Spectrum of Myelodysplastic Syndrome in Patients Evaluated for Cytopenia(s). A Report from a Reference Centre in Saudi Arabia

Abstract

Background/Objective: Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells, characterized by ineffective hematopoiesis, peripheral cytopenias along with hypercellularity of the bone marrow, and marked dysplastic features. Establishing MDS diagnosis is difficult due to nonspecific clinical presentation and imprecise morphological criteria. In anticipation to improve the diagnostic approach in this field, we aimed to characterize the clinical and morphological features of patients presented with cytopenias with a special focus on MDS. Methods: We comprehensively reviewed all medical record of patients who were referred to the hematology laboratory at KFSH-RC, Riyadh, Saudi Arabia, between January 2009 and March 2016 for evaluation of bone marrow aspirates and trephine biopsies due to severe and persistent cytopenia(s) to rule out MDS. Results: A total of 183 patients, 155 adult and 28 pediatric, were identified. In the adult group, MDS was diagnosed in 82 (52.9%) patients, with a male-to-female (M:F) ratio of 1.6:1 and mean age at diagnosis of 50 years. According to the World Health Organization (WHO) 2017 criteria, MDS subtypes were as follows: MDS with single lineage dysplasia (SLD, 5%), MDS with ring sideroblasts and SLD (MDS-RS-SLD 7%), MDS with multilineage dysplasia (MDS-MLD 21%), MDS with deletion of chromosome 5q (MDS del(5q), 2%), MDS unclassifiable (MDS-U7%), hypoplastic MDS (h-MDS 4%), MDS with excess blasts-1 (MDS-EB1, 20%), MDS with excess blasts-2 (MDS- EB2, 28%), and therapy-related MDS (6%). Laboratory and morphological features were described. In both groups, cytogenetic abnormalities were classified according to the Revised International Prognostic Scoring System cytogenetic risk groups. In adults, the dominating cytogenetic abnormalities were monosomy 5 and monosomy 7 seen in 20.7% and 24.4% of patients, respectively. Peripheral cytopenia not due to MDS was diagnosed in 54 (34.8%) patients, with a mean age of 43 years and M:F ratio of 1:1. The cause of these cytopenias were as follows: bone marrow failure (BMF, 22%), peripheral destruction (20%), drug induced (20%), anemia of chronic disease (16%), B12 deficiency (7%), infection (7%), paroxysmal nocturnal hemoglobinuria (4%), idiopathic cytopenia of undetermined significance (2%), and idiopathic dysplasia of undetermined significance (2%). A definite diagnosis of MDS was not possible in 19 patients due to insufficient clinical data. In the pediatric group, MDS was diagnosed in 14/28 (50%) patients, with M:F ratio of 1.8:1 and mean age at diagnosis of 4 years. MDS subtypes (WHO 2017) in 14 patients were as follows: refractory cytopenia of childhood (RCC, 42.8%), MDS-EB1 (42.8%), and MDS-EB2 (14.2%). Laboratory and morphological features were described. The prevalent cytogenetic abnormality was monosomy 7 in six/14 (42.8%) patients. Cytopenias due to other causes were diagnosed in eight/28 patients (28.5%), with a mean age of 6.5 years and M:F ratio of 1.6:1. The causes of non-MDS related cytopenia were: congenital BMF (4 patients), peripheral destruction (2 patients), immune deficiency (1 patient), and viral infection (1 patient). A definite diagnosis of MDS could not be made in six/28 (21.4%) patients. Conclusion: MDS is the cause of cytopenia in a significant number of patients referred for evaluation of cytopenias, appears at younger age, and tends to be more aggressive than that reported in international studies. Anemia, dysplastic neutrophils in the peripheral blood, and dysplastic megakaryocytes in the bone marrow trephine biopsy are the most reliable features in distinguishing MDS from other alternative diagnoses.

Changes in bone marrow and peripheral blood lymphocyte subset findings with onset of hepatitis-associated aplastic anemia

“…In our case, the lack of hemolytic anemia in the initial laboratory findings was sufficient to eliminate GCH. In addition, the bone marrow findings ruled out other diagnoses, such as hemophagocytic syndrome, megaloblastic anemia, bone marrow infiltration of malignancy, myelodysplastic syndrome, acute leukemia, and thymoma [18,19] . Myelodysplastic syndrome was excluded based on the absence of precursor cells, blood cell atypia, and chromosomal abnormalities.…”

“…In addition, the bone marrow findings ruled out other diagnoses, such as hemophagocytic syndrome, megaloblastic anemia, bone marrow infiltration of malignancy, myelodysplastic syndrome, acute leukemia, and thymoma. [18,19] Myelodysplastic syndrome was excluded based on the absence of precursor cells, blood cell atypia, and chromosomal abnormalities. Flow cytometry did not detect glycosylphosphatidylinositolanchored protein-deficient blood cells; therefore, paroxysmal nocturnal hemoglobinuria was ruled out.…”

Assessment of Bone Marrow Failure Syndrome Management Outcome in Pediatrics – Saudi Perspective

“…[3] When it comes to the Saudi experience, a Saudi study by AlMozain et al analyzed 183 (155 adults and 28 pediatric) patients with myelodysplastic syndrome (MDS) and found that the cause of BMFS could not be identified in half of the pediatric cases. [4] Hence, it is pretty evident that the cause of BMFS remains unidentified in most cases in Saudi.…”

Distinct Clinical and Prognostic Features of Myelodysplastic Syndrome in Patients from the Middle East, North Africa, and Beyond: A Systemic Review

“…A few studies have reported the age of onset is younger and the disease more likely to harbor high-risk cytogenetic aberrations in MDS patients in the region. For example, in a recent Saudi Arabian study, the mean age of diagnosis was 50 (±18) years [12]. Interestingly, the data showed that Saudi patients have more aggressive disease at presentation than Western patients, with over 50% of patients classified as having "poor" and "very poor" prognoses following the IPSS-R classification.…”