A chest CT-based nomogram for predicting survival in acute myeloid leukemia.

BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.

Acute Myelomonoblastic Leukemia (My1/De): A Preclinical Rat Model.

BACKGROUND/AIM: Since acute myeloid leukemias still represent the most aggressive type of adult acute leukemias, the profound understanding of disease pathology is of paramount importance for diagnostic and therapeutic purposes. Hence, this study aimed to explore the real-time disease fate with the establishment of an experimental myelomonoblastic leukemia (My1/De) rat model using preclinical positron emission tomography (PET) and whole-body autoradiography. MATERIALS AND METHODS: In vitro [18F]F-FDG uptake studies were performed to compare the tracer accumulation in the newly cultured My1/De tumor cell line (blasts) with that in healthy control and My1/De bone marrow suspensions. Post transplantation of My1/De cells under the left renal capsule of Long-Evans rats, primary My1/De tumorigenesis, and metastatic propagation were investigated using [18F]F-FDG PET imaging, whole-body autoradiography and phosphorimage analyses. To assess the organ uptake profile of the tumor-carrying animals we accomplished ex vivo biodistribution studies. RESULTS: The tracer accumulation in the My1/De culture cells exceeded that of both the tumorous and the healthy bone marrow suspensions (p<0.01). Based on in vivo imaging, the subrenally transplanted My1/De cells resulted in the development of leukemia in the abdominal organs, and metastasized to the mesenterial and thoracic parathymic lymph nodes (PTLNs). The lymphatic spread of metastasis was further confirmed by the significantly higher %ID/g values of the metastatic PTLNs (4.25±0.28) compared to the control (0.94±0.34). Cytochemical staining of the peripheral blood, autopsy findings, and wright-Giemsa-stained post-mortem histological sections proved the leukemic involvement of the assessed tissues/organs. CONCLUSION: The currently established My1/De model appears to be well-suited for further leukemia-related therapeutic and diagnostic investigations.

Effects of D-CAG chemotherapy regimen on cognitive function in patients with acute myeloid leukaemia: A resting-state functional magnetic resonance imaging study.

Post-chemotherapy cognitive impairment, also known as 'chemobrain', is a common neurotoxic complication induced by chemotherapy, which has been reported in many cancer survivors who have undergone chemotherapy. In this study, we aimed to explore the effects of D-neneneba dicitabine, C-nenenebb cytarabine, A-aclamycin, G-granulocyte colony-stimulating factor (D-CAG) chemotherapy on cognitive function in patients with acute myeloid leukaemia (AML) and its possible central mechanisms. Twenty patients with AML and 25 matched healthy controls (HC) were enrolled in this study. The cognitive function of patients before and after D-CAG chemotherapy was evaluated by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). The resting-state functional magnetic resonance imaging data were collected from all patients before and after chemotherapy intervention, as well as HC. Then, resting-state functional magnetic resonance imaging data were preprocessed using DPABI software package and regional homogeneity (ReHo) values of brain regions were calculated. Finally, ReHo values between groups were compared by Resting-State fMRI Data Analysis software package with t-tests and Alphasim method was performed for multiple comparison correction. Moreover, associations between ReHo values of altered brain regions and the scores of FACT-Cog were analysed by Pearson correlation. The total FACT-Cog scores and four factor scores of AML patients increased significantly after treatment. ReHo values showed no significant changes in patients before treatment when compared with HC. Compared with HC, ReHo values of the right middle frontal gyrus, inferior frontal gyrus (opercular part), middle occipital gyrus, and left praecuneus decreased significantly, while ReHo values of the left inferior temporal gyrus, right middle temporal gyrus, and hippocampus increased significantly in patients after treatment. Compared with patients before treatment, ReHo values decreased significantly in the right middle frontal gyrus, inferior frontal gyrus (opercular part), and middle and inferior occipital gyri of patients after treatment. In addition, ReHo values of the right inferior frontal gyrus (opercular part) were negatively correlated with the total scores of FACT-Cog and factor scores of perceived cognitive impairment in patients after treatment. There were also negative correlations between ReHo values of the right middle frontal gyrus and perceived cognitive impairment scores. The present study confirmed that D-CAG chemotherapy might cause impaired subjective self-reported cognitive functioning in AML patients, which might be related to the decreased function of certain regions in the right prefrontal lobe. These findings provided further understanding of the mechanisms involved in post-chemotherapy cognitive impairment and would help develop new therapeutic strategies for 'chemobrain' in AML patients.

Brain 18 F-FET in a Case of Acute Myeloid Leukemia.

ABSTRACT: A 58-year-old woman, with a history of acute myeloid leukemia in complete response, was referred to the emergency department of our hospital for loss of consciousness. A brain MRI showed an intracranial mass suggestive for either primary brain tumor or brain metastasis. 18 F-FET PET/CT revealed increased uptake of the lesion. Metastasis from acute myeloid leukemia was diagnosed after brain biopsy. Whole-body 18 F-FDG PET/CT did not demonstrate other abnormal foci of 18 F-FDG accumulation, whereas brain lesion had an uptake slightly below the adjacent brain.

Intracranial myeloid sarcoma as the first presentation of acute myeloid leukemia and literature review.

INTRODUCTION: Intracranial myeloid sarcoma is a rare extramedullary presentation of acute myeloid leukemia (AML). It can involve the meninges and ependyma presenting as extra-axial mass lesion. Rarely, it can also invade the brain parenchyma. It is commonly seen in children. It is usually misdiagnosed due to its close resemblance to other intracranial tumors (meningioma, metastasis, Ewing's sarcomas, and lymphoma). These are underdiagnosed if they precede the diagnosis of leukemia. CASE REPORT: A 7-year-old boy with isolated intracranial myeloid sarcoma who presented with raised intracranial pressure (ICP) which was successfully managed by surgical excision. CONCLUSION: Isolated intracranial myeloid sarcoma is a rare presentation of AML. Leukemia can be diagnosed early during the postoperative period and can be started on therapy timely. These patients requires regular follow-ups (clinical, laboratory and radiological) to detect relapses early.

Preliminary Study of Confounder-Corrected Fat Fraction and R2* Mapping of Bone Marrow in Children With Acute Leukemia.

BACKGROUND: The bone marrow (BM) evaluation of acute leukemia (AL) mainly depends on invasive BM puncture biopsy. Noninvasive and accurate MR examination technology has potential clinical application value in the BM evaluation of AL patients. Multi-gradient-echo (MGRE) has been found useful to evaluate changes in BM fat and iron content, but has not yet been applied in AL. PURPOSE: To explore the diagnostic capability of BM infiltration of quantitative BM fat fraction (FF) and R2* values obtained from a 3D MGRE sequence in children with primary AL. STUDY TYPE: Prospective. POPULATION/SUBJECTS: Sixty-two pediatric patients with untreated AL and 68 healthy volunteers. AL patients were divided into acute lymphoblastic leukemia (ALL) (n = 39) and acute myeloid leukemia (AML) (n = 23) groups. FIELD STRENGTH/SEQUENCE: 3T, 3D chemical-shift-encoded multi-gradient-echo, T1WI, T2WI, T2_STIR. ASSESSMENT: BM FF and R2* values were assessed by manually drawing regions of interest at the L3, L4, ilium, and 1 cm below the bilateral trochanter of the femur (upper femur). STATISTICAL TESTS: Independent sample t-tests, variance analysis, Spearman correlation. RESULTS: BM FF and R2* at L3, L4, ilium, and upper femur, FFtotal and R2*total were significantly lower in the AL than control group. BM FF did not significantly differ between ALL and AML groups (PL3 = 0.060, PL4 = 0.086, Pilium = 0.179, Pupper femur = 0.149, and Ptotle = 0.097, respectively). The R2* was significantly lower in ALL group than AML group for L3, L4, and R2*total . BM FF was moderately positively correlated with R2* in ALL group, and strongly positively correlated in AML group. Area under the receiver operating characteristic curves showed that BM FF had higher AUC in AL, ALL, and AML (all AUC = 1.000) than R2* (0.976, 0.996, and 0.941, respectively). DATA CONCLUSION: MGRE-MRI mapping can be applied to measure BM FF and R2* values, and help evaluate BM infiltration and iron storage in children with AL. EVIDENCE LEVEL: 1 Technical Efficacy: 2.

Diagnostic yield, indications, and outcomes of cranial imaging in AML patients admitted for intensive induction or consolidation chemotherapy: a single-center experience.

Cranial imaging (CI) is a widely used diagnostic procedure, especially in acute myeloid leukemia (AML) patients with suspected bleeding or infection. However, common clinical decision rules to guide CI do not apply to AML patients and the diagnostic yield and outcomes of CI for AML patients are largely unknown. We retrospectively evaluated all CI from newly diagnosed non-promyelocytic AML patients receiving intensive induction or consolidation chemotherapy between 2007 and 2019 for imaging indications, diagnostic yield, and consequences. A total of 110 of 462 patients (24%) received CI for 152 imagings in distinct clinical situations. Forty-four patients (40%) had at least one new and acute pathological finding. Main indication was focal neurologic deficit, craniocerebral trauma, and suspected cerebral hypertension. The most common new finding was intracranial hemorrhage (13% of all imagings), followed by sinusitis (9%). CI led to therapy change in 21 patients. There were no clear associations between indications, laboratory values, and a positive imaging. Positive imaging was associated with adverse overall survival. Our study suggests that the overall rate of ordered CI was appropriate and that CI should generally be performed at a low threshold. A systematized approach to CI may further increase diagnostic yield but is complicated by variable clinical presentation.

A novel use of CT attenuation value: increased bone marrow density in patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Bone marrow computed tomography (CT) attenuation may increase in patients with myeloproliferative disorders; however, the actual threshold CT attenuation value predictive of myeloproliferative has not been reported. PURPOSE: To determine whether the unenhanced CT attenuation value of the bone marrow may be useful for predicting AML. MATERIAL AND METHODS: We retrospectively analyzed patients with AML (n = 56) who underwent unenhanced CT before treatment, and age- and sex-matched controls without any hematologic disease. For each patient, the CT attenuation value (HU) of the iliac bone was measured and compared between the two groups. Receiver operating characteristic (ROC) curve analysis was used to define the cutoff value for predicting AML on all patients, and only on late elderly patients (aged ≥75 years). RESULTS: Patients with AML showed higher bone marrow CT attenuation value (131.4 ± 58.3 vs. 53.9 ± 67.2 HU; P < 0.001), compared to the controls. The sensitivity and specificity for the diagnosis of AML in all patients were 78.6% and 80.4%, respectively, at a threshold value of 90 HU, whereas they were 83.3% and 91.7%, respectively, at 40 HU in late elderly patients. CONCLUSION: The iliac bone CT attenuation value was elevated in patients with AML and may be useful for predicting AML.

Classification of acute myeloid leukemia M1 and M2 subtypes using machine learning.

BACKGROUND: Classification of acute myeloid leukemia (AML) relies on manual analysis of bone marrow or peripheral blood smear images. We aimed to construct a machine learning model for automatic classification of AML-M1 and M2 subtypes in bone marrow smear images. METHODS: Bone marrow smear images of AML patients were extracted from the Cancer Imaging Archive (TCIA) open database. Classification criteria of AML subtypes were based on the French-American-British (FAB) classification system. Random forest method and broad learning system (BLS) were used to develop the classification model. Morphological features, radiomics features, and clinical features were extracted. The performance of the classification model was evaluated by calculating accuracy, precision, recall, F1-score, and area under the curve (AUC). A total of 50 bone marrow smear images (AML-M1, 31 cases; AML-M2, 19 cases) with 500 slices were included in this study. RESULTS: A total of 43 morphological features, 276 radiomics features, and 1 clinical feature were extracted. Finally, 9 variables including 2 morphological features, 6 radiomics features, and 1 clinical feature were selected into the classification model. The best classification performance was observed in the random forest model with 9 variables, with the average accuracy, AUC, F1-score, recall, and precision of the model being 0.998 ± 0.003, 0.998 ± 0.004, 0.998 ± 0.004, 0.996 ± 0.009, and 1 ± 0, respectively. CONCLUSION: The random forest model performed well for the classification of AML-M1 and M2, which may provide a tool for clinicians to classify AML-M1 and M2.

CT classification of acute myeloid leukemia with pulmonary infiltration.

PURPOSE: To characterize and categorize the CT findings of pulmonary leukemic infiltration (PLI) in patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: Among 435 patients with AML, 20 patients with PLI were retrospectively selected, and clinical characteristics and CT findings were analyzed. PLI was categorized into four patterns according to CT findings: type A, multiple nodules and/or masses; type B, bilateral perihilar airspace opacities (GGA or consolidation) without any nodules or masses; type C, mixture of type A and B; and type D, PLI without visible abnormal lung opacity. The difference in overall survival among four CT patterns was also examined. RESULTS: The frequency of complex karyotypes was higher in AML patients with PLI than in whole AML patients. Percentages of patients with CT findings of type A, B, C, and D were 35%, 20%, 35%, and 10%, respectively. There was a clear difference in the localization of opacities according to the type of infiltrates, i.e., nodules/masses were mainly detected in the lower/peripheral portion. Conversely, GGA was mainly located in the upper/central portion. The median overall survival from diagnosis of PLI was 262 days (range 12-1148). The CT pattern was not significantly associated with survival (p = 0.3), with the exception of patients with type C tending to have significantly better outcomes compared to patients with type B (p = 0.05). CONCLUSION: This classification can contribute in accurate non-invasive diagnosis and possibly in the estimation of prognosis.

Intracranial myeloid sarcoma presentation in distant acute myeloid leukemia remission.

Intracranial myeloid sarcoma (IMS) is a rare central nervous system manifestation of hematopoietic neoplasms of myeloid origin. We report the first case of IMS treatment with an isocitrate dehydrogenase-2 (IDH-2) inhibitor, Enasidenib, following surgical resection, whole-brain radiation, and consolidation Etoposide/Cytarabine therapy. A 42-year-old female was diagnosed with IMS after a 10-year remission of her acute myeloid leukemia (AML). She underwent surgical debulking and had postoperative resolution of her visual symptoms. She received adjuvant radiation and medical management, and continues to show no evidence of recurrence or progression at 17 months postoperatively. This case is notable for an isolated IMS presentation in a patient with a very distant history of AML remission, and without evidence of concurrent bone marrow relapse. The goals of neurosurgical intervention should be symptomatic relief of mass effect and pathological diagnosis, due to the sensitivity of IMS to adjuvant radiation and medical management such as IDH-2 inhibitors.

The role of flexible bronchoscopy in the upper airway pathology of immunosuppressed patients / El papel de la broncoscopia flexible en la patología de vía aérea superior de pacientes inmunodeprimidos

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Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved.

The World Health Organization classification and definition of "myeloid sarcoma" is imprecise and misleading. A more accurate term is "extramedullary acute myeloid leukemia tumor (eAML)." The pathogenesis of eAML has been associated with aberrancy of cellular adhesion molecules, chemokine receptors/ligands and RAS-MAPK/ERK signaling. eAML can present with or without synchronous or metachronous intramedullary acute myeloid leukemia (AML) so a bone marrow evaluation is always recommended. Accurate diagnosis of eAML requires tissue biopsy. eAML confined to one or a few sites is frequently treated with local therapy such as radiotherapy. About 75-90% of patients with isolated eAML will develop metachronous intramedullary AML with a median latency period ranging from 4 to 12 months; thus, patients with isolated eAML may also be treated with systemic anti-leukemia therapy. eAML does not appear to have an independent prognostic impact; selection of post-remission therapy including allogeneic hematopoietic cell transplant (alloHCT) is typically guided by intramedullary disease risk. Management of isolated eAML should be individualized based on patient characteristics as well as eAML location and cytogenetic/molecular features. The role of PET/CT in eAML is also currently being elucidated. Improving outcomes of patients with eAML requires further knowledge of its etiology and mechanism(s) as well as therapeutic approaches beyond conventional chemotherapy, ideally in the context of controlled trials.