Clinical outcomes of three haploidentical transplantation protocols for hematologic malignancies based on data from the Chinese Bone Marrow Transplantation Registry Group.

This study aimed to demonstrate the clinical outcomes of granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG), posttransplantation cyclophosphamide (PTCy) and PTCy combined with lowdose ATG (PTCy with ATGlow)-based haploidentical transplantation protocols in patients with haematologic malignancies. The comparisons were conducted via propensity score matching (PSM) analysis to balance the basic characteristics among different groups and were based on the transplantation data reported to the Chinese Bone Marrow Transplantation Registry Group (CBMTRG) from January 2020 to December 2022. For each patient in the PTCy or PTCy with ATGlow group, patients (at a 1:2 ratio) from the GCSF/ ATG group were selected. In total, the PTCy group (n=122) was matched with G-CSF/ATG Group 1 (n=230), and the PTCy+ATGlow group (n=123) was matched with G-CSF/ATG Group 2 (n=226). Compared with those in the PTCy group, the incidences of 28-day neutrophil engraftment (P=0.005), 100- day platelet engraftment (P=0.002), median time to neutrophil engraftment (P.

Hematopoietic stem cell transplantation activity in China 2022-2023. The proportions of peripheral blood for stem cell source continue to grow: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice.

Hematopoietic Stem Cell Transplantation Activity in China 2020-2021 During the SARS-CoV-2 Pandemic: A Report From the Chinese Blood and Marrow Transplantation Registry Group.

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplantation teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplantation teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (37%) and acute lymphoblastic leukemia (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (13%). The peripheral blood stem cell source accounted for 41% of HIDs and 75% of matched sibling donors. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and total body irradiation-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China.

BACKGROUND: There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China. METHODS: From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups. RESULTS: Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300). CONCLUSIONS: Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

[Expression of Hydrodynamic Injection-mediated PD-L1 in Myeloablative Conditioning Mouse Model].

OBJECTIVE: To establish the mouse model for the expression of PD-L1 by hydrodynamic injection and to study the effects of myeloablative conditioning on hydrodynamic injection-mediated PD-L1 expression. METHODS: Plasmid amplification, hydrodynamic injection, collagenase perfusion, real time PCR, ELISA and flow cytometry were applied to test the expression and function of PD-L1. Also, animal models were set up to test the effects of chemical or radiactive myeloablative conditioning on hydrodynamic injection-mediated PD-L1 expression. RESULTS: The expression of PD-L1 mRNA and protein could be detected as early as 8 h after hyrodynamic injection and reached peak expression by 24 h, and returned to baseline level by 7 d after injection. Serum PD-L1 level reached to 100 µg/ml as early as 24 h after injection and plateaued at 7 d after injection. Serum PD-L1 persisted for 3 weeks and declined to baseline after 1 month of hydrodynamic injection. The PD-L1 function induced by hydrodynamic injection was consistent with literature reports. At each time point, the PD-L1 expression was not different significantly between the myeloablative conditioning group and control group; the mice transfected with PD-L1 showed a higher survival rate than that in control group. CONCLUSION: Myeloablative conditioning does not affect hydrodynamic injection-mediated PD-L1 expression, indicating that the PD-L1 can be used in HSCT mouse model.

Efficacy of ZnPcS2P2 photodynamic therapy solely or with tumor vaccines on mouse tumor models.

BACKGROUND AND OBJECTIVES: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and B7.1 transduced tumor vaccine cells could induce efficient anti-tumor immune response. It is interesting to study whether they could be an adjuvant to photodynamic therapy (PDT). Recent in vitro study proved that novel photosensitizer ZnPcS2P2 has capability of effective photodynamic killing of leukemic cells. In this preliminary study, we evaluated the photodynamic efficacy of ZnPcS2P2 on two tumor models and the improving anti-tumor efficacy of PDT in combination with GM-CSF gene-transduced vaccine and B7.1 gene-transduced vaccine. METHODS: Nude mice bearing human leukemia xenograft and C57BL/6 mice bearing EL-4 thymic lymphoma were used to evaluate photodynamic efficacy of ZnPcS2P2. The EL-4 thymic lymphoma was used to test the improving anti-tumor efficacy of ZnPcS2P2-PDT in combination with GM-CSF gene-transduced vaccine and B7.1 gene-transduced vaccine. Each vaccine was administered near the tumor bed three times: 2 days before PDT, 0 and 2 days after PDT. RESULTS: ZnPcS2P2-PDT could significantly reduce tumor growth and prolong the survival time in both tumor models. Improving anti-tumor efficacy of ZnPcS2P2-PDT was demonstrated when utilizing GM-CSF-transduced vaccine and B7.1-transduced vaccine prior to and after ZnPcS2P2-PDT in lymphoma-bearing mice. Twenty-five percent of lymphoma-bearing mice were completely cured with a combination of PDT and vaccine cells. CONCLUSIONS: ZnPcS2P2-PDT may be a beneficial treatment for hemotopoietic malignance. GM-CSF-transduced vaccine and B7.1-transduced vaccine could strengthen ZnPcS2P2-PDT-elicited anti-lymphoma potency.

[Identification of the isoform in type II receptor of transforming growth factor-beta in patients with acute leukemia and its clinical significance].

Recent research indicates that TGF-beta and type II receptor (TbetaR-II) play an important role in the pathogenesis of tumor. A high frequency of abnormalities in TbetaR-II has been demonstrated in various cancers. To identify the mutation of TbetaR-II in patients with acute leukemia, the bone marrow samples from 6 patients with acute leukemia and 11 normal individuals as control were detected by long-range RT-PCR. To detect a deletion in sequence of the TbetaR-IIgene, the PCR products were cloned to T vector and then sequenced. The results showed that there was existance of the isoform of TbetaR-II in 2 cases out of 6 patients with acute leukemia. These two patients had more poor prognosis than others. In conclusion, there was the isoform of TbetaR-II in partial patients with acute leukemia, and the isoform may be related with prognosis.

[Anti-lymphoma effects of ZnPcS2P2-mediated photodynamic therapy combined with mGM-CSF and mB7.1 gene-modified vaccine].

AIM: To explore the anti-lymphoma efficacy of ZnPcS(2)P(2)-mediated photodynamic therapy(PDT) combined with mGM-CSF and mB7.1 gene-modified high-tumorigenicity lymphoma cells (EL-4 cells) in C57BL/6 mice. METHODS: EL-4/pLXSN, EL-4/GM and EL-4/B7 were generated by consecutive infection of EL-4 cells with respective retroviruses, i.e pLXSN, pLXSNmGM-CSF and pLXSNmB7.1. The total of 40 C57BL/6 mice receiving the inoculation of EL-4 cells five days before the experiment, were randomly divided into five groups with 8 in each group: control group (without any treatment), ZnPc-PDT control group, ZnPc-PDT+EL-4/pLXSN control group, EL-4/B7+EL-4/GM control group and ZnPc-PDT+EL-4/B7+EL-4/GM group. The procedure of PDT was carried out as follows: the mice were injected with ZnPcS(2)P(2) via the lateral tail veins, and 4 h later the tumor was irradiated with 670 nm laser. The size of tumor node was measured every other day. The survival time and relative tumor volume(RTV) of each group were compared. The histological morphology of tumor was observed. RESULTS: Compared with each control group, the survival time of experimental group was significantly prolonged (P<0.01). Moreover, difference of the survival time was measured between ZnPc-PDT control group and EL-4/B7+EL-4/GM control group (P=0.01). CONCLUSION: Tumor-localized immune stimulation by mGM-CSF and mB7.1 remarkably enhanced ZnPc-PDT-elicited anti-lymphoma potency.

[New insight into the mechanism of p53 inducing leukemia cell apoptosis].

OBJECTIVE: To investigate the expression changes of intrinsic cytokines TGF-beta(1) and TNF-alpha, telomerase activity and bcl-2 during ongoing apoptosis of HL-60 and K562 cells induced by p53. METHODS: pN53cG (Val135), a temperature sensitive p53 mutant, which behaved like wild type p53 (wt-p53) at 32.5 degrees C, were introduced into p53-null HL-60 and K562 cells respectively by lipofectin. In the presence of G418, HL-60-pN53cG and K562 pN53cG clones expressing p53 protein were selected. The ongoing expression of intrinsic cytokines (TGF-beta(1) and TNF-alpha), bcl-2 oncogene and hTERT mRNA during the apoptosis of HL-60 and K562 cells induced by p53 and the effects of exogenous p53 gene, TGF-beta(1) and TNF-alpha antisense PS-ODNS on the apoptosis of HL-60 and K562 cells and the expression of bcl-2 were studied by RT-PCR, quantitative RT-PCR, DNA fragmentation, TdT-mediated dUTP nick end labeling (TUNEL) and flow cytometery. The levels of secreted TGF-beta(1) and telomerase activity were detected by ELISA and PCR-ELISA, respectively. RESULTS: (1) The expressions of intrinsic TGF-beta(1) and TNF-alpha mRNA were up-regulated, while that of bcl-2 and hTERT down-regulated. The levels of TGF-beta(1) in the supernatant of HL-60 and K562 cells were increased, and the level of telomerase activity decreased. (2) Antisense PS-ODNS of TGF-beta(1) and TNF-alpha could obviously inhibit the p53 inducing cell apoptosis, and restore bcl-2 mRNA and protein to pre-treated level. CONCLUSIONS: Exogenous p53 induces leukemia cell apoptosis via up-regulating the expression of intrinsic TGF-beta(1) and TNF-alpha and down-regulating the expression of hTERT and bcl-2.

[Effect of p53 gene on telomerase activity and hTERT gene expression in HL-60 cells].

To investigate the change of telomerase activity and human telomerase reverse transcriptase (hTERT) gene expression in HL-60 cells transfected with wild type p53 gene, wild type p53 gene was introduced into HL-60 cells by Lipofectin transfection. Apoptosis was analyzed by TUNEL assay. Telomerase activity and the level of hTERT mRNA were detected by telomeric repeat amplification protocol (TRAP)-ELISA and RT-PCR, respectively. The results showed that the apoptotic rate of HL-60-pN53cG cells was 8.3% and 21.0% respectively after cultured at 32.5 degrees C for 24 h and 72 h. The level of hTERT mRNA was decreased to 68.4% and 55.8% and telomerase activity to 27.3% and 8.9% of control value in HL-60-pN53cG cells at the same points. In conclusions, hTERT mRNA and telomerase activity were down-regulated in HL-60 cells transfected with p53 gene. This may be one of mechanisms of apoptosis induced by wild type p53 gene.

[Study on telomerase activity and expression of hTERT, c-myc and bcl-2 during terminal differentiation of HL-60 cells induced by retinoic acid].

The study was to explore the telomerase activity and the expression of hTERT, c-myc and bcl-2 mRNA during terminal differentiation of HL-60 cells induced by all trans-retinoic acid (ATRA) and to study the possible molecular mechanism. By use of the model of differentiated HL-60 cells induced by ATRA, the telomerase activity was determined by TRAP-PCR-ELISA and the expression of hTERT, c-myc, bcl-2 mRNA was detected by RT-PCR in differentiated HL-60 cells. The results showed that during differentiation of HL-60 cells, the telomerase activity was decreased, the expression of hTERT, c-myc and bcl-2 mRNA was downregulated, and the downregulation of hTERT occurred prior to suppression of telomerase activity. It is concluded that the telomerase activity is related to decrease expression of hTERT, c-myc and bcl-2 mRNA during HL-60 cell differentiation induced by ATRA.