. Primary outcomes were achievement of CR/CRi, overall survival (OS) at 12 months and event-free survival (EFS), defined as the percentage of patients alive and leukemia free at 12 months. Secondary outcomes included median OS, median duration of remission for those obtaining CR and treatment related mortality (TRM) associated with the third induction course. OS was estimated using the Kaplan-Meier method and survival curves were compared using the Log-rank test. Alive patients were censored at their last follow-up. ResultsThirty five patients met the inclusion criteria. The median age was 43 years old (20–62). Thirty one patients (89%) were diagnosed with AML and 4 patients (11%) with ALL or acute leukemia of ambiguous lineage. The median white blood cell count at diagnosis was 23 × 109/L (0.7–223). For AML patients, cytogenetics was favourable in 1 patient (3%), intermediate in 17 (55%) and adverse in 13 (42%). None of the 6 patients with normal karyotype for whom molecular characterisation was performed had a favourable genotype defined as NPM1 mutated without FLT3-ITD mutation. The patient with favourable karyotype had a variant t(8;21)(q22;q22) translocation without KIT mutation. Eighteen patients (51%) were primarily refractory to prior therapy and 17 (49%) had relapsed within 6 months of CR. The third line induction regimen consisted of cyclophosphamide and etoposide in 11 patients (31%), high dose cytarabine-based regimen in 10 (29%), mitoxantrone and etoposide in 7 (20%), fludarabine, cytarabine and idarubicin in 5 (14%) and other regimen in 2(6%). Patients with sustained remission after their third induction course were followed for a minimum of 12 months except for one patient alive and leukemia free at 6 months. Patients who were not in sustained remission have all been followed until death or transition to palliative care.CR after the third induction course was achieved in 6 patients (17%). At 12 months, OS was 11% and EFS was 6%. After the third induction, median OS was 5 months and median duration of remission was 6 months. Among 20 patients treated in our institution, the third induction TRM was 15% and median duration of hospitalisation, excluding patients who died in aplasia, was 38 days (20–70). Median OS was higher in the intermediate than in the adverse cytogenetics group (8 vs 2 mo, p=0.0008, figure 1) and in patients who achieved CR after third induction vs no CR (12 vs 4 mo, p=0.03). There was no difference in median OS between primary refractory and relapsed patients (8 vs 4 months, p=0.52).Allogeneic stem cell transplantation (SCT) was performed in 10 patients (29%) of whom 4 (40%) were in CR before transplantation. The only two long term survivors were in the allogeneic SCT group. Their percentages of blasts at transplant were 3 and 69 %. ConclusionOnly two refractory patients are long term survivors and they share several features: non adverse cytogenetics, young age (20 and 23) and they underwent allogeneic SCT. Adverse cytogenetics impinges negatively on outcome, even in this highly refractory group of subjects.The prognosis of AL patients with persistent disease after 2 induction courses is extremely poor and represents a major unmet therapeutic need. Refractory patients with adverse cytogenetics were unsalvageable in this series. The best approach for patients not in CR after 2 inductions probably remains allogeneic SCT, when possible. We consider that in patients who cannot be offered an allogeneic SCT, administration of a third course of conventional chemotherapy is practically useless. These patients should be considered candidates for investigational treatments. Disclosures:Bergeron: Merck: Research Funding; Roche: Honoraria; Celgene: Research Funding. [Display omitted]

The significance and correlation of SODD and bcl-2 protein expression in acute leukemia of children

OBJECTIVE To explore the expression of SODD and bcl-2 proteins in bone marrow cells of children with acute leukemia (AL), and to examine the relationship of their expression with the classification, clinical features, therapeutic effect and prognosis for AL patients.

Integration of molecular methods for detection of balanced translocations in the diagnosis and follow-up of patients with leukemia

Molecular methods are emerging as important tools for the diagnosis and stratification of patients with leukemia. Together with rearrangements in immunoglobulin and T-cell receptor genes, balanced translocations are the most important genetic lesions amenable to molecular diagnosis. Moreover, many publications have identified significant differences in the prognosis of acute leukemia patients with such balanced translocations. Because not all balanced translocations can be diagnosed by cytogenetic techniques, reversetranscriptase polymerase chain reaction (RT-PCR)-based methods are increasingly employed. This method has the added advantage that it can also be used to monitor for minimal residual disease (MRD). A disadvantage is that the multitude of balanced translocations in leukemia would make efforts to detect all lesions at diagnosis by such standard techniques extremely labor-intensive. Furthermore, difficulties in optimizing semiquantitative PCR assays have limited the utility of these methods for MRD. Recent advances in the design of multiplex PCR, which detects a number of genetic aberrations simultaneously, may improve the diagnostic process. Accurate quantitation of the fusion transcript for balanced translocations has become possible by use of fluorogenic probes and real-time PCR. Together, such methodologies may constitute a novel platform for the integration of molecular methods in clinical decision-making.

Expression and clinical significance of multidrug resistance gene and multidrug resistance-associated protein gene in acute leukemia

To evaluate the relationship between the expression of multidrug resistance gene (mdr1) or multidrug resistance-associated protein gene (MRP) and the prognosis in patients with acute leukemia (AL). The expression of mdr1 and MRP were measured in 55 patients with AL by reverse transcription polymerase chain reaction (RT-PCR). The mdr1 and MRP gene expression levels in the relapsed AL and the blastic phase of CML group (0.735 +/- 0.249, 1.157 +/- 0.447) were significantly higher than those in the untreated group (0.408 +/- 0.186, 0.465 +/- 0.253) (P < 0.01). The complete remission (CR) rate in high mdr1 and MRP expression group was significantly lower than that in low mdr1 and MRP expression group (P < 0.01) in a follow up of 40 AL patients. Increased expression of mdr1 and MRP gene might be an important factor for predicting drug resistance, relapse and unfavorable prognosis in AL patients.