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Objective: To analyze the effect of sorafenib as salvage therapy used before and/or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in refractory relapsed FLT3-positive acute myeloid leukemia (AML)., Methods: A total of 16 patients with refractory relapsed FLT3-positive AML, including 10 refractory relapsed pre-transplantation and 6 relapsed after allo-HSCT, were enrolled in this retrospective study. Sorafenib treatment protocols included sorafenib in combination with chemotherapy inducing remission, and sorafenib monotherapy as mauntenance treatment after complete remission (CR)., Results: Thirteen of the 16 patients achieved CR after one or two courses of induction therapy, including 7 refractory relapsed pre-transplantation and 6 relapsed after allo-HSCT. With a median follow up of 472 (range, 59-1569) days post-transplantation, 12 patients survived and 4 died. Causes of death included leukemia relapse (n=3) and acute graft-versus-host disease (n=1). The 2-year overall and disease-free survival post-transplantation of the 16 patients were (75.0±10.8) % and (50.5±13.7) % respectively. The main side effect of sorafenib was the skin rash. The incidence of rash was lower in the patients used sorafenib pre-transplantation than those post-transplantation (30.0% vs 75.0%, P=0.043)., Conclusion: Sorafenib used as salvage therapy befor and/or after transplantation for refractory relapsed FLT3-positive AML could reduce the relapse rate and improve the survival.

Objective: To explore the rate of breakthrough invasive pulmonary aspergillosis (IPA) in patients receiving surgical resection of pulmonary aspergillosis lesions prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: A retrospective analysis was conducted between January 2007 and June 2014. A total of 16 patients were enrolled, who had persistent pulmonary lesions including cavity (diameter >2.0 cm) or mass with a history of IPA prior to allo-HSCT in Nanfang Hospital of Southern Medical University. Ten of the 16 patients underwent thoracoscopic surgery before transplantation, i. e. surgery group, the other 6 patients did not have surgery because of primary underlying diseases (non-complete remission) or multiple lesions i. e. non-surgery group. Secondary prophylactic agents were administrated based on treatment response to initial antigual therapy. The 1-year cumulative and breakthrough rate of IPA, the median time of secondary antifungal prophylaxis (SAP) and overall survival were compared between surgery and non-surgery groups., Results: Within a median follow-up of 364 days after transplantation (range 73 to 400 days). The success rate of SAP was 15/16. The 1-year cumulative and breakthrough IPA were 0 and 0 in surgery group, compared with 3/6 and 1/6 in non-surgery group. The median duration of SAP in surgery group and non-surgery group was 95(74-134)days and 192.5 (56-280)days respectively, which was significantly shorter in surgery group (P=0.017). The overall survival between two groups was 8/10 and 4/6 (P=0.534). No discontinuation of SAP happened in both groups due to drug-related adverse events., Conclusions: In patients with persistent pulmonary IPA lesions, surgical resection followed by SAP might be effective to reduce breakthrough IPA after transplantation with short duration of prophylaxis.

Objective: To investigate the value of C-reactive protein (CRP) on transplantation day in predicting early post-transplant infections and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: We retrospectively analyzed the clinical data of 78 recipients undergoing allo-HSCT. The clinical reference value of CRP on transplantation day was determined, and its sensitivity and specificity for diagnosing bacteremia was analyzed using receiver-operating characteristic curve (ROC). The incidence of transplant-related complications, overall survival, and relapse rate of the patients were analyzed with respect to the CRP level., Results: The clinical reference value of CRP for diagnosing bacteremia was 23.3 mg/L (AUC=0.735 [95% CI: 0.623-0.848], P=0.001), which had a diagnostic sensitivity and specificity of 0.793 and 0.592, respectively. Compared with the patients with low CRP levels, the patients with high CRP levels tended to have delayed neutrophil reconstitution and platelet engraftment by 0.71 days (P=0.237) and 4.09 days (P=0.048), respectively, and had a significantly higher incidence of bacteremia (17.1% vs 53.5%, P=0.001) and CMV viremia (37.1% vs 72.1%, P=0.003) within 100 days following the transplantation; the incidences of EBV viremia, pulmonary invasive fungal infection, or acute graft versus host disease (aGVHD) showed no significant difference between the two groups (41.9% vs 22.9%, P=0.094; 14.0% vs 5.7%, P=0.285; 51.2% vs 45.7, P=0.656, respectively). During the follow-up for a median of 318 (7-773) days in high-CRP group and for 299 (78-747) days in low-CRP group, the high-CRP group showed a significantly lower 2-year overall survival than the low-CRP group (42.5% vs 78.4%, P=0.022), and tended to have a higher 2-year cumulative relapse rate (52.3% vs 19.8%, P=0.235). Logistic multivariate analysis identified a high CRP level on transplantation day as the independent risk factor for post-transplant bacteremia within 100 days (OR=5.090 [95% CI: 1.115 -23.229], P=0.036)., Conclusion: A high CRP level on transplantation day can be indicative of a high risk of early post-transplant bacteremia and CMV viremia and also a poor prognosis following allo-HSCT.

Objective: To explore the therapeutic effects of sequential intensified conditioning regimen followed by graft-versus-1eukemia (GVL) induction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory advanced acute myeloid leukemia (AML)., Methods: A total of 72 patients with refractory AML undergoing allo-HSCT from May 2001 to June 2013 were enrolled in this prospective study. Intensified conditioning included fludarabine + cytarabine plus total body irradiation + cyclophosphamide + etoposide. Cyclosporine A was withdrawn rapidly in a stepwise fashion if patients who did not experience acute graft-versus-host disease (aGVHD) at Day + 30 post-transplantation. Donor lymphocytes were infused in patients without grade II or more than grade II aGVHD at Day + 60 post-transplantation., Results: The median follow-up time was 655 (1-4 200) d post-transplantation. Except for one died of infection and one died of regimen-related toxicity (RRT), the other 70 patients achieved complete remission at the time of neutrophil reconstitution. The mortality of RRT was 1.4% (1/72). The 1-year cumulative incidence of aGVHD and 2-year incidence of chronic GVHD (cGVHD) post-transplantation were 60.7% ± 5.0% and 58.5% ± 4.7%. The 5-year cumulative incidence of relapse post-transplantation was 29.6% ± 6.6%. The 5-year non-relapse mortality was 28.8% ± 6.0%. The 5-year overall and disease-free survival were 51.0% ± 6.5% and 49.9% ± 6.4%. Multivariate analysis revealed that donor lymphocyte infusion, cGVHD and bone marrow blasts at Day 0 were independent prognostic factors for relapse (HR (95% CI): 0.042 (0.007-0.688), 0.009 (0.003-0.345), 3.385 (1.451-7.899)) and survival (HR (95% CI): 0.315 (0.146-0.621), 0.416 (0.200-0.866), 1.332 (1.158-1.533))., Conclusion: The strategy of sequential intensified conditioning followed by GVL induction has an acceptable toxicity profile, and could decrease the relapse rate and improve the survival for refractory AML.

Objective: To compare the clinical efficacy of HLA- mismatched related donor (MRD) and HLA-matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies., Methods: 174 patients with hematopoietic malignancies undergoing allogeneic HSCT (allo-HSCT) (82 from MRD and 92 from MUD) between June 2002 and December 2012 were enrolled in this retrospective study. Hematopoietic engraftment, graft versus host disease (GVHD), relapse, overall survival (OS) and disease-free survival (DFS) were compared between MRD and MUD group., Results: There was no significant difference between MRD and MUD group in terms of age, gender, disease type and disease status before transplantation (all P>0.05). The incidence of Ⅰ-IV acute GVHD (aGVHD) was 62.2% and 54.3% in MRD and MUD group (P=0.295); the incidence of III-IV aGVHD between the two groups was 15.9% and 9.8% (P=0.229). The incidence of chronic GVHD (cGVHD) was 28.4% and 45.1% in MRD and MUD group (P=0.036), but there was no significant difference in the incidence of extensive cGVHD between the two groups (9.0% vs 12.2%, P=0.525). The mortality of GVHD was 8.5% and 10.9% in MRD and MUD group (P=0.605). The 10-year OS and DFS were (50.1±6.1)% and (48.8±6.1)% in MRD group, compared with (50.5±6.7)% and (46.3±6.2)% in MUD group (P=0.501, P=0.873, respectively). The 10-year cumulative relapse rate was (21.5±5.7)% and (37.6±7.3)% in MRD and MUD group (P=0.194)., Conclusion: MRD is equivalent to MUD in efficacy and safety. Without HLA- matched related donors, MRD is superior to MUD because donor source is unlimited and transplantation could be made promptly according to disease status.

Objective: To explore the impact of courses of intermediate-dose cytarabine (ID-Ara-C) chemotherapy on the efficiency of hematopoietic stem cell mobilization in acute myeloid leukemia (AML) patients with autologous hematopoietic stem cell transplantation (auto-HSCT)., Methods: 90 patients with de novo AML undergoing auto-HSCT between August 1999 and November 2012 were enrolled. All patients received the mobilization regimen of cytarabine and etoposide chemotherapy in combination with recombinant human granulocyte-colony stimulating factor (rhG-CSF). Stem cell apheresis was scheduled when blood leukocyte count recovered greater than 4.0 × 10⁹/L or the proportion of CD34⁺ cells greater than 1% in peripheral blood. The impact of ID-Ara-C courses on the mobilization efficiency was analyzed retrospectively., Results: According to the ID-Ara-C courses, patients were divided into group A (<2 courses), B (2 courses), and C (>2 courses). The median doses of CD34⁺ cells (×10⁶/kg) in three groups were 4.7, 2.7, 2.3, respectively (P=0.003). Of the available 87 patients who could be evaluated, 61 (70.1%) cases had CD34⁺ cells greater than 2.0 × 10⁶/kg, and 26 (29.9%) cases less than 2.0 × 10⁶/kg. Of the 26 patients without satisfactory mobilization efficiency, 7 (15.2%) were in group A, 10 (47.6%) in group B, and 9 (45.0%) in group C (χ²=10.05, P=0.007). In addition, patients with satisfactory mobilization efficiency (CD34⁺ cells ≥ 2.0×10⁶/kg) in groups C needed more times of collection, more volume of blood processed, and even high-dose and longer course of rhG-CSF (P<0.05). In univariate analysis. The ID-Ara-C courses and the cumulative dose were significant correlate with mobilization efficiency. In multivariate analysis, the ID-Ara-C courses was an independent correlation factor for mobilization efficiency (odd ratio=0.623, 95% confidence interval=0.418-0.926, P=0.019). The sex, age, cytogenetic risk, the standard chemotherapy courses did not correlate with mobilization efficiency., Conclusion: The number of ID-Ara-C courses was independent factor for the mobilization efficiency and should be taken seriously in AML patients with auto-HSCT.

A method for the determination of histamine, 2-phenylethylamine, tryptamine, putrescine, cadaverine, spermidine and spermine in fish using micellar electrokinetic capillary chromatography (MECC) was developed. Seven biogenic amines (BAs) were extracted from a sample with 6% perchloric acid, then derivatized with benzoyl chloride. 0.02 mol/L borate buffer (pH 9.2) containing 0.06 mol/L sodium deoxycholate-methanol (95 : 5, v/v) was used as a running buffer. The detection wavelength was set at 214 nm. The separation was achieved within 12 min. Good linearities were observed from the calibration plots in the concentration ranges. The detection limit of histamine was 15 microg/g and those of the other amines were 5 microg/g. The developed method was successfully employed for the simultaneous determination of 7 BAs in fish sample with satisfactory results.