Numerous targeted therapies emerged into clinical trials, which improved the response rate and life quality of multiple myeloma (MM) patients. Series latest developments at targeted therapy for MM patients were reported on 58th American Society of Hematology (ASH) Annual Meeting, especially the results of combination with these novel agents showed a major highlight of this meeting. The advances in the novel targeted and biological therapies will be summarized in this paper.

0.05).Six patients(6/23)in the Gln group developed mucositis and 11 cases(11/11)in the standard group(P

Chromosome Aberrations ; Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 17 ; Humans ; Multiple Myeloma ; genetics

Objective To study the treatment effect by addition of granulocyte-colony-stimulating factor (G-CSF) that could reduce the level of residual disease in patients with Ph-positive chronic myeloid leukemia (CML) who appeared to have achieved a suboptimal response to imatinib (IM) alone. Methods Eleven patients with CML who had achieved≥ 35 % Ph-negativity on treatment of IM were enrolled. The initial dose of imatinib was 400 mg or 600 mg orally daily, and G-CSF, 5 μg/kg subcutaneously daily. The administration of G-CSF was postponed or interrupted in the event of leukocytosis (leukocytes ≥ 30 ×109/L) until the whitecell count fell ＜20 × 109/L. Efficacy was assessed by serial monitoring of blood levels of bcr-abl transcripts.Treatment with G-CSF was discontinued if the patient did not achieve a reduction in the transcript level of at least 0.5 log after 6 months. For patients whose bcr-abl transcript levels continued to decline but had not yet reached molecular remission, treatment was designed to continue for 1 to 6 months. Results Of 11 evaluable patients, nine had an appreciable decline in bcr-abl transcript levels(include 7 cases the reduction was greater than 1 log and 2 cases the reduction was greater than 0.5 log), 2 cases the reduction was lower than 0.5 log.In 7 cases the reduction was greater than 1 log, including five patients who did not achieved complete cytogenetic response and two patients achieved complete molecular responses. No bleeding episodes occurred.No patient discontinued therapy because of toxicity and there were no treatment-related deaths. Conclusion The addition of G-CSF should be considered safely and successfully for patients who fail to obtain optimal response to IM alone and this approach deserves further evaluation.

Objective To promote the differentiation of Flk1+CD31-CD34-cells isolated from adult adipose tissues into pancreatic islet endocrine cells in vitro.Methods Flk1+CD31-CD34-cells were first cultured and plated in medium supplemented with B27,epidermal growth factor(EGF),and basic fibroblast growth factor(bFGF).Next,the culture medium was changed.The glucose concentration in the serum-free medium was increased.At the same time,betacellulin and nicotinamide were added.Reverse transcription polymerase chain reaction(RT-PCR) was used to detect the expression of nestin,ngn3,insulin promoter factor-1(IPF-1),insulin,and glucagon before and after differentiation induction;immunofluorescent staining for nestin,insulin and glucagon and radioimmunoassay(RIA) for insulin.Results Initially,a nestin positive precursor cell population was found,then small round cells increased in number after 6 days.Later on,they were differentiated into islet-like clusters.The induced cells resulted in the formation of clusters which exhibited higher insulin secretion and other pancreatic endocrine hormones.RT-PCR detected an enhanced expression of pancreatic genes in the differentiated cells.Immunofluorescence revealed a high percentage of insulin-expressing cells in the clusters.Furthermore,the intra-cellular insulin content was detected by RIA after the induction culture.Conclusion These cells represent a previously unidentified adult intrinsic pancreatic precursor population and are a promising candidate for cell-based therapeutic strategies.

BACKGROUND: There is no consistently effective therapy for patients with steroid-refractory acute graft-versus-host disease (GVHD). A variety of alternative approaches have been tested, including antithymocyte globulin, mycophenolate mofetil (MMF), pentostatin, and monoclonal antibodies; however, these treatments have been only modestly successful. OBJECTIVE: To further evaluate the efficacy of human adipose-derived stem cells (ASCs) as the salvage therapy for steroid-refractory acute GVHD. DESIGN: A clinical trial.SETTING: Department of Haematology, Henan Institute of Haematology, Henan Tumor Hospital.PARTICIPANTS: The clinical trial was performed at the Henan Institute of Haematology from September 2002 to August 2005. Eight patients were treated with ASCs for grades Ⅲ-Ⅳ steroid-resistant acute GVHD. The study was approved by the Ethics Committee at Henan Tumor Hospital and informed consent was obtained from patients and ASCs donors before they enrolled.METHODS: Eight patients with steroid-refractory grades Ⅲ-Ⅳ acute GVHD received intravenous infusions of ASCs. The ASCs dose was 1.0×106/kg. Seven patients were treated once and one patients twice. Four patients received ASCs from haplo-identical family donors and four from unrelated mismatched donors. MAIN OUTCOME MEASURES: The efficacy of human ASCs as the salvage therapy for steroid-refractory acute GVHD. RESULTS: No side effects were noted after the ASCs infusions. Acute GVHD disappeared completely in seven of eight patients and six of these seven patients are still alive after the median follow-up of 30 months (range 11-90 months) after the initiation of ASCs therapy. All four surviving patients were in good clinical condition and in remission of their hematological malignancy. Two patients died-one with no obvious response to ASCs died of multiorgan failure and one of relapse of leukemia. CONCLUSION: These results suggest that ASCs is a very promising treatment for severe steroid-resistant acute GVHD.

BACKGROUND: The treatment of chronic myelogenous leukemia (CML) is revolutionized by the tyrosine kinase inhibitor imatinib mesylate (imatinib). However, resistance to imatinib is increasingly recognized as a clinical problem, the prognosis of patients who develop imatinib resistance is poor, particularly in acute transformation phase of leukemia.OBJECTIVE: To characterize a novel CML cell line and to further elucidate the mechanisms of resistance to STI571.DESIGN: An observational comparative experiment.SETTING: Henan Institute of Haematology, Henan Tumor Hospital.MATERIALS: Thirty female BALB/c nu/nu mice with 5 weeks old were purchased from Animal Center, Chinese Academy of Medical Sciences. STI571 was kindly provided by Novartis (Nuremberg, Germany). VP-16 was purchased from Bristol-Myers Squibb (Munich, Germany); anti-P-gp from Santa Cruz Company, USA; anti-ab1 from BD Biosciences Company, USA. The disposal of experimental animal was coincidence with the ethical standard.METHODS: The experiment was performed in the Henan Institute of Haematology from September 2003 to November 2005. A novel K562 cell line (K562/VP16) was achieved after exposure of the K562 cells to VP16. A small subpopulation (SP K562/VP16) that was capable of excluding Hoechst 33342 in the K562/VP16 cell line was isolated by flowcytometry sorting. The rest of the K562/VP16 cells were classified as non-SP K562/VP16. In order to elucidate the mechanisms involved in K562/VP16 SP cells which became resistant to STI571, the expression of multidrug-resistant gene 1 (MDR1), Bcr-Abl and P-gp was detected in K562, non-SP K562/VP16, or K562/VP16 SP calls, respectively. Furthermore, one thousand cells of K562, K562/VP16 SP and non-SP cells were injected,respectively, intraperitoneally into the right flanks of ten 5-week-old female BALB/c nu/nu mice. The same experiment was repeated twice.MAIN OUTCOME MEASURES: Comparison of STI571 resistance and oncogenicity of non-SP K562/VP16 and K562/VP16 SP cells.RESULTS: The MDR-1 gene expression of the Mr 170 000 P-gp was detected in K562/VP16 non-SP and K562/VP16 SP cells but not in K562 cells. The expression levels of P-gp in the two K562/VP16 cell lines were similar (P ＞ 0.05).The levels of Bcr-Abl and Abl proteins were similar in the K562 cell line and in non-SP K562/VP16 and K562/VP16 SP cells (P ＞ 0.05). Compared with non-SP K562/VP16, the K562/VP16 SP cells were more resistant to STI571, and this resistance could hardly be reversed by many multidrug resistance inhibitors. In addition, in vivo study showed that the K562/VP16 SP cells induced oncogenicity in mice, while the K562/VP16 non-SP cells failed to do so.CONCLUSION: Bcr/abl gene amplification and MDR1 overexpression may not be an important clinical mechanism in the diversity of resistance development to imatinib treatment, and the development of drug resistance by leukemia cells may be at least partly due to a rare SP cells which drives leukemia occurrence and maintenance. So, these SP cells need to be targeted for effective cancer therapy.

Objective To investigate the clinical characterstics of bone Langerhans-cell histiocytosis (LCH) and evaluate its diagnosis,therapy and prognosis.Methods 25 cases with biopsy confirmed bone LCH during the last 8 years were retrospectively analyzed.Results The patients included 18 males and 7 females,13 children and 12 adults,ranging from 1.5 to 55 years old with a median age of 17.Cases with unifocal lesions were 17,including 11 cases of skull LCH,and the remaining 8 were with multifocal lesions.First symptoms were predominantly pain and local masses,and rarely constitutional symptoms.The manifestation of radiography was osteolytic bony lesions.12 cases had masses in soft tissues.Patients with solitary lesions underwent surgical operation,followed by radiotherapy or chemotherapy.Cases with multifocal lesions received chemotherapy and radiotherapy.Pathological examination showed proliferation of well differentiated histiocytes,and large numbers of infiltrating eosinophils.Positive rates of CD1a,S100,Vimentin and CD68 were higher in immunohistochemistry.Patients with restricted involvement in bones can achieve a satisfactory therapeutic effect.2 cases died when multiple systems were compromised.Conclusion Bone LCH occurs predominantly in children and teenagers,involves solitary bones,and morbidities in males are much higher than females.Skull is most commonly affected.Principal clinical manifestations are pain and local masses.Diagnosis of bone LCH depends on microscopic examination.Combination therapy appears to be an effective method of treatment.Prognosis of disease is related to the degree of bone involvement,histological classification and simultaneously encroachment of other organs.Most patients have good prognosis.

Objective To observe the efficacy and adverse events of L-asparaginasum plus DICE regimen in the treatment of relapsed and refractory non-Hodgkin's lymphoma (NHL). Methods Thirty-one patients with relapsed and refractory NHL were treated with L-asparaginasum plus DICE regimen. Each patient was scheduled to receive 2 to 6 cycles.Results Among the 31 assessable patients,11 (35.5 ％) achieved a complete remission (CR),14(45.2 ％) got a partial remission (PR),2 were stable,4 were progressive.The overall response (CR + PR) rate was 80.7 ％.The median survival was 8 months (rang:2-38 months).The 1-year survival rate was 43.3 ％,the 2-year survival rate was 32.5 ％.The main adverse events were myelosuppression,digestive tract reaction,allergy and edema.No treatment-related death was observed.Conclusion The L-asparaginasum plus DICE regimen is effective and safe for the relapsed and refractory NHL.

Objective To explore the efficacy and safety of moderate-dose of etoposide (VP16) with granulocyte-colony-stimulating factor (G-CSF) for mobilization of peripheral blood stem/progenitor cells.Methods VP16 at 1.2 g/m2 was injected intravenously by six divided doses via a central vein, 2 times every 12 hours for 3 days in 31 patients with malignant lymphoma (30 non-Hodgkin lymphoma and 1 Hodgkin lymphoma). All patients received G-CSF 5 μg/kg were given twice daily subcutaneously from the day of the nadir of white blood cell (WBC) till the day before the last APBSC harvest. Results The mean time for the collection of stem cell was 12 days (10-15) following etoposide chemotherapy. The mean number of mononuclear cell (MNC) and CD+34 cells in collection were 7.8×108/kg (5.2-11.3×108) and 7.2×106/kg (5.3-13.1×106). respectively. 18 patients completed collection with a single apheresis, and 13 patients underwenttwice. All patients were recovered for haematopoiesis in following APBSCT. Median (range) time for the recovery of absolute neutrophil count (ANC)＞0.5×109/L and platelet＞20×109/L were+12 (+9-+18) days and +14 (+10-+21) days respectively. Slight adverse events coursed by the regimen could be tolerated. Conclusion VP16 at moderate dose with G-CSF is an effective and safe mobilizing regimen for autologous peripheral blood stem/progenitor cells in patients with malignant lymphoma. It was suggested to use extensively.