Prognostic significance of EBMT score system for hematological malignancies with allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the impact of EBMT score system in patients with hematological malignancies received allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>A total of 144 consecutive patients were analyzed retrospectively. According to the EBMT score system, including age, disease status before transplantation, interval between diagnoses to transplantation, donor/recipient sex match and donor type, patients were divided into 3 risk groups: low risk (score 0-1), intermediate risk (score 2-3) and high risk (score 4-7).</p><p><b>RESULTS</b>The median follow-up duration were 413 (10-1827) days for all patients and 837 (166-1827) days for alive patients. The estimated 4-year overall survival (OS), transplant-related mortality (TRM) and relapse rate (RR) were (57.5±4.6)%, (21.6±3.7)% and (42.7±6.1)%, respectively. The 4-year OS, TRM and RR were (72.2±9.0)%, (8.1±4.5)% and (27.3±8.7)% in the low-risk group, significantly superior to both intermediate-risk group [(57.7±6.0)%, (23.1±5.1)% and (44.9±8.3)%] and high-risk group [(36.9±10.2)%, (33.5±9.2)% and (51.5±11.8)%] (P<0.01, 0.02 and 0.009 for OS, TRM and RR respectively).</p><p><b>CONCLUSION</b>The EBMT score system provides prognostic significance for OS, TRM and RR in patients with hematological malignancies received allo-HSCT.</p>

Allogeneic peripheral blood stem cell transplantation from sibling donors for 10 patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from sibling donors for treatment of multiple myeloma (MM).</p><p><b>METHODS</b>Ten patients with MM received allo-PBSCT with conditioning consisting of fludarabine plus melphalan and cyclophosphamide mostly.CsA plus mycophenolate mofetil (MMF) and short-term MTX were applied to prevent graft versus host disease (GVHD) in 8 patients, FK506 plus short-term MTX in other 2 patients.</p><p><b>RESULTS</b>All patients engrafted successfully, the median time for ANC > 0.5 × 10(9)/L was 16 (12 - 24) days, and for BPC > 20 × 10(9)/L 23 (16 - 102) days. Five patients developed acute GVHD, and only one III-IV aGVHD. Of 9 patients, 7 developed chronic GVHD. The transplant-related mortality (TRM) at 100 days was 10% (1/10), mainly from heart and renal failure and severe infection. The 1-year expected overall survival (OS), 1-year disease-free survival (DFS) and relapse rate were 67.5%, 55.56% and 11.11% respectively. Up to now, 6 patients were still alive, of them 1 patient have survived over 99 months after allo-PBSCT.</p><p><b>CONCLUSION</b>Young MM patients having HLA-identical sibling donors well tolerated allo-PBSCT based on fludarabine to prolong their OS by reducing TRM, though further work is warranted.</p>

Treatment options and prognosis in newly diagnosed multiple myeloma patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of treatment option on the response and outcomes in multiple myeloma (MM) patients suitable for autologous hematopoietic stem cell transplantation (auto-HSCT).</p><p><b>METHODS</b>A total of 71 newly-diagnosed MM patients less than 65 years admitted to RuiJin Hospital from June 2005 to December 2009 were analyzed retrospectively. Among them, 21 received auto-HSCT (HSCT group) with standard conditioning of melphalan 200 mg/m(2), 30 received conventional chemotherapy (conventional group) and 20 received Bortezomib-based therapy (Bortezomib group). The responses and outcomes of different treatments were analyzed.</p><p><b>RESULTS</b>The median follow-up duration for all patients was 18 (1 - 58) months with estimated 3-year overall survival (3-yr OS) of (79.8 ± 6.3)% and progression-free survival (3-yr PFS) of (54.8 ± 9.0)%. Thirty-four patients achieved complete remission (CR) or very good partial remission (VGPR) on induction therapy, which were 80% for the Bortezomib group, 33.3% for the conventional group and 38.3% for the HSCT group. After auto-HSCT the CR + VGPR rate was increased to 76.1% for the HSCT group. Overall, the 3-yr PFS was (26.3 ± 13.8)% (median 21 months), (40.5 ± 20.1)% (median 25 months) and (93.8 ± 6.1)%(median not reached, P = 0.025) for conventional, Bortezomib and HSCT groups respectively. Univariate analysis demonstrated that CR/VGPR after induction (P = 0.020), best response of CR/VGPR (P < 0.01), autoHSCT (P = 0.002) and maintenance therapy after CR/VGPR (P = 0.0005) were associated with improved PFS and that CR/VGPR after induction (P = 0.009), best response with CR/VGPR (P < 0.01), maintenance therapy for any patients (P = 0.035) and maintenance therapy for patients with CR/VGPR (P = 0.031) were associated with OS. In multivariate analysis, only auto-HSCT (P = 0.039) and best response of CR/VGPR (P = 0.009) were independent prognostic factors for PFS and the best response of CR/VGPR was the only independent prognostic factor for OS (P = 0.005). The estimated 3-yr OS was (62.4 ± 13.7)%, (94.1 ± 5.7)% and (87.9 ± 8.3)% respectively for 3 groups.</p><p><b>CONCLUSIONS</b>For newly-diagnosed MM younger than 65 are suitable for auto-HSCT, the best response of CR/VGPR was associated with OS and PFS. Auto-HSCT is also important prognostic factor for PFS. Induction therapy with Bortezomib can achieve rapid CR/VGPR while auto-HSCT as a crucial consolidation therapy and maintenance therapy maybe also important for improvement of long-term outcome.</p>

Detection of serum free light chain and its clinical significance in nonsecretory multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical significance of serum free light chain (sFLC) levels in nonsecretory multiple myeloma (NSMM).</p><p><b>METHODS</b>Nine NSMM patients were hospitalized in our department from Feb 2002 to Sep 2006 and no M-components was found in their serum and urine by immunofixation electrophoresis (IFE). sFLC was assayed by immuno-nephelometry. The clonality of sFLC was estimated by serum kappa:lambda sFLC ratio. Meanwhile, serum immunoglobulin, total kappa and lambda light chain level were also determined in these patients.</p><p><b>RESULTS</b>Increased serum concentrations of either kappa or lambda sFLC (and abnormal kappa/lambda ratios) were detected in 6 of 9 patients with NSMM although their serum immunoglobulin levels were not elevated and total kappa:lambda light chain ratios (1.32 - 2.20) were in the reference range. All the 9 patients had clonal IgH gene rearrangements.</p><p><b>CONCLUSION</b>Quantification of sFLC by immuno-nephelometry is more sensitive than that of serum total light chain measurement and is helpful in estimating the clonality of the light chain in patients with NSMM.</p>

The impact of autologous stem cell transplantation on the prognosis in multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of autologous stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM) and its impact on the prognosis of MM.</p><p><b>METHODS</b>Retrospective analysis was performed in 28 patients with MM (group A) treated with ASCT in our hospital from October 1998 to February 2007, compared with those not received ASCT in the same time period including 23 patients with near complete response (nCR) or better (group B) and 25 patients with partial response (PR) (group C). The duration of response (DOR), time to progression (TTP) and overall survival (OS) were compared by Kaplan-Meier method in the 3 groups.</p><p><b>RESULTS</b>Eight patients without nCR or better (7 in PR and 1 in MR) after ASCT achieved CR (2 cases) and nCR (5 cases). Complete response (CR) rate was 10.7% (3 cases) and 42.9% (12 cases) before and after ASCT respectively in group A. DOR was 33 months for group A, 17 months for group B and 18 months for group C, and TTP was 45, 43 and 28 months respectively. After a median follow-up of 30 months, patients in group A and in group B had a trenel of longer OS than in group C although there was no statistically significant difference.</p><p><b>CONCLUSIONS</b>ASCT can further enhance the response, prolong the DOR and TTP and probably OS, and therefore improve the quality of life in MM. MM patients not achieved good response by non-ASCT therapy may benefit from ASCT.</p>

Clinical features of multiple myeloma patients with extramedullary disease: a report of 40 cases from a single center / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical and laboratory features and risk factors of multiple myeloma (MM) with extramedullary disease (EM) and its extraosseous localizations at diagnosis and during the course of MM.</p><p><b>METHODS</b>The clinical features, survival rate and prognostic factors were retrospectively analyzed in 40 patients having EM from a total of 418 MM patients hospitalized in Changzheng Hospital from 1993 to 2006.</p><p><b>RESULTS</b>Among the 40 patients, the first three localizations of EM involved soft tissue, pleura or peritoneum and central nervous system (CNS). Median duration of follow-up was 30 months. The median overall survival (OS) was 28 months. Twenty-five patients (6%) were found to have EM at diagnosis (group A), and their median OS was 16 months and 15 patients (3.6%) developed EM during the course of the disease (group B), and their expected median OS was 72 months. There was a significant difference between group A and B (P = 0.0045) for OS. Compared with those in group A, patients in group B had a higher percentage of plasmacytes (P = 0.022) and plasmablasts (P = 0.029) in bone marrow, and less advanced stage for international staging system (ISS) (P = 0.027). Log-rank univariate analysis showed that higher CRP level, higher serum LDH, Stage II and III for ISS, Hb < 110 g/L at diagnosis were poor prognostic factors. However, multivariate analysis with COX model showed none of them were statistically significant.</p><p><b>CONCLUSION</b>EM tumors are not a rare manifestation of MM. Soft tissue in the commonest area involved. Higher serum CRP and LDH level, more advanced stage for ISS, anemia and having EM are poor prognostic factors of MM.</p>

Prognostic factors and staging systems of multiple myeloma: / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies found a range of prognostic factors but no consensus about the proper staging system for multiple myeloma has been achieved. This study explored the prognostic factors to find a staging system for multiple myeloma most suitable for Chinese patients.</p><p><b>METHODS</b>Between February 1990 to August 2004, 206 patients (138 men and 68 women, mean aged (59 +/- 11) years) who were initially diagnosed as multiple myeloma in Changzheng Hospital (Shanghai, China) and had followup records were enrolled in this study. Potential prognostic factors were evaluated by univariate and multivariate analyses. Four staging systems were applied to compare their suitability for the patients.</p><p><b>RESULTS</b>The median survival time of the patients was 33 months. The 1-, 3- and 5-year survival rates were 80.18%, 48.08% and 33.7% respectively. Factors identified as adversely affecting survival were older age, severe bone lesions, low haemoglobin, low platelet, low serum calcium, low serum albumin, high proportion of plasma cells in marrow, high serum creatinine, high serum beta(2) microglobulin and high C-reactive protein. Among these, only C-reactive protein, beta(2) microglobulin, albumin and age were the independent prognostic factors. There were statistically significant survival differences among the three groups in Durie Salmon staging system and Bataille staging system, but not in British Medical Research Council staging system or International Staging System.</p><p><b>CONCLUSIONS</b>High beta(2) microglobulin, high C-reactive protein, low albumin and old age are independent prognostic factors of multiple myeloma. Bataille staging system appears to be optimal for Chinese multiple myeloma patients.</p>

Bortezomib in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and toxicity of bortezomib in combination with dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma(MM).</p><p><b>METHODS</b>Sixteen patients(9 males, 7 females, mean age 57. 5 yrs) with refractory or relapsed MM were treated with bortezomib (1. 3 mg/m(2) ) by intravenous bolus twice a week for 2 weeks, or 3. 5 mg once a week in a 21-day cycle, followed by an intravenous injection of dexamethasone 30 - 40 mg. The patients had received one to four courses at least. Response to bortezomib was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation (EBMT) before initiation of each bortezomib chemotherapy course. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3. 0.</p><p><b>RESULTS</b>The median follow-up duration from the beginning of bortezomib treatment was 6 months. Clinical response was observed in 14 patients (87.5%), including near complete response in 6, partial response in 5, minimal response in 3 and no response in 2. The most common adverse events were gastrointestinal symptoms (nausea and vomiting in 12, constipation in 3, severe diarrhea in 3 patients), thrombocytopenia (8 patients) and fatigue(3 patients). The adverse events were subsided on routine supportive care.</p><p><b>CONCLUSIONS</b>Bortezomib in combination with dexamethasone is an effective therapy with a high response rate and manageable toxicities for patients with relapsed or refractory myeloma.</p>

The effect of cyclin D2 shRNA on the proliferation and apoptosis of LP-1 cell / 中华血液学杂志

<p><b>OBJECTIVE</b>To construct cyclin D2 (CCND2) short hairpin RNA ( shRNA) plasmid for repressing the expression of CCND2 in human myeloma cell line LP-1,and to detect its effect on the proliferation and apoptosis of LP-1 cell.</p><p><b>METHODS</b>A CCND2 shRNA model was constructed and cloned into plasmid pGensil-2, then the plasmid was transfected into LP-1 cell in vitro. The CCND2 expression cell proliferation, cell cycle and cell apoptosis of the transfected LP-1 cells were studied by RT-PCR, trypanosome staining, flow cytometry and annexin V assay.</p><p><b>RESULTS</b>The transfection efficiency of LP-1 cell was 34. 2%. In the transfected LP-1 cell CCND2 mRNA expression was reduced significantly, the cell growth was inhibited significantly and the cell cycle was partly arrested in G, phase. The apoptosis rate of the transfected LP-1 cell after 72 h was (25.7+/-4.8)%.</p><p><b>CONCLUSION</b>The inhibition of CCND2 in LP-1 cells could inhibit the cell growth and induce cell apoptosis. CCND2 maybe a new therapeutic target.</p>

Effects of arsenic trioxide on cell cycle and expression of cyclin dependent kinase inhibitors of multiple myeloma cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the effects of arsenic trioxide (As(2)O(3)) on cell cycle and expression of cyclin dependent kinase inhibitors (CDKIs) in multiple myeloma (MM) cells, and explore its pharmacological mechanism.</p><p><b>METHODS</b>The DNA content of MM cells line HS-Sultan was analyzed by flow cytometry after exposure to As(2)O(3), the effects on expression of CDKI P15, P16 AND P21 were studied by reverse transcriptase PCR.</p><p><b>RESULTS</b>DNA flow cytometric analysis showed that As(2)O(3) induced most of HS-Sultan cells, arrest at G(0)/G(1) phase and a small fraction at G(2)/M phase and apoptosis occurred mainly in S phase. There was no expression of P15 and P16 mRNA in untreated HS-Sultan cells and 1.0 micromol/L As(2)O(3) could make them expressed after exposed 24 or 48 hours respectively. Expression of P12 mRNA was obviously elevated by As(2)O(3) comparing with that of control.</p><p><b>CONCLUSION</b>One of the pharmacological mechanisms of As(2)O(3) is to activate the expression of CDKI P15, P16 and P21, and consequently affect cell proliferation cycle.</p>

Detection of IgH-MMSET fusion gene in multiple myeloma patients and its significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To detect the IgH-MMSET fusion gene resulted from t (4;14) translocation in multiple myeloma and illuminate its significance.</p><p><b>METHODS</b>IgH-MMSET fusion gene was detected in bone marrow specimens of 25 multiple myeloma (MM) patients and MM cell line NCI-H929 using reverse-transcription PCR (RT-PCR) assay followed by nested PCR to increase the sensitivity. The purified PCR products were cloned into pGEM-T vector and then sequenced using M13 forward primers. The fragment sequences were compared with that in GenBank to find matched sequences.</p><p><b>RESULTS</b>Only a 438 base pair long fragment was obtained after RT-PCR assay and was confirmed by sequencing to be a fusion gene product of IgH gene and MMSET gene in MM cell line NCI-H929. The breakpoints were located within the C micro region of IgH gene on chromosome 14 and intron 3 of MMSET gene on chromosome 4. IgH-MMSET hybrid transcripts were detected in 3 of 25 MM patients through nested PCR assay. The amplified fragments of the 3 patients were 237 base pairs (bp), 239 bp and 239 bp in length, respectively. The breakpoints on chromosome 4 were identical to that of NCI-H929 cell.</p><p><b>CONCLUSIONS</b>The formation of IgH-MMSET fusion gene is resulted from t (4;14) translocation in MM. The incidence rate is 12.0%. The presence of IgH-MMSET fusion gene may predict poor prognosis.</p>