Systemic mastocytosis (SM) with RUNX1-RUNX1T1 positive acute myeloid leukemia (AML) is a rare myeloid tumor with no standard treatment. Two cases of SM patients with RUNX1-RUNX1T1 positive AML treated with sequential avapritinib after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were reported in Henan Cancer Hospital. Mast cell in bone marrow disappeared, C-KIT mutation and RUNX1-RUNX1T1 fusion gene remained negative. Allo-HSCT sequential avapritinib is an effective treatment for SM patients with RUNX1-RUNX1T1 positive AML.

Objective:To investigate the efficacy and safety of avapritinib in the treatment of molecular biologically positive core binding factor-acute myeloid leukemia (CBF-AML) with KIT mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:We retrospectively analyzed the clinical data of six patients with molecular biologically positive CBF-AML with KIT mutation after allo-HSCT, who were treated with avapritinib at Henan Cancer Hospital from December 2021 to March 2023, and evaluated the efficacy and safety of avapritinib.Results:After 1 month of treatment with avapritinib, the transcription level of the fusion gene decreased in six patients, and the transcription level decreased by ≥1 log in five patients. In four patients who received avapritinib for ≥3 months, the fusion gene turned negative, and the median time to turn negative was 2.0 (range: 1.0-3.0) months. Up to the end of follow-up, four patients had no recurrence. The most common adverse reaction of avapritinib was myelosuppression, including neutropenia in two cases, thrombocytopenia in two cases, and anemia in one case. The non-hematological adverse reactions were nausea in two cases, edema in one case, and memory loss in one case, all of which were grades 1-2.Conclusion:Avapritinib was effective for molecular biologically positive CBF-AML patients with KIT mutation after allo-HSCT. The main adverse reaction was myelosuppression, which could generally be tolerated.

Objective To systematically evaluate the effect of red ginseng on improving metabolic syndrome,and to provide basis for clinical practice.Methods Retrieval from PubMed,Embase,The Cochrane Library,Web of Science,Clinical Trials Gov,WanFang Data and CNKI databases,articles of RCTs about red ginseng on improving metabolic syndrome were included.The searching range was from the establishment of the database to May 2022.The articles were screened according to inclusion and exclusion criteria,and then the inclusion study was analyzed through RevMan 5.4.1 software.Results Totally 17 randomized controlled trials involving 957 patients were included.Compared with the control group,red ginseng exhibited significant effect on fasting blood glucose,total cholesterol,low-density lipoprotein,systolic blood pressure and diastolic blood pressure(P<0.05),and its effect was related to the disease,age,duration of administration and dosage.Conclusion Red ginseng could significantly improve the symptoms of hyperglycemia,hyperlipidemia and hypertension in metabolic syndrome,which provides a theoretical basis for clinical use of red ginseng in treating metabolic syndrome.

To analyze the prognostic factors of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute lymphoblastic leukemia (ALL).The clinical data of 33 relapsed patients in 95 ALL patients receiving allo-HSCT were analyzed retrospectively. The median time of relapse was 5.7 (0.7-52.3) months. Extramedullary relapse was recorded in 10 cases (10.5%), bone marrow relapse in 15 cases (15.8%), and both extramedullary and marrow relapse were seen in 8 cases (8.4%). The median time of EMR was 7.4(0.7-52.3) months. The most commonly involved organ was central nervous system, followed by testis and bone. The 3-year OS rate in EMR patients was (33.3±11.1) %. Univariate analysis showed that disease state before transplantation ( P=0.026), extramedullary infiltration before transplantation ( P=0.005), conditioning regimens ( P=0.033) and acute graft-versus-host disease(aGVHD) ( P=0.013) were significantly correlated with EMR. Multivariate analysis suggested that extramedullary infiltration ( RR=5.067, 95 %CI1.542-16.645, P=0.007) and aGVHD( RR=3.585, 95 %CI1.245-10.320, P=0.018) were independent predictive factors of EMR in ALL patients after allo-HSCT.

Objective:To evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia.Methods:A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively.Results:Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR ( P<0.05). Multi-variable analysis revealed that CR2 or progressive disease ( RR=3.468,95% CI 2.189-7.786), abnormal karyotype ( RR=1.494,95% CI 1.020-2.189) and extramedullary disease before transplantation ( RR=8.627,95% CI 3.921-18.452) were independent risk factors of EMR. Conclusions:The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.

Objective:To explore the clinical characteristics, diagnosis, treatment and prognosis of patients with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).Methods:The main clinical manifestations, auxiliary examination results, diagnosis and treatment process, and follow-up data of 5 patients with POEMS syndrome in Fujian Medical University Union Hospital from April 2017 to November 2018 were retrospectively analyzed, and the features of diagnosis and treatment were discussed with review of literature.Results:The patients with POEMS syndrome had typical manifestations of polyneuropathy (5 cases), organomegaly (4 cases), increased extravascular volume load (4 cases), endocrine changes (5 cases), etc. The patients were also accompanied by clinical manifestations of skin changes (2 cases), bone damage (3 cases), kidney damage (2 cases), anemia (4 cases), etc. Three cases were misdiagnosed as chronic Guillain-Barré syndrome. Five patients were followed up regularly, with a median follow-up time of 16 months (13-33 months). Until the end of follow-up, 1 patient who received DVD regimen chemotherapy had a disease-free survival time of 22 months and a survival time of 24 months; 1 patient underwent autologous hematopoietic stem cell transplantation after receiving pretreatment of melphalan scheme, and the survival time was 6 months; the remaining 3 patients were in the disease-free survival period, and among which 1 patient survived 9 months without disease after autologous hematopoietic stem cell transplantation, 1 patient survived 16 months without disease, and 1 patient survived 18 months without disease.Conclusions:The onset of POEMS syndrome is insidious, its clinical manifestations are complex, and it is easy to be misdiagnosed or missed. Clinicians should strengthen their understanding of this disease.

Objective: To observe the pregnancy outcome among patients with chronic myeloid leukemia (CML) treated with Nilotinib (NIL) . Methods: Clinical data of pregnancy delivery in CML patients treated with NIL from March 2015 to January 2019 were retrospectively collected. Results: A total of 11 patients were recruited with median pregnancy age 28 (25-40) years. The median duration of NIL treatment before pregnancy was 34 (3-48) months. There were 12 pregnancies, included 2 planned ones and 10 (83.3%) unplanned. In the 10 unplanned patients, 9 (90.0%) received NIL 600 mg/d. The median exposure time were 4 (4-7) weeks. In eight patients with delivery outcomes, 5 cases had well-developed babies, 2 had spontaneous abortion and 1 case with an baby of syndactyly deformity, whose mother was exposed to NIL 600 mg/d for 7 weeks in the early trimester of pregnancy. Seven infants were 4 boys and 3 girls with the median height at birth 50 (41-54) cm and median weight 3.2 (3.0-4.6) kg. They all grew with a normal pattern and well developed. Now the median age is 19 (4-41) months. The disease status during 12 pregnancies included 3 cases in CMR, 2 cases in MR^4.0, 3 cases in MMR, 4 cases not acquiring MMR. The median time of drug discontinuation was 35 (15-36) weeks during pregnancy. No patient lost CHR during this period. Conclusions Female CML patients exposed to NIL 600 mg/d for 4 weeks in early pregnancy can give birth to normal babies, but there is still a risk of spontaneous abortion and congenital malformations.

Objective: To investigate the influence of additional clonal chromosome abnormalities in Ph negative cells (CCA/Ph^-) on the efficacy of chronic myeloid leukemia (CML) after tyrosine kinase inhibitors (TKI) treatment. Methods: The clinical data of 28 CML patients with CCA/Ph^- treated in Henan Cancer Hospital from July 2014 to December 2017 were analyzed retrospectively. The univariate analysis was carried out by Kaplan-Meier method. Multivariate analysis was done by Cox proportional risk model. Results: A total of 28 CCA/Ph^-patients were recruited including 17 males and 11 females with median age of 42.5 years old. The most common CCA/Ph^-were trisomy 8 (60.7%), monosomy 7 (14.3%). 64.3% CCA/Ph^-were transient and 35.7% recurrent (more than 2 times). Cytopenia in two or three lineages of peripheral blood was seen in 42.9% patients. As to the efficacy, 89.3% patients achieved major cytogenetic response (MCyR), 25% with major molecular response (MMR). The median follow-up time was 26.5 months. Treatment failure (TF) of TKI occurred in 32.1% patients with median duration of response 8 (1-41) months. Univariate analysis showed that TF rate was significantly correlated with the frequency of CCA/Ph^-and cytopenia (all P<0.05). The MMR rate was also significantly correlated with cytopenia (P<0.05). Cytopenia of two lineages or pancytopenia was an independent risk factor related to MMR rate (RR=3.868, 95%CI 1.216-12.298, P=0.022) . Conclusions Cytopenia in CCA/Ph^-appears to be an independent risk factor of MMR in CML patients with TKI treatment. The recurrent CCA/Ph^-may link to higher treatment failure rate. Drug withdrawal or alternative strategy should be considered according to response and the ABL kinase mutations.

Objective: To investigate the characteristics and prognosis of clonal chromosomal abnormalities appearing in Philadelphia negative metaphases (CCA/Ph^-) cells in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy. Methods: The clinical data of 30 cases with CCA/Ph^- during TKI treatment in Henan Cancer Hospital from August 2007 to July 2017 were retrospectively analyzed. The univariate factor was analyzed by Kaplan-Meier method. Multiple-factor was analyzed by Cox proportional risk model. Results: Of the 30 cases, 19 (63.3%) were males. At the first detection of CCA/Ph^- the median age was 44 (rang 14-68) years old and the median treatment of TKI was 13 (rang 2-94) months. The clones proportion of first detected CCA/Ph^-≥ 50% was found in 18 (60.0%) cases. TKI treatment for 3 months with BCR-ABL^IS less than 10% was seen in 14 (46.7%) patients. 63.3% (19/30) of CCA/Ph^- was transient (only one time) and 36.7% (11/30) was repeated (≥2 times) . Trisomy 8 dominant accounted for 60.0% (18/30) , -7/7q- for 13.3% (4/30) , loss of chromosome Y 6.7%. With a median of follow-up 50 months, 76.7% (23/30) cases were in complete cytogenetic response (CCyR) ; 63.3% (19/30) in major molecular response (MMR) , 43.3% (13/30) in undetectable minimal residual disease (UMRD) . The median event-free survival rate of (EFS) were 44 months, and 2-year and 5-year EFS were (82.1±7.3) % and (52.4±12.8) %, respectively. The median overall survival (OS) were 50 months, and 2-year and 5-year OS rates were (92.6±5.0) % and (77.2±14.7) %, respectively. Univariate analysis shows that the 2-year EFS of who in males, more than 2 times CCA/Ph^-, BCR-ABL^IS>10% at 3 months after TKI were significantly lower than women, transient CCA/Ph^-, and BCR-ABL^IS≤10% (P<0.05) . The 2-year OS rate in whom the occurrence frequency of CCA/Ph^- more than twice was significantly lower than those with transient CCA/Ph^- (P<0.05) . Multivariate analysis showed that CCA/Ph^- was an independent risk factor (RR=4.741, 95%CI 1.21-18.571, P=0.018) for EFS in CML patients. Conclusion Trisomy 8, -7/7q-, and -Y were the most common CCA/Ph^- during TKI treatment, with high clones proportion of ≥50%. CCA/Ph^- mainly occurred transiently or was permanent occasionally. CCA/Ph^- recurrence (≥2 times) was an independent risk factor for EFS and OS in CML with TKI.

Objective To analyze the clinical features,efficacy and outcomes in patients with transplantation associated thrombotic microangiopathy (TA-TMA).Methods The clinical data of 9 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were retrospectively analyzed from January 2011 to August 2018 in Affiliated Tumor Hospital of Zhengzhou University.Results There were 6 male and 3 female patiens with a median age of 31 (12-38) years.The median time from transplantation to TA-TMA was 76 (24-155) days.The baseline blood and biochemical parameters at diagnosis of TA-TMA included median hemoglobin (Hb) 66 (58-77) g/L,platelet (PLT) count 22 (4-38) × 109/L,serum lactic dehydrogenase (LDH) 655 (305-4 238) U/L,blood urine nitrogen (BUN)level 15.9 (4.8-26.2) mmol/L,blood creatinine (Cr) level 118 (24-380) μmol/L.The proportion of median peripheral blood schistocytes was 2.6％(1.2％-9％).All patients had positive urinary occult blood tests,and urinary protein was seen in 4 patients.Three patients had mental symptoms.Coombs tests were all negative.The main treatments of TA-TMA composed of reduction and withdrawal of calcineurin inhibitor,steroids and plasma exchange.Response was seen in 4 patients.Patients who did not response to the treatment had a higher proportion of schistocytes,more severe acute graft-versus-host disease (aGVHD),more elevated serum LDH and other transplant-related complications.Conclusions TA-TMA after allo-HSCT is a serious complication with high mortality rate.The proportion of schistocytes in peripheral blood,serum LDH level and comorbidities are prognostic factors of clinical outcome.