Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

Dysregulation of LncRNA ANRIL mediated by miR-411-3p inhibits the malignant proliferation and tumor stem cell like property of multiple myeloma via hypoxia-inducible factor 1α.

Long non-coding RNA (lncRNA) ANRIL has been reported to be closely related to the relapse of multiple myeloma patients. However, the functional role and underlying mechanism of lncRNA ANRIL in multiple myeloma are not known. This study aims to investigate the biological function of lncRNA ANRIL in multiple myeloma. In this study, compared with normal tissues from healthy donors, lncRNA ANRIL and HIF-1α expressions were up-regulated in tumor tissues from multiple myeloma patients. miR-411-3p expression was down-regulated in tumor tissues from multiple myeloma patients. Besides, lncRNA ANRIL can interact with miR-411-3p. HIF-1α was confirmed to be a target of miR-411-3p. Correlation analysis showed that lncRNA ANRIL expression was negatively correlated with miR-411-3p expression. HIF-1α expression was negatively correlated with miR-411-3p expression. Further transfection experiments showed that knockdown of ANRIL or overexpression of miR-411-3p significantly inhibited cell proliferation, tumor formation ability and tumor stem cell like property, promoted cell apoptosis in vitro. Finally, miR-411-3p mimic reduced tumor volume, improved survival rate, suppressed malignant proliferation and tumor stem cell like property in U266 xenograft model. Our results demonstrate that lncRNA ANRIL mediated by miR-411-3p promotes the malignant proliferation and tumor stem cell like property of multiple myeloma through regulating HIF-1α.

[The clinical study of invasive fungal infection in 76 cases of hematologic diseases].

OBJECTIVE: To investigate the risk factors, clinical features, efficacy and adverse reactions in patients of hematologic diseases with invasive fungal infections (IFI). METHODS: The risk factors and clinical features were retrospectively analyzed to compare the efficacy and safety of itraconazole with amphotericin B in treatment of IFI in 76 patients with hematologic diseases. RESULTS: Of the 76 patients, 68 (89.5%) used broad-spectrum antibiotics, 64 (84.2%) were treated with more than 2 courses chemotherapy, 43 (56.6%) were under agranulocytosis, 34 (44.7%) were using glucocorticoid for long terms, 27 (35.5%) were with peripheral or central venous catheter. The overall effective rates of itraconazole and amphotericin B were 60.5% and 61.5% respectively (P = 0.929). There was a significant difference between itraconazole and amphotericin B in hypokalemia (14.0% vs 42.4%, P = 0.005) while no other differences in adverse reactions were found. CONCLUSIONS: The risk factors of patients in hematologic diseases with IFI include chemotherapy, using broad septum antibiotics and agranulocysis. The therapeutic effect of itraconazole and amphotericin B in treatment of IFI is similar. The adverse reactions of itraconazole is less and slighter than amphotericin B.

[Analysis of Clinical Features and Risk Factors for Oral Ulcers and Bloodstream Infection in Patients with Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the risk factors of oral ulcers and bloodstream infection in patients with hematopoietic stem cell transplantation. METHODS: The clinical data of 401 hematopoietic stem cell transplant patients in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were retrospective analyzed, and the risk factors of oral ulcers and bloodstream infection statistical and analyzed. RESULTS: Among the 401 patients, the incidence of oral ulcers was 61.3% (246/401), and the incidence of bloodstream infection was 9.0% (36/401). A total of 40 strains of pathogenic bacteria were isolated from 36 patients, including 26 strains of Gram negative strains (65%), 13 strains of Gram positive strains (32.5%), and 1 strain of fungi (2.5%). Single-factor analysis showed that oral hygiene was associated with the occurrence of bloodstream infection, and the Multi-factor analysis showed that age ≥14 years old, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers. CONCLUSION: The incidence of oral ulcers in patients with hematopoietic stem cell transplantation is high. The age ≥14 years, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers in patients, and oral hygiene was associated with the occurrence of bloodstream infection.

[Gene Mutation and Overexpression of Newly Diagnosed Multiple Myeloma Patients].

OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION: There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

[The Clinical Characteristics and Outcomes of the Patients with POEMS Syndrome].

OBJECTIVE: To analyze the clinical characteristics of patients with POEMS syndrome and explore its effective treatment strategies. METHODS: The clinical data of 75 patients with POEMS syndrome treated in The First Affiliated Hospital of Zhengzhou University from June 2012 to June 2018 were collected and retrospectively analyzed. The clinical characteristics, treatment regimes and outcomes of the patients were summarized. RESULTS: The median age of 75 diagnosed patients was 50 (30-81) years old and 100% (75/75) of the patients were accompanied with peripheral neuropathy, 77.3% (58/75) with organ enlargement, 82.7% (62/75) with endocrine abnormality, 93.3% (70/75) with monoclonal plasma cell diseases and 64.0% (48/75) with skin changes. Among the 75 patients, 5 cases gave up treatment, while the others showed varying degrees of improvement after treatment. The hematological complete remission (CRH) rate of the 70 patients was 28.6% and the rate of neurological remission (RN) was 85.7%. BD and RD regimens showed better efficacy in CRH and RN than old schemes, such as VAD and COP (P<0.05). Two patients underwent sequential autologous hematopoietic stem cell transplantation (HSCT) after BD chemotherapy and achieved ideal therapeutic effects, including the significant improvement of peripheral neurological symptoms and the M protein turned negative. The median follow-up time of the 70 patients was 42 (4-103) months, while the 2-year overall survival rate (OS) was 86.7%, and the 5-year OS was 81.0%. CONCLUSION: The clinical manifestations of POEMS syndrome are complex and diverse, the clinicians therefore should be vigilant to reduce the misdiagnosis and missed diagnosis. Bortezomib or Lenalidomide can be recommended as the first-line medicines and autologous HSCT should be considered for appropriate patients.

[The Expression and Significance of Serum Protein ROCK2 in Patients with Chronic Graft-Versus-Host Disease].

OBJECTIVE: To investigate the expression and clinical significance of serum protein ROCK2 in patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The patients were divided into cGVHD group and control group (without cGVHD). The expression levels of serum protein ROCK2 were detected by ELISA in patients with or without cGVHD after allo-HSCT. RESULTS: The expression level of ROCK2 in serum of cGVHD patients was significantly higher than those in control group, moreover, the expression level of ROCK2 in severe cGVHD group was significant higher than that in moderate and mild cGVHD group (P<0.001). The expression level of ROCK2 was significantly decreased in the serum of cGVHD patients after treatment（P＜0.01）; the expression level of ROCK2 was significantly higher in the serum of cGVHD patients with lung as the target organ（P＜0.01）. The median survival time of patients with severe cGVHD were significantly shorter than that of patients with mild and moderate cGVHD（P＜0.05）. CONCLUSION: ROCK2 shows certain reference value in the evaluation of severity and prognosis of cGVHD, and may be a new target for the treatment of cGVHD.

Maintenance Treatment With Low-Dose Decitabine After Allogeneic Hematopoietic Cell Transplantation in Patients With Adult Acute Lymphoblastic Leukemia.

BACKGROUND: Post-transplant relapse remains a principal leading cause of failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with adult acute lymphoblastic leukemia (ALL). The aim of this study was to investigate the efficacy and safety of low-dose decitabine on the prevention of adult ALL relapse after allo-HSCT. METHODS: In this prospective study, we enrolled 34 patients with ALL who underwent allo-HSCT from August 2016 to April 2020 and received low-dose decitabine maintenance treatment after transplantation. The primary objectives were cumulative incidence of relapse rate (CIR), overall survival (OS), and disease-free survival (DFS). The secondary objectives were graft-versus-host disease (GVHD) and safety. RESULTS: Among the enrolled 34 patients, 6 patients relapsed and 6 patients died. The 2-year CIR, OS, and DFS were 20.2, 77.5, and 73.6%, respectively. Subgroup analysis revealed the 2-year CIR, OS, and DFS rates of 12 patients with T-ALL/lymphoblastic lymphoma (LBL) were 8.3, 90, and 81.5%, respectively. None of the seven patients with T-ALL relapsed. During maintenance treatment, only one patient (2.9%) developed grade IV acute GVHD and four (11.8%) patients had severe chronic GVHD. Thirty-two patients (94.1%) developed only grade I to II myelosuppression, and two patients (5.8%) developed grade III to IV granulocytopenia. CONCLUSIONS: Maintenance treatment with low-dose decitabine after allo-HSCT may be used as a therapeutic option to reduce relapse in patients with adult ALL, especially in patients with T-ALL. Our findings require confirmation in larger-scale controlled trials. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trials Registry, identifier ChiCTR1800014888.

Hematopoietic stem cell transplantation activity in China 2019: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Between 2008 and 2019, 58,914 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout China. In this report, we focus on 2019 data and describe current trends in HSCT in China. There was continued growth in transplant activity in China, with a rapid increase in haploidentical HSCT. In 2019, a total of 12,323 cases of HSCT were reported from 149 transplant teams, 78% (9597 cases) were allogeneic HSCTs. Haploidentical donor (HID) HSCT accounted for 60% (5771 cases) of allogeneic HSCT. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (24%), and the largest proportion of non-malignant diseases comprised aplastic anemia (AA) (13%). Multiple stem cell source composed 70% of HID and 28% of MSD, which was typical in China. The BuCy based regimen (59%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu based regimen (23%) and TBI-based regimen (12%). This survey clearly shows comprehensive information about the current state and recent trends for HSCT in China. Further efforts should be made to obtain detailed information.

[Clinical and Pathological Characteristics of Related-Renal Damage in Patients with POEMS Syndrome].

OBJECTIVE: To investigated the clinical and pathological characteristics of related-renal damage in patients with POEMS syndrome. METHODS: Five patients diagnosed as POEMS syndrome in our hospital were selected. Their clinical manifestation, pathological characteristics of kidney and laboratory examination were analyzed retrospectively. Among the 5 patients, three males and two females with a median age of 50 years old. The mean interval before diagnosis was 13.0±7.2 months. RESULTS: All the patients showed neuropathy, endocrinopathy, monoclonal plasma cell-proliferative disorder, skin changes and extravascular volume overload, in which 4 patients showed organomegaly. Proteinuria was found in 5 patients, and microhematuria was found in 4 patients. Moreover, 4 patients showed an elevated blood urea, while 2 patients showed creatinine elevation. 1 patient at chronic kidney disease (CKD)-G1 stage, 2 patients at CKD-G2 stage, and 1 patient at CKD-G3b stage, moreover, 1 patient at CKD-G5 stage. Endothelial injury and mesangial lesion were the main characteristics of renal pathology. 3 patients were pathologically diagnosed as thrombotic microangiopathy kidney damage, while 2 patients as light chain amyloidosis. CONCLUSION: POEMS syndrome is a multi-systemic disease with complex clinical manifestations. 5 patients had different degrees of renal insufficiency. Endothelial injury and mesangial lesion are the main features of renal pathology.

[Prognostic Value of CD123 in Acute Myeloid Leukemia Patients with Intermediate Risk in Normal Karyotype].

OBJECTIVE: To investigate the expression of CD123 in patients with acute myeloid leukemia (AML) and its relationship between clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis. METHODS: 365 patients with newly diagnosed AML (except M3) treated in the First Affiliated Hospital of Zhengzhou University were enrolled and retrospective analysis, and multi-parameter flow cytometry was performed to detect the expression of CD123 in myeloid leukemia cell population. CD123≥20% was defined as positive. Clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis of CD123+ and CD123- patients were compared and analyzed. RESULTS: The positive rate of CD123 in 365 newly diagnosed AML patients was 38.9%. Compared with the CD123- group, the white blood cell count (WBC), lactate dehydrogenase (LDH) level and bone marrow blast cell ratio were higher in the CD123+ group, and the ratio of NPM1 and DMNT3a gene mutations and the CBFß-MYH11 fusion gene was significantly increased, while the ratio of CEBPA gene mutation and AML-ETO fusion gene was significantly reduced. The rate of first inducing complete remission and total remission in CD123+ group was significantly lower than that in CD123- group. There was no significant difference in recurrence rate between the two groups (P>0.05). Survival analysis showed that in 77 AML patients with normal karyotype and intermediate risk, the 2-year overall survival (OS) rate and event-free survival (EFS) rate of the CD123+ group were significantly lower than those of the CD123- group. Multivariate analysis showed that CD123 was an independent prognostic risk factor for OS and EFS in AML patients with normal karyotype and intermediate risk. CONCLUSION: CD123 positive indicates that AML patients have higher tumor burden and are more difficult to reach remission. It is an independent risk factor for OS and EFS in patients with normal karyotype and intermediate risk, which is important to evaluate the prognosis of patients with AML without specific prognostic marker.

[Comparision of Mutational Spectrum between Elderly and Young Adults with Acute Myeloid Leukemia Based on Next Generation Sequencing].

OBJECTIVE: To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS). METHODS: The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (＜60 years old) were compared. RESULTS: The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ2=7.180, P=0.007) and (20.0% vs 6.7%) ( χ2=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ2=16.653, P=0.000) and (23.6% vs 8.7%)(χ2=9.041, P=0.003) respectively. CONCLUSION: The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.

[Gene Mutation in Acute Lymphoblastic Leukemia by DNA Sequencing].

OBJECTIVE: To analyze the characteristics of gene mutation in adult ALL and its clinical significance. METHODS: Clinical data of 134 primary adult ALL patients and DNA sequencing results of 16 kinds of gene mutation were collected. The characteristic of gene mutation and clinical significances were statistically analyzed. RESULTS: In 31 cases of 134 ALL cases (23.13%) the gene mutations were detected as follows: 19 cases of 114 B-ALL cases (16.67%), 11 cases of 19 T-ALL cases (57.89%) and 1 case of T/B-ALL. The incidence of T-ALL gene mutation was significantly higher than that of B-ALL (χ2=13.574, P<0.01). Twelve gene mutations were found, and the mutation rates was IL7R, NOTCH1, FLT3, TP53, FBXW7, PAX5, IKZF1, CREBBP, JAK3, JAK1, PHF6 and PTEN from high to low. Among 108 non-transplantable follow-up patients there was no significant difference in 1-year overall survival rate (49.7% vs 67.4%) and median non-recurrence survival time (214 days vs 260 days) between the gene mutation group (23 cases, 21.30%) and the non-mutation group(85 cases, 78.70%). There was a significant difference in 1-year survival rate between NOTCH1 mutation group (4 cases, 3.77%) and non-mutation group (102 cases, 96.23%) (50.0% vs 65.8%,χ2=9.840, P<0.01). CONCLUSION: There may be multiple gene mutations in adult ALL patients. IL7R and NOTCH1 are the most common gene mutations and NOTCH1 mutation may indicate poor prognosis. Detection of gene mutations is helpful to understand the pathogenesis of ALL and evaluate the prognosis of adult ALL patients.

[Change of Autophagic Activity of U266 Cells after Bortezomib -Resistance and Its Mechanisms].

OBJECTIVE: To explore the changes of autophagic activity after resistance of U266 cells to bortezomib (Bor) and its mechanisms. METHODS: The proliferation inhibition rate, 50% inhibitory concentration (IC50), drug-resistance coefficient, drug-resistance reversed multiple by 3-methyladenine (3-MA) in U266 and U266/Bor cells treated with Bor were detected and calculated by using MTT method, then the proliferation inhibition curve was drawed. The Western blot was used to detect the expression of LC3-I, IC3-II, p-mTOR, Beclin-1, ATG5 and ATG7 proteins. RESULTS: The Bor showed the its proliferation inhibition effect on U266 cells and U266/Bor cells, IC50 of Bor on U266 and U266/Bor cells on 24 hours were 35.7 nmol/L and 526.5 nmol/L respectively; the drug-resistance coefficient was 14.7; the drug-resistance reversed multiple by 3-MA was 2.7. The expression of LC3-II, Beclin11, ATG5 and ATG7 in U266/Bor cells was higher than that in U266 cells; after the treatment with Bor for 24 h, the expression levels of LC3-II, Beclin-1, ATG5 and ATG7 in U266 cells all decreased, as compared with levels before treatment; while the expression levels of LC3-II, Beclin-1, ATG5 and ATG7 in U266/Bor cells were higher than those before treatment. There were no significant difference of p-mTOR expression among U266, U266+Bor, U266/Bor, U266/Bor+Bor cells. CONCLUSION: The increase of autophagy closely relates with resistance of U266 cells to bortezomib, moreover with up-regulation of Beclin-1, ATG5 and ATG7 expression.

[Reversal Effect of Pioglitazone on Multidrug Resistance in K562/ADR Cells and Its Mechanism].

OBJECTIVE: To explore the reversal effect of pioglitazone (PIO) on multidrug resistance in K562/ADR cells and its mechanism. METHODS: The proliferation inhibition rate, half inhibition concentration (IC50) and drug-resistance reversal multipe were detected and the curve of proliferation inhibition rate was drawn by MTT assay, the transcription of PPARγ, CYP2C8 and CYP2J2 genes was detected by RT-PCR; the expression of PPARγ, CYP2C8 and CYP2J2 proteins was detected by Western blot. RESULTS: The IC50 of PIO on K562 and K562/ADR cells for 60 h was 326.7 µmol/L and 349.1 µmol/L respectively. The reversal multiple of 30 µmol/L PIO on ADR-resistance of K562/ADR cells was 6.4. After treatment of K562/ADR cells with PIO, the transcription of CYP2C8 and CYP2J2 and the protein expression of CYP2C8 and CYP2J2 significantly decreased, the transcription of PPARγ gene and the expression of PPARγ protein were not changed. CONCLUSIONS: Pioglitazone can reverse the adriamycin-resistance in K562/ADR cells that is closely related to the decrease of protein expression of CYP2C8 and CYP2J2. Pioglitazone is an effective multidrug resistance reversal agent for tumors.

Comparison of outcomes after human leukocyte antigen-matched and haploidentical hematopoietic stem-cell transplantation for multiple myeloma.

BACKGROUND: Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs). METHODS: Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up. RESULTS: Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90-30.10%) and 24.2% (95% CI, 13.81-34.59%) for the MRD group and 16.80% (95% CI, 1.71-31.89%) and 28.70% (95% CI, 8.71-48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24-71.36%) and 45.4% (95% CI, 33.44-57.36%), and 65.6% (95% CI, 47.18-84.02%) and 26.8% (95% CI, 7.59-46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD. CONCLUSION: Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

[Long Non Coding RNA RP11-69I8.3 Expression in Acute Leukemia and Its Cinical Significance].

OBJECTIVE: To investigate the expression of long non coding RNA RP11-69I8.3 in acute leukemia and its clinical significance. METHODS: lncRNA RP11-69I8.3 expression was detected by RT-PCR in bone marrow samples from 17 healthy controls, 32 newly diagnosed AML patients and 32 newly diagnosed ALL patients, and 25 ALL patients of complete remission after chemotherapy. Meanwhile, the clinical data were collected and the relation of lncRNA RP11-6918.3 expression with the clinical characteristics was analyzed. RESULTS: Compared with the control group, there was no significant difference in the expression of lncRNA RP11-69I8.3 in AML group(P>0.05). lncRNA RP11-69I8.3 lowly expressed in untreated ALL group(P=0.001). Compared with the de novo ALL group, lncRNA RP11-69I8.3 was highly expressed in complete remission ALL group (P<0.013). In 32 de novo ALL patients,the expression of lncRNA RP11-69I8.3 in children was significantly lower than that in adult(P=0.017). There was no correlation of the expression of lncRNA RP11-69I8.3 with the sex, WBC count, HB level, Plt count, LDH level, T or B type, ratio of bone marrow blast cell, BCR/ABL and WT1 fusion gene expression, chromosome karyotype, extramedullary infiltration, whether complete remission after one chemotherapy, whether relapse. In 26 B-ALL patients, there was no correlation between lncRNA RP11-69I8.3 and the immunophenotype. CONCLUSION: The expression of lncRNA RP11-69I8.3 in the untreated AML is not significantly different from the control group. lncRNA RP11-69I8.3 is low expressed in ALL group, highly expressed in ALL group with complete remission. In untreated ALL, the expression of lncRNA RP11-69I8.3 in children is significantly lower than that in adult. In B-ALL patients, the lncRNA RP11-69I8.3 is not relevant with the immunophenotype.

[Expression of Long-Chain Non-coding RNA RP11-87C12.5 in Acute Lymphocytic Leukemia and Its Cinical Significance].

OBJECTIVE: To investigate the expression of long-chain non-coding RNA RP11-87C12.5 in acute lymphocytic leukemia and its clinical significance. METHODS: LncRNA RP11-87C12.5 expression was detected by RT-PCR in bone marrow samples from 17 control group, 33 newly diagnosed ALL patients and 26 complete remission ALL patients after chemotherapy, at the same time the clinical data were collected and the clinical significance of IncRNA RP11-87C12.5 expression was analyzed. RESULTS: Compared with control group, lncRNA RP11-87C12.5 expression increased in newly diagnosed ALL group (P=0.021); compared with newly diagnosed ALL group, IncRNA RP11-87C12.5 expression decreased in complete remission ALL group (P=0.039). lncRNA RP11-87C12.5 expression in newly diagnosed ALL group did not relate with sex, age, T or B type, WBC count, Hb level, Plt count, LDH level, bone marrow blast ratio, BCR/ABL fusion gene expression, chomosome karyotypes, WT1 gene, extrameanllary infiltration or no,complete remission or no after one chemotherapy and relapse or no. In 27 cases of ALL, IncRNA RP11-87C12.5 expression significantly increased in cCD79a low expression group, compared with cCD79a high expression group (P=0.004). IncRNA RP11-87C12.5 expression did not relate with other CD molecules of immunoclassification. CONCLUSION: The expression of LncRNA RP11-87C12.5 is high in newly diagnosed ALL group and low in complete remission ALL group. In B-ALL, the expression of IncRNA RP11-87C12.5 significantly enhances in cCD79a low expression group. In newly diagnosed ALL group, compared with low expression group, lncRNA RP11-87C12.5 high expression group have higer remission rate and relapse rate, but the difference was not statistically significant.