[Study on Immunophenotypes and Gene of Acute Lymphoblastic Leukemia--Review].

Transplantation-associated thrombotic microangiopathy (TA-TMA) is one of the fatal complications of hematopoietic stem cell transplantation(HSCT). The pathogenesis of TA-TMA has not been fully elucidated. The latest researches show that the abnormal activation of the complement system may lead to widespread endothelial injury which may play an important role in the pathogenesis of this disease. Incontrotable hypertension, proteinuria, increase of soluble C5b-9 concentration and early pericardial effusion are the risk factors of TA-TMA . In this review, the latest advances of pathogenesis, early diagnosis, treatment and other aspects of the progress of TA-TMA are summarized, so as to provide new ideas to early diagnosis and treatment in TA-TMA.

Prognostic significance of osteopontin in acute myeloid leukemia: A meta-analysis.

Osteopontin (OPN) has been investigated in the field of tumor research for several years. However, the prognostic role of OPN overexpression in acute myeloid leukemia (AML) remains controversial. A meta-analysis of four studies, including a total of 492 patients, was performed to determine the association of OPN with overall survival (OS) in AML patients. The random-effects model of Der Simonian and Laird was used to synthesize data; hazard ratio (HR) with its 95% confidence interval (CI) was used as the effect size estimate. It was observed that serum-based OPN was inversely correlated with OS and the difference was statistically significant (HR=1.83; 95% CI: 1.43-2.35; P<0.001). Experimental findings indicate that OPN overexpression is associated with a poor prognosis in AML and may be of prognostic value for AML stage and metastasis.

Infections during induction therapy of protocol CCLG-2008 in childhood acute lymphoblastic leukemia: a single-center experience with 256 cases in China.

BACKGROUND: Infections remain a major cause of therapy-associated morbidity and mortality in children with acute lymphoblastic leukemia (ALL). METHODS: We retrospectively analyzed the medical charts of 256 children treated for ALL under the CCLG-2008 protocol in Beijing Children's Hospital. RESULTS: There were 65 infectious complications in 50 patients during vincristine, daunorubicin, L-asparaginase and dexamethasone induction therapy, including microbiologically documented infections (n = 12; 18.5%), clinically documented infections (n = 23; 35.3%) and fever of unknown origin (n = 30; 46.2%). Neutropenia was present in 83.1% of the infectious episodes. In all, most infections occurred around the 15 th day of induction treatment (n = 28), and no patients died of infection-associated complications. CONCLUSIONS: The infections in this study was independent of treatment response, minimal residual diseases at the end of induction therapy, gender, immunophenotype, infection at first visit, risk stratification at diagnosis, unfavorable karyotypes at diagnosis and morphologic type. The infection rate of CCLG-2008 induction therapy is low, and the outcome of patients is favorable.

[The Clinical features of myeloma bone disease.].

OBJECTIVE: To analyze the clinical features of patients with newly diagnosed myeloma bone disease (MBD). METHOD: Clinical features of MBD in two hundred and five patients with newly diagnosed multiple myeloma (MM) were analyzed retrospectively. The relationship between outcome of different grades of MBD patients and their prognosis was compared. RESULTS: (1) Among the 205 patients, one hundred and fifty (72.7%) had bone pain as the first symptom. (2) According to X-ray evaluation, there were 23 (11.3%) of grade 0, 14 (6.9%) grade 1, 23 (11.3%) of grade 2, 68 (33.3%) grade 3 and 76 (37.2%) grade 4. (3) Patients with grade2-4 MBD had significantly higher ECOG performance score, marrow plasmacytes, marrow CD138(+) CD38(+) cell percentage and serum IL-6 level than those with grade 0 - 1 did (P < 0.05). Patients with grade 4 MBD presented with hypocalcemia (P < 0.05) more often than those with grades 0 - 3 diseases did. (4) There was no significant difference in response to initial induction chemotherapy among the five groups (P = 0.642). (5) Univariate analysis demonstrated that the time to progression (TTP) in grade 2 - 4 MBD groups was significantly shorter than that in grade 0 - 1 groups (P = 0.029). (6) Multivariable COX analysis did not indicate lytic bone changes was a independent prognostic factor for OS and TTP. CONCLUSION: There is a rather high incidence of MBD in MM patients in China. Patients with extensive X-ray bone lesions have more severe hematologic parameters than those without bone lesions did, and severe bone lesions is an important adverse prognostic factor for TTP.

Clinical Features of Bone Complications and Prognostic Value of Bone Lesions Detected by X-ray Skeletal Survey in Previously Untreated Patients with Multiple Myeloma.

Multiple myeloma is usually associated with the presence of lytic bone lesions. We reviewed the clinical and laboratory features of patients with newly diagnosed myeloma bone disease and evaluated the prognostic significance of different X-ray image patterns in symptomatic MM patients. We retrospectively reviewed 260 patients with newly diagnosed MM. X-ray image patterns of patients were correlated with hematologic parameters, therapeutic reaction and patient survival. Patients with the X-ray imaging pattern of grade 2-4 had significantly higher marrow plasma cells levels, marrow CD138(+) D38(+) cell percentage, ECOG performance score, and serum IL-6 level than grade 0-1. Univariate analysis demonstrated that skeletal lytic changes associated with rapid progression. There is a high incidence of myeloma bone disease (MBD) in patients of MM in China. Patients of extensive bone lesions have more severe alterations in hematologic parameters than do those without bone lesions and severe bone lesions is an important adverse prognostic factor associated with a short TTP.

Immunosuppressive effect of IDO on T cells in patients with chronic hepatitis B*.

AIM: Recently indoleamine 2,3-dioxygenase (IDO) has drawn considerable attention as a mechanism of immune regulation. Our study was to observe the role of IDO in immune tolerance of chronic hepatitis B (CHB), so as to provide a novel approach for reestablishment of active immunity. METHODS: Peripheral venous blood samples were taken from 50 CHB patients and HBV viral load, T lymphocyte subsets as well as the mRNA, protein and activity of IDO were detected. The correlations between HBV viral load, T lymphocyte subsets and IDO were statistically analyzed. Blood samples from 50 healthy people were tested as a control group. RESULTS: In CHB patients, the mRNA, protein and activity of IDO were all significantly more than those in control group (mRNA:[2.11 +/- 0.615] x 10(3) vs. [0.143 +/- 0.026] x 10(3); protein: 0.22 +/- 0.06 vs. 0.02 +/- 0.0017; activity: 26.07 +/- 8.12 vs. 4.98 +/- 1.65; P < 0.05) and IDO mRNA was positively correlated with HBV viral load (r = 0.502, P < 0.001) and alanine aminotransferase (ALT) (r = 0.65, P < 0.01). Furthermore, IDO mRNA, protein and activity were negatively correlated with CD4(+) T cells (r = -0.622, -0.682, -0.549 respectively, P < 0.05), CD8 (+) T cells (r = -0.487, -367, -294 respectively, P < 0.05) and the ratio of CD4/CD8 (r = -0.426, -0.533, -0.397 respectively, P < 0.05). CONCLUSION: IDO closely correlates with HBV viral load and is responsible for immunotolerance against HBV. Suppression of IDO could be a novel approach to break tolerance in CHB.

[Influence of mesenchymal stem cells on UCB CD34+ cell expansion and characteristics].

The aim of this study was to investigate the support effects of mesenchymal stem cells (MSCs) on umbilical cord blood (UCB) CD34+ cell (HSPC) expansion in vitro and its influence on cell characteristics including the surface marker of CD34+ cells, homing adhesion molecules and colony-forming ability. The mononucleated cells (MNCs) were isolated from UCB, then the CD34+ cells were isolated from freshly obtained MNCs by immunomagnetic beads, the MSC feeder cells exposed to gamma-ray of 137Cs were prepared by MSC feeder. The CD34+ cells were inoculated in different culture media. Experiment was divided into 3 groups: HSPC+CK group in which cytokines were added to medium (SCF, FL and TPO); HSPC+MSC group in which CD34+ cells were inoculated on MSC feeder; HSPC+MSC+CK group in which cytokines and MSC feeder cells were added to medium. After culture for 4, 7, 10, 14 days the MNC amount was counted and expansion ability of CD34+ cells was evaluated. The immunotypes of CD34+ cells and subsets, homing adhesion molecules and colony-forming ability in different groups detected by flow cytometry. The results showed that the amount of MNCs and CD34+ cells all obviously increased during culture for 14 days, the expansion levels of MNCs in 3 groups were HSPC+MSC+CK group>HSPC+CK group>HSPC+MSC group in proper order. Within 10 days of expansion in vitro amount of MNCs obtained significant expansion, meantime the expansion of CD34+ cells was higher also. The CD34+ count in 3 groups at day 4 of culture decreased significantly as compared with 0 day of culture (p<0.01). The CD34+ cells ratios in 3 groups after expansion were HSPC+MSC group>HSPC+MSC+CK group>HSPC+CK group in proper order (p<0.01), while CD34+ subset levels in 3 groups were different, the CD34+CD38- cells in HSPC+CK group at 4 days of culture increased transiently (62.71%), then quickly decreased, the CD34+CD38- cell ratio at day 7 was 0.05%, while the CD34+CD38- cell ratio in HSPC+MSC group at day 7 was 18.92%, difference was significant as compared with HSPC+CK group (p<0.05). The analysis of colony-forming units showed that the colony-forming ability at various time points after expansion all sustained in high level. It is concluded that in short-time (<7 day) culture of UCB CD34+ cells the combination of MSCs with cytokines can significantly expand the CD34+ cells and make the HSPCs to maintain original biologic characteristics.