Objective: To investigate the value of platelet count in predicting the efficacy of rituximab treatment in chronic primary immune thrombocytopenia (ITP). Methods: A retrospective study was conducted in 103 chronic ITP patients hospitalized in our medical center between January 2011 and December 2014. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of platelet count in different time points were analyzed for the predictor of treatment response. Optimal cutoff values were established using ROC analysis. Results: A total of 103 patients were included in the study. There were 46 males and 57 females, with a median age of 30 (18-67) years. At day 1, 3 and 7 after the first dose of rituximab, there was no significant difference in platelet counts between the success group (PLT≥50×10(9)/L after treatment) and the failure group (PLT≤50×10(9)/L after treatment) (P>0.05). At day 14 after rituximab treatment (PTD 14), platelet counts became significantly different in the success and failure groups[41(8-384)×10(9)/L vs 23(0-106)×10(9)/L, P=0.003], and remained different thereafter, with increasing significance in the subsequent follow-ups. Patients were divided further using an optimal cut-off platelet count of 50×10(9)/L on PTD 14, PTD 30, and PTD 60, and PPV and NPV values were calculated for predicting eventual success and failure. Conclusion: Response can be predicted by obtaining platelet counts at 14, 30 and 60 days after rituximab treatment. The study proposed a protocol that guides patient monitoring and management planning.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the clinical characteristics and long-term outcome of Chinese young patients (≤40 years) with essential thrombocythemia(ET), and to develop a thrombosis predicting model specific for young patients with ET, so as to provide a new evidence for risk stratification and treatment.

METHODSMedical records of 125 Chinese young patients with newly diagnosed of ET were retrospectively analyzed.

RESULTSThe median age at diagnosis was 32 (18-40) years old, with 37 males and 88 females. During follow-up, 18 patients (14.4%) experienced major thrombotic events. JAK2 V617F (HR=8.895, P=0.001), history of thrombosis (HR=8.001, P<0.001) and WBC≥12.0×10/L (HR=5.225, P=0.002) were independent risk factors for thrombosis. The incidence of thrombosis and risk factors in young patients were different from that in general ET population, so a thrombosis predicting model specific for young patients with ET was developed. In this model, JAK2 V617F (score 2), history of thrombosis (score 2) and WBC≥12.0×10/L (score 1) were used to divide the patients into low risk (score 0), intermediate risk (score 1-2) and high risk (score≥3) groups. These 3 groups exhibited significantly different thrombosis-free survival (χ=32.223, P<0.001). Antiplatelet treatment could prevent the occurrence of thrombosis (HR=0.081, P<0.001), while cytoreductive agents significantly decreased the risk of thrombosis only in intermediate and high risk groups (14.3% vs 36.4%, χ=4.416, P=0.036). Seven patients (5.6%) evolved to myelofibrosis, and one of them finally progressed in to acute leukemia. The only risk factor for evolution was WBC≥15.0×10/L (χ=5.434, P=0.020). Neither antiplatelet treatment nor cytoreductive agents could prevent disease progression.

CONCLUSIONThe incidence of thrombosis and risk factors in young patients with ET are different from that in general ET population. The thrombosis-predicting model specific for young patients with ET is useful for guiding therapeutic decisions.

BACKGROUNDEssential thrombocythemia is a subgroup of myeloproliferative neoplasms. Previous studies identified mutations of JAK2, CALR, and MPL that are closely related with the pathogenesis of myeloproliferative neoplasms. All these mutations contribute to the hyperactivation of JAK2/STAT pathway. However, a small proportion of essential thrombocythemia patients does not display such mutations. The pathogenesis of "triple-negative" form of essential thrombocythemia remains unknown.

OBJECTIVETo investigate the clinical characteristics of triple-negative essential thrombocythemia and related mutation genes.

METHODSTo identify the mutations associated with triple-negative essential thrombocythemia, next-generation sequencing was used to conduct targeted sequencing of 360 genes in samples from 68 patients.

RESULTSAt least one missense mutation was detected in all the patients and all the detected genes. After screening the data, it was observed that 10 genes with the 10 highest mutation were follows: FLT3, SH2B3, ASXL1, ADAMTS1, TET2, TP53, EGFR, CUX1, GATA2, and MPL.When only rare genes (i.e., with a frequency in Asian populations lower than 5%, as estimated by the 1000 Genomes Project) were analyzed, the most frequently mutated genes in the patients were TET2 (33.82%), SH2B3(29.41%), and ASXL1 (23.53%). Our study identified some mutations that did not previously reported. Although all these mutations need further validation, high incidence rates may indicate relevance of the respective mutations to essential thrombocythemia pathogenesis. Some of the detected mutations have been previously reported; these mutations were also found in a large proportion of our subjects.

CONCLUSIONwhole-exon sequencing can provide a higher level of accuracy for gene mutation analysis and assist in identifying mutations that contribute to illustrate the pathogenesis of essential thrombocythemia.

Calreticulin ; DNA Mutational Analysis ; Humans ; Janus Kinase 2 ; Mutation ; Myeloproliferative Disorders ; Receptors, Thrombopoietin ; Thrombocythemia, Essential