The Prognostic Value of Early Relapse after Autologous Hematopoietic Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To assess the impact of early relapse (ER) after autologous hematopoietic stem cell transplan-tation (AHSCT) on overall survival (OS) for multiple myeloma (MM) patients.@*METHODS@#Clinical data of 37 patients with MM undergoing AHSCT in department of hematology of Shanxi Bethune Hospital from January 2012 to December 2017 were retrospectively analyzed. The effect of ER on OS of patients was analyzed. The effects of international staging system (ISS) staging, cytogenetics, pre-transplant efficacy, minimal residual disease, and age on OS of the patients were also analyzed respectively.@*RESULTS@#Among the 37 patients, 13 cases (35.1%) had ER, and 24 cases (64.9%) had non-ER. 3 patients with ER had extramedullary disease, but none with non-ER showed extramedullary disease. More than or equal to very good partial rate (VGPR) in patients with ER and without ER were 3 cases (23.1%) and 15 cases (62.5%), respectively, and the curative effect of the former was significantly lower than that of the latter (P<0.05). The median follow-up time was 31 (12-96) months, and median OS time was 93 months in all the patients. The median survival time of patients with ER was 17 months, and the median progression free survival was 7 months, both were significantly shorter than 93 months and 38 months of patients with non-ER (P<0.05). Univariate analysis showed that the OS was affected by ER, cytogenetic abnormalities (FISH), and ≥VGPR before transplantation. Multivariate analysis showed that ER was an independent prognostic factor.@*CONCLUSION@#The prognosis of patients with ER after AHSCT in newly diagnosed MM is poor. ER is an independent prognostic factor of survival.

Mechanism of IGF-1 in Pathological Pain / 中国生物化学与分子生物学报

Pathological pain is also called chronic pain, including neuropathic pain, inflammatory pain, and cancer pain. These three types of pain mainly come from complications or late effects of various diseases. Pathological pain is a kind of sensation, different from visual, auditory and other independent existence, but mixed with other sensations. It is difficult to distinguish accurately, which brings great difficulties to clinical treatment and patient recovery. Although the search for analgesic targets has been extensively and deeply studied in pain-related fields, there is still a lack of effective therapies or drugs with less or no side effects. Insulin-like growth factor-1 (IGF-1) is a member of the insulin-like growth factor family, which is widely expressed in the central nervous system and peripheral nervous system and exerts neurotrophic and nerve repair effects, and has received increasing attention in the field of pain in recent years. However, in the study of pathological pain, some scholars have found that IGF-1 plays two opposite roles of neuroprotection and neurotoxicity in the occurrence and maintenance of neuropathic pain and inflammatory pain, which can not only promote the transmission of nociceptive information but also block the transmission of nociceptive information. In cancer pain, it is found that IGF-1 only participates in the transmission of nociceptive signals and then plays a neurotoxic role. This paper briefly reviews the mechanism of IGF-1 participation in three kinds of pathological pain, and discusses the possibility of IGF-1 as an analgesic target.

Prophylactic effect of TLR5 agonist flagellin on acute graft versus host disease after allogeneic hematopoietic stem cell transplantation and its mechanism / 中国实验血液学杂志

This study was aimed to investigate the prophylactic effect of Toll like receptor (TLR)5 agonist flagellin on acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its possible mechanism. The animal model with allo-HSCT aGVHD was established by using purebred mice (male mouse C57BL/6 as donor, female mouse BALB/c as recipient) with complete-unidentical major histocompatibility antigen. The recipient mice were randomly divided into 3 groups: group 1 in which mice were injected with high purity (95%) flagellin before and after allo-HSCT respectively, group 2 in which mice received allo-HSCT without injection of flagellin, group 3 in which mice were radiated alone. The aGVHD features of mice in group 1 and 2 were observed and compared. The results showed that the typical symptoms of aGVHD appeared in transplanted mice. The death peak of mice in group 2 appeared at day 4-5 after transplantation. The aGVHD symptoms were obviously alleviated and the mean survival time was prolonged significantly in mice group 1 as compared with mice in group 2 (P < 0.05). The comparison of WBC count in peripheral blood of mice in 3 groups before transplantation showed no significant difference (P > 0.05), while WBC count of mice in group 1 and 2 showed the significant difference at days 14 and 21 after transplantation (P < 0.05). The pathological appearances of aGVHD in mice of group 1 were obviously reduced as compared with mice in group 2. The flow cytometric detection of Treg cell/CD4(+) T cell levels at different time before and after transplantation demonstrated that the Treg cell level in mice of group 1 at weeks 2-4 after transplantation significantly increased as compared with mice in group 2 (P < 0.05). It is concluded that flagellin can effectively prevent the aGVHD occurrence after allo-HSCT, reduce the symptoms and pathological changes of aGVHD, obviously prolong mean survival time of mice in group 1. The mechanism of flagellin effect may be associated to increase of Treg cell level in mice after allo-HSCT.

Effect of bortezomib on the drug sensitivity of imatinib resistant K562/G01 cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of bortezomib (BOR) on the drug sensitivity of imatinib-resistant chronic myeloid leukemia cell line K562/G01 cell and its mechanism.</p><p><b>METHODS</b>MTT assay was used to detect the inhibition effect of cell growth, flow cytometry to cell cycle, and real time-PCR to the expression of COX-2 and mdr1 mRNA.</p><p><b>RESULTS</b>Combination of 10 and 20 nmol/L BOR with imatinib could significantly enhance the sensitivity of K562/G01 to imatinib, the reverse factor was 1.83 and 2.72-fold respectively. Cell cycle arrested at G(2)/M phase could be observed by flow cytometry on BOR treatment. The over-expression of COX-2 and mdr1 could be down-regulated by BOR.</p><p><b>CONCLUSIONS</b>BOR can enhance the imatinib sensitivity of imatinib resistant K562/G01 cell. The mechanism may be related to cell cycle phase arrested at G2/M and down-regulation of COX-2 and mdr1 expression.</p>

Relationship between CD4(+)CD25(+) regulatory T cells, IL-2, TGF-beta and acute graft-versus host disease after allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was aimed to investigate the relationship between CD4(+)CD25(+) regulatory T cells, IL-2, TGF-beta and acute graft-versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The percentage of peripheral blood CD4(+)CD25(+) Treg cells in CD4(+) T cells of 13 patients with hematological malignancies after allo-HSCT were detected by flow cytometry; serum levels IL-2 and TGF-beta in these patients were measured by ELISA. The results indicated that all the patients achieved engraftment. 5 patients developed aGVHD of grade I-II, 4 patients developed aGVHD of grade III-IV. The percentage of peripheral blood CD4(+)CD25(+) Treg cells out of CD4(+) T cells in patients without aGVHD was higher than that in patients with aGVHD (p < 0.05); the serum level of IL-2 in patients without aGVHD was lower than that of patients with aGVHD (p < 0.05); the serum level of TGF-beta in patients without aGVHD was higher than that of patients with aGVHD (p < 0.05). It is concluded that CD4(+)CD25(+) Treg cell level and the serum level of IL-2 and TGF-beta all are related to incidence and severity of aGVHD. These factors may be used as indicators for early evaluating and monitoring aGVHD after allo-HSCT.