Quantifying Bone Marrow Fat Fraction and Iron by MRI for Distinguishing Aplastic Anemia from Myelodysplastic Syndromes.

BACKGROUND: Bone marrow of patients with aplastic anemia (AA) is different from that of patients with myelodysplastic syndrome (MDS) and is difficult to identify by blood examination. IDEAL-IQ (iterative decomposition of water and fat with echo asymmetry and least-squares estimation) imaging might be able to quantify fat fraction (FF) and iron content in bone tissues. PURPOSE: To determine if IDEAL-IQ measurements of bone marrow FF and iron content can distinguish between patients with AA and MDS. STUDY TYPE: Retrospective. POPULATION: Fifty-seven patients with AA, 21 patients with MDS, and 24 healthy controls. FIELD STRENGTH/SEQUENCE: 3.0 T, IDEAL-IQ sequence. ASSESSMENT: Three independent observers evaluated the IDEAL-IQ images and measured FF and R2* in the left posterior superior iliac spine. STATISTICAL TESTS: Kruskal-Wallis test, linear correlations, and Bland-Altman analysis were used. A P-value of <0.05 was considered statistically significant. RESULTS: The FF in patients with AA (79.46% ± 15.00%) was significantly higher than that in patients with MDS (42.78% ± 30.09%) and control subjects (65.50% ± 14.73%). However, there was no significant difference in FF between control subjects and patients with MDS (P = 0.439). The R2* value of AA, MDS, and controls was 145.38 ± 53.33, (171.13 ± 100.89, and 135.99 ± 32.41/second, respectively, with no significant difference between the three groups (P = 0.553). DATA CONCLUSION: Quantitative IDEAL-IQ magnetic resonance imaging may facilitate the diagnosis of AA and distinguish it from MDS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Prospective cardiac magnetic resonance imaging survey in myelodysplastic syndrome patients: insights from an Italian network.

We prospectively evaluated changes in cardiac and hepatic iron overload (IO) and in morpho-functional cardiac parameters and myocardial fibrosis by magnetic resonance imaging (MRI) in patients with low-risk and intermediate-1-risk myelodysplastic syndromes (MDS). Fifty patients enrolled in the Myocardial Iron Overload in MyElodysplastic Diseases (MIOMED) study were followed for 12 months. IO was quantified by the T2* technique and biventricular function parameters by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Twenty-eight patients (71.89±8.46 years; 8 females) performed baseline and follow-up MRIs. Thirteen patients had baseline hepatic IO, with a higher frequency among transfusion-dependent patients. Out of the 15 patients with a baseline MRI liver iron concentration <3 mg/g/dw, two (non-chelated) developed hepatic IO. Thirteen (46.4%) patients had an abnormal T2* value in at least one myocardial segment. One patient without hepatic IO and non-transfused had baseline global T2* <20 ms. Among the 15 patients with no baseline myocardial IO (MIO), 2 worsened. There was a significant increase in both left and right ventricular end-diastolic volume indexes. Thirty-six percent of patients showed myocardial fibrosis correlating with aging. Two new occurrences were detected at the follow-up. In conclusion, by a more sensitive segmental approach, MIO is quite frequent in MDS patients and it can be present also in non-transfused patients and in absence of detectable hepatic iron. The incidence of cardiac and hepatic IO and of myocardial fibrosis and the increase in biventricular volumes after a 12-month interval suggest performing periodic MRI scans to better manage MDS patients.

How to treat myelodysplastic syndrome with clinical features resembling Behçet syndrome: a case-based systematic review.

The association between myelodysplastic syndrome (MDS) and Behçet syndrome (BS) is recognized for over 25 years. High frequency of trisomy 8 and intestinal ulcers are striking features of this association. There are no recommendations for how these patients should be treated. A systematic literature review was performed in PubMed using the keyword combination "(((((intestinal) OR gastrointestinal) OR ulcer) OR Behcet*)) AND ((myelodysplastic syndrome) OR MDS)" in March 2019. Our aim was to gain insight regarding clinical responses to individual treatment modalities. A recent case was also presented and included in the analysis. Data from 41 articles reporting on a total of 53 patients carried adequate information to assess treatment responses. Glucocorticoids provided benefit in 23 of 43 patients. Azacitidine, decitabine, thalidomide, and cyclosporine contributed to a clinical improvement in 4/6, 2/3, 3/4, and 5/8 patients respectively. Hematopoietic stem cell transplantation was successful in 9 of 13 patients. With the use of TNF inhibitors, azathioprine, and mesalamine derivatives, clinical improvement was observed in 3/11, 0/4, and 6/18 patients respectively. Patients with MDS and BS-like features who are resistant to glucocorticoids have so far benefited more from treatment approaches directed at MDS, rather than the immunosuppressive agents used for BS.

Convalescent (immune) plasma treatment in a myelodysplastic COVID-19 patient with disseminated tuberculosis.

During the ongoing COVID-19 pandemic due to the SARS-CoV-2 virus of which evidence-based medical paradigms cannot be easily applied; difficult clinical decisions shall be required particularly in the 'difficult-to-treat' cases of high risk group with associated comorbidities. Convalescent immune plasma therapy is a promising option as a sort of 'rescue' treatment in COVID-19 immune syndrome, where miraculous antiviral drugs are not available yet. In this report, we aim to convey our experience of multi-task treatment approach with convalescent immune plasma and anti-cytokine drug combination in a COVID-19 patient with extremely challenging comorbidities including active myeloid malignancy, disseminated tuberculosis and kidney failure.

Myelodysplastic Syndrome Related to Successful Treatment With 177 Lu-PSMA for Metastatic Castration-Refractory Prostate Cancer.

ABSTRACT: 177 Lu-vipivotide tetraxetan ( 177 Lu-PSMA-617/LuPSMA) received recent EMA approval for metastatic castration-resistant prostate cancer, with promising data for earlier stages. Secondary myeloid neoplasm following exposure to DNA-damaging therapy (therapy-related myelodysplastic syndrome [MDS]) is a rare severe complication of 177 Lu-oxodotreotide. We present a 77-year-old man, with synchronous liver, bone, and lymph node metastatic prostate cancer, having developed a low-risk MDS with SF3B1 mutation, 1 month after the sixth administration of LuPSMA. Although on partial metabolic and biological response with PSA nadir at 7 months after therapy, life quality was significantly altered by MDS.

Radiological presentation of transient perivascular inflammation of carotid artery syndrome in a patient with myelodysplasia.

Transient Perivascular Inflammation of Carotid artery syndrome (TIPIC syndrome) is a non-specific inflammatory thickening of the carotid artery. The exact etiology of this syndrome is poorly understood. We will describe the radiological findings of a rare case of TIPIC syndrome in a patient with myelodysplastic syndrome and discuss the potential pathophysiological mechanisms.

Complete Femoral Osteonecrosis in the Setting of Myelodysplastic Syndrome.

ABSTRACT: A 76-year-old man was diagnosed with a hematological neoplasm combining myelodysplastic and myeloproliferative characteristics back in July 2021. Five months after the diagnosis, his condition got more severe when the blasts rose up to 14%, so he was started on hypomethylating agent-based therapy. A few weeks later, the patient was hospitalized after developing fever and a pain in the right thigh. To exclude any source of occult infection, an 18 F-FDG PET/CT was performed. FDG PET/CT showed a complete lack of metabolism in the right femur. An MRI and a biopsy confirmed the suspected diagnosis of osteonecrosis.

Quantitative Assessment of Bone Marrow Activity Using 18 F-FLT PET in Aplastic Anemia and Myelodysplastic Syndromes.

PURPOSE: Peripheral cytopenias are typical of blood test abnormalities associated with a variety of conditions, including aplastic anemia (AA) and myelodysplastic syndromes (MDSs). We prospectively investigated the feasibility of quantitative analysis of whole-body bone marrow activity using PET with 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) in AA and MDS. PATIENTS AND METHODS: Sixty-eight patients with cytopenia underwent 18 F-FLT PET/MRI scan, with simultaneous bone marrow aspiration and biopsy for hematopoiesis evaluation. SUVs were measured in the vertebrae (Th3, 6, and 9 and L3), bilateral iliac crests, and extremities. SUV and bone marrow pathology were compared between AA and MDS and analyzed in relation to severity of AA and prognosis of MDS. RESULTS: Of the 68 patients with cytopenia, 12 were diagnosed with AA, 27 with MDS, 12 with bone marrow neoplasia, 2 with myelofibrosis, and 15 with other conditions. Iliac 18 F-FLT SUVs were significantly correlated with bone marrow cell numbers and cell density ( r = 0.47, P < 0.001 and ρ = 0.65, P < 0.001, respectively). There was a significant positive correlation between iliac and vertebral SUVs in AA and MDS ( r = 0.65, P < 0.05 and r = 0.70, P < 0.001, respectively), and the slope of the regression line was significantly steeper in AA than in MDS ( P < 0.05). In AA patients, vertebral 18 F-FLT SUVs significantly decreased with disease progression, and in MDS patients, higher whole-body 18 F-FLT uptake was associated with shorter overall survival (hazards ratio, 3.18; 95% confidence interval, 1.07-9.47; P = 0.037). CONCLUSIONS: Quantitative whole-body bone marrow imaging using 18 F-FLT PET helps distinguish AA from MDS and assess the severity of AA and prognosis of MDS.

Musculoskeletal manifestations of chronic anemias.

This article provides an overview of the current use of diagnostic imaging modalities in the evaluation of a heterogeneous group of disorders causing chronic anemias by impaired blood cell production (inherited bone marrow failure syndromes of childhood, aplastic anemia and myelodysplastic syndromes, ß-thalassemia) or increased blood cell destruction (sickle cell disease). During the course of these disorders, various musculoskeletal abnormalities can be encountered, including marrow hyperplasia, reversion of yellow marrow to red marrow, growth disturbances, and, occasionally, extramedullary hematopoiesis. Diagnostic imaging may help the clinician to identify specific complications related to either the disease (e.g., bone infarction and acute osteomyelitis in sickle cell disease) or transfusion (e.g., iron overload due to increased hemolysis) and iron chelation (e.g., desferrioxamine-related dysplastic bone changes and deferiprone-related degenerative arthritis) treatments. In this field, magnetic resonance imaging plays a pivotal role because of its high tissue contrast that enables early assessment of bone marrow changes before they become apparent on plain films or computed tomography or metabolic changes occur on bone scintigraphy or positron emission tomography scan. Overall, familiarity with the range of radiological appearances in chronic anemias is important to diagnose complications and establish appropriate therapy.

Myelodysplastic Syndrome Presenting With Diffuse Bone Marrow Uptake on 68Ga-PSMA PET/CT.

We present the case of a 67-year-old man with prostate cancer who had no findings of recurrence, except diffuse radiotracer uptake in the bone marrow in Ga-PSMA PET/CT. Bone marrow uptake was also represented as multiple focal increased spots without any corresponding lytic or sclerotic lesions in CT. MRI revealed a high and homogeneous T2 signal within the bone marrow, without any contrast-enhanced or diffusion-restricted lesions. Further workup, including a bone marrow biopsy, revealed the diagnosis of myelodysplastic syndrome.

TP53 mutations are associated with very complex karyotype and suggest poor prognosis in newly diagnosed myelodysplastic syndrome patients with monosomal karyotype.

AIM: The aim of this study was to evaluate the clinical and molecular characteristics of myelodysplastic syndrome (MDS) patients with monosomal karyotype (MK). METHODS: Eighty MDS patients with MK diagnosed between January 2010 and December 2018 were included in the retrospective study. Seventy-three had complex karyotype (CK) and 46 had very CK (vCK, ≥ 5 abnormalities). Clinical information was collected, and a panel of 37 genes, on which mutations have been previously reported to be associated with MDS patients, was analyzed by next-generation sequencing. Genetic and biological features and their association with survival were evaluated. RESULTS: Monosomy 5, 7, and 17 were the most frequent and mainly occurred in patients with vCK. While median overall survival (OS) for all patients was 12.8 months with 95% CI 9.1-16.5, patients with vCK had shorter OS (8.4 months with 95% CI 3.9-12.8) than those with non-vCK (16.1 months with 95% CI 11.5-20.8) (P = .02). At least one gene mutation was detected in 76 patients (95%), TP53 mutations were detected in 57 patients, and their median OS was significantly shorter than those without TP53 mutations (9.5 months with 95% CI 7.5-11.5 vs 26.1 months with 95% CI 8.0-44.2, P < .01). In 34 patients who received treatment with decitabine, 25 with TP53 mutations had higher overall response rate than those with wild-type TP53 (60% vs 22.2%, P = .03). However, OS was still significantly shorter in those with TP53 mutations (10.1 vs 26.1 months, P = .03). Multivariate analysis confirmed that TP53 mutations was an independent poor prognostic factor on OS. CONCLUSIONS: CK and vCK overlap in most of the MDS patients with MK. TP53 mutations occur more frequently in MDS patients with vCK, and both TP53 mutations and vCK are adverse prognostic factors.

Phenotypic landscape of granulocytes and monocytes by multiparametric flow cytometry: A prospective study of a 1-tube panel strategy for diagnosis and prognosis of patients with MDS.

BACKGROUND: Multiparametric flow cytometry (MFC) was recently reported to be a helpful additional tool in the diagnosis of myelodysplastic syndromes (MDS). However, numerous aberrancies have been reported that makes their evaluation difficult as part of a routine diagnosis. METHODS: Here, we validated a 1-tube panel for the evaluation of granulocytic and monocytic maturation by MFC and correlated our findings with diagnosis and prognosis of MDS. A total of 251 samples with MDS suspicion were prospectively analyzed and compared to an internal reference database leading to the calculation of the Diff score. RESULTS: The associated specificity and sensitivity values of this scoring system were 92.1% and 60.4% in a first learning cohort and 96.7% and 65.2% in a second independent validation cohort. The combination of the Diff score with the concomitantly calculated Ogata score increased the sensitivity to 74.2% and 78.3% in the learning and validation cohorts, respectively. Finally, a normal Diff score in MDS patients was associated with a significant prolonged progression-free survival. CONCLUSIONS: Taken together, the present data indicate that our strategy is a sensitive and specific MFC tool for the diagnosis of MDS-related cytopenia(s) which could be also useful for predicting evolution of these diseases.

Dual-layer detector spectral CT versus magnetic resonance imaging for the assessment of iron overload in myelodysplastic syndromes and aplastic anemia.

BACKGROUND: The purpose of this study is to investigate the performance of dual-layer detector spectral CT for iron deposition compared to magnetic resonance imaging (MRI) T2* imaging. METHODS: Thirty-one patients with a clinical history of myelodysplastic syndromes and aplastic anemia underwent liver and cardiac T2*-weighted unenhanced MRI on a three-tesla MRI scanner, and underwent unenhanced CT scan laterally on a 128-row spectral detector CT. R2* values of the liver, septal muscle, and paraspinal muscle were calculated. Attenuation differences (ΔH) in the liver and myocardium were calculated between the lower (50 keV) and higher (120 keV) energy levels. RESULTS: The liver and cardiac T2* values were 9.54 ± 5.63 ms and 21.41 ± 2.44 ms, respectively. The liver-to-muscle and myocardium-to-muscle T2* value ratios were 0.37 ± 0.23 and 0.79 ± 0.19, respectively. The liver and cardiac ΔH were - 1.13 ± 4.24 HU and 2.22 ± 4.41 HU, respectively. There was a strong linear correlation between the liver R2* and ΔH (r = - 0.832, P < 0.001), but weak correlation existed between the cardiac R2* and ΔH (P = 0.041). CONCLUSIONS: Dual-layer detector spectral unenhanced CT seemed to be equally valuable to MRI T2* imaging for evaluating liver iron overload.

Ankylosing spondylitis in a patient with myelodysplastic syndrome: an association with HLA-B27 or coincidence?

The authors report an unusual case of myelodysplastic syndrome (MDS) associated with ankylosing spondylitis (AS). A 40-year-old-man with MDS presented with chronic low back pain for 6 years. Four years ago, MDS was diagnosed during routine blood analysis for the work-up of his articular complaints. His initial articular complaints were attributed to extramedullary manifestations of MDS. Persistent low back pain with increasing intensity finally led the patient to seek medical attention. Radiograph of the pelvis showed bilateral asymmetric sacroiliitis. A diagnosis of AS was established on the basis of modified New York criteria. Although various autoimmune phenomena associated with MDS have been described, this is the first report of AS in the setting of MDS. Causal relationship between these two disorders is currently unknown. Increased risk of hematological diseases as well as AS in individuals with a positive HLA-B27 provides a feasible explanation for this rare observation.

[Abnormal bone marrow uptake of 99mTc-tetrofosmin in myelodysplastic syndrome with ineffective hematopoiesis: a case report].

Eighty-four-year-old male patient with liver cirrhosis, suffered from dyspnea on August 2006. Four months later, his symptom has remained and he was admitted to our hospital. A white blood cell decrease and anemia were observed by the blood test. He underwent echocardiography and 99mTc-tetrofosmin myocardial scintigraphy (99mTc-Tf) at rest, which showed no abnormal cardiac imaging. But 99mTc-Tf whole-body planar imaging showed extremely increased bone marrow uptake. 99mTc-HMDP bone scintigraphy also showed abnormal hot spots in the same skeletal regions. Bone marrow biopsy revealed myelodysplastic syndrome like findings. 201Tl and 99mTc as tracers for myocardial perfusion imagings were used to evaluate coronary heart disease, but increased uptake of these tracers were reported in malignant tumors and bone metastasis. He did not have malignant tumor or bone metastasis, so increased uptake of 99mTc-Tf and 99mTc-HMDP was thought to be caused by hyperactive flow with ineffective hematopoiesis. We report a case that abnormal skeletal uptake of 99mTc-Tf which was caused by ineffective hematopoiesis of myelodysplastic syndrome.

Myelodysplastic syndrome presenting as a Behçet's-like disease with aortitis.

A 46-year-old Hispanic man presented with fever, genital ulcers, left eye redness and chest pain. Physical examination was notable for a healed oral ulcer and scrotal ulcers, and bilateral superficial thrombophlebitis. He was found to have new-onset pancytopenia. CT of the chest showed pericardial and pleural effusions and rapidly progressing inflammation of the aortic arch and ascending vessels. Although the patient had Behcet's disease (BD)-like symptoms, pancytopenia could not be explained by the diagnosis, prompting a bone marrow biopsy which showed myelodysplastic syndrome. This report highlights the importance of excluding alternate disorders before making a diagnosis of Behcet's disease if atypical, BD-incompatible or incomplete constellations of symptoms and findings are present.