Cyclosporine A improves survival in lower-risk hypoplastic myelodysplastic syndromes: a single-center retrospective study from China

Sally B. Killick (Writing Group Chair), Nick Bown, Jamie Cavenagh, Inderjeet Dokal, Theodora Foukaneli, Peter Hillmen, Robin Ireland, Austin Kulasekararaj, Ghulam Mufti, John A Snowden, Sujith Samarasinghe, Anna Wood (BCSH Task Force Member), Judith C.W. Marsh on behalf of the British Society for Standards in Haematology. The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust, Bournemouth, Northern Genetics Service, Newcastle upon Tyne, St Bartholomew’s Hospital, Barts Health NHS Trust, London, Barts and The London School of Medicine and Dentistry, Queen Mary University of London and Barts Health NHS Trust, London, Addenbrooks Hospital, University of Cambridge, Cambridge, Leeds Teaching Hospitals, Leeds, Kings College Hospital NHS Foundation Trust, London, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield Great Ormond Street Hospital for Children NHS Foundation Trust, London, West Hertfordshire NHS Trust, Watford.

Acquired Somatic Mutations in T Cells in Patients with Aplastic Anemia and Hypoplastic Myelodysplastic Syndromes

Role of S-Phase Fraction in Differentiating Aplastic Anemia from Hypoplastic Myelodysplastic Syndrome

The Presence Of Leukemogenic Mutational Events In Paroxysmal Nocturnal Hemoglobinuria Suggests That Clonal Architecture Of Bone Marrow Failure Is Similar To Myelodysplastic Syndrome

27-Year-Old Woman With Pancytopenia

Clinicopathological Features and Mutational Analysis of Patients with Aplastic Anemia and Hypoplastic Myelodysplastic Syndrome

Karyotypic and Genetic Abnormalities Associated with Clonal Evolution in Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal Nocturnal Hemoglobinuria Clones in Children with Acquired Aplastic Anemia: A Multicentric Study

BackgroundParoxysmal nocturnal haemoglobinuria (PNH) clones in children are rare but commonly associated with aplastic anaemia (AA) and myelodysplasia.ObjectiveThis study aimed to determine the prevalence of PNH clones in paediatric patients with idiopathic AA, identify differences in clinical and laboratory features and outcomes, and determine the impact of clone size on clinical presentation.MethodsPatients with confirmed idiopathic AA who were tested for PNH between September 2013 and January 2018 at the Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa, were included. PNH clones were detected in neutrophils and monocytes by flow cytometry using fluorescent aerolysin, CD24, CD66b and CD14.ResultsTwenty-nine children with AA were identified and 11 were excluded. Ten patients (10/18, 55.6%) had PNH clones ranging from 0.11% to 24%. Compared to the PNH-negative group, these children were older (median: 10 years vs 4 years, p = 0.02) and had significantly lower total white cell counts (median 1.7 × 109/L vs 3.2 × 109/L; p = 0.04). There was no difference in median absolute neutrophil count or haemoglobin concentration. Four patients in each group received immunosuppressive therapy (IST). At six months, all four patients with PNH clones had responded, compared to one in the PNH-negative group.ConclusionMore than half of children with AA had a PNH clone. The size of the clone did not impact clinical severity; however, IST use may positively impact prognosis. We recommend early initiation of IST in patients with AA to avoid delays associated with human leukocyte antigen typing.

Hypoplastic MDS Is a Distinct Clinico-Pathological Entity with Somatic Mutations Frequent in Patients with Prior Aplastic Anaemia with Favorable Clinical Outcome

It is often difficult and challenging task to differentiate aplastic anemia (AA) from hypoplastic myelodysplastic syndrome (HMDS) among the patients with bone marrow aplasia. This is possibly because of the considerable clinical, cytological and histological similarities between these two disorders. As prognostic and therapeutic approach to AA and HMDS are different, it is imperative to differentiate them at the time of initial diagnosis. Various attempts have been made in the past to differentiate AA from HMDS. In the present study, we explored the value of certain new parameters i.e. S-phase fraction (SPF) and aneuploidy that could be used for this purpose. The study included 46 consecutive patients with aplastic anemia, 15 patients with HMDS along with 32 age and sex-matched control subjects. S-phase fraction and aneuploidy analysis was carried out by flow cytometry using Mod Fit-LT V3.0 software. The mean SPF value was significantly lower (p=0.02) in patients with AA and higher (p=0.01) in HMDS as compared to that of the control. Aneuploidy was present in 15.2% patients with AA and in 33.3% HMDS cases. During follow-up, 4 patients with AA developed MDS, out of these, three patients had aneuploidy as well as high SPF value at the time of diagnosis. Two patients with HMDS who had aneuploidy and high SPF, converted into AML. Eleven patients died during the study, in whom 8 had aneuploidy and high SPF value. We conclude that high SPF value and presence of aneuploidy favour the diagnosis of HMDS rather than AA. SPF and aneuploidy may be important parameters in patients with AA to predict their propensity to evolve into myelodysplastic syndrome and acute myeloid leukemia. SPF value may also be useful in the early diagnosis of HMDS before morphologically evidence of dysplasia is apparent.

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.

Germline alterations of hematopoietic growth factor receptors and maladaptive somatic genetic rescue leads to myeloid neoplasia

Usefulness of Functional Image Analysis Using Positron Emission Tomography for the Discrimination between Hypoplastic Myelodysplastic Syndromes and Aplastic Anemia.

Aplastic anemia (AA) is a rare bone marrow failure syndrome marked by hypocellular bone marrow and pancytopenia, typically without abnormal infiltration or reticulin fiber increase. It often presents as acute, severe cytopenia in young adults and can have high mortality if untreated. Recent advancements, including immunosuppressive therapy (IST) combined with eltrombopag and hematopoietic stem cell transplantation (HSCT), have improved patient outcomes. This review discusses current etiopathogenesis involving immune dysregulation, genetic mutations, and environmental triggers. Accurate differential diagnosis, distinguishing AA from myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria, is essential for effective treatment. We also highlight emerging therapies, such as mismatched unrelated donor (MMUD) transplantation and precision medicine targeting genetic abnormalities. AA, with an incidence of 2–4 per million annually, peaks at ages 15–25 and over 60. These insights continue to reshape AA prognosis and management. This disease typically manifests as acute, severe cytopenia, particularly in young adults, and has a high mortality rate if untreated. Advances in treatment, including IST combined with eltrombopag and HSCT, have significantly improved outcomes. In this review, we explore the current etiopathogenesis, including immune dysregulation, genetic mutations, and environmental factors. The differential diagnosis of AA, distinguishing it from conditions such as myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria, is critical for tailored treatment. AA remains a rare disease, with an annual incidence of 2–4 per million, and peaks in occurrence during the ages of 15–25 and over 60. These advancements in understanding and managing AA continue to transform its prognosis and patient care.