Regulatory T cells for tolerance

Regulatory T cells (Tregs) are critical mediators of immune homeostasis and hold significant promise in the quest for transplantation tolerance. Progress has now reached a critical threshold as techniques for production of clinical therapies are optimised and Phase I/II clinical trials are in full swing. Initial safety and efficacy data are being reported, with trials assessing a number of different strategies for the introduction of Treg therapy. It is now more crucial than ever to elucidate further the function and behaviour of Tregs in vivo and ensure safe delivery. This review will discuss the current state of the art and future directions in Treg therapy.     

Sporadic late‐onset nemaline myopathy as a rare cause of slowly progressive muscle weakness with young adult onset

Introduction: Sporadic late‐onset nemaline myopathy (SLONM) is a rare intractable acquired myopathy characterized by progressive muscle weakness and atrophy, usually with middle to late adult onset. Autologous peripheral blood stem cell transplantation (auto‐PBSCT) has been reported to be a promising treatment for SLONM. Methods: In this study we performed clinical characterization, muscle histopathological analysis, and muscle power monitoring after auto‐PBSCT in a 27‐year‐old HIV‐negative man with monoclonal gammopathy. Results: He showed improved muscle strength after treatment with high‐dose melphalan and auto‐PBSCT. Conclusions: Considering the recent reports of successful treatment of SLONM, early and correct diagnosis of this condition in association with monoclonal gammopathy is important. SLONM should be added to the list of diseases to consider in the differential diagnosis of progressive muscle weakness with young adult onset. Muscle Nerve 51 :772–774, 2015     

Peripheral blood stem cell versus autologous bone marrow transplantation for Hodgkin's disease: equivalent survival outcome in a single-centre matched-pair analysis

A matched-pair retrospective analysis was used to compare 70 patients who had undergone peripheral blood stem cell transplantation (PBSCT) with 70 who had undergone autologous bone marrow transplantation (ABMT) for Hodgkin's disease. All transplants took place at a single centre using the same conditioning regimen (BEAM). Patients were matched for sex, previous chemotherapy and relapse status: factors which have previously been shown to have prognostic significance for transplant outcome in Hodgkin's disease at this centre. The two groups were also generally comparable for unmatched patient and disease characteristics. Toxic deaths and 90 d outcome were not different between the two groups. Three-year overall survival was 68.6% for the ABMT group and 78.2% for the PBSCT group (P = 0.078); progression-free survival was 59.4% for the ABMT group and 58.1% for the PBSCT group (P = 0.255), and relapse rates were 36.9% and 42.6% respectively (P = 0.30). Within the limitations of retrospective analysis, we conclude that there is no major overall or progression-free survival advantage for PBSCT compared to ABMT in Hodgkin's disease.     

Successful treatment with splenectomy and interferon alpha against recurred hemophagocytic syndrome in remission state of anaplastic large cell lymphoma following high-dose therapy and autologous peripheral blood stem cell transplantation

A 25-yr-old man had been diagnosed as having CD30(+) anaplastic large cell lymphoma associated with hemophagocytic syndrome (HS). He received aggressive frontline chemotherapies and consolidation with autologous peripheral blood stem cell transplantation (PBSCT) following high-dose chemotherapy combined with splenic irradiation (720 cGy in fraction of 180 cGy). However, HS recurred on day 50 of PBSCT without radiologic evidence of lymphoma relapse. On day 56 of PBSCT, splenectomy was performed and pathology showed massive sinusoidal infiltration of histiocytes. On day 68 of PBSCT, administration of interferon alpha was started and maintained for 24 months. HS was completely resolved and he has been alive well and in complete remission (CR), 60 months after initial diagnosis.     

Update on ocular graft-versus-host disease

Ocular graft-versus-host disease (oGVHD) occurs as a complication following hematopoietic stem cell transplantation and is associated with significant ocular morbidity resulting in a marked reduction in the quality of life. With no current consensus on treatment protocols, management becomes challenging as recurrent oGVHD often refractory to conventional treatment. Most authors now diagnose and grade the disease based on criteria provided by the National Institutes of Health Consensus Conference (NIH CC) or the International Chronic oGVHD (ICCGVHD) consensus group. This article will provide an insight into the diagnostic criteria of oGVHD, its classification, and clinical severity grading scales. The inflammatory process in oGVHD can involve the entire ocular surface including the eyelids, meibomian gland, corneal, conjunctiva, and lacrimal system. The varied clinical presentations and treatment strategies employed to manage them have been discussed in the present study. The recent advances in ocular surface imaging in oGVHD patients such as the use of meibography and in vivo confocal microscopy may help in early diagnosis and prognostication of the disease. Researching tear proteomics and identification of novel potential tear biomarkers in oGVHD patients is an exciting field as they may help in objectively diagnosing the disease and monitoring the response to treatment.     

Hepatitis B Virus Reactivation in a Patient With Chronic GVHD After Allogeneic Peripheral Blood Stem Cell Transplantation

We report a patient with fatal hepatitis B virus (HBV) reactivation after treatment for chronic graft-versus-host disease (GVHD) following allogeneic peripheral blood stem cell transplantation to treat chronic myelogenous leukemia. The presence of antibodies to hepatitis B surface antigen (HBsAb) prior to transplantation indicated previous HBV infection. Liver damage first developed 8 months after transplantation with the disappearance of HBsAb. Hepatitis B antigen was first noted during an examination of liver damage that occurred 22 months after transplantation. Retrospective examination of serum by real-time detection polymerase chain reaction (RTD-PCR) revealed HBV in both the first and second episodes of liver damage (89 copies/mL and 2 x 10(6) copies/mL, respectively). HBV may have been reactivated, leading to fatal liver damage in this HBsAb-positive patient. We propose that RTD-PCR-based analysis should be performed to diagnose liver dysfunction after hematopoietic stem cell transplantation.     

SDF-1α与G-CSF动员造血干细胞的相关性研究

目的 :探讨趋化因子基质细胞衍生因子 (SDF 1α)与造血干细胞移植中G CSF动员造血干细胞的关系。方法 :应用酶联免疫吸附 (ELISA)试验检测 8例自体外周血造血干细胞移植 (auto PBSCT)病人及 9例异基因外周血干细胞移植 (allo PBSCT)供者应用G CSF前 1天、后第 5天血浆SDF 1α水平的变化。结果 :应用G CSF前 1天 ,allo PBSCT供者及auto PBSCT病人SDF 1α的血浆水平分别为 ( 1918.0 1± 73 .2 2 )pg/ml;( 14 43 .42± 175 .3 7)pg/ml ,应用G CSF后第 5天 ,SDF 1α血浆水平分别降至为 ( 1841.94± 60 .70 )pg/ml;( 13 12 .2 8±111.3 3 )pg/ml,二者比较有统计学意义。allo PBSCT供者在G CSF动员前 1天、后第 5天的SDF 1α血浆水平均高于auto PBSCT病人。结论 :SDF 1α不参与G CSF诱导造血干细胞的动员过程 ,auto PBSCT病人的SDF 1α血浆水平的降低可能是骨髓基质细胞功能受损的表现。     

First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of first-line high-dose chemotherapy (HDCT) combined with peripheral blood stem cell transplantation (PBSCT) for patients with advanced extragonadal germ cell tumors (EGGCT). METHODS: Six male patients with advanced non-seminomatous EGGCT were treated with HDCT combined with PBSCT following 2-3 cycles of conventional-dose induction chemotherapy. The regimens used for HDCT were carboplatin, etoposide and ifosfamide (ICE) in five patients and ICE plus paclitaxel (T-ICE) in one patient, and that for induction therapy was cisplatin, etoposide and bleomycin (PEB) in all patients. As a rule, HDCT was continuously administered until alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin normalized (beta-HCG). RESULTS: Following 1-6 courses of HDCT (median, 4 courses), beta-HCG and AFP were normalized in all patients, and five and one patient were diagnosed as showing partial remission and stable disease, respectively. Five patients underwent surgical resection of residual tumors after HDCT, yielding necrotic tissue in two, mature teratoma in two, and viable cancer tissue in one, and the surgical margin was negative in all patients. At a median follow-up of 36 months, five patients were alive and disease-free, whereas the remaining one died of disease progression. Although all patients had grade 3 hematological toxicity, there was no treatment-related death by combining PBSCT. CONCLUSIONS: First-line HDCT with PBSCT could be safely administered to patients with advanced EGGCT, and the antitumor effect of this treatment was comparatively favorable. First-line HDCT therefore may represent an attractive option for patients with advanced EGGCT.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.