Positivity Rate of Systematic Bone Marrow Smear Above 60-Year-Old Patients with Newly Diagnosed Immune Thrombocytopenia to Screen for Associated Hematological Malignancy. Results from the French Prospective Multicenter Carmen Registry
Authors: Comont Thibault , Brun Natacha , Germain Johanne , Dingremont Claire , Castel Brice , Arista Sophie , Madaule Serge , Montané de la Roque Phillipe , Prudhomme Laurent , Sailler Laurent , Balardy Laurent , Alric Laurent , Recher Christian , Carreiro Miguel , Gaches Francis , Lapeyre-Mestre Maryse , Beyne-Rauzy Odile , Adoue Daniel , Moulis Guillaume , investigators Group Carmen 
Published: November 2019

Introduction:There are discrepancies across recommendations about the indication of bone marrow smear in adults diagnosed for immune thrombocytopenia (ITP). The 2011 American Society of Hematology guidelines do not recommend bone marrow smear in case of typical ITP. In contrast, the 2010 international consensus and the 2017 French guidelines recommend systematic bone marrow smear in adults aged >60 years even in case of typical ITP to detect a blood cancer, particularly myelodysplastic syndrome. This recommendation is driven from expert consensus. Data are lacking about the positivity rate of this examination in older patients with typical ITP. The aim of this study was to assess the positivity rate of bone marrow smear at ITP diagnosis in >60-year-old patients with no other clinical or biological sign of hematological malignancy.
Methods:Data source was theCARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry. All adult patients with an incident diagnosis of ITP in the French Midi-Pyrénées region (South of France, 3 million inhabitants) are prospectively enrolled since June 2013 in the multicenter CARMEN registry. ITP is defined by international guidelines (platelet count <100 x 109/L and exclusion of other causes of thrombocytopenia). Investigations performed at ITP diagnosis in a real-life basis, including bone marrow smear, are recorded with their results. Study population was selected among the patients included in the CARMEN registry from June 2013 to December 2018. Inclusion criteria were: age>60 years; absence of clinical signs of hematological malignancy (lymphadenopathy, hepatomegaly, splenomegaly); isolated thrombocytopenia on blood count; bone marrow smear performed at ITP diagnosis. We described patients with abnormal bone marrow smear and implications for ITP management.
Results:We identified 114patients (66 men and 48 women) satisfying all inclusion criteria. Mean age at ITP diagnosis was 76 years (standard deviation - SD: 9 years). Platelet count at diagnosis was 32.7 x 109/L (SD: 27.7 x 109/L) and 58 patients presented with bleeding: skin bleeding only (n=33), oral bleeding (n=17), epistaxis (n=10) and hematuria (n=3). Only one patient had an abnormal bone marrow smear corresponding to a characterized hematological disease: a myelodysplastic syndrome. It was a 62-year-old man without medical history who presented in 2014 with extensive skin bleeding, and isolated thrombocytopenia (6 x 109/L). Other blood count parameters were: hemoglobin: 15.2 g/dL; MCV: 83 fL; leukocytes: 5.3 x 109/L; polynuclear neutrophils: 3.5 x 109/L; lymphocytes: 1.0 x 109/L; monocytes: 0,3 x 109/L . Bone marrow smear revealed normal cellularity. The megakaryocytic lineage was normally represented with significant number of megakaryocytes with multiple separated nuclei. Significant dysgranulopoiesis was also observed with pseudo-Pelger-Huët anomaly and cytoplasmic hypogranulation. Some erythroblasts with defective haemoglobination or cytoplasmic vacuolation were present. This aspect was compatible with the diagnosis of myelodysplastic syndrome with multilineage dysplasia (MDS-MLD). Karyotype was normal. The patient was initially treated for ITP with steroids and intravenous immunoglobulins (with partial response), then with danazol (complete response), eltrombopag (after loss of response to danazol and ocular bleeding, resulting in complete response) and more recently romiplostim (after loss of response to eltrombopag, resulting in complete response). He was treated in 2019 by rituximab to spare exposure to thrombopoietin receptor agonists, without efficacy. Before Rituximab, another bone marrow smear was performed (4 years after the first one) with the same cytologic and cytogenetic features (MLD-MDS with normal caryotype).
Conclusions:Diagnosis of hematological malignancy is very uncommon in >60 year-old patients who present with typical ITP. Myelodysplastic syndrome was found in 1 (0.8%) patient in this series, and did not impact the management or the evolution of the patient with a five-year follow-up. Overall, this study sustains guidelines that does not recommend systematic testing for bone marrow examination in >60 year-old patients with typical ITP.

Disclosures
Comont: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Recher:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; Macrogenics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Beyne-Rauzy:Novartis: Research Funding; Cellgene: Research Funding. Moulis:CSL Behring: Research Funding; Amgen pharma: Research Funding, Speakers Bureau; Novartis pharma: Research Funding, Speakers Bureau.