The big trouble for invasive fungal infection(IFI)is how to define the diagnosis.Delayed therapy is the main reason of the death in the IFI patients,which underlines the importance of empiric therapy.Both cost-effectiveness ratio and patients' particular status should be considered when choosing an antifungal drug.Amphotericin B,Itraconazole,voriconazole,caspofungin and micafungin are all recommended.But there are still plenty of questions unanswered about empiric therapy,for example,how to establish th therapy based on scientific evidence.

Hematopoietic stem cell transplantation (HSCT) is an effective and sometimes the only curative therapy for patients with certain hematological diseases.HSCT has been practiced in China for approximately fifty years,and great improvements have been made within the past decade,especially in fields such as haploidentical HSCT system,strategies to overcome relapse and GVHD.This review will describe the current situation and provide a prospective of these novel characteristics of HSCT system in China.

Arsenicals ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Medicine, Chinese Traditional ; Oxides ; therapeutic use

China ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; therapy ; Practice Guidelines as Topic

Hematopoietic stem cell transplantation (HSCT) is the only effective curative therapy for patients with certain hematological diseases. Haploidentical HSCT has been practiced worldwide for approximately twenty years. Significant improvements on this therapy were made in China within the past decade, with the novel non-in-vitro, T-cell-depleted haploidentical HSCT system. This review de-scribes the current situation and provides a prospective overview of these novel HSCT systems in China.

Objective To investigate the effieacy and safety of intravenous itraconazole for the treatment of invasive fungal infection(IFI)in patients with hematological disease or undergoing allogeneic hematopoietic stem cell transplantation(HSCT).MethodsSix hundred and sixty-six patients with above mentioned conditions and diagnosed as IFI from January.2007 to July,2007 were enrolled.Intravenous itraconazole was administered at a dose of200 nag every 12 hours for 2 days and followed by 200 mg every 24 hours.Patients were then switched to oral itraconazole according to the clinical situation Responses were determined on the basis of clinical and microbiological criteria.Results The probability of defervescence Was 69.8%and the total response rates among related to itraconazole were the proven.probable and possible IFI patients were 73.7%.68.1%and 68.2%(P=0.380).Adverse effects were found in 58 patients (8.7%).which were mainly mild to medium reversible dysfunction of liver and gastrointestinal tract, Conclusion Itraconazole is an effective and safe antifungal agent for patients with hematological disease or undergoing HSCT and is suitable for empirical antifungal therapy.

Allo-HSCT is a potentially curative therapy for many hematological malignancies,the basis of which is graft-versus-leukemia(GVL) effect.However,acute graft-versus-host disease(GVHD) is responsible for 15% to 40% of mortality and is the major cause of morbidity after transplantation.Therefore,separation of GVHD and GVL partially or completely could improve the transplant outcomes.This study focuses on the effects of G-CSF on T cells in peripheral blood stem cell grafts and bone marrow grafts and its mechanisms after in vivo G-CSF application.The separation of GVHD and GVL effect and the mechanisms of which after in vivo G-CSF and interleukin-11(IL-11) treatment of healthy donors were investigated.The main contributions of this research are listed as follows:(1) Immune tolerance of T cells was induced simultaneously in peripheral blood stem cell grafts and bone marrow grafts after in vivo G-CSF application;(2) T cell hyporesponsiveness and polarization of T cells from Th1 to Th2 were maintained after mixture of G-CSF-mobilized peripheral blood grafts(G-PB) and G-CSF-primed bone marrow grafts(G-BM) according to different proportions in vitro;(3) Treating donor with G-CSF and IL-11 decreased GVHD and retained GVL effect;(4) The incidence of acute GVHD was decreased after Allo-HSCT using G-PB and G-BM as allografts;(5) In combination with other techniques,the HLA barriers were overcomed using G-PB and G-BM as allografts;(6) The incidences of acute GVHD were significantly decreased and the GVL effects were retained or enhanced in relapsed patients after treatment by G-CSF-mobilized peripheral blood graft infusion compared with those received steady-state peripheral blood lymphocyte infusion,indicating that GVHD and GVL could be partially separated in clinical settings.Based on our results,we would conclude that the issues on the deficiency of donors are resolved,and novel strategies offered for the prophylaxis and treatment of patients with hematological malignancies who relapse after Allo-HSCT.Further studies on the mechanism of the separation of GVL and GVHD are warranted.

Imatinib mesylate,as the first generation Bcr-Abl tyrosine kinase inhibitor,has brought revolutionary treatment for Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML);it has been recommended as the first-line treatment for CML by NCCN Practice Guidelines in Oncology in 2008 and European LeukemiaNet(ELN) criteria.However,imatinib has three limitations:first,it is expensive and can not be stopped if efficancy to be maintained;Second,some 20%~30% of patients develope resistance to imatinib;and third,the CML patients can not be cured with imatinib.Taking into consideration of the situation in China,we recommend individual therapy using TKI,HSCT,interferon and cytotoxic drugs for CML patients in China.

The indications for patients with Myelodysplastic Syndrome (MDS) to receive allogeneic hematopoietic stem cell transplantation (Allo-HCT) are:intermediate risk-2 and high risk groups according to IPSS,and intermediate risk-1 group with poor karyotype,severe multilineage cytopenia or infusion-dependent.Constant follow-up and evaluation is important for therapeutic decision.Unrelated or related haploidentical donor could be an alternative in case of absence of identical sibling donor.Remission through chemotherapy before the transplantation is recommended in patients with advanced MDS who receive reduced-intensity conditioning.Demethylation drugs followed by Allo-HCT do not show additional transplantation-related toxicity,whose efficiency remains to be determined.

Insulin-like growth factors, their receptors and insulin-like growth factor binding protein constitutes insulin-like growth factor system. Studies in vivo and vitro suggest that they can regulate cell growth and proliferation. Insulin-like growth factors have a potent mitogenic effects which dependent on interaction between insulin-like growth factors and their receptors. IGFBP family contains six high-affinity members with variable functions and mechanisms of actions. In addition to functioning as simple carrier proteins, IGFBP can inhibit or promote IGFs by IGF-dependent or IGF-independent mechanism. Recent findings show that the IGFBP is correlated with the initiation and progression of tumor growth.