BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.

Follicular lymphoma (FL) is an indolent lymphoma derived from B cells, and most patients have a good prognosis, high remission rate and long overall survival. However, approximately 2%-3% of FL patients develop aggressive lymphoma during treatment or surveillance each year. Transformed FL has high heterogeneity and poor prognosis, and may be involved in clonal evolution by a variety of molecular mechanisms such as bcl-2 mutation, myc mutation, histone modification genes mutation, CDKN2A/B deletion and disruptions in the tumor microenvironment. At present, there are no standard biomarkers available to predict the transformation and prognosis. In this paper, the pathological characteristics, gene mutation and tumor microenvironment of FL histologic transformation are reviewed.

Extranodal NK/T cell lymphoma (ENKTCL) is a group of highly aggressive non-Hodgkin lymphoma associated with epstein-barr virus infection. Asparaginase-based chemoradiotherapy regimens are not effective in advanced patients. In recent years, anti-programmed-death receptor 1 (PD-1)/programmed-death receptor ligand 1 (PD-L1) immunotherapy has developed rapidly, which can effectively improve the prognosis of ENKTCL patients. But some patients with ENKTCL still have low response rate. This article reviews the mechanisms of resistance to anti-PD1/PD-L1 therapy and other immune targets in ENKTCL recently to change the traditional treatment mode of ENKTCL through the combination of different targeted drugs.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Objective:To explore the correlation between the expression of signaling lymphocyte activation molecule family 6 (SLAMF6) on peripheral blood CD8 +T cells and perforin and granzyme B and the clinical significance in patients with newly diagnosed severe aplastic anemia(SAA). Methods:The indicators of blood routine and bone marrow and peripheral blood samples of 32 newly diagnosed SAA patients admitted to Henan Provincial People′s Hospital from January 2016 to June 2019 were collected for retrospective analysis. Flow cytometry was used to detect the expression of SLAMF6, perforin and granzyme B on samples CD8 +T cell before therapy and 6 months after therapy (11 cases received transplantation, 21 cases received immunosuppressive therapy [IST]). Spearman correlation analysis was performed to determine the association between clinical indicators and laboratory test results. The expression of SLAMF6, perforin and granzyme B was also detected in 10 healthy people (normal group) and 13 myelodysplastic syndromes/paroxysmal nocturnal hemoglobinuria (MDS/PNH) patients (MDS/PNH group). Results:(1) At diagnosis: the expression of SLAMF6 was significantly lower in the SAA group than that in the normal group and the MDS/PNH group ([56.40±6.37]% vs [84.34±5.81]% and [82.24±4.98]% (both P<0.001]). The expression of perforin was significantly higher in the SAA group (32.73±8.46) than that in the normal control group (23.75%±5.10%), and the MDS/PNH group (26.12%±5.53%) (both P<0.05). The expression of granzyme B was also significantly higher in the SAA group (36.23%±7.94%) than that in the normal control group (21.67%±5.05%) and the MDS/PNH group (21.79%±5.10%) (both P<0.001). The expression of SLAMF6 was positively correlated with the hemoglobin ( r=0.804), and reticulocyte absolute values ( r=0.656) in peripheral blood, percentage of granulocytes ( r=0.643) and erythrocytes ( r=0.622) in bone marrow of SAA patients (all P<0.05). Expression of SLAMF6 was negatively correlated with perforin ( r=-0.792) and granzyme B ( r=-0.908) on CD8 +T cells in patients with SAA (both P<0.001). (2) After treatment: the expression of SLAMF6 in peripheral blood CD8 +T cells of 30 surviving patients was higher than pre-treatment ([79.19±12.69]% vs [56.40±6.37]%, P<0.001). The expressions of perforin and granzyme B were lower than pre-treatment level (both P<0.05). The expression of SLAMF6 on CD8 +T cells in 11 transplanted patients was higher than before transplantation ([86.54±3.75]% vs [56.40±7.35]%, P<0.001). The expressions of perforin and granzyme B were lower than before transplantation (both P<0.05). The expression of SLAMF6 on CD8 +T cells in 12 IST-respond patients was higher than that before treatment, while the perforin and granzyme B levels were lower than pre-treatment (all P<0.05). The post-treatment expressions of SLAMF6, perforin and granzyme B were similar as before treatment levels in 7 IST-unrespond patients (all P>0.05). Conclusion:SLAMF6 is significantly down-regulated on CD8 +T cells in newly diagnosed SAA, negatively correlated with the effective factors of CD8 +T cells, which might participate in the immune regulatory of CD8 +T cells as a negative regulatory factor in patients with SAA. The SLAMF6 is significantly up-regulated after hematopoietic recovery, while there is no significant change in treatment-unrespond patients, which could thus serve as an useful diagnostic and therapeutic index of patients with SAA.

Objective:To investigate the effects of additional chromosomal abnormalities (ACA) in Philadelphia chromosome-positive (Ph +) cells on biological characteristics, therapy efficacy, and prognosis of patients with primary chronic myeloid leukemia (CML) -chronic phase (CP) and those who developed CML-accelerated phase/blast phase (AP/BP) during therapy. Methods:The clinical data of 410 patients with Ph + CML, including 348 patients with primary CML-CP and 62 patients who progressed to CML-AP/BP during treatment, who were admitted to Henan People's Hospital from January 2013 to June 2020 were retrospectively analyzed to categorize into high-risk, non-high-risk, and non-ACA groups according to the ELN2020 criteria. The effects of high- and non-high-risk ACA on biological characteristics, therapy efficacy, and prognosis were compared. Results:①Among the 348 patients with primary CML-CP, 20 patients (5.75% ) had ACA, including 3 and 17 patients with high-risk and non-high-risk ACA, respectively, whereas the remaining 328 patients did not have ACA. There were no significant differences in baseline clinical characteristics between those with and without ACA ( P>0.05 for all) . The rates of complete hematological response, complete cytogenetic response, major molecular remission, and 5-year overall survival (OS) were not significantly different between the non-high-risk ACA and non-ACA groups ( P>0.05 for all) ; however, the 5-year progression-free survival of the non-high-risk ACA group (42.0% ) was significantly lower than that of the non-ACA group (74.5% ) ( χ2=4.766, P=0.029) .②Of the 62 patients who progressed to CML-AP/BP during treatment, 41 patients (66.13% ) had ACA, including 28 and 13 patients with high-risk and non-high-risk ACA, respectively, whereas the remaining 21 patients did not have ACA. Platelet counts of the high-risk ACA group (42.5×10 9/L) were lower than those of the non-high-risk (141×10 9/L) and non-ACA groups (109×10 9/L) ( χ2=4.968, P=0.083) . There was no significant difference in the incidence of point mutations in ABL kinase among the three groups ( P=0.652) . The complete cytogenetic response of the high-risk ACA group (5.3% ) was significantly lower than that of the non-ACA group (46.7% ) ( χ2=5.851, P=0.016) . The 5-year OS of the high-risk ACA group was lower than that of the non-ACA group (46.2% vs 77.8% , χ2=3.878, P=0.049) . Subgroup analysis revealed that the 5-year OS rate of the high-risk group Ⅱ, which included -7/7q-, i (17q) , and complex karyotype comprising ≥2 high-risk ACA, was significantly lower than that of the non-ACA group (28.6% vs 77.8% , χ2=8.035, P=0.005) whereas the 5-year OS rate was not significantly different between high-risk group Ⅰ, which included +8,+Ph, and complex ACA with +8/+Ph, and the non-ACA group (54.5% vs 77.8% , χ2 =1.514, P=0.219) . Conclusion:Due to different disease stages and ACA/Ph + types, treatment response and prognosis vary among patients with CML harboring ACA/Ph +. The emergence of high-risk ACA during therapy suggests worse therapy efficacy and prognosis. Strict and standardized cytogenetic monitoring is critical for early detection, precise diagnosis, and treatment of these patients.

Diffuse large B-cell lymphoma (DLBCL) is the most common invasive non-Hodgkin lymphoma, which responds well to R-CHOP regimen immunochemotherapy, but 30%-40% of the patients eventually develop relapsed and refractory DLBCL. Therefore, the discovery of new prognostic markers is essential to improve the diagnosis and treatment of DLBCL. Immune escape is an important mechanism for the occurrence and development of DLBCL. Studies have shown that TIM-3, BTLA and LAG-3 are highly expressed in DLBCL, which could inhibit the effective function of immune cells in tumor microenvironment, and promote the immune escape of lymphoma cells. Thus, they promote the occurrence and development of DLBCL and affect the effect of conventional chemotherapy. It is important to explore the effects of the above three inhibitory molecules on DLBCL, and they are expected to become new targets for the treatment of DLBCL.

Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.

Objective:This study aims to investigate the characteristics of gene mutation and clinical prognosis in de novo acute myeloid leukemia (AML) patients with myelofibrosis (MF) .Methods:From January 1, 2016, to February 1, 2020, 103 newly diagnosed AML patients in Henan Provincial People’s Hospital who simultaneously underwent bone marrow biopsy examination were included. They were divided into the AML-MF group (MF grades 1-3) and the AML without MF group (MF grade 0) , and the clinical features, gene alterations, chemotherapy efficacy, and prognosis were compared between the two groups retrospectively.Results:①MF was confirmed in 44.7% of AML patients (46/103) , of which 84.8% (39/46) were MF-1 and 15.2% (7/46) were MF-2/3, while MF was not confirmed in 55.3% (57/103) of AML patients. The median of WBC in the AML-MF group was significantly higher than in the AML without MF group [11.205 (0.69-191.82) ×10 9/L vs 4.64 (0.18-95.10) ×10 9/L, P=0.024]. More patients in the AML-MF group had nucleated erythrocytes in the peripheral blood (43.5% vs 24.6% , χ2=4.119, P=0.042) . All four AML-M 0 patients were in the AML-MF group, while AML without MF group had a higher proportion of AML-M 2 ( P=0.014) . ②FLT3-ITD and NPM1 mutations were more frequent in the AML-MF group ( P=0.021 and 0.039) , while CEBPA mutation was more frequent in the AML without MF group ( P=0.029) . ③The CR rate in the AML-MF group was significantly lower than in the AML without MF group (69.7% vs 93.2% ) ( χ2 =7.412, P=0.006) . Multivariate analysis showed that MF, especially the grade of fibrosis, was an independent risk factor for CR in de novo AML. ④The 3-year OS of patients in the AML-MF group was significantly lower than in the AML without MF group (20.5% vs 72.2% , χ2=4.032, P=0.045) . Subgroup analysis showed that OS and PFS of AML-MF1 and AML-MF 2/3 groups were also significantly worse than those of the AML without MF group ( P=0.001) and MF, especially MF ≥2, was an independent marker for inferior OS and PFS in de novo AML ( P=0.021 and 0.044) . Conclusion:AML-MF has unique laboratory and clinical characteristics. MF is an independent risk factor for CR, OS, and PFS in AML. Evaluation of MF is very significant for therapy efficacy and prognosis judgment in de novo AML.

Multiple myeloma bone diseases (MMBD) is a series of osteolytic changes caused by plasma cells malignant proliferation,including bone pain,hypercalcemia,osteoporosis,pathological fracture,etc.MMBD has insidious onset,high misdiagnosis rate and poor prognosis.The broken-up bone homeostasis model due to the activated osteoclasts and inhibited osteoblasts is considered as the core mechanism.More and more studies suggest that osteocyte is the key to regulate the activity of osteoclasts and osteoblasts,and the occurrence of MMBD is regulated by some cytokines.This article reviews the mechanisms of MMBD.