Bone Marrow Imaging of Appendicular Skeleton by Multi-Detector Computed Tomography in Patients with Aplastic Anemia and Hypoplastic MDS.
Authors: Ugai Tomotaka , Sugihara Hiroki , Nishida Yuki , Yamakura Masayuki , Takeuchi Masami , Matsue Kosei 
Published: October 2019

Abstract
Abstract 2817

Background:
Myelodysplastic syndrome (MDS) and aplastic anemia (AA) are the heterogeneous group of bone marrow failure disorders. AS both shows profound hypocellular marrow without minimal morphologic atypia, differentiation of MDS and AA is often difficult by bone marrow and laboratory examination alone. Red to yellow marrow conversion is occurs with age in the appendicular skeleton (AS), where red marrow is converted to yellow marrow until the age of early 20s. Although abnormal distribution of red marrow in appendicular skeleton has previously reported in small series of patients with MDS, leukemia and lymphoma by MRI, no further study has published so far. Here, we examined distribution of red marrow in AS by low-dose multi-detector CT (MDCT) in AA and MDS. We analyzed the relationship between the abnormal medullary pattern in AS with laboratory variables, subsequent development of leukemic transformation and survivals MDS patients.

Patients:
We performed a low-dose MDCT of humerus and femurs in 64 untreated adult patients with AA (N=15) and MDS (N=49). Retrospective review of clinical and laboratory features including complete blood count, % of bone marrow blast, chromosomal analysis, and International Prognostic Scoring System (IPSS) was performed. WHO classification of MDS patients was as follows: RA (N=17), RARS (N=2), RCMD (N=9), RAEB (N=19) and MDS unclassified (N=2). Overall survival (OS) and leukemia-free survival (LFS) were analyzed in 49 MDS patients by the Kaplan-Meier and differences between curves were calculated by two-sided log-rank test. Multivariate analysis was Used to assess the effects of prognostic factors - hemoglobin, platelet, bone marrow blast, cytogenetic abnormalities, IPSS score, WHO classification, and MDCT patterns.

CT image acquisition and Image analysis:
Non-enhanced CT examinations were performed from the base of skull down to the knee joint by MS-CT scanner (AQUILION 64, Tohshiba, Tokyo, Japan). Bony canal of humeral and femoral bone were visualized by coronal and sagittal axis image reconstruction. The effective radiation dose associated with whole body MD-CT was 10.1 mSv. (ICRP 26). The dose was comparable to whole body CT (2.4 mSv.). Medullary CT density of humerus and femurs were measured and the results were expressed as Hounsfield unit (HU). As the normal adult bone marrow was composed of rich adipocytes and called yellow marrow, it is represented by low density CT value between −30 to −100 HU. The value above −30 HU observed in long bony canals was considered as high density lesions. Medullary pattern of appendicular skeletons were categorized as follows: (1) fatty; showing a low signal density marrow (2) focal; showing abnormally focal high density lesions: (3) diffuse; showing uniformly high density marrow.

Results:
All 15 patients with AA showed a fatty (N=10, 66%) or focal (N=5, 33%) pattern in medullary AS on MDCT and none of them showed diffuse pattern. Conversion from fatty to focal marrow was observed in 9 of 15 AA patients after successful immunosuppressive treatment. Among the 49 patients with MDS, 15 (31%) had fatty pattern, 21 (43%) had focal pattern, and 13 (27%) had diffuse pattern. Patients with diffuse infiltration pattern on MDCT had a significantly low hemoglobin concentration (p<0.01) and shorter OS (p<0.01) compared to those with fatty or focal medullary pattern. The characteristics of the patients with diffuse pattern did not differ significantly in terms of sex, age, WBC count or karyotype from those of the patients with fatty or focal pattern. Among 13 MDS patients with diffuse pattern, 6 developed AML during their follow-up periods (median, 17 months; range, 2 to 38 months). LFS and OS of 13 patients with diffuse patterns were significantly shorter than that of the 36 patients with fatty and focal patterns (74% vs 19% at 3 years; p<0.01 and 79% vs 40% at 3 years; p<0.01, respectively). On multivariable analysis, diffuse pattern on MDCT was emerged as independently negative prognostic impact on LFS and OS in patients with MDS.

Conclusions:
This study showed that MDCT imaging of the appendicular skeletons provided important information for the diagnosis and prognosis of patients with MDS and AA.

Disclosures:
No relevant conflicts of interest to declare.