OBJECTIVETo estimate the long-term outcomes and the prognostic factors of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia (AML).

METHODSThe CR rate, overall survival (OS) rate, relapse free survival (RFS) rate were retrospectively assayed in 143 de novo AML patients who received the HAD/HAI induction chemotherapy. The outcomes were compared among prognostic groups according to world health organization (WHO) classification, genetic prognosis and initial white blood cell (WBC) count. The role of consolidation chemotherapy consisting of middle-dosage Ara-C (MD-Ara-C) on long term survival was evaluated.

RESULTSOf 143 patients, 112 (78.3%) achieved CR after the first course of HAD/HAI induction treatment, and early death occurred in only one case. Notably, the CR rate of patients with an initial WBC count ≥100×10(9)/L was not significantly different from those with an initial WBC count<100× 10(9)/L (70.4% vs 80.2%, P=0.266). The CR rate for the patients with favorable, intermediate and unfavorable integrated genetics risk factors was 93.7%, 71.4% and 61.3%, respectively, the difference between groups was statistically significant (P=0.001). Patients with FLT3-ITD mutation obtained similar CR rate (70.6%) to that of patients with FLT3 wild type (79.3%, P=0.528).The estimated 5-year OS rate and 5-year RFS rate for all patients was 40.0% and 37.0%, respectively, with a median follow-up of 24 (range 1-104) months. The median survival time was 30 [95%CI (12, 48)] months. 5-year OS and 5-year RFS of the 96 patients who achieved CR after first course chemotherapy without undergoing allo-HSCT in complete remission was 47.0% and 38.0%, respectively. 5-year OS was significantly higher in MD-Ara-C consolidation group than in no MD-Ara-C consolidation group among CR patients without allo-HSCT (58.0%, 19.0%, respectively, P=0.004). In patients who obtained CR after first course and received MD-Ara-C consolidation without allo-HSCT, the 5-year OS of patients with hyperleukocytosis was not significantly lower than that of patients without hyperleukocytosis (55.5%, 58.8%, respectively,P=0.419). FLT3-ITD mutation patients showed similar 5-year OS to that of wild type FLT3 patients (51.4%, 60.2%, respectively, P=0.482). And furthermore, 5-year OS of favorable, intermediate and unfavorable integrated genetics groups were 59.1%, 62.5%, 51.9%, respectively (P=0.332) in this subgroup.

CONCLUSIONHAD/HAI induction chemotherapy with sequential consolidation of MD-Ara-C could obtain satisfactory CR rate and long-term survival rate in de novo AML, especially for patients with hyperleukocytosis or FLT3-ITD mutation. It yet remains to be verified by large sample, prospective studies.

Cytarabine ; therapeutic use ; Daunorubicin ; therapeutic use ; Harringtonines ; therapeutic use ; Humans ; Idarubicin ; therapeutic use ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; drug therapy ; Leukocyte Count ; Prognosis ; Prospective Studies ; Remission Induction ; Retrospective Studies ; Survival Rate

Objective To characterize the molecular profile in patients with Ph negative myeloproliferative neoplasms ( MPN) by exploring 49 gene mutations.Methods Targeted gene sequencing were performed to analyze 49 MPN-associated genes in 51 patients with Ph negative MPN, of which CARL ( exon 9 ) , NPM1 ( exon 12 ) and CEBPA ( TAD, BZIP domains ) were investigated by using Sanger sequencing simultaneously, while FLT3-ITD was assessed by PCR method. Results Mutations were detected in 73.5%(36/49) of genes, and the mutational rates of JAK2-V617F, CALR (exon 9) and MPL were 60.8%( 31/51 ) , 7.8%( 4/51 ) and 7.8%( 4/51 ) respectively, whereas the mutational rates of ASXL1, SETBP1, and SF3B1 were around 10%.In addition, 96.1%(49/51) of patients harbored at least one mutation, and more than half of the patients (52.9%,27/51) possessed 3 or 4 gene mutations.The amount of gene mutations was significantly higher in patients with JAK2-V617F mutation than those without JAK2-V617F or CALR (exon 9) mutation (P<0.05).The last finding was that there was no statistically significant difference in the amount of mutations among four MPN subtypes ( PV, ET, PMF, and MPN-U) . Conclusion Most patients with Ph negative MPN possesses three or more gene mutations, with various mutational profiles.

ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong （BL 40）" on neuropathic pain in a rat model of chronic constriction injury （CCI） of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups （8 rats in each group）， sham-operated group， model group， Tuina group， and blockade group. The CCI model was established in the model group， Tuina group， and the blockade group by ligating the sciatic nerve with catgut， while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14， rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong （BL 40）" using a dynamic pressure distribution measurement system （5 N pressure， 2 Hz frequency， 10 min per session， once daily）. The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline （10 mg/kg） once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold （MWT） and paw withdrawal latency （PWL） were measured before surgery and on day 3， 7， 10， and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair， measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 （Iba-1）， CD206， CD68， interleukin-10 （IL-10）， and β-endorphin （β-EP） precursor pro-opiomelanocortin （POMC） in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group， the model group showed significantly reduced MWT and PWL on day 3， 7， 10， and 14 （P＜0.01）. Compared with the model group， the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 （P＜0.05）. Compared with the Tuina group， the blockade group exhibited higher MWT on day 7， 10， and 14， and higher PWL on day 10 （P＜0.05）. Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group， while the model group exhibited myelin collapse， distortion， and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse， whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group， the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn （P＜0.05 or P＜0.01）. Compared with the model group， the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally， the Tuina group showed elevated levels of CD206， IL-10， and POMC， whereas the blockade group had decreased CD206 levels （P＜0.05）. ConclusionTuina at "Weizhong （BL 40）" alleviates neuropathic pain in CCI rats， potentially by regulating microglial activation in the spinal cord， inhibiting M1 polarization while promoting M2 polarization， and activating the IL-10/β-EP pathway to exert analgesic effects.