Simple Blood Test May Predict Early Death Risk in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a high-risk hematologic malignancy linked to significant early mortality despite many advances in supportive care and induction strategies.¹ Early death is an ongoing critical challenge in patients with AML who are undergoing intensive chemotherapy, with most events taking place within the first 30 to 90 days following diagnosis.²

While risk stratification tools such as the European LeukemiaNet (ELN) classification provide prognostic insight, these models are primarily designed to predict long-term outcomes and may not adequately capture the risk of early clinical deterioration during induction therapy.^3,4

Finotto et al evaluated whether Endothelial Activation and Stress Index (EASIX) scores could serve as a rapid predictor of early mortality and intensive care unit (ICU) admission in patients with newly diagnosed AML undergoing intensive induction therapy.¹

AML and the Need for Early Risk Prediction

AML is recognized through its rapid proliferation of immature myeloid blasts, causing bone marrow failure, cytopenias, and life-threatening complications.¹ Despite advances in induction therapy, early mortality remains a significant concern, driven by patient frailty, disease burden, and disparities in care.^2,4

Patients with AML in a critical state require frequent ICU-level care, with prior data showing high rates of organ dysfunction and mortality upon being admitted.⁵ Traditional prognostic models such as comorbidity-based indices and genetic classification systems are not designed to capture acute physiologic instability at presentation.^6,7 This gap limits the early identification of patients at the highest risk of clinical deterioration during induction chemotherapy.

The EASIX Score: A Simple Biomarker of Physiologic Stress

EASIX was initially formulated as a surrogate marker of endothelial injury in hematologic malignancies and transplant populations. It is calculated using routinely available laboratory values: lactate dehydrogenase (LDH) multiplied by creatinine, then divided by platelet count. This composite expresses multiple biological processes associated with AML, including tumor burden (LDH elevation), renal dysfunction or tumor lysis (creatinine), and bone marrow failure (thrombocytopenia).^8,9

Though it was primarily developed as a marker of endothelial activation, EASIX can also reflect broader systemic physiologic stress in acutely ill patients.^10,11 Prior data has demonstrated its predictive value for complications including sepsis, thrombotic microangiopathy, and mortality in hematologic populations.^9-11

Study Design

The researchers analyzed data from 158 adult patients with newly diagnosed AML being treated with intensive induction chemotherapy (7 + 3 regimen) at a tertiary care center. Patients who were receiving palliative or low-intensity therapy were excluded. The EASIX score was calculated on day 1 of treatment initiation. Patients were stratified into risk groups based on the upper quartile (log2-EASIX ≥ 3.53). The outcomes included ICU admission and all-cause mortality within 3 months of diagnosis.³

Key Findings

Among the 158 participants, 27.8% required ICU admission, with 12% facing mortality within 3 months. High EASIX scores were significantly associated with poor early outcomes in multivariate analysis¹:

• 3-month mortality rate: 32.5% (high EASIX) vs 5.1% (low EASIX)
• ICU admission rate: 50% (high EASIX) vs 19.6% (low EASIX)

In a multivariate analysis adjusted for age, sex, C-reactive protein, ECOG performance status, and ELN risk classification, a high EASIX score was an independent predictor of 3-month mortality (OR, 6.60 [95% CI, 1.93-22.50]) and ICU admission (OR, 4.05 [95% CI, 1.63-10.05]). Predictive performance was moderate to strong, with an area under the curve of about 0.75 for 3-month mortality and 0.64 for ICU admission.¹

Clinical Implications

These findings suggest that EASIX scores may serve as a rapid, inexpensive tool for risk stratification at the time of AML diagnosis. The EASIX score identifies patients at risk of early physiologic collapse during induction therapy, unlike genetic risk models that guide long-term prognosis.

Patients with high EASIX scores may represent a subgroup with increased physiologic vulnerability who could benefit from consideration of lower-intensity treatment strategies, such as venetoclax-based combinations, rather than standard intensive induction.

Pharmacists can support the early identification of high-risk patients by facilitating timely EASIX calculation at diagnosis and flagging results that may warrant escalated monitoring for tumor lysis syndrome, infection, and renal dysfunction, or prompt consideration of treatment modification.

REFERENCES

1. Finotto T, Tauveron-Jalenques U, Barrière S, Adelou S, Futier E. EASIX score is predictive of early fatal complications in newly diagnosed acute myeloid leukemia. Ann Hematol. 2026;105(25):275. doi:10.1007/s00277-026-07031-y

2. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2019;129(4):424-447. doi:10.1182/blood-2016-08-733196

3. Walter RB, Othus M, Borthakur G, et al. Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J Clin Oncol. 2011;29(33):4417-4423. doi:10.1200/JCO.2011.35.7525

4. Juliusson G, Antunovic P, Derolf Å, et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009;113(18):4179-4187. doi:10.1182/blood-2008-07-172007

5. Azoulay E, Mokart D, Pène F, et al. Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium––a groupe de recherche respiratoire en réanimation onco-hématologique study. J Clin Oncol. 2013;31(22):2810-2818. doi:10.1200/JCO.2012.47.2365

6. Ma TT, Lin XJ, Cheng WY, et al. Development and validation of a prognostic model for adult patients with acute myeloid leukaemia. EBioMedicine. 2020;62:103126. doi:10.1016/j.ebiom.2020.103126

7. Sorror ML, Storer BE, Fathi AT, et al. Development and validation of a novel acute myeloid leukemia–composite model to estimate risks of mortality. JAMA Oncol. 2017;3(12):1675-1682. doi:10.1001/jamaoncol.2017.2714

8. Penack O, Luft T, Peczynski C, et al. Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study. J Immunother Cancer. 2024;12(1):e007635. doi:10.1136/jitc-2023-007635

9. Pennisi M, Sanchez-Escamilla M, Flynn JR, et al. Modified EASIX predicts severe cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells. Blood Adv. 2021;5(17):3397-3406. doi:10.1182/bloodadvances.2020003885

10.Korell F, DeFilipp Z, Schreck N, Luft T; Taskforces Allogeneic Stem Cell Transplantation. Validation of pre-conditioning EASIX for prediction of sepsis after allogeneic stem cell transplantation. Intensive Care Med. 2023;49(11):1408-1410. doi:10.1007/s00134-023-07193-7

11. Jodele S, Fukuda T, Vinks A, et al. Eculizumab therapy in children with severe hematopoietic stem cell transplantation–associated thrombotic microangiopathy. Biol Blood Marrow Transplant. 2014;20(4):518-525. doi:10.1016/j.bbmt.2013.12.565