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.

Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.

Objective To investigate the clinical effect of free posterior interosseous artery perforator flap combined with muscle fascia for repairing soft tissue and extensor tendon defect of hand.Methods Fifteen cases of hand skin soft tissue and extensor tendon defect admitted to Ningbo No.6 Hospital from December 2017 to December 2020 were repaired with free posterior interosseous artery perforator flap combined with extensor carpi ulnaris muscle fascia transplantation,and curative effect was observed.Results All flaps survived and patients were followed up for 6-24 months.The texture and thickness of the flap were satisfactory,and the recovery of the finger extension and flexion function were good.The excellent and good rate of hand tendon repair was 66.7%.In three cases with nerve anastomosis,the skin flap sensation recovered to S3.Conclusion The free posterior interosseous artery perforator flap combined with muscle fascia has a good clinical effect in repairing hand skin soft tissue and tendon defect.

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.

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 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 observe regular monitoring in patients with chronic myeloid leukemia (CML) who received tyrosine kinase inhibitor (TKI), and to analyze its influencing factors. Methods A total of 857 patients with CML in Henan Tumor Hospital from October 2012 to October 2016 were collected. Patients were told to receive regular monitoring after receiving TKI treatment, including blood routine, bone marrow, BCR-ABL fusion gene and chromosomes. All patients were divided into good and poor compliance groups according to regular monitoring. Chi-square test was used to compare ABL kinase domain mutations rate and mortality between two groups. TKI species, level of education, duration from diagnosis to treatment, teaching times, sites of follow-up, convenience of transportation, annual income and gender were recorded respectively, and the factors affecting regular monitoring were analyzed by using single and multiple factor analysis. Results There were 390 and 467 patients in good and poor compliance groups respectively. Treatment failure rate was 19.49％ (76/390) and 25.91％ (121/467) in good and poor compliance groups respectively, the mutation rate was 28.95％ (22/76) and 7.44％ (9/121) respectively. The difference of ABL kinase domain mutation in patients with treatment failure of both groups was statistically significant (χ 2 =16.287, P < 0.01). The mortality was 0.77％ (3/390) in good compliance group, and 2.78％ (13/467) in poor compliance group, and the difference was statistically significant (χ 2 = 4.543, P = 0.033). The single factors analysis showed that TKI species, level of education, duration from diagnosis to treatment, teaching times, sites of follow-up, convenience of traffic and annual income were related with regular monitoring (all P < 0.05). Multiple-factor analysis showed that inconvenient transportation (β = 1.56, 95％ CI 1.74-3.74, P = 0.014), low education level (β = 1.67, 95％ CI 0.81-3.12, P = 0.041) and low income (β = 2.87, 95％ CI 1.31-4.51, 95％CI 1.74-3.74, P = 0.011) were independent factors for poor compliance in regular monitoring. In the result detection, 56 fusion genes fluctuated. Conclusions CML patients who received regular monitoring have a low treatment failure rate and mortality. Inconvenient transportation, low education level and low outcome are independent risk factors for regular monitoring. The single monitoring result can not prompt treatment effect, and thus it needs to review and monitor for many times.