[Efficacy and safety analysis of umbilical cord blood combined with haploid hematopoietic stem cell transplantation in the treatment of malignant hematological malignancies].

Objective: To investigate the efficacy and safety of umbilical cord blood combined with haploid HSCT (haplo-cord HSCT) in the treatment of hematological malignancies. Methods: The data of 82 patients with hematologic malignancies who received haplo-cord HSCT from January 2017 to June 2021 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. There were 52 male and 30 female patients, aged [M(Q1, Q3)] 29 (20, 41) years. All patients received myeloablative preconditioning regimen. The day of the donor stem cell infusion was recorded as day 0 (0 d), the day before the infusion was recorded as day-1 (-1 d), and the day after the infusion was recorded as day+1 (+1 d), and so on. Eighty-two patients received transfusion of peripheral blood and/or bone marrow stem cells from unrelated cord blood and haplotype donors after the myeloablative preconditioning regimen. The graft-versus-host disease (GVHD) prophylaxis regimen was 8 mg/kg ATG combined with cyclosporine, morte-macrolide, and methotrexate. Patients were evaluated for implantation and the occurrence of transplant-related complications such as GVHD, infection, hemorrhagic cystitis, and long-term patient survival. Results: The time of neutrophil engraftment [M(Q1, Q3)] was 13 (11, 15) days and 15 (13, 21) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 98.8% (81/82) and 100-day cumulative incidence of platelet engraftment was 92.7% (76/82). The cumulative incidence of acute graft-versus-host disease (aGVHD) in degree Ⅱ-Ⅳ and Ⅲ-Ⅳ was 24.4% (20/82) and 6.1% (5/82), respectively. The cumulative incidence of chronic GVHD in+18 months was 13.5% (11/82). The follow-up time [M(Q1, Q3)] was 26 (13, 41) months, and the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR) and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.5% (95%CI: 59.7%-81.3%), 66.1% (95%CI: 56.1%-76.1%), 6.3% (95%CI: 5.7%-26.9%) and 20.8% (95%CI: 12.0%-29.6%), respectively. The cumulative incidence of cytomegalovirus and EBV reactivation was 37.8% (31/82) and 14.6% (12/82), respectively. The cumulative incidence of hemorrhagic cystitis was 32.9% (27/82). Conclusion: The efficacy of haplo-cord HSCT in the treatment of hematologic malignancies is reliable, with rapid hematopoietic reconstitution, low incidence of GVHD and virus reactivation.

[Efficacy and prognosis of the dynamic monitoring lymphocyte to monocyte ratio in patients with diffuse large B-cell lymphoma].

Objective: To investigate the efficacy and prognosis of the dynamic monitoring lymphocyte to monocyte ratio (LMR) in patients with diffuse large B-cell lymphoma (DLBCL). Methods: The clinical data of 261 patients with DLBCL in the Affiliated Cancer Hospital of Zhengzhou University between March 2012 to March 2018, were analyzed retrospectively. The optimal cut-off values of LMR was determined using the receiver operating characteristic curve (ROC) method. Patients were divided into low LMR group and high LMR group according to the optimal cut-off value. The changes of LMR before and after treatment in two groups were dynamically monitored, and the relationship between LMR and efficacy and survival were analyzed. Results: Complete remission (CR) rate in patients with high LMR (64.7%) before treatment was significantly higher than that in patients with low LMR (33.3%) (P<0.05). Compared with the 5-year overall survival(OS) and progress free survival(PFS) (56.96% and 43.55%, respectively) in the low LMR group, the 5-year OS and PFS (82.92% and 66.25%, respectively) in the high LMR group were higher, and the difference was statistically significant (all P<0.05). Patients with elevated LMR after treatment in the high or low LMR group had a significant higher 5-year OS and PFS compared with patients with LMR reduction(P<0.05). LMR in both high and low LMR group were significantly lower at the last follow-up than those at the disease recurrence (all P<0.05). Both single and multivariate analyses showed that low LMR was an independent prognostic factor in patients with DLBCL (all P<0.05). Conclusions: LMR can be used as an indicator of risk stratification, efficacy, disease replase and prognosis in patients with DLBCL. Low LMR before and after treatment were poor prognostic factors in patients with DLBCL.

Genetic study of early-onset Graves' disease in the Chinese Han population.

Graves' disease (GD) is a complex autoimmune disorder in which genetic and environmental factors are both involved in the pathogenesis. Early-onset patients have a shorter exposure time to environmental factors and are, therefore, good models to help understand the genetic architecture of GD. Based on previous studies of early-onset GD, 11 single nucleotide polymorphisms (SNPs) and their related SNPs (R2 > .6), SNPs located within a ±1-Mb region of the FOXP3 gene, and 20 validated GD-risk SNPs were selected and screened for genotyping in 3735 GD and 4893 control patients to investigate whether early-onset GD is a subtype of GD with distinct susceptibility genes. Ultimately, we did not confirm the reported genetic markers of early-onset GD in our Chinese Han population but found that a GD-risk SNP located in the human leukocyte antigen class I region-rs4947296-was more strongly correlated with early-onset GD than non-early-onset GD. In addition, heterogeneity analysis of GD patients suggests that it may be more reasonable to define early-onset GD as an onset age ≤20 years.

[The clinical safety and efficacy of low dose subcutaneous decitabine in treating acute myeloid leukemia and intermediate- or higer-risk myelodysplastic syndromes in the elderly patients].

To retrospectively analyze the safety and efficacy of low dose subcutaneous decitabine regimen in patients with acute myeloid leukemia (AML) and intermediate- or higer-risk myelodysplastic syndrome (MDS). Of 6 AML cases, 2 achieved complete remission (CR), 2 with partial remission(PR), 1 with stable disease(SD), 1 with progressive disease(PD). As to the 8 MDS patients, one achieved CR and 6 with hematologic improvement (HI), 1 case SD. Low dose subcutaneous decitabine regimen could be an alternative choice of older AML or MDS patients.

[Clinical characteristics and analysis of patients with hematological diseases and HCV-Ab positive].

Objective: To observe the biological characteristics of patients with hematological diseases and hepatitis C antibodies positive and to investigate features of HCV infection and reactivation. Methods: A total of 85 patients with seropositive HCV at the hematology ward in Henan Cancer Hospital between October 2010 and October 2015 were analyzed. The clinical characteristics and laboratory data were retrospectively reviewed. Original disease treatment information was obtained from the medical records. Results: The positive rate of HCV-Ab was 1.2%, which was significantly higher than that of the general population(1.2% vs 0.4%, P<0.001). Of the 25 patients who showed anti-HCV seroconversion during the period of treatment or follow-up, serum ALT level was elevated in 15 patients(60.0%)and AST level got synchronous increase in 14 patients (56.0%). Of the 85 patients with positive HCV-Ab, 13 (15.3%) patients suffered from HCV reactivation with hepatic injury in varying degrees after chemotherapy or HSCT. Conclusions: Patients with hematological diseases have high incidence of HCV infection and reactivation, and most of them have hepatic injury. Chemotherapy and HSCT are important risk factors for HCV reactivation.

[Thalidomide combined with interferon and interleukin-2 in treatment of relapsed or refractory acute myelogenous leukemia].

In 12 patients with relapsed or refractory acute myelogenous leukemia (AML), the efficacy and safety of a novel regimen, namely thalidomide combined with interferon and interleukin 2 (IL-2), were initially explored.All the patients have received the triple-drug regimen for at least one cycle.Three patients achieved incomplete remission (CRi), 3 patients with partial remission.The overall response rate (ORR) was 50%.

[A single-center retrospective study of salvage allogeneic hematopoietic stem cell transplantation pretreated with MeCBA regimen for refractory/relapsed acute myeloid leukemia].

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

[Analysis of 9 cases of pediatric-type follicular lymphoma].

Objective: To summarize the pathological diagnosis, clinical features, treatment methods and outcomes of pediatric-type follicular lymphoma (PTFL). Methods: Clinical data including the pathology, clinical features, treatment methods, and follow-up results of 9 PTFL patients admitted to Henan Cancer Hospital from February 2017 to February 2023 were analyzed retrospectively. Results: The age of onset in 9 children was 6 to 18 years, all the patients were males. The clinical manifestation was local painless lymph node enlargement in the head and neck, with a stage of Ⅰ-Ⅱ. The histomorphological characteristics of PTFL were similar to those of classic follicular lymphoma (FL). The germinal center of most follicles were enlarged, the mantle zone disappeared, centroblasts were easily visible, and the histological grade were mostly grade Ⅲ, which may be accompanied by the "starry sky" phenomenon. Monoclonal peaks can be seen in B cell clonal rearrangements (BCR). Immunohistochemistry (IHC) showed CD20 positive, CD10 positive, Bcl-6 positive, Bcl-2 negative, C-myc negative, and Ki-67 was 70%-95%. Fluorescence in situ hybridization (FISH) test was negative for t (14, 18), Bcl-2 translocation, and C-myc translocation. Six cases underwent surgical resection, and 3 cases underwent surgical resection combined with chemotherapy. Up to February 2023, with a follow-up time of 45 to 72 months, all children survived without any recurrence and were in a complete remission state. Conclusions: PTFL is mainly characterized by adolescent male onset, with early clinical manifestations and pathological manifestations of high-level histological status, high proliferation index, and lack of t (14; 18)/Bcl-2 translocation and Bcl-2 expression. It is mainly treated by localized surgical excision and has a good prognosis.

[Efficacy and safety analysis of eltrombopag and recombinant human thrombopoietin combined with immunosuppressive therapy for severe aplastic anemia].

Objective: To evaluate the efficacy and safety of combination therapy of eltrombopag, recombinant human thrombopoietin (rhTPO) , and standard immunosuppressive therapy (IST) for severe aplastic anemia (SAA) . Methods: A total of 16 cases with SAA treated with IST combined with eltrombopag and rhTPO were retrospectively analyzed. Results: At 3 months, the total response rate was 81.3%, and the complete hematological response rate was 37.5%. At 6 months, the total response rate was 87.5%, and the complete hematological response rate was 50.0%. The median time of platelet transfusion independence was 35 (16-78) days, the median time of red blood cell transfusion independence was 47.5 (15-105) days, the median platelet transfusion was 5.5 (3-20) U, and the median red blood cell transfusion was 6.5 (2-16) U. Conclusion: The combination of eltrombopag and rhTPO can improve the hematological response rate of IST for SAA and the quality of hematological remission with minimal toxic effects.

Evidence of heterogeneity in the antibody response against the platelet antigen 3a; recognition of an 11-mer peptide carrying the HPA-3a polymorphic determinant.

BACKGROUND: The immune processes involved in the development of alloantibodies against the human platelet antigens in alloimmune disorders remain unclear. Antibody recognition of the platelet antigens on their respective platelet glycoproteins has been shown to be dependent on glycoprotein conformation. Furthermore, the post-translational modification of glycoproteins adds complexity to the alloantigenic determinants. METHODS: Nine anti-HPA-3a sera along with several control sera were tested for reactivity to an 11-mer peptide straddling the HPA-3a/b polymorphism. Sera found to specifically recognize the 3a peptide were further assessed by platelet pre-exposure and immunoblotting. RESULTS: Three of the nine antisera were found to specifically recognize an 11-mer synthetic 3a peptide by ELISA. Further analysis of all anti-HPA-3a sera by Western blot showed that only those reactive to the 3a peptide were able to bind both reduced and non-reduced GPIIb. CONCLUSION: The results presented in this study provide the first known evidence for the identification of an antibody population capable of recognizing a linear and non-glycosylated form of the HPA-3a epitope.

[Fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation].

Objective: To explore the availability and safety of fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Four acute leukemia patients suffered from refractory diarrhea after allo-HSCT. One of them was refractory intestinal infection, the others were intestinal graft versus host disease. One or two doses of fecal microbiota, 3.4-6.0 U for one dose, were infused via nasal-jejunal tube. The curative effect and side effects were reviewed. Results: Three cases achieved complete remission while 1 was stable disease. The side effects included fever, abdominal pain and diarrhea, which all were Ⅰ grade. Conclusion: Fecal microbiota transplantation was effective and safe for refractory diarrhea after allo-HSCT.

[Therapeutic effect of combined use of interferon alpha-1b, interleukin-2 and thalidomide on reversing minimal residual disease in acute myeloid leukemia].

Objective: To explore the effect of combination regimen of interferon alpha-1b, interleukin-2 and thalidomide (ITI regimen) on minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) who were in hematologic remission but MRD-positive. Methods: Eighteen patients (17 from Tumor Hospital of Zhengzhou University and 1 from the First People's Hospital of Pingdingshan City) with AML admitted from July 2016 to June 2018, who were in hematologic remission but MRD-positive were treated with different doses of ITI regimen, and the MRD levels were monitored. Results: Among 18 patients who received a conventional dose of ITI regimen for 1 to 2 months, 7 patients had undetectable MRD, 3 had significant decrease in MRD levels, 3 had elevated MRD level and had hematologic recurrence. Three patients with elevated MRD level received a higher dose of ITI regimen, 2 of them turned to MRD negative and the other 1 patient had decreased MRD level. The total response rate was 72.2%, and the response rate in patients with MRD > 1.0% was 57.1% (4/7) , and that of patients with MRD < 1.0% was 81.8% (9/11) , respectively. Conclusion: The ITI regimen can reduce the MRD level of patient with AML who are in hematologic remission but MRD-positive. The therapeutic effect could be improved by a higher dose administration of ITI regimen, and therapeutic effect may be negatively correlated with MRD level before treatment.

[Comparison of clinical efficacy between first-generation and second-generation tyrosine kinase inhibitors based regimen in the treatment of patients with BCR-ABL positive acute lymphoblastic leukemia].

Objective: To explore the clinical efficacy and prognostic factors of first-generation and second-generation tyrosine kinase inhibitors (TKI) based regimen in the treatment of patients with BCR-ABL positive acute lymphoblastic leukemia (ALL) . Methods: Retrospectively analyze the clinical characteristics and prognostic factors of 89 patients with BCR-ABL positive ALL from April 2012 to June 2018 in our hospital, the clinical efficacy of first-generation and second-generation TKI was compared. Results: 60 patients were classified into the first-generation TKI (imatinib) group, and 29 patients were in the second-generation TKI (dasatinib) group. There were no significant differences in gender, age, WBC, hemoglobin concentration, PLT, chromosomal karyotype, the types of fusion genes, allogeneic hematopoietic stem cell transplantation (allo-HSCT) and TKI initiation time between the two groups. The first-generation and second-generation TKI groups, for which the complete remission (CR) rate at the fourth week of induction therapy was 83.3% and 89.7% (P=0.637) , respectively, and the complete molecular remission (CMR) was 48.3%and 58.6% (P=0.363) , respectively, the difference was not statistically significant. The 2-year overall survival (OS) rate of first-generation and second-generation TKI group was 34.9% and 64.0% (χ(2)=4.743, P=0.029) , the 2-year relapse free survival (RFS) rate was 17.2% and 55.0% (χ(2)=8.801, P=0.003) , respectively. Multivariate analysis showed that complete molecular remission (HR=0.281, 95%CI 0.151-0.523, P<0.001) was independent favorable prognostic factor for overall survival (OS) , complete molecular remission (HR=0.209, 95%CI 0.112-0.390, P<0.001) and second-generation TKI (HR=0.318, 95%CI 0.158-0.641, P=0.001) were independent favorable prognostic factors for RFS. Conclusion: For TKI-based regimen of BCR-ABL positive ALL, second-generation TKI is superior to first-generation TKI in OS and RFS time.

[Clinical analysis of autologous hematopoietic stem cell transplantation in the treatment of advanced/recurrent nasal type extranodal NK/T-cell lymphoma].

Objective: To analyze the efficacy and safety of asparaginase based chemotherapy bridging autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of 16 patients with nasal type extranodal NK/T-cell lymphoma (ENKTL). Methods: From January 2012 to June 2017, 16 patients with nasal type extranodal NK/T-cell lymphoma reached complete remission by L-asparaginase based regimens, and then received auto-HSCT. Results: ①Of the 16 patients, 12 were males and 4 females, with a median age of 35.5 (14-61) years. There were 11 patients in the first complete remission (CR1) and 5 in the second CR (CR2) before transplantation, respectively. EB virus (EBV) DNA (EBV-DNA) was negative and positive in 13 and 3 cases respectively before transplantation. ②Hematopoietic reconstitution was achieved in all 16 cases. The median time for neutrophils implantation was 12 (8-17) days, and that of platelet implantation was 15.5 (12-24) days. ③To the last follow-up, there were no transplant related deaths, 3 patients died of disease progression. The median overall survival (OS) time and progression-free survival time (PFS) were not reached. Seven patients lived with no disease progression more than 2 years. ④The OS and PFS of patients at CR(1) before auto-HSCT are better than that of patients at CR(2), but there was no statistically significant difference (P=0.162, P=0.123). There was no significant difference in OS and PFS between EBV-DNA negative and positive patients before transplantation (P=0.280, P=0.244). Conclusions: L-asparaginase based regimens bridging auto-HSCT is a safe and highly effective for advanced-stage and relapsed ENKTL treatment.

[The expression of CRLF2 in adult Ph negative acute B lymphocytic leukemia and its prognostic significance].

Objective: To detect the expression of CRLF2 in adult Ph negative acute B lymphocytic leukemia (B-ALL) in newly diagnosed cases, and to investigate the relationship between CRLF2 and the general clinical characteristics, efficacy and prognosis. Methods: 103 cases of newly diagnosed adult B-ALL patients were investigated from Apr 2016 to Dec 2017 in the Department of Hematology, Henan Cancer Hospital. Bone marrow samples was used to detect the expression of CRLF2 in leukemic cells. The expression of CRLF2 ≥20% was defined as CRLF2-high group and <20% was defined as CRLF2-low group. The clinical characteristics and prognosis of the two groups were compared. Results: The Median overall survival (OS) and disease free survial (DFS) in CRLF2-high group were 9.0 months and 4.25 months, respectively. CRLF2-low group were 15.5 months and 10.25 months, respectively. There was a statistically significant difference in median OS and DFS between the two groups (P=0.007, P=0.000) . The 18-month OS and DFS in CRLF2-high group were 38.6% and 25.1%, respectively. CRLF2-low group were 57.8% and 42.3%, respectively. Multivariate analysis showed high expression of CRLF2 was an independent risk factor for OS (HR=2.991, 95% CI 1.429-6.261, P=0.004) and DFS (HR=2.374, 95%CI 1.146-4.960, P=0.041) in patients. Conclusion: Patients with high expression of CRLF2 had poor prognosis.

[Synchronous lymphoma and carcinoma-clinical analyses of 17 patients].

Objective: To explore the clinical features of patients with synchronous lymphoma and carcinoma. Methods: The clinical data of 17 patients with Synchronous lymphoma and carcinoma from February 2012 to October 2017 were analyzed retrospectively. Results: Among 17 patients of lymphoma, 1 case HL, 2 cases B-NHL, 6 cases MZBL, 3 cases DLBCL, 1 case mantle cell lymphoma (MCL) , 3 cases NK/T- cell lymphoma, 1 case anaplastic large cell lymphoma(ALCL). In terms of 17 patients with carcinoma, 3 cases esophageal carcinoma, 3 cases gastric carcinoma, 2 cases colorectal carcinoma, 7 cases thyroid carcinoma, 1 case hepatocellular carcinoma and lung cancer. Up to 15 patients received operation, and some of them combined with chemotherapy, radiotherapy and autologous transplant. Follow-up analysis showed that 3 cases was undergoing treatment, 2 cases lost follow-up, 4 cases died, 3 cases achieved CR, 3 cases remained to be at SD, and 2 cases assessed for progression or recurrence. Conclusion: The relationship between lymphoma and carcinoma was under discussion, patients with synchronous lymphoma and carcinoma were not unusual. We herein should raise awareness to avoid misdiagnosis.

[Sorafenib in combination with chemotherapy as first-line therapy for FLT3-ITD positive acute myeloid leukemia].

Objective: To analyze the clinical features of acute myeloid leukemia patients with Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation and the therapeutic effect of sorafenib in combination with chemotherapy as first-line therapy for these patients. Methods: Clinical features and therapeutic effect were retrospectively analyzed in 53 AML patients with FLT3-ITD mutation diagnosed in Henan Cancer Hospital from January 2013 to August 2016. The biological characteristics and clinical efficacy of chemotherapy in combination with or without Sorafeinb were analyzed. Results: FLT3-ITD mutation was identified in 53 AML patients, 22 cases (41.5%) were M(5) subtype. The median of the peripheral WBC was 61.00 (0.98-920.00) ×10(9)/L, and there were 50 (94.3%) patients with WBC>10×10(9)/L. The median of blast cell in bone marrow was 0.730 (0.234-0.966) . The total remission rate of all these 53 patients was 56.6% (30/53) . The complete remission (CR) rates in patients treated with chemotherapy in combination with sorafenib and patients with chemotherapy alone were 86.4% (19/22) and 35.5% (11/31) , respectively. The 1-year overall survival rates of the two groups were 78.3%% and 50.0% (P=0.041) , and 1-year progression free survival rates were 75.9% and 42.4% (P=0.044) , respectively. Conclusion: AML patients with FLT3-ITD mutation have the characteristics of high peripheral WBC, high blast cells in bone marrow and accompanying with M(5) subtype. Sorafeinb combined with chemotherapy can significantly improve CR rate and short term survival.