Ph染色体阴性骨髓增殖性肿瘤加速/急变期患者的临床特征及预后因素分析

OBJECTIVE: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase（MPN-AP/BP）. METHODS: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. RESULTS: ① Sixty-seven patients with MPN-AP/BP with a median age of 60（range, 33–75）years, including 31 males（46.3％）and 36 females（53.7％）, were analyzed. Forty-eight patients progressed from primary myelofibrosis（PMF）, and 19 progressed from other myeloproliferative neoplasms（MPNs）, which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase（LDH）levels than those who progressed from other MPNs（925.95 vs. 576.2 U/L, P＝0.011）, and there were higher proportions of patients who progressed from PMF with splenomegaly（81.4％ vs. 57.9％, P＝0.05）, a myelofibrosis grade of ≥2（93.6％ vs. 63.2％, P＝0.004）, and a shorter duration from diagnosis to the transformation to AP/BP（28.7 vs. 81 months, P＝0.001）. ② JAK2V617F, CALR, and MPLW515 were detected in 41（61.2％）, 13（19.4％）, and 3（4.5％）patients, respectively, whereas 10（14.9％）patients did not have any driver mutations（triple-negative）. Other than driver mutations, the most frequently mutated genes were ASXL1（42.2％, n＝27）, SRSF2（25％, n＝16）, SETBP1（22.6％, n＝15）, TET2（20.3％, n＝13）, RUNX1（20.3％, n＝13）, and TP53（17.2％, n＝11）. The ASXL1 mutation was more enriched（51.1％ vs. 21.1％, P＝0.03）, and the median variant allele fraction（VAF）of the SRSF2 mutation（median VAF, 48.8％ vs. 39.6％; P＝0.008）was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype（hazard ratio, 2.53; 95％ confidence interval, 1.06–6.05; P＝0.036）was independently associated with worse overall survival（OS）. Patients who received allogeneic stem cell transplantation（allo-HSCT）（median OS, 21.3 vs. 3 months; P＝0.05）or acute myeloid leukemia-like（AML-like）therapy（median OS, 13 vs. 3 months; P＝0.011）had significantly better OS than those who received supportive therapy. CONCLUSION: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.