Untreated Acute Myeloid Leukemia Research Articles

Phase I Trial of Escalating Doses of the Bcl-2 Inhibitor Venetoclax in Combination with Daunorubicin/Cytarabine Induction and High Dose Cytarabine Consolidation in Previously Untreated Adults with Acute Myeloid Leukemia ( AML)

Phase I Trial of Escalating Doses of the Bcl-2 Inhibitor Venetoclax in Combination with Daunorubicin/Cytarabine Induction and High Dose Cytarabine Consolidation in Previously Untreated Adults with Acute Myeloid Leukemia ( AML)

Clinical Profile of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate (ADC), in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Clinical Profile of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate (ADC), in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Fried Frailty Phenotype Predicts Mortality for Newly Diagnosed Older Patients with Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Fried Frailty Phenotype Predicts Mortality for Newly Diagnosed Older Patients with Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Iadademstat Shows Efficacy in Elderly AML Patients in Combination with Azacitidine. Alice Trial

Introduction: Acute Myeloid Leukemia (AML) is an elderly disease with a rising incidence in the past decades. Probability to achieve complete remission and survival rates decrease with age with standard chemotherapy options leading to very poor outcomes with less than 20% 5-year overall survival rates. It has been shown that Lysine-specific demethylase 1 (LSD1) is a partner in some gene transformation in AML and helps sustain the oncogenic process. Iadademstat is a potent and selective LSD1 inhibitor that has shown to be effective in preclinical models, both alone and in combination with other compounds, including azacitidine (Aza). A Phase I FiM study in acute leukemia showed that iadademstat exhibits a good safety profile and preliminary anti-leukemic activity as monotherapy. Iadademstat in combination with Aza may thus offer an alternative option for such a population with limited therapeutic options. Methods: ALICE is a Phase IIa clinical trial to assess the safety, tolerability and dose finding of iadademstat in combination with Aza and also to measure the clinical activity of the combination as overall response rate (ORR), time to response (TTR) and duration of response (DOR). Other assessments include hematological improvement and overall survival, along with PK/PD measures (including a set of 6 blood biomarkers). The dose finding stage (Part 1) planned to dose a maximum 18 patients with a starting dose of iadademstat of 90 μg/m2/d in combination with Aza. Iadademstat may be escalated or de-escalated depending on the observed dose limiting toxicities. Once the Recommended Dose (RD) is identified, an expansion cohort of 18 patients will be enrolled and treated with iadademstat combined with Aza (Part 2). ALICE includes subjects ≥ 60 years of age with AML according to World Health Organization (WHO) classification, who are considered by the investigator to be ineligible for intensive chemotherapy at that time or have refused standard chemotherapy and who have not received prior treatment for AML other than hydroxyurea. Results: According to the Safety Monitoring Committee of the study, the selected RD of iadademstat was 90μg/m2/d. This decision was made based on first dose finding cohort including 6 subjects with the observation of 1 DLT due to a differentiation syndrome (the sole SAE reported due to treatment) and based on the fact that the selected dose: i) was able to saturate LSD1 target engagement in PBMCs after 5 days of treatment; ii) was well tolerated (11 treatment cycles were completed at the moment of decision) and iii) demonstrated the first signs of efficacy. A short median time to first response was observed (around 1.5 months). Analysis of the first patients yielded an ORR in 4 of 5 evaluable patients (80%): in all of them the best observed response was CRi as per July 2019. A lower maintenance regime has been established for those patients that had attained CRi. The first patient that has followed this strategy has become transfusion independent. To date, no grade 3-4 non-hematological adverse events have been reported. The patient assessments of the still-ongoing subjects from Part 1 and all new enrolled study subjects in the expansion cohort will be presented following a November 2019 cut-off, with particular emphasis on available preliminary efficacy outcomes. Conclusions: To date, data from this Phase II study supports that iadademstat in combination with azacitidine in elderly previously untreated AML patients has a manageable toxicity and is a meaningful candidate for specific combinations in this and future leukemia studies. These encouraging results will be enriched with the inclusion of up to 18 additional patients in the expansion cohort and with longer clinical observation periods to better assess the frequency, deepness and duration of the responses. Disclosures Buesa: Oryzon Genomics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Mendelion SL: Membership on an entity's Board of Directors or advisory committees. Somervaille:Novartis: Consultancy. Arevalo:Oryzon Genomics: Employment. Xaus:Oryzon Genomics: Employment. Gutierrez:Oryzon Genomics: Employment. Bullock:Oryzon Genomics: Consultancy.

Use of CD70 Targeted Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Acute Myeloid Leukemia (AML)

Background: CAR-T cells have led to a revolution in the treatment of advanced hematologic malignancies. Since these cells target antigens that are expressed on the cellular surface, it is imperative that there is near ubiquitous tumor expression with minimal expression vital human tissues. Finding targets with these characteristics in myeloid malignancies has been challenging. Typical markers expressed on the surface of AML are also expressed on essential innate immune effector cells (e.g. neutrophils) which, if targeted, could lead to prolonged absence of this immune arm, which is not survivable or replaceable. Current approaches rely on the use of CAR-T cells against common myeloid targets (e.g. CD123, CD33) as an ablative strategy with a planned allogeneic stem cell transplant rescue to eradicate the CAR-T cells afterwards. These solutions have resulted in significant toxicity with several deaths resulting from CD123-targeted CAR-T cells. Another approach has involved gene editing donor progenitor cells to delete CD33, repopulation of the marrow with these CD33 negative cells, and then treatment with CD33-targeted CAR-T cells. (Kim, Cell 2018). However, this approach is challenging, costly, and genomic editing of stem cells remains a concern. CD70 is an immune checkpoint found on antigen presenting cells and activated T cells. Multiple studies have shown a strong degree of expression on AML blasts and leukemic stem cells, with minimal normal tissue expression (Perna, Cell 2017, Riether J Exp Med 2017). A Phase 1 study of a CD70 targeted antibody drug conjugate in combination with azacitidine (which has been shown to increase CD70 expression on leukemic stem cells) for untreated AML patients has shown impressive results (Blood 2018 132:2680, Blood 2017 130:2652). Based on these findings, we explored CD70-targeting CARs for the treatment of AML. Methods: Based on our success with a trimeric ligand-based CAR of another TNFα family member, APRIL, for multiple myeloma (Schmidt Blood 2018 132:2059), we generated monomeric and trimeric second-generation ligand-based CAR constructs to target CD70 on AML. In vitro effector function was compared by cytotoxic potency and cytokine production. In vivo anti-tumor efficiency was assessed in a xenograft mouse model of AML. Effect of surface CD70 expression on AML cell lines after co-culture with azacitidine was assessed. Results: CAR T cell manufacturing of both constructs was accomplished successfully (transduction efficiency 70-93%) from three different healthy donors with no apparent fratricide. CD70 CARs were efficacious in in vitro cytotoxicity assays targeting an AML cell line Molm13. Unexpectedly, monomeric CD70 targeted CAR-T cells were superior to trimeric in cytotoxicity assays and, thus, were carried forward for in vivo assays. Next, we treated NSG mice that had been engrafted with Molm13 and demonstrated a substantial dose-dependent therapeutic effect with prolonged survival of CAR treated mice compared to those treated with untransduced T-cells (UTD). Treated mice demonstrated a CAR-T robust expansion in the peripheral blood assessed by flow cytometry that was commensurate with individual animal treatment responses. Bone marrow from these mice revealed substantially reduced CD70 in all groups. Preliminary in vitro co-culture of AML cells with azacitidine showed increased CD70 expression. Conclusion: CD70 based CAR-T targeting of AML is effective in vitro and in vivo. Combination treatment with azacitidine may increase target antigen expression and lead to synergistic activity and represents a viable therapeutic strategy that warrants further investigation. Treatment of AML engrafted NSG mice with CD70 CAR-T cells in conjunction with azacitidine is ongoing. Disclosures Frigault: Xenetic: Consultancy; Novartis: Consultancy; Juno/Celgene: Consultancy; Foundation Medicine: Consultancy; Incyte: Consultancy; Nkarta: Consultancy; Kite/Gilead: Honoraria. Maus:INFO PENDING: Other: INFO PENDING.

Venetoclax and Azacitidine for Older Newly Diagnosed Patients with Acute Myeloid Leukemia: A Single-Institution Pilot Study Using Measurable Residual Disease to Guide Therapy

Venetoclax and Azacitidine for Older Newly Diagnosed Patients with Acute Myeloid Leukemia: A Single-Institution Pilot Study Using Measurable Residual Disease to Guide Therapy

Precision Medicine Treatment in Older AML: Results of Beat AML Master Trial

Precision Medicine Treatment in Older AML: Results of Beat AML Master Trial

Outcomes after Stem Cell Transplant in Older Patients with Acute Myeloid Leukemia Treated with Venetoclax-Based Therapies

Outcomes after Stem Cell Transplant in Older Patients with Acute Myeloid Leukemia Treated with Venetoclax-Based Therapies

Outcomes in Molecular Subgroups and Resistance Patterns with Ten-Day Decitabine and Venetoclax (DEC10-VEN) in Acute Myeloid Leukemia

Outcomes in Molecular Subgroups and Resistance Patterns with Ten-Day Decitabine and Venetoclax (DEC10-VEN) in Acute Myeloid Leukemia

The Impact of PHF6 Mutations in Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, and Acute Myeloid Leukemia

The Impact of PHF6 Mutations in Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, and Acute Myeloid Leukemia

Overall Survival of Glasdegib in Combination with Low-Dose Cytarabine and Azacitidine By Bone Marrow Blasts Among Adult Patients with Previously Untreated Acute Myeloid Leukemia: Comparative Effectiveness Using Indirect Treatment Comparisons

Introduction Acute myeloid leukemia (AML) is an orphan disease with one of the lowest five-year survival rates among myeloid malignancies in United States adults. Older AML patients face a much lower 5-year survival rate than their younger counterparts (8% for those aged 60-65 years vs. 38% for those under 45 years). Current therapies are limited and historically include low-dose cytarabine (LDAC), decitabine, azacitidine (AZA) and best supportive care. A phase II randomized study (Cortes et al, 2019) among previously untreated AML patients who are not eligible for intensive chemotherapy demonstrated improved overall survival (OS) in patients treated with glasdegib (GLAS) in combination with low-dose cytarabine (LDAC) compared to patients receiving LDAC alone. There are two trials comparing AZA with conventional care regimens that report data by bone marrow blasts (BMB) count: Fenaux et al. (2010) for patients with 20-30% BMB and Dombret et al (2015) for patients with over 30% BMB. In clinical practice, AZA may be restricted to the 20-30% BMB population, which is important to consider when comparing treatment options. Therefore, as there are currently no head-to-head comparisons for GLAS+LDAC vs AZA, two separate indirect treatment comparisons (ITCs) were performed in different BMB populations (i.e., 20-30% and >30% BMB). ITCs is an accepted method to support evidence-based comparative effectiveness decision making and ultimately help to optimize treatment and outcomes of patients with previously untreated AML. Method ITCs were conducted in a classical frequentist statistical framework based on the Bucher method. Patient-level data of the Cortes study (data-cut: January 2017) was divided into two subgroups in terms of BMBs, 20-30% (n=30) and >30% (n=80) to match the patient population of Fenaux et al (n=34) and Dombret et al (n=399) accordingly. GLAS+LDAC and AZA were compared in terms of overall survival and results were reported in terms of hazard ratio (HR) with corresponding 95% confidence intervals (95% CI). AZA was chosen as the reference treatment in the ITC. Results In the 20-30% BMB population, the estimated OS HR of GLAS-LDAC in comparison to AZA was 0.46 (95% CI: 0.10-2.14). In the >30% BMB population, the estimated OS HR of GLAS-LDAC in comparison to AZA was 0.61 (95% CI: 0.35-1.08). Conclusion These ITCs suggest that GLAS+LDAC is trending towards being a better treatment option for improving OS in patients with AML compared with AZA, irrespective of the level BMB. These results are consistent with previously published ITC results for this treatment comparison. The results of this ITC should, however, be interpreted with caution due to methodological limitations. First, the relatively small number of patients and deaths result in high uncertainty (as exemplified by the 95% CIs) and, second, patient baseline characteristics (including cytogenetic risk, ECOG status and de novo status) between trial arms and over the different trials were either imbalanced or not reported. While more research is needed, current evidence suggests that GLAS+LDAC may be the preferred treatment option for previously untreated AML patients irrespective of BMB levels. Disclosures Van Beekhuizen: Ingress-health: Consultancy, Other: funding from Pfizer. Bell:Pfizer Inc.: Employment, Equity Ownership. Gezin:Ingress-health: Consultancy, Other: funding from Pfizer. Cappelleri:Pfizer: Employment, Equity Ownership. Heeg:Ingress-Health: Employment. Selya-Hammer:Pfizer Inc: Employment, Equity Ownership. Charaan:Pfizer Inc: Employment, Equity Ownership. Chan:Pfizer Inc: Employment, Equity Ownership.

Correlation of miR-181a and three HOXA genes as useful biomarkers in acute myeloid leukemia.

MiR-181a is a small, noncoding RNA that plays important roles in the pathogenesis and prognosis of acute myeloid leukemia (AML). A group of HOXA genes, including HOXA7, HOXA9, and HOXA11, has been established as an independent predictor for AML prognosis. In this study, we aimed to investigate the association between miR-181a and HOXA7, HOXA9, and HOXA11 and explore their roles in predicting prognosis in AML. Bone marrow samples of 46 untreated AML patients and 9 healthy donors were collected. Mononuclear cells were purified using density-gradient centrifugation in Ficoll, and quantitative real-time PCR was used to detect miR-181a and HOXA gene expression level. HOXA7, HOXA9, and HOXA11 were negatively correlated with miR-181a, and their expression levels varied among AML subtypes, karyotypes, and risk status. Higher miR-181a and lower HOXA gene expressions were significantly associated with lower risk status and better response to chemotherapy. In our study, we found miR-181a expression was negatively correlated with three HOXA genes and they were associated with AML risk status and prognosis in granulocytic AML. It further supported that miR-181a could be a useful marker for AML prognosis and possibly worked by regulating HOXA gene clusters.

Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia

AbstractVenetoclax is approved for older untreated acute myeloid leukemia (AML) patients. Venetoclax was available prior to approval off-label. We assessed our single-institution off-label experience with venetoclax/azacitidine, comparing outcomes with a clinical trial cohort that administered this regimen at the same institution. Thirty-three untreated AML patients unfit or unwilling to receive induction chemotherapy and prescribed venetoclax/azacitidine off-trial were retrospectively analyzed and compared with 33 patients who received the same therapy on trial. Outcomes were compared, and comparisons were made to a theoretical scenario in which off-trial patients received induction. Digital droplet polymerase chain reaction evaluated measurable residual disease (MRD). Off-trial venetoclax was attainable in nearly all patients for whom this was desired. The complete remission (CR)/CR with incomplete blood count recovery rate was 63.3% for off-trial patients who received treatment and 84.9% for trial patients (P = .081). The median overall survival for off-trial patients who received treatment was 381 days (95% confidence interval [CI], 174, not reached) vs 880 days (95% CI, 384, not reached) for trial patients (P = .041). Prior exposure to hypomethylating agents was associated with worse outcomes. Response rates with venetoclax/azacitidine were not inferior to a theoretical scenario in which patients received induction, and early death rates were less than expected with induction. MRD negativity was achievable. Newly diagnosed AML patients treated in a “real-world” scenario with off-trial venetoclax/azacitidine had inferior outcomes compared with patients treated in the setting of a clinical trial. Additionally, this therapy may be as effective, and less toxic, when compared with induction chemotherapy.

Aberrant activation of RPB1 is critical for cell overgrowth in acute myeloid leukemia

Acute myeloid leukemia (AML) is a group of highly aggressive malignancies with a 5-year overall survival of less than 40%. Cell overgrowth with defective apoptosis is a hallmark of AML, but little is known about how it occurs. Here, we show that aberrant activation of the largest subunit of RNA polymerase II (RPB1) encoded by POLR2A gene is critically involved in this hallmark. We retrospectively analyzed the expression profiles of POLR2A and RPB1 in a panel of AML cell lines, primary AML patients and peripheral blood samples. Meanwhile, correlation analysis was used to explore the correlation between the expression of RPB1 with tumor burden and overall survival time in untreated AML samples. RNA-Seq approach was performed to identify the differentially expressed genes between RPB1 silencing AML cells with control cells after knocking out RPB1. Furthermore, orthotopic AML models were established with RPB1 silencing and control cells to investigate the effects of RPB1 protein level on leukemia cell growth. In most AML patients, RPB1 was aberrantly activated and closely associated with poor prognosis, but not in normal hematopoietic cells. Global transcriptomic analysis revealed that POLR2A knockout strongly impaired growth of AML cells by selectively depleting a substantial set of AML-related oncogenic and anti-apoptosis genes such as MYC, RUNX2, MEIS1, CDC25A and BCL-2. Silencing RPB1 by genetic technology led to a potent regression of human refractory AML in mouse models. These findings reveal that dysregulated RPB1 is a central oncogenic hub that drives overgrowth by hijacking an array of oncogenic and anti-apoptosis factors. Targeting RPB1 is a potential therapeutic for treating AML.

Selinexor in combination with decitabine in patients with acute myeloid leukemia: results from a phase 1 study

Current treatment options for older and relapsed or refractory (R/R) acute myeloid leukemia (AML) patients are limited and represent an unmet need. Based on preclinical studies showing strong anti-leukemic effects in vivo, this phase I dose-escalation study assessed the safety and preliminary clinical activity of the oral exportin-1 inhibitor, selinexor, in combination with the hypomethylating agent, decitabine 20 mg/m2, in adults with R/R AML and in older (age ≥ 60) untreated AML patients. There were no protocol-defined dose limiting toxicities. The recommended phase 2 dose of selinexor was 60 mg (∼35 mg/m2) given twice-weekly. Notable grade ≥3 toxicities included asymptomatic hyponatremia (68%), febrile neutropenia (44%), sepsis (44%), hypophosphatemia (36%), and pneumonia (28%). In 25 patients, the overall response rate was 40%. Modification of selinexor to a flat dose of 60 mg, twice-weekly for two weeks after decitabine, improved tolerability of the regimen and demonstrated preliminary clinical activity in poor-risk patients with AML.

A Phase 1b Master Trial to Investigate CPX-351 in Subjects With Previously Untreated Acute Myeloid Leukemia

A Phase 1b Master Trial to Investigate CPX-351 in Subjects With Previously Untreated Acute Myeloid Leukemia

Targeted Alpha-Particle Therapy for Hematologic Malignancies

IntroductionThe short range and high linear energy transfer of α-particles offer the potential for efficient tumor killing while sparing surrounding normal cells. Hematologic malignancies are ideally suited to targeted α-therapy because of easy accessibility of malignant cells in blood and bone marrow and their radiosensitivity. MethodsA series of clinical trials were conducted to assess the safety and antileukemic effects of lintuzumab, an anti-CD33 antibody, labeled with the α-emitters bismuth-213 (213Bi) and actinium-225 (225Ac) in patients with acute myeloid leukemia (AML). ResultsInitial studies showed that 213Bi-lintuzumab had antileukemic activity and could produce remissions after partial cytoreduction with cytarabine. A phase I trial demonstrated that a single infusion of 225Ac-lintuzumab could be given safely at doses up to 111 kBq/kg with antileukemic activity at all dose levels studied. A second phase I study showed that 28% of older patients with untreated AML had objective responses after receiving fractionated-dose 225Ac-lintuzumab and low-dose cytarabine. A phase II study of 225Ac-lintuzumab monotherapy in this population produced remissions in 69% of patients receiving two fractions of 74 kBq/kg and 22% of patients receiving two 55.5-kBq/kg fractions. ConclusionsStudies with 213Bi-lintuzumab provided proof of principle for systemically administered α-particle therapy. 225Ac-lintuzumab was active against advanced AML and produced remissions in older patients with untreated AML in combination with low-dose cytarabine and as a single agent. These studies provide the rationale for development of 225Ac-lintuzumab in combination with a variety of agents in AML and in other hematologic malignancies such as myelodysplastic syndrome and multiple myeloma.

The Association of Circulating T Follicular Helper Cells and Regulatory Cells with Acute Myeloid Leukemia Patients

Objective: This study aims to investigate the association of circulating T follicular helper (cTfh) cells and T follicular regulatory (cTfr) cells with acute myeloid leukemia (AML) patients. Methods: A total of 22 newly diagnosed, untreated AML patients as well as 26 healthy controls were enrolled. Percentages of cTfh and cTfr cells were detected using flow cytometry. Results: Compared to healthy controls, a significantly higher percentage of cTfr cells was observed in AML patients (4.10 ± 11.18 vs. 0.63 ± 0.38%) (p < 0.05). In addition, a significantly lower cTfh/cTfr ratio was found in the AML patients’ group when compared to the control group (9.04 ± 9.19 vs. 11.66 ± 5.68) (p < 0.05). A lower level of plasma IL-2 and TGF-β1 was found in AML patients. Based on the complete remission (CR) response after one cycle of inductive chemotherapy, patients were divided into two groups at sample collection: AML with and without CR. Significantly lower percentages of cTfr cells and a higher cTfh/cTfr ratio were found in the group of AML patients with CR than in the AML patients without CR. Conclusion: There was a significantly higher percentage of cTfr cells in AML patients. cTfr cells may have a potential association with the pathogenesis of AML patients.

Evaluation of event-free survival as a robust end point in untreated acute myeloid leukemia (Alliance A151614)

AbstractEvent-free survival (EFS) is controversial as an end point for speeding approvals in newly diagnosed acute myeloid leukemia (AML). We aimed to examine the robustness of EFS, specifically timing of complete remission (CR) in defining induction failure and impact of hematopoietic cell transplantation (HCT). The study included 1884 untreated AML patients enrolled across 5 trials conducted through Alliance for Clinical Trials in Oncology using anthracycline and cytarabine induction chemotherapy. EFS was defined as time from randomization/registration to induction failure, relapse, or death. Three definitions of induction failure were evaluated: failure to achieve CR by 60 days after randomization/registration, failure to achieve CR by the end of all protocol-defined induction courses, and failure to achieve CR by the end of all protocol-defined treatment. We considered either censoring or no censoring at time of non–protocol-mandated HCT. Although relapse and death are firm end points, the determination of induction failure was not consistent across studies. There was minimal impact of censoring at HCT on EFS estimates; however, median EFS estimates differed considerably based on the timing of CR in defining induction failure, with the magnitude of difference being large enough in most cases to lead to incorrect conclusions about efficacy in a single-arm trial, if the trial definition was not consistent with the definition used for the historical control. Timing of CR should be carefully examined in the historical control data used to guide the design of single-arm trials using EFS as the primary end point. Trials were registered at www.clinicaltrials.gov as #NCT00085124, #NCT00416598, # NCT00651261, #NCT01238211, and #NCT01253070.

PS1018 TUMOR IMMUNE ESCAPE MEDIATED BY TH17CCR4‐CCR6+ CELLS AND IL‐6/IL‐10/IL‐17A IN ACUTE MYELOID LEUKEMIA

Background:Acute myeloid leukemia (AML) is a hematologic neoplasm characterized by the proliferation of bone marrow myeloblasts. Most of patients achieve remission after intensive chemotherapy, although they still relapse. The immune system play an important role in the pathogenesis of AML, where myeloblasts are be able to switch the immunological synapsis disabling the generation of an anti‐tumor response. In this sense, the presence of a greater number of Th17 lymphocytes has been described in AML.Aims:To elucidate whether the myeloblats modulate the Th17 population and more specifically the two Th17 subpopulations: CCR4+ and CCR4‐.Methods:From February 2015 to March 2018, 20 AML diagnosed patients at the CHN and 20 controls were included. Blood samples were collected at diagnosis from AML patients and in controls. We identified by flow cytometry the populations of T helper cells (Th1, Th2, Th17 CCR4‐CCR6+, Th17 CCR4+CCR6+) with the following monoclonal antibodies: CD3 Horizon‐V450, CCR3 FITC, IFNγRβ PE, CCR4 PE‐Cy7, CD4 PerCP, CCR6 APC, CD45 APC‐H7, CCR5 FITC, CXCR3 APC in a FACSCanto II. Serum level of cytokines were also analysed by CBA Human Th1/Th2/Th17 Cytokine Kit (BD) for IL‐2, IL‐4, IL‐6, IL‐10, TNFα, IFNγ, and IL‐17A. We also study the polimorfism of IL‐17A (rs2275913) and IL‐17F (rs763780) by allele discrimination by real‐time PCR. The SPSS software was used to perform Student́s test or Mann‐Whitney test for unpaired samples between patients and controls, and simple linear regression was used to study the association between levels of cytokines and Th subpopulations in AML patients. P &lt; 0,05 was considered to be statistically significant.Results:Patients and controls characteristics were showed in table 1. Th1 and Th2 cells levels did not differ between AML patients and controls. The mean of Th17 CCR4‐CCR6+ cells was significantly higher in AML patients (192 ± 178/μl) than those in controls (67 ± 38/μl), and the difference was statistically significant (p = 0,027). However, Th17 CCR4+CCR6+ cells levels did not differ between groups. We did not find significant differences in the levels of IL‐2, IL‐4, TNFα and IFNγ citokines. Th17 related cytokines were significantly higher in AML patients than in controls and statistically significant. The mean of cytokines (pg/ml) in AML and in controls was 32,79 ± 86,64 vs 0 (p &lt; 0,01), 3,03 ± 2,65 vs 0,24 ± 0,52 (p &lt; 0,001), 14,37 ± 14,12 vs 2,38 ± 4,17 (p = 0,012), for IL‐6, IL‐10 and IL‐17A respectively. No association was find by simple linear regression between the levels of IL‐6, IL‐10 and IL‐17A, and the Th17 subpopulations. There are also no significant differences between the polymorphisms studied of IL‐17 in patients and controls.imageSummary/Conclusion:Th17 subpopulations could play a role in the pathophysiology of AML. The most relevant subpopulation described is the Th17 CCR4+CCR6+. Protumoral and antitumor properties have been described for this subpopulation and associated cytokines (IL‐6, IL‐10 and IL‐17A). However, our results show an increase in the levels of the Th17 CCR4‐CCR6+ subpopulation and in IL‐6, IL‐10 and IL‐17A in untreated AML patients. The lack of association between Th17 subpopulations and cytokines implies that AML generates a protumoral microenvironment, where Th17 subpopulation and associated cytokines are regardless regulated by the tumor. Specifically, the downregulation of CCR4 antigen expression prevents the cells from migrating and having an antitumor effect and the upregulation of IL‐6, IL‐10 and IL‐17A secretion very likely from Th17 CCR4+CCR6+ could contribute to the progression of the disease.