Disease Characteristics and Prognosis of Myelodysplastic Syndrome Presenting with Isolated Thrombocytopenia
Authors: Waisbren Julie B , Dinner Shira N. , Helenowski Irene , Gao Juehua , McMahon Brandon , Stein Brady 
Published: October 2019

Abstract

Background
Myelodysplastic syndrome (MDS) presenting with isolated thrombocytopenia (TCP) represents a rare subset of this heterogenous malignancy. Prior small studies have suggested an indolent course. However, because this presentation is uncommon, there are clinical challenges in diagnosis and management. The aim of this study is to better define the morphologic, cytogenetic, and prognostic features of MDS presenting with isolated TCP.
Methods
Using the Northwestern University Electronic Data Warehouse, MDS patients were selected between 2004 and 2014 using ICD-9 codes and billing data. The diagnosis of MDS was determined by a practicing hematologist/oncologist according to World Health Organization criteria and confirmed with bone marrow biopsy results. Inclusion criteria were patients with isolated thrombocytopenia as defined by (PLT) <100×109/L, absolute neutrophil count (ANC) > 1.5×109/L and hemoglobin (Hgb) > 10 g/dl. Those with rapidly progressive TCP, confounding bone marrow disorders or those with suspected secondary causes of cytopenia were excluded. Data obtained from patient charts included demographics, peripheral blood counts, bone marrow biopsy results, bleeding complications, treatment history, and disease progression. IPSS-R scores were calculated on all patients. Overall survival rate and acute myeloid leukemia (AML) free event rates were determined via the Kaplan Meier method and compared between risk groups using the log-rank test. A P-value < 0.05 was considered statistically significant.
Results
Baseline characteristics:
Of 404 MDS patients, 50 (12%) presented with isolated TCP. Among these 50, the median age was 72 and 34 were men (68%). Fourteen patients had TCP for greater than 2 years before diagnosis. Idiopathic thrombocytopenic purpura (ITP) was the presumed diagnosis in 17 patients. Median cell counts at the time of diagnosis were hemoglobin 12.0 g/dl, WBC 4.4 x 109/L and PLT 64 x 109/L. The most common cytogenetic profile was normal (n=28), and del 20q was the most common mutation seen in isolation (n=4) or in combination (n=3). Seven patients had complex cytogenetic profiles. Twenty-four patients fell into IPSS-R low or very low risk categories, 18 patients were IPSS-R intermediate (Int) risk and 7 patients were IPSS-R high or very high risk.
Treatment + outcomes:
Ten patients developed AML, 3 with low risk disease, 4 with Int-risk disease, 4 with high or very high-risk disease and 1 with an unknown IPSS-R score. Twenty-three patients were treated with hypomethylating agents including 5-Azacitidine or Decitabine. Three patients received thrombopoietin (TPO) receptor agonists. It is unclear by retrospective chart analysis if treatment resulted in improved outcomes. Fourteen of the 50 MDS patients presenting with isolated TCP died. Causes of death included AML (n=6), sepsis (n=4), intracranial bleeding (n=1), and unknown (n=1). Nine of the 14 patients who died were treated with hypomethylating agents, TPO agonists or both. There were 2 cases of major bleeding events, each intracranial and each in patients with PLT counts over 50.
Discussion
In our tertiary care center, the prevalence of isolated TCP in MDS was 12%. Patients with isolated TCP and MDS had similar demographics compared to patients with MDS at large. There were 17 patients (34%) that were first diagnosed with ITP. Need for bone marrow biopsy in asymptomatic patients with isolated TCP and normal peripheral smears is not clearly defined, however may be indicated in patients with demographics more typical of MDS (older male). The patients in this study distributed across all IPSS-R categories and many had an aggressive course. This is in contrary to previous studies that have suggested that MDS with isolated TCP has a relatively favorable prognosis. Next generation sequencing may uncover additional mutations in these patients that would help with risk stratification and development of targeted therapies. For example RUNX1 mutation carriers have been shown to present with thrombocytopenia and an increased risk of MDS/AML, and GATA2 mutants present with rapid onset MDS and often have a poor prognosis. Despite varying degrees of thrombocytopenia, incidence of major bleeding events was low. Treatment remains uncertain in this unique MDS subgroup. More studies are needed to address treatment options, including safety and efficacy of TPO agonists for this patient population.

Disclosures
Stein: Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees.