Purpose: To determine if temporarily blocking sex steroids prior to stem cell transplantation can increase thymus function and thus enhance the rate of Tcell regeneration. Experimental Design: This was a pilot study of luteinizing hormone^releasing hormone agonist (LHRH-A) goserelin given 3 weeks prior to allogeneic or autologous hemopoietic stem cell transplantation and administered up to 3 months posttransplantation. Patients (with or without LHRH-A administration) were assessed from 1week to 12 months posttransplantation for multiple immunologic variables by flow cytometry (particularly naI« ve T cells), quantitative PCR to assess T-cell receptor excision circle levels (as a correlate of thymus function), CDR3 length analysis to determine the variability of the TCR repertoire, and in vitro assays to determine functional T cell responses. Results: LHRH-A administration prior to stem cell transplantation significantly increased neutrophil and lymphocyte numbers within the first month of posttransplantation. Most importantly, total and naI« ve CD4 + T cell regeneration together with T-cell receptor excision circle production, T cell repertoire regeneration, and peripheral T cell function were also significantly enhanced at multiple time points posttransplant. In addition, an increase in disease-free survival (P = 0.04) was seen in the autologous setting. Although LHRH-A administration increased T cell responses in vitro, it did not exacerbate graft-versus-host disease in the allogeneic setting. Conclusions: This study provides an important new approach to the improvement of immune reconstitution in patients undergoing hemopoietic stem cell transplantation and may have generic applications in manyTcell^based disorders.

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A prospective study was undertaken of 22 patients with chronic hyperplastic candidosis and 50 age and sex matched individuals with no evidence of oral mucosal disease. Specifically the relationship between the inherited ability to secrete blood group antigens in saliva and chronic hyperplastic candidosis was investigated. The proportion of non-secretors of blood group antigens was significantly higher in patients with chronic hyperplastic candidosis (68%) compared to the control subjects (38%). The inability to secrete blood group antigens in saliva may therefore be a risk factor in the development of, or persistence of chronic hyperplastic candidosis.

, CM Vajdic 5 and CAST study group 6 Population-based evidence on second cancer risk following autologous haematopoietic SCT (HCT) is lacking. We quantified second cancer risk for a national, population-based cohort of adult Australians receiving autologous HCT for cancer and notified to the Australasian Bone Marrow Transplant Recipient Registry 1992Registry -2007. Cancer diagnoses and deaths were ascertained by linkage with the Australian Cancer Database and National Death Index. Standardized incidence ratios (SIRs) were calculated and Cox regression models were used to estimate within-cohort risk factors treating death as a competing risk. During a median 2.5 years follow-up, second cancer risk was modestly increased compared with the general population (SIR 1.4, 95% confidence interval 1.2-1.6); significantly elevated risk was also observed for AML/myelodysplastic syndrome (SIR ¼ 20.6), melanoma (SIR ¼ 2.6) and non-Hodgkin lymphoma (SIR ¼ 3.3). Recipients at elevated risk of any second cancer included males, and those transplanted at a younger age, in an earlier HCT era, or for lymphoma or testicular cancer. Male sex, older age (445 years) and history of relapse after HCT predicted melanoma risk. Transplantation for Hodgkin lymphoma and older age were associated with lung cancer risk. Second malignancies are an important late effect and these results inform and emphasize the need for cancer surveillance in autologous HCT survivors.Bone Marrow Transplantation (2014) 49, 691-698; doi:10.1038/bmt.2014.13; published online 17 February 2014Keywords: autologous transplantation; outcomes; risk; surveillance INTRODUCTION Autologous haematopoietic SCT (HCT) is increasingly being used in Australia and elsewhere as a therapy for several haematopoietic and solid organ malignancies. 1,2 Life expectancy following HCT has also improved, 3 increasing the number of HCT survivors globally. Characterizing late effects and identifying those at risk will maximize the long-term health of HCT recipients.Second cancers are a recognized late effect of chemo-radiation therapy in general, and in the HCT setting specifically. 4-11 The cumulative incidence of second cancer after autologous HCT may be as high as 29% after 15 years, 11 with the greatest excess risk observed for AML and myelodysplastic syndromes (MDSs). 10,[12][13][14][15] Most prior studies have examined second cancer risk in recipients of allogeneic and autologous HCT, with the largest based on international transplant registry cohorts. 9 Furthermore, most studies ascertained second cancers from hospital records or by self-report, potentially under-estimating risk. There are no population-based estimates of the risk of secondary cancer in adult recipients of autologous HCT. We examined the incidence and risk factors for second cancer in a national, population-based cohort of 7765 adult Australian autologous HCT recipients, 1992HCT recipients, -2007