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Editorials
Immune thrombocytopenia in myeloid and lymphoid clonal disorders: an intriguing association
Francesco Rodeghiero
Hematology Project Foundation – affiliated to the Hematology Department of San Bortolo Hospital, Vicenza, Italy E-mail: FRANCESCO RODEGHIERO - rodeghiero@hemato.ven.it
doi:10.3324/haematol.2020.275933
In this issue of Haematologica, Jachiet et al.1 present the first systematic study on the association of severe immune thrombocytopenia (ITP) with preleukemic clonal myeloid disorders. Patients from 16 French Departments of Hematology and Internal Medicine were accrued between January 1999 and July 2019, under the coordination of the French Network of Dysimmune Disorders Associated with Hemopathies. A total of 41 cases, 17 with myelodysplastic syndrome (MDS) and 24 with chronic monomyelocytic leukemia (CMML), meet- ing the 2016 World Health Organization classification2 and a maximum period of 10 years between the diagnosis of ITP and MDS/CMML were retained for the final retro- spective analysis. The majority of cases (73%) were scored as low-risk with a median Revised International Prognostic Scoring System score of 3.3 ITP, mainly of chronic type, was diagnosed with bona fide criteria and could be anterior, concomitant or posterior to the diagno- sis of the myeloid disorder. These patients were com- pared to 200 MDS/CMML patients without ITP and to a control group of 75 patients with primary ITP without MDS/CMML.
Patients with MDS/CMML with associated ITP had more severe bleeding and a multirefractory profile to firstline treatments for ITP compared to those with pri- mary ITP alone and showed a moderate response to thrombopoietin-receptor agonists. They had a lower rate of progression toward acute myeloid leukemia than MDS/CMML patients without ITP but, disappointingly, the overall survival was similar. Limited cytogenetic and molecular studies did not contribute to differentiate MDS/CMML with or without ITP, apart from a higher prevalence of 20q deletion in cases with ITP, but high- throughput next-generation sequencing was not used to describe genetic profiles.
In addition to these interesting clinical findings, the study by Jachiet et al. poses a preliminary question: is the “association” of ITP with low-grade myelodysplastic dis-
orders (whichever comes first) just casual or is it indeed related to a shared pathogenic mechanism? In other words, is the prevalence of this association beyond what could be expected by chance alone?
Unfortunately, Jachiet et al.1 did not report the number of patients with MDS/CMML from which the ITP cases were identified, thus hampering any estimation of the prevalence of ITP associated with MDS/CMML, unlike another French study reporting 61 low-risk MDS patients in nine of whom (15%) ITP was identified as the cause of thrombocytopenia (platelet count <70x109/L) on the basis of a greater reduction in platelet lifespan and low bone marrow blast infiltration (<10%) not justifying the severity of the thrombocytopenia. Indeed, splenectomy was successful in three of these cases.4 A much lower per- centage (3%) of thrombocytopenia of putative autoim- mune nature was identified among 1,408 MDS patients included in the Moffitt Cancer Center database and at King’s College Hospital.5
Conversely, limited investigations have tackled the problem from the other side, by reporting the incidence of co-occurrence or subsequent development of MDS in patients first presenting with ITP. The only large study on this issue is based on the identification of 2,885 adults with incident ITP requiring healthcare and accessing the French health insurance national database over a 3-year period.6 Among these patients, 2.3% were concomitantly affected by MDS. Interestingly, some reports of “primary” ITP later developing into MDS are also available and it is noteworthy that in the study by Jachiet et al.1 ITP preced- ed the diagnosis of MDS/CMML in 36% of cases by sev- eral months to years. In another retrospective French series of 516 patients with ITP, the diagnosis of CMML was unveiled by the finding of thrombocytopenia in eight cases (1.4%) and 13 additional cases were identified through a systematic literature review of patients in whom the diagnosis of CMML was associated with or heralded by (in some cases several years before) isolated
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