Abstract

Thrombocytosis at diagnosis is uncommon in myelodysplastic syndromes (MDS) and MDS/myeloproliferative syndromes (MDS/MPD). We conducted a retrospective analysis of 388 consecutive patients (pts) diagnosed with MDS and MDS/MPD between January 1980 and July 2006, to determine the effect of thrombocytosis on prognosis. The influence of thrombocytosis on the probabilities of progression to a higher grade of MDS, transformation to AML, and 5-year overall survival (OS) was determined by a case-matched design using the Kaplan Meier method and Cox regression analyses. A frequency summary of all 31 pts with MDS and MDS/MPD and platelet count > 400 × 106/mL at diagnosis is described. Using pre-defined matching criteria, 25 pts with thrombocytosis were case-matched with 50 control pts (1:2 matching ratio; relative risk 2, power 82%, α 0.05), for year of diagnosis, WHO classification and IPSS prognostic score. Of 388 pts with MDS or MDS/MPD, 31 (8% [95% CI, 5.3%-10.7%]) had thrombocytosis at diagnosis. The majority (N = 22, 71%) was re-classified as MDS/MPD (CMML = 12 [39%], RARS-T = 7 [23%], MDS/MPD-U = 3 [9%]) and N=9 (29%) as MDS (RARS = 5 [16%], 5q- = 2 [7%], MDS-U = 2 [6%]) according to the current WHO classification of myeloid disorders. Karyotypic abnormalities were noted in only 27% pts. The Jak-2 V617F mutation was present in 2 pts, both with RARS-T. The IPSS risk category was Low in the majority (18 pts), Int-1 in 3 pts and Int-2 in 1 pt. On > 95 patient-years of follow-up, the risks of major bleeding or thrombosis were low (0.04 and 0.01 events/patient-year, respectively). Marked thrombocytosis required cytoreduction with hydroxyurea in 6 pts and anagrelide in 1 pt, with good clinical response. Six of 31 (19%) pts progressed to a higher grade of MDS (CMML-2 or RAEB-2). Three pts (9.6%) transformed to AML, while 1 developed marked myelofibrosis. Death occurred as a consequence of AML in 3 pts, cytopenias due to MDS in 3 pts and sepsis in 1 pt. The cause of death was unrelated to MDS in 10 pts, and unknown in 3 pts. Eleven pts are currently alive. Matched case-control analyses showed that in pts with thrombocytosis, the probability of progression to a higher grade of MDS was lower (p = 0.03) but the risk of transformation to AML was equivalent to control pts. The median OS of pts with thrombocytosis was 35.4 months (range 0.3 - 60 months) compared to 27.6 months (range 0.5 - 60 months) for case-matched controls (p = 0.07). In conclusion, this study shows that the majority of pts presenting with myelodysplasia and thrombocytosis fall in the MDS/MPD category of the new WHO classification (most commonly CMML or RARS-T) and have low-risk features (IPSS category Low or Int-1). Thrombocytosis may reach levels requiring cytoreduction with hydroxyurea or anagrelide. The risks of spontaneous bleeding or thrombosis, progression of disease and myelofibrosis are low and the overall survival is comparable to that of case-matched pts without thrombocytosis. This is the only study that has examined the effect of thrombocytosis itself on prognosis by comparing pts with thrombocytosis to controls case-matched for standard prognostic factors.

Author notes

Disclosure: No relevant conflicts of interest to declare.