Characteristics and Outcomes of Therapy-Related Acute Myeloid Leukemia: Results of Retrospective Analysis of 116 Adult Patients

Background:Therapy related acute myeloid leukemia (t-AML) is a late complication following cytotoxic therapy for a primary neoplasm or a non-neoplastic disorder as autoimmune diseases and a highly fatal complication in patients treated for first primary malignancy. Therapy related AML are considered to have a worse prognosis and inferior outcome compared with de novo AML. The aim of this retrospective analysis is to describe clinical and biological characteristics and outcomes of these poor prognosis patients. Methods:This retrospective analysis include 116 adult patients in 2 institutions (Leon Berard cancer center and Lyon Sud university hospital) between January 2006 and June 2019 treated with chemotherapy and/or radiation for different previous malignancies and who subsequently developed AML. We analyzed demographic characteristics, parameters related to previous malignancies (type, delay until occurrence of AML and treatment), to AML (cytogenetic and mutational profile, treatment and outcome). Event for overall survival (OS) was death and patients were censored at the date of last contact if alive or at the date of allogeneic HSCT. Event for disease free survival were death and first relapse. Results:We analyzed retrospectively, 116 adult patients (57 male and 59 female) with median age of 67.5 [19 to 87] years diagnosed with t-AML according to 2016 revised WHO criteria and caused by exposure to chemotherapy and/or radiotherapy for previous solid tumors in 81 pts (70%) or hematologic malignancies in 35 pts (30%). Median time between diagnosis of previous neoplasm and AML was 5.4 [0.4-34.3] years. For the treatment of previous cancer, 48 pts (41%) received chemotherapy alone, 17 pts (15%) radiotherapy and 51 pts (44%) received both modalities. T-AML occurred after exposure to alkylating agents in 12 pts (12%), to agents targeting topoisomerase II in 7 pts (7%), to both agents in 65 pts (66%) and other treatment in 15 pts (15%). Cytogenetic profile was performed in 108 pts and was favorable in 4 pts (3.7%), intermediate in 46 pts (42.8%), unfavorable in 47 pts (43.5%) and assessment failed in 11 pts (10%). Eighty eight available leukemia samples were analyzed using molecular RT-PCR and, more recently, NGS profiling. Gene mutations concern 8 pts for FLT-3, 20 pts for Evi1, 1 pt for IDH1, 1 pt for IDH2 and 8 pts were TP53 mutated. Treatment of t-AML consisted in intensive chemotherapy (IC) in 59 pts (51%), hypomethylating agents (HMA) or low dose cytarabine in 29 pts (25%), best supportive care (BSC) in 28 pts (24%). Only 15 pts underwent allogeneic hematopoietic stem cell transplantation. Median overall survival (OS) [95% CI] was 7.75 months [5.55-12.32] and median progression free survival (PFS) [95% CI] was 6.14 months [5.22-9.07] in whole cohort. According to cytogenetic risk group and as expected, the median survival is significantly longer in favorable than in intermediate and unfavorable risk group (45.3 vs 15.2 vs 5.4 mths for OS with p = 0.005 and 45.3 vs 10.3 vs 5.3 mths for PFS with p = 0.007). Conclusion:This descriptive analysis confirm data of literature with poor prognosis and worse survival in unfavorable and intermediate risk groups of t-AML. However, pts with no comorbidities and candidate to IC had a significant better survival than those receiving HMA or BSC and should be considered for allogeneic transplantation Figure Disclosures No relevant conflicts of interest to declare.

Download Full-text

Acute Myeloid Leukemia Treatment Outcomes: First Report from Single Center Retrospective Study in Kazakhstan

10.21203/rs.3.rs-757253/v1 ◽

2021 ◽

Author(s):

Jamilya Saparbay ◽

Gulnara Kulkayeva ◽

Vadim Kemaykin ◽

Aset Kuttymuratov ◽

Zhanna Burlaka ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Good Prognosis ◽

Event Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Acute Myeloid

Abstract Acute myeloid leukemia (AML) is the most common hematological malignancy in adults. In the last decade, internationally approved AML treatment guidelines, including hematopoietic stem cell transplantation are widely used in Kazakhstan. The categorization of acute myeloid leukemia was done according to the French-American British classification. The prognosis of patients at the time of diagnosis was determined by cytogenetic tests following the guidelines of the European LeukemiaNet. The overall survival and event-free survival were analyzed using the Kaplan-Meier method, and hazard ratios were defined with Cox regression. Totally 398 patients with AML were treated in the National Research Oncology Center between 2010 and 2020. The mean age was 38.3 years. We have found the correlation between ethnicity, cytogenetic group, white blood cell count, and treatment approaches with overall and event-free survival. There was a significantly longer OS in a cytogenetic group with a good prognosis compared with intermediate and poor prognosis. The median survival time in the group with a good prognosis was 43 months, 23 months in the intermediate group (p=0.7), and 12 months in the poor prognosis group (p=0.016). There was a significantly longer OS for the group of patients who received hematopoietic stem cell transplantation (HSCT), 52 months versus 10 months in the group who received chemotherapy only, p-value < 0.0001. Prognostic factors, such as cytogenetic group, initial WBC count, and treatment approaches are significantly associated with patient survival. Our study data were consistent with previous reports.

Download Full-text

High Disease-Free and Overall Survival Rate Following Allogeneic Hematopoietic Stem Cell Transplantation for FLT3-Mutated Acute Myeloid Leukemia Even in Non-Remission Status

Blood ◽

10.1182/blood.v128.22.2283.2283 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2283-2283 ◽

Cited By ~ 1

Author(s):

Aya Nishida ◽

Mitsuhiro Yuasa ◽

Kosei Kageyama ◽

Kazuya Ishiwata ◽

Shinsuke Takagi ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myeloid Leukemia ◽

Research Funding ◽

Poor Prognosis ◽

Hematopoietic Stem ◽

Remission Status ◽

Disease Free ◽

Acute Myeloid

Abstract [Background] FMS like tyrosine kinase 3 (FLT3) mutations occur in about 30% of patients with acute myeloid leukemia (AML). Patients with FLT3-mutated AML have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). So far, there is still limited data available on allo-HSCT for FLT3-mutated AML in non-remission status. [Objective and method] To assess the clinical features and outcome of allo-HSCT for FLT3-mutated AML, we retrospectively analyzed patients underwent first allo-HSCT for FLT3-mutated AML excluding acute promyelocytic leukemia (FAB M3) from January 2011 to March 2016. [Result] During the study period, 332 patients received first allo-HSCT for AML in our institute. One hundred and thirty-eight were tested for the presence of FLT3-mutation and 35 showed positive results and were subjected to the analysis. The median follow-up day of survivors was 602 (101-1867). The median age of the patients was 55 years (range, 21-72). Twenty-one patients had de novo AML, 12 had AML with myelodysplasia related changes, and 2 had therapy related AML. Eighteen had normal karyotype, 4 had complex, and 13 had others. Seven were in remission (5 in CR1, and 2 in CR2), and 28 were in non-remission (8 in primary induction failure, 13 in relapse 1, and 7 in chemo naïve status). Twenty-nine patients used unrelated cord blood, 2 did unrelated bone marrow, and 4 did related peripheral blood stem cell as grafts. All but 1 received myeloablative pretransplant conditionings. At 2 years after transplantation, overall survival (OS), disease free survival (DFS), relapse rate (RR), and non-relapse mortality (NRM) of whole studied population were 65.9%, 50.2%, 28.4%, and 21.4%, respectively. Among those in non-remission before transplantation, OS, DFS, RR, and NRM at 2 years post-transplant were 62.2% (Figure 1A), 49.9%(Figure 1B), 24.3%, and 25.8%, respectively. Only younger age (<55 years) was the factor associated with better OS with statistical significance in multivariate analysis. [Conclusion] Our data indicated that allo-HSCT could overcome the poor prognosis of FLT3-mutated AML even for those in non-remission status, despite the profound chemo-resistant character of FLT3-mutated AML. Figure 1A Figure 1A. Figure 1B Figure 1B. Disclosures Izutsu: Abbvie: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen Pharmaceutical K.K.: Honoraria; Eisai: Honoraria; Kyowa Hakko Kirin: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria; Mundipharma KK: Research Funding.

Download Full-text

EVI1 Expression Predicts Poor Survival in Acute Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation with Myeloblastic Conditioning

Blood ◽

10.1182/blood.v124.21.5308.5308 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5308-5308

Author(s):

Xuefeng He ◽

Suning Chen ◽

Wu Depei ◽

Aining Sun

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Cell Transplantation ◽

Myeloid Leukemia ◽

Hematopoietic Stem ◽

Poor Prognostic Factor ◽

Free Survival ◽

Long Time ◽

High Level ◽

Acute Myeloid

Abstract The ecotropic viral integreation site 1 (EVI1 or MECOM) gene mapping to chromosome 3q26 exerts significant oncogene biological effects of anti-apoptosis, proliferation and differentiation on hematopoietic cells. It is considered as a poor prognostic factor in acute myeloid leukemia (AML). EVI1 positive AML accounts for about 10% of de novo AML pts. The remission rate and long time survive are poor. Whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could salvage such kind of malignancy is still unknown. We conducted a survey of 161 AML pts (median age, 35 years[y]; range 8-60y) after first complete remission undergoing myeloblastic allo-HSCT at the first affiliated hospital of Soochow University. Source of hematopoietic stem cells came from match or partial matched related, unrelated or umbilical cord blood (UCB) donors (Table 1). Pretreated specimens were obtained and real-time polymerase chain reaction was performed to detect expression of EVI1-1d (one major splice of EVI1) and common EVI1 (cEVI) (normalized to PBGD gene). Standard plasmids of EVI1 and PBGD were prepared as calibrators. 13 nonmalignant single lineage cytopenia pts were tested as baseline. Quantities of EVI1-1d and cEVI ranges from negative to 154.2%PBGD and negative to 1214.3%PBGD in each group. Above five and ten folds to baseline in EVI1-1d and cEVI respectively were considered as positive. Accordingly 27 pts were EVI1 positive while 134 pts were negative (16.8% vs 83.2% separately). Unfavorable cytogenetic abnormalities showed a high proportion in EVI1 pos (11/27) than neg group (12/134). 5 and 40 mutations were detected in each group. Three cytogenetic abnormality concerning 11p15 pts expressed high level of EVI1. Positive expression of EVI1 indicated significant shorter progress-free survival and overall survival (P= 0.0352 and 0.0436 respectively) comparing with negative group (Figure 1). Table 1. Sources of donors Matched (n) Partial mathed (n) siblings 82 5 Parents or sons/daughters / 30 Unrelated PBSC 26 10 Unrelated UCB 3 5 Figure 1 Figure 1. Figure 2 Figure 2. Progress-free Survival (upper) and Overall Survival (below) in myeloblastic allo-HSCT pts according to EVI1 expression In conclusion, high level of evi1 expression predicts worse prognosis even after myeloblastic allo-HSCT. New treatment strategies post allo-HSCT are needed to improve long time survival in such kinds of pts. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Treatment results of pediatric acute myeloid leukemia with epigenetic drugs addition

Oncohematology ◽

10.17650/1818-8346-2020-15-2-19-28 ◽

2020 ◽

Vol 15 (2) ◽

pp. 19-28 ◽

Cited By ~ 1

Author(s):

V. S. Nemirovchenko ◽

M. A. Shervashidze ◽

T. T. Valiev ◽

K. L. Kondratchik

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Risk Group ◽

Relapse Free Survival ◽

Treatment Results ◽

Free Survival ◽

Epigenetic Drugs ◽

Treatment Groups ◽

Acute Myeloid

Background. Currently, overall survival rate for pediatric patients with acute myeloid leukemia (AML) do not exceed 70 %. The intensity of modern AML chemotherapeutic programs has reached its limit, and further chemotherapy dose escalation for treatment results improvement is impossible, because it fraught with life-threatening complications. It is investigating a new ways of tumor treatment for improvement of AML patient’s survival level: therapeutic efficacy of targeted and epigenetic drugs.Objective: to evaluate the efficacy of epigenetic drugs (azacitidine, decitabine, all-trans-retinoid acid and valproic acid) in combination with AML-BFM 2004 protocol for treatment of pediatric AML.Materials and methods. 80 patients with primary AML diagnosis were enrolled the study. Age was ranged from 8 months to 17 years (median 6.7 ± 0.6 years). From June 2012 to January 2018 all patients were subdivided in two treatment groups. 1st group included 34 patients treated with NII POH AML 2012 protocol, 2nd group – 46 patients treated by AML-BFM 2004 protocol.Results. 3-year relapse-free survival in 1st group, regardless of prognostic risk group, was 66.7 ± 11.7 %, 2nd group – 68.9 ± 9.9 %. Eventfree survival (EFS) for patients from 1st group was 66.7 ± 11.7 %, form 2nd group – 50.4 ± 10.2 %. Overall survival in 1st group was 66.7 ± 14.3 %, 2nd group – 66.9 ± 7.5 %. For patients with unfavorable risk from 1st treatment group 3-year relapse-free survival was 69.1 ± 11.9 %, 2nd – 64.9 ± 11.3 % (p = 0,8). EFS – 69.1 ± 11.9 and 44.8 ± 11.3 % respectively (p = 0,13). 3-year overall survival for patients with unfavorable risk group was 69.4 ± 14.6 and 64.4 ± 7.9 % in 1st and 2nd treatment groups respectively.Conclusion. The efficacy of decitabine in “window” regimen was higher in contrast to azacitidine; epigenetic therapy with AML-BFM 2004 protocol allow us to achieve a higher EFS, because of induction mortality and infection-related death decrease – EFS in 1st group was 16 % higher than in 2nd. Besides, EFS in unfavorable risk group, who treated with epigenetic drugs, was 25 % higher – 69.1 ± 11.9 % and 44.8 ± 11.3 % in 1st and 2nd groups respectively (p = 0.13). Nevertheless, overall survival in both groups was the same – 66 % (1st – 66.7 ± 14.3 % and 2nd – 66.9 ± 7.5 %).

Download Full-text

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

Blood ◽

10.1182/blood.v106.11.3288.3288 ◽

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.

Download Full-text

H2.0-Like Homeobox (HLX) Induces Unlimited Clonogenicity, Blocks Differentiation, and Cooperates with FLT3-ITD in the Induction of Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v120.21.651.651 ◽

2012 ◽

Vol 120 (21) ◽

pp. 651-651

Author(s):

Ashley Pandolfi ◽

Boris Bartholdy ◽

Masahiro Kawahara ◽

Laura Barreyro ◽

Britta Will ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Dna Binding ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Target Genes ◽

Hematopoietic Stem ◽

Differentiation Block ◽

Acute Myeloid

Abstract Abstract 651 Acute myeloid leukemia (AML) is an aggressive disease which is associated with poor clinical outcome. Less than one third of patients achieve durable remission with current treatment regimens, and prognostication and risk stratification are challenging. Identification and functional studies of genes and pathways which regulate leukemic transformation and maintenance is instrumental to understanding the pathogenesis of AML and for development of novel therapeutic strategies. Several members of the Hox (class I homeobox) family of transcription factors have been implicated in the regulation of normal hematopoiesis and leukemogenesis. Less is known about the role of non-clustered (class II) homeobox genes. We found that a new non-clustered homeobox gene, H2.0-like homeobox (HLX), regulates early hematopoiesis and promotes AML in mice and humans. HLX is 2 to 16 fold overexpressed in more than 80% of patients with AML, across all major disease subtypes. Higher levels of HLX are associated with poor overall survival in 3 different, large cohorts of AML patients (N=601, p=2.3×10−6), and HLX holds up as an independent prognostic factor in a multivariate analysis. ShRNA-mediated inhibition of HLX in both murine and human AML cells significantly inhibits leukemic growth and clonogenic capacity, and overcomes the differentiation block of AML cells. When we analyzed pre-leukemic hematopoietic stem and progenitor cells (HSPC) in a PU.1 URED/D AML mouse model, we found a 4-fold elevation of Hlx, suggesting that Hlx is involved in malignant transformation. Overexpression of HLX in wildtype HSPC in a competitive, congenic transplantation model led to near complete depletion of long-term HSC and 16-fold enrichment of myeloid progenitors with a surface phenotype slightly past the GMP stage (CD45+Kit−CD34−CD44highCD49bhighCD11bmid). Overexpression of HLX in HSPC in vitro led to a myeloid differentiation block and to formation of aberrant, CD34−Kit− progenitors with unlimited serial clonogenicity. The mechanism of action of Hlx is so far unknown. The presence of a C-terminal homeobox domain suggests Hlx may directly interact with DNA, however, no studies have shown DNA binding by Hlx or identified direct Hlx target genes. We find that mutation of only two residues of the Hlx homeodomain is sufficient to completely abrogate the differentiation block induced by HLX overexpression in HSPC, indicating Hlx is acting through the DNA-binding ability of its homeodomain. Furthermore, we have now identified direct HLX target genes in both HSPC and AML cells using a combination of expression microarrays and chromatin-immunoprecipitation (chIP). We find that HLX regulates a set of genes which mediate its leukemia-promoting functions, such as BTG1, and we have used chIP to identify a subset of these genes, including PAK1, that are direct targets of HLX. Internal tandem duplications of FLT3 (FLT3-ITD) are seen in approximately 25% of all AML patients, and confer a poor prognosis. Correlative analyses showed that AML patients with mutant FLT3 and low HLX have overall survival similar to WT FLT3 patients, and survive significantly longer than patients with mutant FLT3 and high HLX (p=0.005), demonstrating that FLT3 mutations confer poor prognosis only if HLX is highly expressed, and suggesting that HLX and mutant FLT3 functionally cooperate. We find that co-expression of HLX and FLT3-ITD leads to dramatically enhanced cytokine independent growth and clonogenicity of 32D cells as well as primary murine HSPC in vitro. When we retrovirally co-expressed HLX and FLT3-ITD, or FLT3-ITD alone (plus an empty control), in primary Lin−Kit+ cells and transplanted them into congenic recipient animals, we found that four weeks after transplantation donor chimerism was 4-fold increased on average in the peripheral blood (PB) and bone marrow (BM), and by 12 weeks post-transplantation mice expressing FLT3-ITD and HLX developed AML with large numbers of leukemic blasts in the PB and BM. We have generated knock-in mice conditionally overexpressing Hlx from the Rosa26 locus and ongoing studies include crossing these mice into FLT3-ITD knock-in animals. In summary, our studies have identified HLX as a novel key transcription factor involved in the regulation of early hematopoiesis and AML pathogenesis, and suggest HLX and downstream pathways as promising new therapeutic targets in AML. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

First report from a single center retrospective study in Kazakhstan on acute myeloid leukemia treatment outcomes

Scientific Reports ◽

10.1038/s41598-021-03559-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

G. U. Kulkayeva ◽

V. M. Kemaykin ◽

A. M. Kuttymuratov ◽

Z. I. Burlaka ◽

J. Z. Saparbay ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Good Prognosis ◽

Event Free Survival ◽

Hematopoietic Stem ◽

Free Survival ◽

Acute Myeloid

AbstractAcute myeloid leukemia (AML) is the most common hematological malignancy in adults. In the last decade, internationally approved AML treatment guidelines, including hematopoietic stem cell transplantation are widely used in Kazakhstan. The categorization of acute myeloid leukemia was done according to the French-American British classification. The prognosis of patients at the time of diagnosis was determined by cytogenetic tests following the guidelines of the European LeukemiaNet. The overall survival and event-free survival were analyzed using the Kaplan–Meier method, and hazard ratios were defined with Cox regression. In total, 398 patients with AML were treated in the National Research Oncology Center between 2010 and 2020. The mean age was 38.3 years. We found a correlation between ethnicity, cytogenetic group, white blood cell count, and treatment approaches with overall and event-free survival. There was a significantly longer OS in a cytogenetic group with a good prognosis compared with intermediate and poor prognosis. The median survival time in the group with a good prognosis was 43 months, 23 months in the intermediate group (p = 0.7), and 12 months in the poor prognosis group (p = 0.016). There was a significantly longer OS for the group of patients who received hematopoietic stem cell transplantation (HSCT), 52 months versus 10 months in the group who received chemotherapy only, p-value < 0.0001. Prognostic factors, such as cytogenetic group, initial WBC count, and treatment approaches are significantly associated with patient survival. Our study data were consistent with the most recent studies, available in the literature adjusted for the population in question.

Download Full-text

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽

10.1182/blood-2009-05-223784 ◽

2009 ◽

Vol 114 (26) ◽

pp. 5352-5361 ◽

Cited By ~ 211

Author(s):

Jih-Luh Tang ◽

Hsin-An Hou ◽

Chien-Yuan Chen ◽

Chieh-Yu Liu ◽

Wen-Chien Chou ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Remission Rate ◽

Adult Patients ◽

Poor Prognostic Factor ◽

The Impact ◽

Runx1 Mutation ◽

Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

Download Full-text

Relationship Between Cleaved L-Selectin Levels and the Outcome of Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v92.9.3115 ◽

1998 ◽

Vol 92 (9) ◽

pp. 3115-3122 ◽

Cited By ~ 9

Author(s):

M. Extermann ◽

M. Bacchi ◽

N. Monai ◽

M. Fopp ◽

M. Fey ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

High Plasma ◽

Multivariate Statistical ◽

Free Survival ◽

The Mean ◽

American Society ◽

The Relationship ◽

Acute Myeloid

Abstract High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acute myeloid leukemia (AML). sL-selectin can inhibit blast cell adhesion to vascular endothelium and may thereby influence the phenotype of AML. In this study, we have investigated the relationship between sL-selectin levels and clinical presentation or disease outcome in 100 patients with AML. Fifty-eight patients were found to have sL-selectin levels ≥3.12 μg/mL (≥3 SD above the mean of healthy controls: “increased”). Patients with extramedullary disease such as lymphadenopathies, splenomegaly, hepatomegaly, and/or muco-cutaneous infiltration had significantly increased sL-selectin levels (P < .001). sL-selectin levels were significantly heterogeneous in the French-American-British subtypes (P = .0003). Patients with “normal” sL-selectin levels had higher probability of achieving complete remission (CR) than with “increased” levels: 81% versus 64%, respectively (P = .06). When adjusting for clinically relevant covariates predictive for CR (sex, age, Auer rods), “normal” sL-selectin levels were significantly associated with CR (odds ratio, 3.08; 95% confidence interval [CI], 1.10 to 8.58;P = .03). Moreover, patients with “increased” sL-selectin levels (≥3.12 μg/mL) had shorter event-free survival (EFS) (median 7.3 v 12 months, P = .008) and overall survival (median 1 v 2.05 years, P = .03) than patients with sL-selectin <3.12 μg/mL. Multivariate statistical analysis (adjusted for age and presence of Auer rods) indicated that sL-selectin was an independent prognostic factor for EFS (hazard ratio [HR], 1.96; 95% CI, 1.21 to 3.17, P = .006) and overall survival (HR, 1.80; 95% CI, 1.09 to 2.98; P = .02). Thus, plasma sL-selectin may be a useful prognostic marker in the evaluation of AML at diagnosis. © 1998 by The American Society of Hematology.

Download Full-text

High CXCR2 expression predicts poor prognosis in adult patients with acute myeloid leukemia

Therapeutic Advances in Hematology ◽

10.1177/2040620720958586 ◽

2020 ◽

Vol 11 ◽

pp. 204062072095858

Author(s):

Wei Tang ◽

Zunyan Li ◽

Xian Li ◽

Zhonghua Huo

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Mononuclear Cells ◽

Cox Proportional Hazards ◽

Adult Patients ◽

The Cancer Genome Atlas ◽

Clinical Parameters ◽

Cxcr2 Expression ◽

Acute Myeloid

Aims: This study aimed to assess the associations between clinical parameters, long-term outcomes, and expression of chemokine receptor CXCR2 in patients with acute myeloid leukemia (AML). Methods: From May 2013 to May 2017, 83 adult patients newly diagnosed with AML in the Affiliated Hospital of BeiHua University and Jilin Chemical Hospital, were enrolled in this study. The expression of CXCR2 in bone marrow mononuclear cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Clinical information and RNA-sequencing datasets of The Cancer Genome Atlas (TCGA) ( n = 136) were obtained. The associations between clinical parameters, prognosis, and CXCR2 expression were analyzed. Results: From both cohorts, patients with AML with M4 and M5 subtypes showed higher CXCR2 expression levels than those with other French-American-British (FAB) subtypes. Patients with extramedullary leukemia infiltration had higher CXCR2 levels than those without. In our cohort, patients with high CXCR2 levels (⩾2.099) had lower relapse-free survival (RFS) ( p < 0.000001) and overall survival (OS) ( p = 0.000107) than those with low levels (<2.099). High CXCR2 levels (⩾2.082) also indicated a poor OS in the TCGA cohort but only in patients younger than 65 years (5-year OS: 7.7% versus 29.9% in those with CXCR2 levels < 2.082). High CXCR2 levels independently predicted poor prognosis in AML patients, as determined by Cox proportional hazards models. Conclusion: Our results suggest that high CXCR2 expression associates with the monocytic lineage of AML and is an independent risk factor for poor patient prognosis.

Download Full-text