Chronic myeloid leukemia with extreme thrombocytocis at the diagnosis: a new subset

Background: Chronic myeloid leukemia (CML) is the result of t(9;22) balanced translocation and/or presence of BCR-ABL1 fusion gene. Usually CML presents with marked leukocytosis and only in rare cases CML can present at the diagnosis with an isolated and marked thrombocytosis, defined as platelet count >1000x109/L. There are no data on the optimal treatment of these subcategories of “theoretically high risk” patients in the era of tyrosine kinase inhibitors (TKIs). Aims: To identify a specific subset of CML chronic phase patients with extreme thrombocytosis (platelet count >1000x109/L) at diagnosis and to assess clinical outcomes: overall survival, progression free survival and cumulative response in terms of CCyR and/or MMR at 12 and 24 months. Methods: Data were collected and evaluated through the analysis of 1591 CML CP patients registered in 16 Italian Haematological Departments from January 2002 to December 2015. Results: The incidence of extreme thrombocytosis at diagnosis was 5,4% (87/1591). Median age was 59 years (range 18-87), F/M 63/24. Median spleen size below the costal margin was 0 cm (range 0-15), and liver size below the costal margin was 0 cm (range 0-3). Median white blood cell count was 31.600x106/microl(range 6.340-390.000), median haemoglobin level was 11,8 g/dl (range 7,7-16,3), and median platelet count was 1466x109/L. (range 1054-4720). Sokal score was low in 6 patients (6,8%), intermediate in 23 (26,4%) and high in 55 (63,2%). Hasford score was low in 17 patients (22%), intermediate in 22 (28,6%) and high in 38(49,42%) out of 77 evaluable cases. Coagulation tests were available in 59/87 (67,8%), and aPTT was abnormal in only three patients (5%). Bleeding time test was available only in 5 patients and was prolonged in all of them (median value 41 sec1”). Iron assessment was reported in 56 out of 87 patients and was consistent with iron deficiency in 7 patients (12,5%); assessment of the, JAK2V617F mutation was performed in 43 (49,4%) patients. At diagnosis, 9 out of 87 (10.3%) patients showed haemorragic or thrombotic complications, with only 3 of grade >2 according to the NCI-CTC. In order to reduce severe thrombocytosis, 73/87 patients (83%) received hydroxyurea before starting TKI and in two patients thrombocytapheresis was reported [s1]. As first line TKI 63/87 (72,4%) patients received imatinib, 16 (18,4%) dasatinib and 8 (9,2%) nilotinib. Seventy-seven out of 87 patients were evaluable after 12 months of treatment, and 67 of 77 (87%) obtained cCyR or major molecular response (MMR). Sixty-seven patients were evaluable at 24 months of treatment and 51 out of 67 (76,1%) were in cCyR and/or MMR. After a median follow-up of 66 months (range 3-179), 81/87 (93,1%) patients are still alive. Six patients (6,9%) died: two from myocardial infarction, three from concomitant neoplasia, and one from GvHD. Nine (10,3%) patients developed primary resistance to imatinib and they were shifted to the second line. Eight additional patients developed secondary resistance, mainly after imatinib. Summary/Conclusions: The incidence of extreme thrombocytosis in CML chronic phase is rare;this subset of patients shows the following peculiarities: predominance of female sex, high or intermediate risk score with a favourable outcome in terms of both cumulative response rate and survival, low incidence of thrombotic/haemorragic risk [s1]. Due to the inclusion of patients prior to the acquisition of JAK2 V617F in the differential diagnosis of thrombocytosis, only half of the patients were assessed for this mutation.