Low Platelet Counts at Diagnosis Predict Better Survival for Patients with Intermediate-Risk Acute Myeloid Leukemia

2019 ◽  
Vol 143 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Yimin Zhang ◽  
Haihui Gu ◽  
Qi Chen ◽  
Ying Zhang ◽  
Hui Cheng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Negative Impact ◽  
Disease Free Survival ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Risk Patients ◽  
Immature Cells ◽  
Acute Myeloid

Background: Aggressive growth of primitive and immature cells in the bone marrow results in reductions in megakaryocyte and platelet (PLT) counts, leading to thrombocytopenia in acute myeloid leukemia (AML). However, not all AML patients show thrombocytopenia at the time of diagnosis, and the association of PLT count with patient survival is largely unknown. Methods: A retrospective study was performed to determine PLT counts at diagnosis in the peripheral blood in 291 newly diagnosed AML patients and assess the association of PLT counts with the overall survival (OS) and disease-free survival (DFS) of these patients. Results: Low PLT counts (≤40 × 109/L) were associated with better outcomes for the whole cohort (5-year OS, 55.1 ± 3.8 vs. 35.3 ± 3.5%, p < 0.001; 5-year DFS, 49.1 ± 3.8 vs. 25.7 ± 4.0%, p < 0.001) and intermediate-risk patients (5-year OS, 64.5 ± 5.4 vs. 41.0 ± 4.8%, p < 0.001; 5-year DFS, 60.8 ± 5.6 vs. 28.6 ± 5.6%, p < 0.001). Moreover, low PLT counts were related to deeper molecular remission. Low PLT counts correlated with better survival of intermediate-risk AML patients treated with chemotherapy only. Allogeneic hematopoietic stem cell transplantation attenuated the negative impact of high PLT counts on the survival of intermediate-risk patients. Furthermore, univariate and multivariate analyses demonstrated that PLT count at diagnosis was an independent prognostic factor for intermediate-risk AML. Conclusion: PLT count at diagnosis predicts survival for patients with intermediate-risk AML.

Autologous Bone Marrow Transplantation as an Intensive Consolidation Therapy for Adult Patients in Remission from Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5121-5121
Author(s):  
Andre S. Jung ◽  
Asad Bashey ◽  
Peter R. Holman ◽  
Eva Carrier ◽  
Januario Castro ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Consolidation Therapy ◽  
Free Survival ◽  
Risk Patients ◽  
Disease Free ◽  
Acute Myeloid

Abstract Introduction: Autologous peripheral blood stem/progenitor cell transplantation (APBSCT) has been investigated as a potential therapeutic option to improve outcome in patients with acute myeloid leukemia. The optimal consolidation therapy for adults in remission without a histo-compatible donor has yet to be clearly established. Patients and Methods: This was a retrospective analysis of forty patients (23 females and 17 males) diagnosed with de novo acute myeloid leukemia, who were without a histo-compatible donor, that underwent APBSCT between the year 2000 and 2006 at a single institution. The patients’ age ranged from 18 to 73 with a median age of 50. Cytogenetic analysis was available on 37 of the patients. Complete remission (CR) was confirmed by bone marrow morphology and immunophenotype analysis by flow cytometry. Patients in remission were further consolidated with variable cycles of chemotherapy prior to stem cell transplantation. For stem cell mobilization, patients received high-dose cytarabine (2000mg/m2) and etoposide (5mg/kg) for three days followed by G-CSF at 10μg/kg, starting 10 days after the chemotherapy, before the peripheral stem cell collection. The preparative regimen prior to transplantation with unpurged stem/progenitor cells consisted of a combination of intravenous busulfan (0.8 mg/kg for 16 doses) and cyclophosphamide (60 mg/kg for two doses) (37 patients) or busulfan and melphalan (3 patients). Patients were then followed for treatment-related mortality, disease free survival, and overall survival. The analysis was stratified according to age, cytogenetic risk, and remission state. Results: There was no treatment-related mortality. Nineteen out of forty patients had relapse of their disease. The relapse rate was lowest in the low risk cytogenetic group who were under the age of 60 and highest in the high risk cytogenetic group who were over the age of 60. The overall 5 year survival for all patients was 47%. When stratified for cytogenetic risk and age, the overall survival for low, intermediate, and high cytogenetic risk patients under the age of 60 were 67%, 59%, and 75% respectively. The overall survival for intermediate and high cytogenetic risk patients over the age of 60 were 33% and 0% respectively. The projected rate of disease free survival at 5 years was 40%. When stratified for cytogenetic risk and age, the disease free survival for low, intermediate, and high cytogenetic risk patients under the age of 60 were 33%, 52%, and 50% respectively. Disease free survival for intermediate and high cytogenetic risk patients over the age of 60 were 33% and 0%. Comparing patients in CR1 versus patients in CR2, the overall survival was 47% in CR1 and 50% in CR2. The disease free survival, when grouped as above, were 41% for those in CR1 and 33% for those in CR2. Conclusion: APBSCT is a reasonable and safe intensive consolidation therapy for those patients without a compatible HLA matched donor in first or second complete remissions, notably for those under the age of 60 regardless of their cytogenetic risk. The number of standard consolidations prior to APBSCT may be an important variable predicting outcome.

Prognostic Implication and Biological Roles of RhoH in Acute Myeloid Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 939-939
Author(s):  
Akira Katsumi ◽  
Toshihiro Iwasaki ◽  
Ryohei Tanizaki ◽  
Akihiro Abe ◽  
Hitoshi Kiyoi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Disease Free Survival ◽  
Intermediate Risk ◽  
Free Survival ◽  
Wbc Count ◽  
Disease Free ◽  
Low Expression ◽  
Acute Myeloid

Abstract The Rho family of small GTPase, including Rho, Rac and Cdc42, has been well characterized as a molecular switch that transduces signals from plasma membrane to the downstream effectors. RhoH gene, a member of the Rho family, is specifically expressed in hematopoietic cells. As RhoH is GTPase-deficient and constitutively active, the activity of RhoH is directly related to its level of expression. Previous reports demonstrated that the aberrant somatic hypermutation of RhoH is a novel mechanism of lymphomagenesis, possibly through its deregulated expression, suggesting that RhoH is the proto-oncogene. The known function of RhoH is antagonizing Rac and mediating activation of ZAP-70 in T lymphocytes. Recent report demonstrated that hairy cell leukemia is characterized by low expression of RhoH, and reconstitution of this gene limits malignant progression and protects against mortality. Although the functions of RhoH in lymphoid cells have been clarified, the biological roles of RhoH in the myeloid cells are unknown. The question that whether RhoH expression affects the prognosis of acute myeloid leukemia patients still remains unanswered. Here, we analyzed the expression level of the RhoH gene transcript in bone marrow samples from 90 newly diagnosed acute myeloid leukemia patients using a real-time fluorescence detection method. The RhoH/GAPDH ratio was calculated, and the median of 90 samples was 1.57. The patients were then divided into RhoH high (i.e. RhoH/GAPDH above 1.58) and RhoH low groups. The expression level of RhoH was not related to the FAB classification, age, WBC counts, cytogenetics or complete remission rate. In addition, RhoH expression was not associated with the known gene mutations such as NRAS, FLT3 and TP53. Kaplan–Meier analysis demonstrated that low expression of the RhoH transcript was a predictor of worse prognosis in both overall (Fig.1A) and disease-free survival (Fig. 1B). Patients were then categorized into favorable, intermediate, unfavorable and unknown cytogenetic groups based on the Southwest Oncology Group and Medical Research Council cytogenetic risk category definition. Kaplan–Meier analysis for both overall and disease-free survival was performed for 65 (72.2%) patients in the intermediate risk group. The results indicated that low expression of the RhoH transcript is a worse prognostic factor for both overall and disease-free survival in the intermediate risk group (p = 0.03 and 0.001, respectively). Multivariate analyses showed that presence of theTP53 mutation (relative risk (RR), 10.175; p = 0.0036), high WBC count (RR, 3.457; p = 0.0003) and low RhoH expression (RR, 2.272; p = 0.0091) were independent poor prognostic factors for overall survival. The same analysis revealed that the presence of the TP53 mutation (RR, 14.292; p = 0.0168), low RhoH expression (RR, 4.854; p = 0.0002), high WBC count (RR, 2.901; p = 0.0187) and presence of FLT3/ITD (RR, 2.515; p = 0.0419) were independent poor prognostic factors for disease-free survival. Next, we investigated the biological roles of RhoH in AML. Overexpression of RhoH leads to dephosphorylation of Bad at Serine (S)-75 (corresponding to murine S112) possibly through deactivation of Rac. Contrastingly, RhoH expression does not affect phosphorylation of S99 (corresponding to murine S136) of Bad and S473 of Akt. It is possible that low expression of RhoH (i.e. high GTP-Rac) contributes to chemotherapy resistance in leukemia cells. Taken together, our results highly suggest that RhoH transcript level is an effective molecular marker to further stratify the patients in the intermediate risk group of AML, and that inhibition of Rac and its signalling components might provide a useful anti-leukemic strategy. Figure 1 Figure 1.

Predictable Prognostic Factor of CD56 Expression in Acute Myeloid Leukemia with t(8:21) Including Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3288-3288
Author(s):  
Deok-Hwan Yang ◽  
Yeung-Chul Mun ◽  
Ho-Jin Shin ◽  
Yeo-Kyeoung Kim ◽  
Je-Jung Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Cd56 Expression ◽  
Disease Free ◽  
Acute Myeloid

Abstract CD56 expression in acute myeloid leukemia (AML) has been associated with extramedullary leukemia and multi-drug resistance, but the clinical and prognostic significances are not yet clearly defined. Recently, some investigators reported that AML patients with t(8;21) showed more frequent CD56 expression rate and the expression of CD56 antigen adversely affected disease-free survival (DFS). It could explain a diverse clinical outcome in AML patients with favorable cytogenetics. This study investigated CD56 expression in 37 adult de novo AML patients with t(8:21) between November 1996 and June 2005 at three institutions. Immunophenotyping was performed with flow cytometry (Coulter EPICS XL) and considered positive if at least 20% of blasts expressed. CD56 was expressed in 25 cases (67.6%). There was no statistically significant differences in age, sex, leukocyte count, the percentage of bone marrow blasts or the presence of additional cytogenetic abnormalities between the CD56+ and the CD56- group. The complete remission (CR) rate to standard dose cytarabine or N4-behenoyl-1-D-arabinofuranosylcytosine (BH-AC) and idarubicin was similar in both groups (91.7% v 88.7%; P=0.73), but the relapse rate to high-dose cytarabine or allogeneic hematopoietic stem cell transplantation (HST) was quite different (60% v 25%; P=0.08). Allogeneic HST was performed from siblings in 15 patients (40.5%) who achieved CR, 8 patients (32.0%) in CD56+ and 7 patients (58.3%) in CD56- group (P=0.16). The median durations of DFS were significantly shorter in CD56+ (median, 12.2 months) than in the CD56- group (median, not reached) (P =0.02). Also, the median durations of survival showed the same results in the CD56+ group (median, 14.9 months) compared with the CD56- group (median, not reached) (P=0.01). Within fifteen transplanted patients, the median durations of DFS in eight CD56+ patients was significantly shorter than seven CD56- patients (median, 24.4 months v not reached; P=0.02)(Fig.1 and 2).We concluded that CD56 expression was associated with reduced DFS and survival for AML patients with t(8:21) including transplanted patients. Although further larger studies are needed, we suggested that CD56 expression at diagnosis is a predictable prognostic factor in AML with t(8:21). Fig. 1 Disease-free survival (DFS) and Overall survival (OS) for patients with t(8:21) with CD56+ (n−25) and CD56− (n−12) group. Fig. 1. Disease-free survival (DFS) and Overall survival (OS) for patients with t(8:21) with CD56+ (n−25) and CD56− (n−12) group. Fig. 2 Within transplanted patients, decreases from survival (DFS) for patients with t(8:21) with and without CD56 expression. Fig. 2. Within transplanted patients, decreases from survival (DFS) for patients with t(8:21) with and without CD56 expression.

A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial

Blood ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 971-978 ◽  
Author(s):  
Christoph Röllig ◽  
Christian Thiede ◽  
Martin Gramatzki ◽  
Walter Aulitzky ◽  
Heinrich Bodenstein ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Risk Model ◽  
Cox Model ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Intermediate Risk ◽  
Npm1 Mutation ◽  
Prognostic Groups ◽  
Acute Myeloid

Abstract We present an analysis of prognostic factors derived from a trial in patients with acute myeloid leukemia older than 60 years. The AML96 trial included 909 patients with a median age of 67 years (range, 61-87 years). Treatment included cytarabine-based induction therapy followed by 1 consolidation. The median follow-up time for all patients is 68 months (5.7 years). A total of 454 of all 909 patients reached a complete remission (50%). Five-year overall survival (OS) and disease-free survival were 9.7% and 14%, respectively. Multivariate analyses revealed that karyotype, age, NPM1 mutation status, white blood cell count, lactate dehydrogenase, and CD34 expression were of independent prognostic significance for OS. On the basis of the multivariate Cox model, an additive risk score was developed that allowed the subdivision of the largest group of patients with an intermediate-risk karyotype into 2 groups. We are, therefore, able to distinguish 4 prognostic groups: favorable risk, good intermediate risk, adverse intermediate risk, and high risk. The corresponding 3-year OS rates were 39.5%, 30%, 10.6%, and 3.3%, respectively. The risk model allows further stratification of patients with intermediate-risk karyotype into 2 prognostic groups with implications for the therapeutic strategy. This study was registered at www.clinicaltrials.gov as #NCT00180115.

Prospective Evaluation of Allogeneic Hematopoietic Stem-Cell Transplantation From Matched Related and Matched Unrelated Donors in Younger Adults With High-Risk Acute Myeloid Leukemia: German-Austrian Trial AMLHD98A

2010 ◽  
Vol 28 (30) ◽  
pp. 4642-4648 ◽  
Author(s):  
Richard F. Schlenk ◽  
Konstanze Döhner ◽  
Silja Mack ◽  
Michael Stoppel ◽  
Franz Király ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Younger Adults ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Acute Myeloid

Purpose To assess the impact of allogeneic hematopoietic stem-cell transplantation (HSCT) from matched related donors (MRDs) and matched unrelated donors (MUDs) on outcome in high-risk patients with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. Patients and Methods Between 1998 and 2004, 844 patients (median age, 48 years; range, 16 to 62 years) with AML were enrolled onto protocol AMLHD98A that included a risk-adapted treatment strategy. High risk was defined by the presence of unfavorable cytogenetics and/or by no response to induction therapy. Results Two hundred sixty-seven (32%) of 844 patients were assigned to the high-risk group. Of these 267 patients, 51 patients (19%) achieved complete remission but had adverse cytogenetics, and 216 patients (81%) had no response to induction therapy. Allogeneic HSCT was actually performed in 162 (61%) of 267 high-risk patients, after a median time of 147 days after diagnosis. Graft sources were as follows: MRD (n = 62), MUD (n = 89), haploidentical donor (n = 10), and cord blood (n = 1). The 5-year overall survival rates were 6.5% (95% CI, 3.1% to 13.6%) for patients (n = 105) not proceeding to HSCT and 25.1% (95% CI, 19.1% to 33.0%; from date of transplantation) for patients (n = 162) receiving HSCT. Multivariable analysis including allogeneic HSCT as a time-dependent covariable revealed that allogeneic HSCT significantly improved outcome; there was no difference in outcome between allogeneic HSCT from MRD and MUD. Conclusion Allogeneic HSCT in younger adults with high-risk AML has a significant beneficial impact on outcome, and allogeneic HSCT from MRD and MUD yields similar results.

Distinct association of RUNX family expression with genetic alterations and clinical outcome in acute myeloid leukemia

2020 ◽  
Vol 29 (3) ◽  
pp. 387-397
Author(s):  
Yangli Zhao ◽  
Tingjuan Zhang ◽  
Yangjing Zhao ◽  
Jingdong Zhou
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Outcome ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Differentially Expressed ◽  
Aberrant Expression ◽  
Hematopoietic Stem ◽  
Frequent Event ◽  
Acute Myeloid

BACKGROUND: The runt-related transcription factor family (RUNXs) including RUNX1, RUNX2, and RUNX3 are key transcriptional regulators in normal hematopoiesis. RUNXs dysregulations caused by aberrant expression or mutation are frequently seen in various human cancers especially in acute myeloid leukemia (AML). OBJECTIVE: We systemically analyzed the expression of RUNXs and their relationship with clinic-pathological features and prognosis in AML patients. METHODS: Expression of RUNXs was analyzed between AML patients and normal controls from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. Correlations between RUNXs expression and clinical features together with survival were further analyzed. RESULTS: All RUNXs expression in AML patients was significantly increased as compared with controls. RUNXs expression was found to be significantly associated with genetic abnormalities such as RUNX1 mutation, t(8;21) and inv(16)/t(16;16). By Kaplan-Meier analysis, only RUNX3 overexpression was associated with shorter overall survival (OS) and disease-free survival (DFS) among non-M3 AML patients. Notably, in high RUNX3 expression groups, patients received hematopoietic stem cell transplantation (HSCT) had markedly better OS and DFS than patients without HSCT among both all AML and non-M3 AML. In low RUNX3 expression groups, there were no significant differences in OS and DFS between HSCT and non-HSCT groups among both all AML and non-M3 AML. In addition, a total of 835 differentially expressed genes and 69 differentially expressed microRNAs were identified to be correlated with RUNX3 expression in AML. CONCLUSION: RUNXs overexpression was a frequent event in AML, and was closely associated with diverse genetic alterations. Moreover, RUNX3 expression may be associated with clinical outcome, and helpful for guiding treatment choice between HSCT and chemotherapy in AML.

Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1997-2004 ◽  
Author(s):  
G Del Poeta ◽  
R Stasi ◽  
G Aronica ◽  
A Venditti ◽  
MC Cox ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Free Survival ◽  
Negative Phenotype ◽  
Acute Myeloid

Abstract Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

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