Clinical study on high-dose etoposide with granulocyte colony-stimulating factor for mobilization of autologous peripheral blood stem cells in patients with hematologic malignancies / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effectivity and safety of single high-dose (HD) etoposide (Vp16) with granulocyte colony-stimulating factor (G-CSF) for mobilization of autologous peripheral blood stem cells (PBSC) in patients with hematologic malignancies.</p><p><b>METHODS</b>80 patients of hematologic malignancies including 20 patients with acute leukemia (AL), 23 with multiple myeloma (MM), 35 with non-Hodgkin's lymphoma (NHL) and 2 with Hodgkin's lymphoma (HL) received Vp16 (1.6 g/m(2)) continuous intravenous infusion for 10 hrs on day 1. G-CSF at 10 µg/kg once daily subcutaneous injection began to use on day of ANC lower than 1×10(9)/L and continued until PBSC collection was completed. Autologous PBSC (APBSC) was collected on day of WBC greater than 5×10(9)/L and continuing until the collection goal was met (target value: MNC ≥ 6.0×10(8)/kg and CD34(+) ≥ 2.0×10(6)/kg). The patients received APBSC after conditioning regimen. The number of the cells collection, time of hematopoietic reconstruction, adverse effect and so on were observed during the course of stem cell mobilization and collection.</p><p><b>RESULTS</b>PBSC was collected on day 11 (range: 7 - 25 days) of after Vp16 administration with a median collection time of 2 (range 1 - 5). 3/80 patients with AML got stem cell mobilization failure. 5 of 6 patients who failed to mobilize before got successful stem cell mobilization, 1/6 patient with AML-M(5) got a second failure after the mobilization of VP16 whose first time's mobilization using Ara-C did not succeed. The median number of CD34(+) cells collected in 77 patients who got successful mobilization was 4×10(6)/kg \[range (1.59 - 24.68)×10(6)/kg\]. The collection of 20 patients with AL and 23 with MM were got detection for minimal residual disease, no pollution of tumor cells were happened. All patients could tolerate the whole course of stem cell mobilization. 29/80 (36.25%) patients got a 4 grade leucopenia, 19/80 (23.75%) patients got infection.</p><p><b>CONCLUSION</b>Single high-dose etoposide with G-CSF for mobilization of APBSC has a higher achievement ratio, a controllable adverse effect, a promising hematopoiesis recovery, which is an effective and safe mobilizing regimen for patients with hematologic malignancies.</p>

Progressive transformation of lymph node germinal centers: a case report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To improve the understanding of progressive transformation of lymph node germinal centers (PTGC) and to explore its clinical, histopathologic and immunohistochemical features and the differential diagnosis between the related disease of germinal center hyperplasia.</p><p><b>METHODS</b>The clinical manifestation, laboratory bindings, treatment and outcome of a patient with PTGC were presented.</p><p><b>RESULTS</b>The main manifestation of the patient was painless peripheral lymphadenopathy. Histopathologic examination of an axillary lymph node showed reactive follicular hyperplasia and the progressive transformation changes germinal centers. The borderline between the germinal center and the mantle layer was obscured. The cells in the progressive transforming germinal centers were positive for CD20(+), CD5(+), CDw75(+).</p><p><b>CONCLUSION</b>PTGC is a rare lymphoid disorder. Histopathology and immunohistochemistry are important basis of the diagnosis.</p>

Change of cytokine expressions on bone marrow mesenchymal stem cells in patients with bone marrow failure syndromes and its significance / 中国实验血液学杂志

This study was aimed to investigate the expressions of multiple cytokines on bone marrow mesenchymal stem cells (MSC) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), and its significance. The semi-quantitative reverse transcriptase-PCR (RT-PCR) was used to detect the expressions of IL-1β, SCF, G-CSF at mRNA level in bone marrow MSC of patients with AA and MDS. The real time quantitative polymerase chain reaction (RQ-PCR) technique was used to detect the mRNA expression of TPO in bone marrow MSC of AA and MDS patients. The results indicated that the expression of SCF in AA group was much lower than that in the normal control group (p < 0.05), and the expression of TPO in AA group was higher than that in the normal control group (p < 0.05), while the expression of IL-1β of AA had no significant difference when compared with the normal control group (p > 0.05). Compared with normal control group, the expressions of SCF of MDS patients was lower (p < 0.05), but the expressions of IL-1β and TPO did not show significant difference (p > 0.05). The expressions of IL-1β, SCF and TPO were no significant difference between AA and MDS groups (p > 0.05). Neither the AA patients, MDS patients nor the normal control group had the expression of G-CSF. It is concluded that the expression of SCF and TPO in bone marrow MSC of AA patients are obviously abnormal, the expression of SCF is also abnormal in bone marrow MSC of MDS patients.

Effects of proteasome inhibitor bortezomib on NF-kappaB activity and ICAM-1 mRNA expression of K562 cells / 中国实验血液学杂志

This study was aimed to investigate the effects of proteasome inhibitor bortezomib (Velcade, PS-341) on the activation of NF-kappaB and the expression of intercellular adhesion molecule-1 (ICAM-1) in K562 cells. The K562 cells were incubated in the culture of RPMI 1640 with 10% calf serum in 12-well plates and exposed to 0, 10, 20, 30, 50 and 100 nmol/L of bortezomib for 6 hours. The activation of NF-kappaB was analyzed by SP immunohistochemistry, meanwhile RT-PCR was performed to detect expression of ICAM-1. The results showed that the activation of NF-kappaB and the expression of ICAM-1 in K562 cells decreased significantly after bortezomib treatment. The inhibitory effect on ICAM-1 was probably related with the activity suppression of NF-kappaB. It is concluded that proteasome inhibitor bortezomib downregulates the expression of K562 cell ICAM-1 by inhibiting the activity of NF-kappaB, which provides a new way for the target therapy in acute leukemia.

Clinical study of bortezomib in combination with dexamethasone for the treatment of multiple myeloma / 中国实验血液学杂志

The objective of study was to evaluate the efficiency and safety of bortezomib for the treatment of multiple myeloma. Bortezomib in combination with dexamethasone was administered as first-line treatment in all 7 newly diagnosed patients with multiple myeloma. The patients with refractory myeloma were treated with bortezomib in combination with dexamethasone or with other traditional agents such as mitoxantrone and thalidomide. The results showed that according to the EMBT criteria, out of 7 patients one achieved complete response (CR), five achived partial response (PR) and one achived minor response (MR). The 3 patients with refractory/relapsed myeloma achieved PR (2/3) and MR (1/3). The overall response rate (CR + PR) was 80%. The most frequent adverse events observed were thrombocytopenia in three patients, diarrhea and peripheral neuropathy in one respectively. In conclusion, bortezomib demonstrates efficiency in the treatment of new-diagnosed and refractory/relapsed multiple myeloma, and the side effects from treatment are acceptable and manageable.

Effects of As2O3, dexamethasone and thalidomide on apoptosis and cytoplasmic Ca2+ of myeloma cell line U266 / 中国实验血液学杂志

To investigate the influence of As2O3, dexamethasone (Dex) and thalidomide (Thal) on apoptosis-induced myeloma cell line U266 cytoplasmic calcium concentrations ([Ca2+]i), U266 cells were incubated in the culture of RPMI 1640 with 15% FBS in 24-well plate and exposed to different concentrations of As2O3, Dex and Thal for 8 hours, respectively, then cell apoptosis was analyzed by fluorescence microscopy and flow cytometry (FCM) with Annexin V-FITC/PI double staining, and cytoplasmic free calcium were detected on FCM through Fluo-3/AM loading. The results indicated that (1) apoptotic cells were gradually increased with enhancement of As2O3, Dex and Thal concentrations; (2) apoptotic cell rates increased from 0.56% in control to 31.54%, 28.35% and 21.97% respectively after treatment with As2O3, Dex and Thal; (3) As2O3, Dex induced U266 cell apoptosis accompanied with raise of [Ca2+]i; (4) [Ca2+]i had no statistically significant changes in Thal-induced apoptotic U266 cells. It is concluded that the raise of [Ca2+]i is one of the mechanisms for As2O3 and Dex-induced U266 cells apoptosis, whereas Thal-induced U266 apoptosis has no significant relation to [Ca2+]i changes.

Expression of HOXB4 in cord blood progenitor cells expanded in vitro / 中国实验血液学杂志

HOXB4, a member of homeobox gene family, is closely related to the self-renewing and proliferative ability of primitive hematopoietic stem/progenitor cells (PHSC/PHPC). This study was aimed to investigate the self-renewing level of cord blood progenitor cells (CBPC) expanded in vitro. The HOXB4 expression at mRNA level was assayed by using real time RT-PCR. The results indicated that as culture prolonged, the total cells, CD34(+) cells greatly increased, however the HOXB4 expression gradually declined, even down to undetectable level similar to that of mature lymphocytes. Meanwhile, it was shown that CD34(+) cells co-cultured with bone marrow mesenchymal stem cells (BM-MSC) could abate the decline of HOXB4 expression. It is concluded that the self-renewing potential of CD34(+) cells gradually decreased during expansion in vitro, co-culture with BM-MSC was helpful to CD34(+) cell expansion and slowed the loss trend of its self-renewal.

Effects of proteasome inhibitor PS-341 on the multiple cytokine expressions of mesenchymal stem cells from bone marrow in patients with multiple myeloma / 中国实验血液学杂志

To explore the effects of proteasome inhibitor PS-341 on the cytokine expressions of mesenchymal stem cells (MSC) in patients with multiple myeloma (MM), MSCs of 11 patients were cultured in medium of RPMI 1640 containing 10% FBS. When cells grew to 5 x 10(5) - 1 x 10(6), cells were exposed to 50 nmol/L PS-341 for 4 hours, then harvested. The expressions of IL-6, IL-1beta and SCF were detected by RT-PCR. The results indicated that after treatment with PS-341 the expressions of IL-6, IL-1beta and SCF of MSCs decreased markedly, especially that of IL-1beta, compared with control (P < 0.05, P < 0.01, P < 0.05, respectively). There were obviously differences of IL-1beta expression between refractory/relapsed group and complete remission (CR) group and IL-1beta expression was inhibited more seriously in CR group, whereas there were no significant differences of IL-6 and SCF expression between two groups; IL-1beta expression of patients treated with PS-341 was not detected; there were not effects of IL-1beta expression on expressions of IL-6 and SCF. It is concluded that proteasome inhibitor PS-341 downregulated the expressions of IL-6, IL-1beta and SCF of MSCs in patients with MM.

Expressions of IL-1?,IL-6,SCF,TPO on bone marrow stromal cells in patients with multiple myelo-ma / 肿瘤研究与临床

Objective To study multiple cytokine mRNA expressions of bone marrow stromal cells in patients with multiple myeloma(MM),as well as to explore the role of these cytokines in the occurrence and development of MM.Methods Semi-quantitiative RT-PCR was used to detect the mRNA expressions of IL- 1?,IL-6,SCF,TPO.Results The mRNA expression levels of IL-1? and IL-6 were higher than that of nor- mal controls and other hematological malignancies(P