Hypoplastic Myelodysplastic Syndrome Research Articles

Pediatric Myelodysplastic Syndrome: Experience from a Single Center

Pediatric myelodysplastic syndrome (MDS) is a group of heterogeneous clonal disorder with lesser frequency compared to adults. Additionally, there is much rare data in pediatric age group in relation to presentational findings and treatment.The clinical and laboratory data, in addition to therapeutic interventions and outcomes of 47 patients in a single centre who were diagnosed between January 2001-May 2014 were summarized.Median age of the study group was 2.8 years (0.1-16.8). The most common complaints at presentation included fever (27%), fatigue (17%), bleeding (15%), abdominal distention (13%), in addition to other rare presentational complaints including pallor, rash, vomiting, irritability, jaundice, stridor, abdominal pain and easy bruising. The underlying disorder was established as: neurofibromatosis in 5, Down syndrome in 3, secondary to prior chemotherapy in 2 (ALL and PNET), Fanconi anemia in 1, Jacobsen syndrome in 1, Klinefelter in 1. Final diagnosis was MDS in 22, JMML in 19, hypoplastic MDS in 4 and chemotherapy related MDS in 2. Median Hb, WBC, thrombocyte counts at presentation were 8.7 g/dl (4.1-12.7), 10.3x109/L (1.3-117) and 55x109/L (4-1515), respectively. Of the mutations studied related to MDS in 22 of the patients, k-ras positivity was the most common (23%). The most common cytogenetic abnormality was chromosome 7 related abnormalities (25%). Of the patients, 21 (45%) are alive and of these alive patients 62% are alive subsequent to hematopoietic stem cell transplantation.The patients with pediatric MDS may present with various complaints and they may have underlying genetic diseases causing propensity for MDS. The survival is better among patients who underwent hematopoietic stem cell transplantation. DisclosuresNo relevant conflicts of interest to declare.

Comparison of Peripheral Blood and Bone Marrow Molecular Profiling in Primary Myelodysplastic Syndromes (MDS)

AMM and MA – Joint first authorsDiagnosis of myelodysplastic syndromes (MDS) relies on demonstrating peripheral blood (PB) / bone marrow (BM) dysplasia and cytogenetic abnormalities, forming the backbone of the revised International Prognostic Scoring System (IPSS-R). However, assessment of dysplasia is operator dependent and metaphase cytogenetic analysis (MC) is often normal or uninformative creating diagnostic challenges, particularly in patients with early or low risk MDS. Impressive advances have taken place in the last decade in the identification and chronicling of the genetic lesions leading to phenotypic diversity of MDS. We sought to evaluate the value of single nucleotide polymorphism array (SNP-A) based cytogenetic assessment and high throughput sequencing of the 24 genes most frequently mutated in MDS to determine if genetic abnormalities in the BM are reflected in the PB thus enabling easy assessment of response to treatment and/or disease progression.A MiSeq based gene panel comprising of 24 frequently mutated MDS genes: ASXL1, CBL, CEBPA, DNMT3A, ETV6, EZH2, FLT3, GATA2, IDH1, IDH2, JAK2, KDM6, KIT, KRAS, NPM1, NRAS, RUNX1, SF3B1, SRSF2, STAG2, TET2, TP53, U2AF1, ZRSR2 and CytoHD/750K SNP-A karyotyping was applied to both PB and BM concurrent samples. Genomic aberrations and non-synonymous variant calls were filtered using public databases to exclude polymorphisms.PB and BM from 201 MDS patients [median 62 years (17-88)] followed up for median 21 months (0.3-171) was analysed. Sixty (30%) patients received supportive care only whilst others were treated with MDS/AML directed therapies. The WHO subtypes were: 5q- syndrome (n=26), refractory cytopenia/s (RA/RCMD, n=53), refractory anaemia with excess blasts/acute myeloid leukaemia (RAEB/AML, n=51), refractory anaemia with ringed sideroblasts (RARS/RCMD-RS, n=20) and other subtypes (including myeloproliferative and hypoplastic MDS, n=51). Based on the IPSS-R risk groups 62% had low risk disease: classified as very low (n=35), low (n=89), intermediate (n=42), high (n=16) and very high (n=19) risk groups. Metaphase cytogenetic analysis was normal (NK-MC) in 113(56%), abnormal (AK-MC) in 65(32%) patients and in 23(12%) MC failed. SNP-A was informative in all patients identifying a normal (NK-SNP) in 93(46%) and abnormal (AK-SNP) in 108(54%) patients, respectively. A comparison of BM and PB by SNP-A, showed 190 patients having an identical karyotype (95% concordance). BM SNP-A identified 36 (32%) patients with SNP-A abnormalities not detected by MC, changing the IPSS-R in 49 (24%) patients overall. Inclusion of SNP-A abnormalities changed the IPSS-R risk group in 28 (25%) of NK-MC patients; from good to intermediate (n=21), poor (n=5) and very poor (n=2) groups, respectively. In 9/11 patients with discordant SNP-A karyotypes between BM and PB, the IPSS-R remained unchanged. We found no difference in the clonal burden between PB and BM for gains and CN-LOH. However, for deletions, the clonal size was significantly lower in BM [median 1.4 (1 – 1.9)], than PB [median 1.5 (1 – 1.95), p<0.001].Mutational profiling from 183 patients revealed 248 and 240 mutations in BM and PB, respectively. BM and PB mutation profiles were identical in 171 patients (93% concordance) (Fig 1). In 11/12 patients with discordant mutation profiles, additional identical mutations and SNP-A abnormalities were noted in both BM and PB. Similarly, clone size was lower (p= 0.53) in the PB [median 27%, (1%-96%)] compared to BM [median 30%, (1%-100%)] and, in addition, there was no difference in the overall number or the type of mutation between the BM and PB. Interestingly, analysis of known poor risk MDS gene mutations (ASXL1, EZH2, RUNX1, P53 and U2AF1) identified 85 mutations in BM compared to 80 in the PB. In 5 patients where these mutations were discordant, additional identical mutations were detected in both BM and PB. Patients with ASXL1 and TP53 mutations had significantly lower clonal burden in PB (p<0.001) compared to BM in contrast to RUNX1 and EZH2 where there was no difference in the clone size. Using PB we were able to show that both SNP-A defects and gene mutations were efficiently detected when compared with BM.This study confirms that PB can reliably substitute for BM for all molecular assays in MDS; which is highly relevant for the clinical assessment of this relatively elderly group of patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Hypocellular acute leukemia: study of clinical and hematological features

Hypocellular acute leukemia was previously referred to as smoldering leukemia. This is currently defined as having ≥20 % blasts in peripheral blood or bone marrow with cellularity of less than 20 % in bone marrow biopsy at presentation. Hypocellular variants of acute myeloid leukemia (AML) are commoner than that of acute lymphoid leukemia (ALL). They may pose a diagnostic challenge to the treating clinician and pathologist as they can simulate hypoplastic myelodysplastic syndrome and aplastic anemia. It is of utmost importance to distinguish these overlapping disorders as treatment modalities differ. Details of clinical features, complete blood counts, bone marrow aspirate findings, percentage cellularity, pattern of infiltration in trephine biopsies, and immunophenotyping by flow cytometry or immunohistochemistry were analyzed in cases diagnosed as hypocellular acute leukemia. Hypocellular acute leukemia constituted 2.5 % (8/316) of all diagnosed cases of acute leukemia during the study period. Seven of the eight cases of hypocellular acute leukemia were hypocellular AML while one was hypocellular ALL. Median age of patients was 45 years, with a male:female ratio of 1.7:1. Mean duration of symptoms was 1.2 months, with most common presenting feature being fever. None of the patients except one had an antecedent hematologic disorder or chemotherapy or radiotherapy. Hypocellular acute leukemia is important to recognize from other overlapping disorders. Clinical parameters and laboratory data including immunophenotyping can aid in distinguishing them.

Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

P. Fenaux1, D. Haase2, G. F. Sanz3, V. Santini4 & C. Buske5 on behalf of the ESMO Guidelines Working Group* Service d’Hematologie Clinique, Groupe Francophone des Myelodysplasies (GFM), Hopital St Louis (Assistance Publique, Hopitaux de Paris) and Paris 7 University, Paris, France; Clinics of Hematology and Medical Oncology, University Medicine, Goettingen, Germany; Department of Haematology, Hospital Universitario y Politecnico La Fe, Valencia, Spain; Functional Unit of Haematology, AOU Careggi, University of Florence, Firenze, Italy; Comprehensive Cancer Center Ulm, Institute of Experimental Cancer Research, University Hospital, Ulm, Germany

Use of eltrombopag for the treatment of thrombocytopenia in hypoplastic myelodysplastic syndrome

Use of eltrombopag for the treatment of thrombocytopenia in hypoplastic myelodysplastic syndrome

Immunological derangement in hypocellular myelodysplastic syndromes.

Hypocellular or hypoplastic myelodysplastic syndromes (HMDS) are a distinct subgroup accounting for 10-15% of all MDS patients, that are characterized by the presence of bone marrow (BM) hypocellularity, various degree of dysmyelopoiesis and sometimes abnormal karyotype. Laboratory and clinical evidence suggest that HMDS share several immune-mediated pathogenic mechanisms with acquired idiopathic aplastic anemia (AA). Different immune-mediated mechanisms have been documented in the damage of marrow hematopoietic progenitors occurring in HMDS; they include oligoclonal expansion of cytotoxic T lymphocytes (CTLs), polyclonal expansion of various subtypes of T helper lymphocytes, overexpression of FAS-L and of the TNF-related apoptosis-inducing ligand (TRAIL), underexpression of Flice-like inhibitory protein long isoform (FLIPL) in marrow cells as well as higher release of Th1 cytokines, such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). It has also been documented that some HMDS patients have higher frequency of polymorphisms linked both to high production of proinflammatory cytokines such as TNF-α and transforming growth factor-β and to the inhibition of T-cell mediated immune responses such as interleukin-10, further suggesting that immune-mediated mechanisms similar to those seen in AA patients may also operate in HMDS. Clinically, the strongest evidence for immune-mediated hematopoietic suppression in some HMDS is the response to immunosuppression including mainly cyclosporine, anti-thymocyte globulin and/or cyclosporine, or alemtuzumab. Here we review all these immune mechanisms as well as the influence of this deranged cellular and humoral immunologic mileau on the initiation and possible progression of MDS. All these observations are pivotal not only for a better understanding of MDS pathophysiology, but also for their immediate clinical implications, eventually leading to the identification of MDS patients who may benefit from immunosuppression.

Challenges in bone marrow pathology

Bone marrow diagnosis presents unique challenges: distinction between benign and neoplastic conditions may be subtle and the pathologist must effectively incorporate information from several morphologic modalities (trephine biopsy, aspirate smear, peripheral blood smear) as well as a myriad of ancillary testing results. In this Short Course, several difficult diagnostic scenarios will be explored using actual clinical cases that illustrate key points in the differential diagnosis of bone marrow diseases. These will include hypocellular bone marrow (in which distinction between hypoplastic myelodysplastic syndrome and aplastic anemia may be difficult), fibrotic bone marrow, and marrow lymphoid infiltrates, with discussion of both B-cell and T-cell lymphomas. Hypercellular bone marrow raises distinct differential diagnoses depending on whether the patient is cytopenic or presents with elevated counts, and can reflect a myeloid neoplasm or various reactive conditions in either situation. An accurate diagnosis relies on understanding the spectrum of diseases that can produce specific patterns in the bone marrow and awareness of clues that help distinguish among the differential diagnostic possibilities. Depending on the clinical context, the pathology may variably weigh morphology, clinical information, and ancillary test results in arriving at the final diagnosis.

Myelodysplastic syndromes: Classification

The updated WHO classification system for myelodysplastic syndromes (MDS) includes some new entities, in particular refractory cytopenias with unilineage dysplasia (RCUD). The following review article presents a short overview regarding all subvariants of MDS but with special emphasis on the rare subtypes of MDS that can be exclusively recognized histomorphologically: (1) Hypoplastic MDS (MDS-hypo), (2) Fibrotic MDS (MDS-F) and MDS with associated systemic mastocytosis (SM-AHNMD).

Proteins related to the spindle and checkpoint mitotic emphasize the different pathogenesis of hypoplastic MDS

Some studies show that alterations in expression of proteins related to mitotic spindle (AURORAS KINASE A and B) and mitotic checkpoint (CDC20 and MAD2L1) are involved in chromosomal instability and tumor progression in various solid and hematologic malignancies. This study aimed to evaluate these genes in MDS patients. The cytogenetics analysis was carried out by G-banding, AURKA and AURKB amplification was performed using FISH, and AURKA, AURKB, CDC20 and MAD2L1 gene expression was performed by qRT-PCR in 61 samples of bone marrow from MDS patients. AURKA gene amplification was observed in 10% of the cases, which also showed higher expression levels than the control group (p=0.038). Patients with normo/hypercellular BM presented significantly higher expression levels than hypocellular BM patients, but normo and hypercellular BM groups did not differ. After logistic regression analysis, our results showed that HIGH expression levels were associated with increased risk of developing normo/hypercellular MDS. It also indicated that age is associated with AURKA, CDC20 and MAD2L1 HIGH expression levels. The distinct expression of hypocellular patients emphasizes the prognostic importance of cellularity to MDS. The amplification/high expression of AURKA suggests that the increased expression of this gene may be related to the pathogenesis of disease.

Thoughts on differential diagnosis between aplastic anemia and hypoplastic myelodysplastic syndrome

Thoughts on differential diagnosis between aplastic anemia and hypoplastic myelodysplastic syndrome

Histopathological and Immunohistochemical Evaluation of Bone Marrow Biopsy in Myelodysplastic Syndromes

SUMMARY In myelodysplastic syndromes (MDS), bone marrow biopsy (BMB) is now considered part of a multidisciplinary approach to bone marrow (BM) examination that must include cytological and cytogenetic assessment, while flow-cytometry and molecular studies can provide additional useful information. Undervalued in the past, BM histology has recently grown in importance in terms of diagnosis (i.e., MDS with BM fibrosis, hypoplastic MDS) and prognostic assessment (i.e., clusters of CD34+blasts). Thus, BM histology must be considered complementary and not overlapping with the results of the other methods of BM study. Moreover, in recent years, numerous clinico-pathological studies have evidentiated, codified and standardized a series of histopathological parameters that are now considered essential for an effective and clinically useful histomorphological evaluation of the BMB. The aim of this work is to describe the histopathological and immunohistochemical approach to BMB that the pathologists of the Lombard Hematological Network (Rete Ematologica Lombarda [REL]; Italy) are carrying out on a standardized and shared basis in MDS patients.

P-123 Evaluation of pro-survival pathways, included autophagy, in high-risk MDS bone marrow after treatment with 5-azacitidine to restore normal hematopoiesis

Myelodysplastic syndromes (MDS) are clonal diseases defined by clinical, morphologic, and genetic features often shared by related myeloid disorders. The diagnostic boundaries between these diseases can be arbitrary and not necessarily reflective of underlying disease biology or outcomes. In practice, measures that distinguish MDS from related disorders may be difficult to quantify and can vary as disease progression occurs. Patients may harbor findings that are not consistent with a single diagnostic category. Several overlap disorders have been formally described, such as the myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). These disorders are characterized by hematopoietic dysplasia with increased proliferation of monocytes, neutrophils, or platelets. They may have mutational profiles that distinguish them from the disorders they resemble and reflect important differences in pathophysiology. MDS also shares diagnostic borders with other diseases. For example, aplastic anemia and hypoplastic MDS can be difficult to distinguish in patients with pancytopenia and bone marrow hypocellularity. Genetic features may help in this regard, because they can identify differences in prognosis and risk of progression. The boundary between MDS and secondary acute myeloid leukemia (sAML) is arbitrarily defined and has been redefined over the years. Genetic studies have demonstrated that sAML clones can precede clinical progression from MDS by many months, suggesting that MDS with excess blasts could be viewed as an overlap between a dysplastic bone marrow failure syndrome and an oligoblastic leukemia. This review will describe the diagnostic boundaries between MDS, MDS/MPNs, sAML, clonal hematopoiesis of indeterminate potential, clonal cytopenia of undetermined significance, and aplastic anemia and how genetic approaches may help to better define them.

P-256 Hypoplastic myelodysplastic syndrome – A single centre experience

P-256 Hypoplastic myelodysplastic syndrome – A single centre experience

P-093 Hypoplastic myelodysplastic syndromes are not a specific clinical entity

P-093 Hypoplastic myelodysplastic syndromes are not a specific clinical entity

P-196 Postsplenectomy evolution in one case of hypoplastic myelodysplastic syndrome

P-196 Postsplenectomy evolution in one case of hypoplastic myelodysplastic syndrome

P-224 Treatment of hypoplastic MDS with ATG, CsA, MPN and allogeneic stem cell transplantation

P-224 Treatment of hypoplastic MDS with ATG, CsA, MPN and allogeneic stem cell transplantation

Gingival myeloid sarcoma in myelodysplastic syndrome

To the Editor, Myeloid sarcoma (MS) of the gingiva is an extremely rare observation in the context of different myeloproliferative disorders [1–3], including chronic myelomonocytic leukemia (CMML) [1, 4] and acute myeloid leukemia (AML). In CMML patients, gingival hypertrophy is often associated with tumor progression and a more aggressive disease [4]. Although the evolution of myelodysplastic syndrome (MDS) in overt AML is a common occurrence, isolated gingival MS in patients with stable MDS without AML progression has been only exceptionally observed [3]. Herein, we report on a case of gingival MS occurred as isolated AML progression in a previously diagnosed MDS. The patient was a 63year-old Caucasian male who was diagnosed as having MDS, subtype refractory cytopenia with multilineage dysplasia; he presented with trilinear cytopenia (transfusion-dependent severe anemia, thrombocytopenia, and neutropenia), bone marrow (BM) hypocellularity with 3 % of blasts and a cytogenetic abnormality consistent with trisomy 8. According to the IPSS [5] and WPSS [6], the MDS risk was classified as Int-1 and intermediate categories, respectively. The patient had always been healthy and had no significant comorbidities; in particular, no oral and/or gastrointestinal diseases were reported. Given the immune-mediated pathogenesis likely involved in most forms of hypoplastic MDS [7], the patient was managed by cyclosporine. This treatment effort resulted in a substantially maintained stable disease without any significant toxicity. Six months after the diagnosis, the patient complained a well-circumscribed little enlargement of the right upper gingiva surrounded by a painful ulcer. An excision biopsy of the intraoral mass was performed. Histological analysis showed submucosal infiltration by aggregates of myeloperoxidase and CD68 positive myeloid blast cells. A comprehensive hematological revaluation, including BM aspirate and trephine biopsy and a karyotype analysis, revealed a stable MDS without any evidence of AML progression in the BM; in particular, the percentage of blast cells was the same of that found at the MDS diagnosis. Cytogenetic analysis confirmed the presence of trisomy 8. Two courses of fludarabine and high dose of cytosine arabinoside regimen were given resulting in the disappearance of the gingival swelling and the BM blast cells. A suitable donor was not available, for which autologous stem cell transplantation (ASCT) with busulfan and cyclophosfamide conditioning regimen was given as consolidation treatment. However, 3 months after ASCT, he presented a relapse of AML, without any extramedullary localization. AML rapidly progressed until the patient’s death. The unusual intraoral localization of MS and the presence of the trisomy 8 in our case, may suggest a possible link between these findings. Indeed, recurrent oral ulcers and the excess of chromosome The authors have no affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. The authors declare that they have full control of all primary data and they agree to allow the journal to review their data if requested. A. Tendas : L. Scaramucci :M. Giovannini : L. Cupelli : A. Perrotti : P. de Fabritiis Hematology Unit, S. Eugenio Hospital, Rome, Italy

Treatment and hematopoietic SCT in aplastic anemia

This edition of the journal Bone Marrow Transplantation is the dedicated to the diagnosis and treatment of aplastic anemia, a disease that has had an important role in developing SCT and maybe even modern hematology. This was borne out of a project to design algorithms for the diagnosis and treatment of this disease, comprising different clinical issues such as different age groups and disease severity, as well as strategies arising from the unavailability of a specific type of donor. Aplastic anemia is an orphan disease with an incidence of 1–2 patients per million inhabitants per year, and given the different paths in the algorithms this breaks down into even smaller distinct sub-entities. Without wishing to stress the common place of personalized medicine, these distinct situations require individualized attention. Often, the approach to patient care has to differ, be it while caring for the child or the older person being diagnosed with aplastic anemia, according to severity of the disease and response to initial treatment as well as depending on the availability or not of a matched donor. Given the difficulty to study rare diseases, we also designed these algorithms with the intention to standardize treatment and to record treatment outcome. Diagnostic procedures need to be standardized; congenital disease has to be ruled out in the young, hypoplastic myelodysplastic syndrome in the older patient and procedures are discussed in the chapter on the diagnosis of acquired aplastic anemia. Outcome of patients with aplastic anemia has greatly improved over the past decades and to a large part this is due to progress in supportive care, given that our currently used immunosuppressive and transplant regimens were developed in the 1970s. This progress includes treatment of infectious complications and transfusional support, among others. In younger patients, the primary decision in treatment is to choose between transplantation versus immunosuppression. We have learned recently through a randomized trial conducted at the National Institutes of Health that not all antithymocyte globulin regimens are equal.1 Standards for immunosuppression are to be found in the chapter on front line immunosuppressive treatment as well as current standards on upfront BMT with a sibling donor. Older patients with a donor are recommended to be treated with immunosuppression, but patients failing this treatment are candidates for BMT using a reduced intensity regimen containing fludarabine. Patients without a sibling donor failing immunosuppressive treatment may have an unrelated donor search initiated and may undergo marrow transplantation from an unrelated donor. Transplant rates in Europe for aplastic anemia continue to increase2 and this is mostly due to the increased use of unrelated donors following publications showing that outcomes with unrelated donors were similar to outcomes with sibling donors. The average age of patients with aplastic anemia is ~16 years, that is, half the patients are children, but the disease can occur in all age groups. There is a specific chapter on the management of aplastic anemia in children and also on the management of aplastic anemia in the older adults. The issue is rounded up by particular chapters on second- and third-line treatment options, including cord blood transplantation, transplantation from mismatched family donors (that is, haploidentical donors) and experimental immunosuppressive regimens including Campath. These specific protocols are detailed here to incite treating physicians to manage these patients according to common treatment protocols and to report outcomes in order for us to progress toward improved outcomes for these patients. All these chapters have been written by members of the aplastic anemia working party of the European Group for Blood and Marrow Transplantation and the algorithms are the fruits of many discussions held during our biannual group meetings. We hope to provide a platform for the reader that may help him in all clinical situations that can be encountered with these patients. For this reason, the working title of this project had been ‘the complete treatment algorithm’.

Diagnosis of acquired aplastic anemia

Since the introduction of the concept of aplastic anemia (AA) by Paul Ehrlich in 1888 and despite the current better understanding of the underlying mechanisms involved in this disease, a clear delimitation among BM failure syndromes is still a matter of debate. The diagnosis of AA can be difficult basically due to the overlapping morphological characteristics with other BM failure disorders. This paper reviews critical data relevant to the diagnosis of acquired AA and recommends work out steps and main considerations to determine severity and characterization of the disease. The diagnostic challenge in the differentiation between AA and hypoplastic myelodysplastic syndromes is also addressed. The definition of the response criteria to treatment belongs to the diagnostic tasks and it is included in this review as well as an overview of novel tools for the diagnosis of AA.

Bone Marrow Imaging of Appendicular Skeleton by Multi-Detector Computed Tomography in Patients with Aplastic Anemia and Hypoplastic MDS.

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.