Effects of bortezomib combined with methylprednisolone in treatment of 33 cases of relapsed or refractory multiple myeloma / 中国实验血液学杂志

The aim of this study was to explore the clinical effect and toxicity of bortezomib combined with methylprednisolone in treatment of relapsed or refractory multiple myeloma (MM). Clinical data of 33 patients (23 male, 10 female; aged from 38 to 85 years old) were analyzed retrospectively. The median diagnosis time was 25 (2 - 120) months. 33 patients received bortezomib (0.9 - 1.1) mg/m(2) on days 1, 4, 8, 11, in combination with methylprednisolone 40 mg/d (4 cases), 80mg/d (13 cases), 120 mg/d (2 cases), 200 mg/d (9 cases), 300 mg/d (5 cases) respectively. The median follow-up time was 10(3-60) months. The used therapy courses were 1 - 8 (mean 4 courses). The results indicated that 24 cases showed the response of different degree, the overall response rate (ORR) was 72.7% (24/33). 32 patients received ≥ 2 therapy courses, and ORR was 71.9% (23/32). 16 patients received 4 therapy courses, and ORR was 93.8% (15/16 cases). 7 patients received 6 therapy courses and the ORR was 100% (7/7 cases). Main side-effects were thrombocytopenia, infection and peripheral neuropathy. The median survival time was 41.5 (2 - 120) months and the 2-year, 3-year and 5-year overall survival rate were 80%, 59.1% and 21.1%, respectively. It is concluded that bortezomib combined with methylprednisolone is an effective therapy with higher response rate, and safe in treatment of relapsed or refractory multiple myeloma.

Multiple myeloma complicated with spinal infiltration / 中国实验血液学杂志

This study was aimed to investigate the clinical features of multiple myeloma (MM) complicated by spinal infiltration (extramedullary plasmacytoma) so as to enhance the understanding of this kind of MM and reduce the missed diagnosis for these MM patients. 10 patients with MM complicated by spinal infiltration were enrolled in this study. Bone marrow, blood, hepatic and renal function, electrolyte, beta2 microglobulin, C-reactive protein and immunoglobulin (M-protein) were detected. The involved spinal sites were examined by using magnetic resonance imaging (MRI) or computerized tomography (CT). 10 patients were staged according to International Stage System (ISS) and Duric-Salmon stage system. The clinical data of patients were analyzed. The results showed that among 10 cases of MM complicated by spinal infiltration, involved pectoral cord was observed in 7 cases, involved lumbar cord in 2 cases and sacral cord in 1 case. The treatment with operation and protocol containing cisplatin, ifosfamide etoposide, prednisone, and bortezomib in combination with other drugs indicated that the total remission rate was 80% (8/10), no serious adverse responses was observed. In conclusion, the patients with MM complicated by spinal infiltration must be diagnosed and treated as early as possible. Once paraplegia happened in patients, the therapeutic efficacy and prognosis would be very poor.

Bortezomib combined with other drugs for treating 60 cases of multiple myeloma / 中国实验血液学杂志

The aim of this study was to investigate the efficacy and safety of bortezomib-combined with dexamethasone, methylprednisolone and other drugs in the treatment of patients with multiple myeloma (MM). 60 MM patients including 19 de novo patients, out of them 14 patients received the treatment using regimen of bortezomib in combination with thalidomide (BT), 5 patients received bortezomib-methylprednisolone regimen (BMP). Out of 41 patients with refractory or relapsed myeloma 26 cases of MM received the treatment using regimen of bortezomib combined with methylpreamsolone (BMP), 6 cases received the treatment using regimen of bortezomib combined with cyclophosphamide, prednisone and thalidomide (BCPT), 5 cases received the treatment using regimen of bortezomib combined with cis-diaminodichloroplatimm, etoposide, cydophosphomide and dexamethasone (BDECD), 4 cases received the treatment using regimen of bortezomib combined with dexamethasone (BD). Each patient received treatment of 2-8 courses at least. Response was assessed according to the criteria of the Bladè. Adverse events were graded according to the common Toxicity Criteria, version 3.0 (NCI CTCAE, USA). The median follow-up from the start of bortezomib treatment was 9 months. The results showed that out of 19 newly diagnosed patients, 6 cares achieved CR, 6 cases achieved nearly CR, 5 cases achieved PR, 1 case achieved MR, resulting in an ORR of 94.7%. Out of 41 refractory or relapsed patients, 5 cases achieved CR, 10 cases got nearly CR, 14 cases were PR and 5 cases were MR, resulting in an ORR of 82.92%. The main toxicities were fatigue, gastrointestinal disorders, peripheral neuropathy, thrombocytopenia, herpes zoster, skin rash. All adverse events were diminished by using routine ways. In conclusion, bortezomib combined with or the drugs is a very effective regimen, its side effects are predictable and manageable.

The significance of IGF-1, VEGF, IL-6 in multiple myeloma progression / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the alteration and significance of IL-6, vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1) in MM progression and the interaction between the three cytokines.</p><p><b>METHODS</b>Bone marrow samples from 28 patients with multiple myeloma (MM) (evolution group and steady group), 10 iron deficiency anemia (as normal control) and 2 monoclonal gammopathy of undetermined significance (MGUS) were studied. Bone marrow stromal cells (BMSCs) were established from the bone marrow MNCs. ELISA was performed to detect the concentration of IL-6, VEGF, IGF-1 in culture supernates.</p><p><b>RESULTS</b>(1) The levels of IL-6 and VEGF secreted by BMSCs were increased in an order from normal control to steady group to evolution group (P < 0.05). However, the concentration of IGF-1 did not increase in MM patients (P > 0.05). (2) The levels of IL-6, VEGF and IGF-1 in the coculture supernates of U266 and BMSCs were increased significantly (P < 0.05), being in an ascending order from normal control to steady group to evolution group (P < 0.05). (3) BMSCs stimulated by exogenous IL-6, VEGF or IGF-1, secreted more VEGF, IGF-1/IL-6, IGF-1/VEGF, IL-6 than unstimulated (P < 0.05). (4) The levels of IL-6, VEGF, IGF-1 secreted by BMSCs from MGUS were similar to that from control group.</p><p><b>CONCLUSIONS</b>IL-6, VEGF, IGF-1 levels associate with evolution of MM; IL-6, VEGF and IGF-1 induce an increase in cytokines secretion of BMSCs.</p>

Study of anti-myeloma activity of interleukin-2 activated bone marrow in vitro / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the anti-myeloma activity of interleukin-2 activated bone marrow (ABM).</p><p><b>METHODS</b>Bone marrow mononuclear cells (BMMNC) from multiple myeloma and iron-deficiency anemia patients were cultured in the presence of rIL-2. The anti-myeloma activity of ABM against U266 cells, cells expressing surface CD45, CD38, CD138, the levels of TNF-alpha and IFN-gamma in ABM culture supernatant were measured with MTT method, flow cytometry and ELISA method respectively after bone marrow was activated with rIL-2 for 24 and 72 hours.</p><p><b>RESULTS</b>The tumor-killing activities against U266 cells of ABM were significantly increased compared with that of non-activated bone marrow (NBM) at 72 hours [(69.70 +/- 26.57)% vs (43.20 +/- 12.39)%, P < 0.05] and 24 hours [(34.25 +/- 11.93)% vs (26.53 +/- 5.48)%]. The CD45(-)CD38(+)CD138(+) cells of ABM from myeloma group at 72 hours were decreased from (8.46 +/- 3.66)% to (4.79 +/- 1.56)% (P < 0.05). TNF-alpha and IFN-gamma were detectable after cultured for 24 hours in both normal control group and myeloma group and went higher at 72 hours. The level of TNF-alpha and IFN-gamma were significantly increased in ABM compared with that in NBM (P < 0.05). Meanwhile, there was a positive relationship between the level of TNF-alpha, IFN-gamma and cytotoxicity of ABM from normal control group at 24 hours and 72 hours (P < 0.05), and was a negative relationship between TNF-alpha and IFN-gamma levels and the CD45(-)CD38(+)CD138(+) cells in myeloma group at 72 hours (P < 0.05).</p><p><b>CONCLUSION</b>Normal BMMNCs activated with rIL-2 have tumor-killing activities against U266 cells. Myeloma cells and tumor burden were decreased in myeloma bone marrow after the marrow was activated with rIL-2. Production of TNF-alpha and IFN-gamma from bone marrow cells including T cells, monocyte-macrophages and NK cells activated with rIL-2 might be involved in anti-myeloma activity of ABM.</p>

Detection of gene expression alteration of myeloma cells treated with arsenic trioxide / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of arsenic trioxide on multiple myeloma (MM) cell gene expression and explore the molecular mechanism of arsenic trioxide therapy for MM.</p><p><b>METHODS</b>U266 cells were divided into two groups, group A as control group and group B as test group. Cells were cultured for 48 hours, and total RNA and mRNA were extracted. Suppression subtractive hybridization (SSHs) was performed to distinguish the differentially expressed genes. The products were cloned into pGEM-T Easy Vector, and transfected into the competent host JM109 to construct two subtractive libraries. Positive colonies were selected by blue-white screening, and the plasmids were extracted. Homologous comparison was conducted in GenBank.</p><p><b>RESULTS</b>Five downregulated clones were isolated in the first SSH: (1) Aminopeptidase N, (2) Homosapiens tumor translationally-controlled protein 1, (3) Human ATP synthetase A chain, (4) Signal recognition particle A10, (5) Mitochondrial ATP synthetase/ATPase subunit 6. Four upregulated clones were isolated in the second SSH: (1) Calcium-binding protein A10, (2) Keratin 6A, (3) 45 kD MIP repetitive element containing splicing factor and (4) poly(A)-binding protein.</p><p><b>CONCLUSIONS</b>Arsenic trioxide exerts proliferation inhibition and apoptosis induction on MM cells by regulating genes expression.</p>

Application of flow cytometry in the differential diagnosis of lymphoma/leukemia with aberrant antigen expression / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the application of flow cytometry in the differential diagnosis of lymphoma/leukemia with aberrant antigen expression.</p><p><b>METHODS</b>The results of flow cytometry of 30 lymphoma/leukemia cases with aberrant antigen expression, of which 3 cases being lymphomas, 8 B-cell leukemia, 1 T-cell leukemia, 17 acute non-lymphoid leukemia and 1 acute non-lymphoid leukemia involving lymph nodes were analyzed. Immunohistochemistry (EnVision) for CD79a, CD3 and MPO was performed on all cases.</p><p><b>RESULTS</b>Eleven cases of B-cell lymphoma/leukemia were cytoplasmic CD79a (cCD79a)-positive, cytoplasmic CD3 (cCD3epsilon) and cytoplasmic MPO (cMPO)-negative. Five of these cases were positive for CD5 and 2 for CD5, 1 or 2 for myeloid marker(s). The T-cell leukemia cases were cCD3epsilon-positive, cCD79a and cMPO-negative, they also co-expressed CD13 and CD33. The mantle cell lymphoma cases were positive for CD3, CD13 and CD33. Of the 8 B-cell leukemia cases, 4 were positive for CD5, 3 for CD13 and 1 for CD13 and CD33. The 18 acute non-lymphoid leukemia cases (including 1 acute non-lymphoid leukemia case involving lymph nodes) were cMPO-positive and cCD79a and cCD3epsilon-negative. Eight of the 18 expressed T-cell markers (including 1 case of acute non-lymphoid leukemia involving lymph nodes), 8 expressed B-cell markers, 2 expressed both T and B-cell markers.</p><p><b>CONCLUSIONS</b>Flow cytometry can demonstrate aberrant antigen expression in lymphoma/leukemia cells and is helpful in delineating their cell origin. The technique is thus useful in the differential diagnosis of lymphoma/leukemia.</p>