Use of azathioprine for graft-vs-host disease is the major risk for development of secondary malignancies after haematopoietic stem cell transplantation: a nationwide population-based study

Background:

As more patients are treated by haematopoietic stem cell transplantation (HSCT), development of secondary malignancy (SM) becomes an increasingly common issue in long-term survivors.

Methods:

We conducted a nationwide population-based study of the Taiwanese population to analyse patients who received HSCT between January 1997 and December 2010. Standardised incidence ratios (SIRs) were used to compare the risk of SM in HSCT patients and the general population. Multivariate analysis was performed to identify independent predictors of SM.

Results:

Patients receiving HSCT had a significantly greater risk of developing SM (SIR 2.00; 95% confidence interval (CI) 1.45–2.69; P<0.001). Specifically, the incidence increased for cancers of the oral cavity (SIR 14.18) and oesophagus (SIR 14.75) after allogeneic HSCT. Multivariate analysis revealed an increased SIR for cancer in patients who received the immunosuppressant azathioprine. The risk of SM also increased with greater cumulative doses of azathioprine.

Conclusions:

This study demonstrates an increased incidence of SM in Taiwanese patients who received allogeneic HSCT, especially for cancers of the oral cavity and oesophagus. This finding is different from results in populations of Western countries. Physicians should be cautious about azathioprine use for graft-vs-host disease after HSCT.     

A comparative study of the iron status of patients with oesophageal adenocarcinoma to determine suitability for a clinical trial of iron chelation therapy

Introduction

The incidence of oesophageal adenocarcinoma (OAC) is rising dramatically and overall survival remains extremely poor. Iron has been shown to potentiate tumourigenesis in OAC, and iron chelation therapy demonstrates promise in vivo as an adjunct to neoadjuvant and palliative chemotherapy. OAC, however, has traditionally been associated with iron deficiency anaemia. The aim of this study was therefore to formally quantify the iron status of OAC patients in order to guide the design of future clinical trials involving iron chelation therapy.

Methods

Demographic and cancer specific data were collected prospectively from all patients presenting with OAC and gastric adenocarcinoma (GAC). Patients had haemoglobin, serum iron, serum ferritin and serum transferrin receptor (sTfR) levels measured to assess systemic iron status. In addition, the sTfR/log ferritin (sTfR-F) index was calculated.

Results

Average haemoglobin, serum iron, serum ferritin, sTfR and sTfR-F index values for all patients presenting with OAC were within normal sex specific reference ranges. No statistical difference in iron status was observed between OAC patients presenting with resectable and advanced OAC. Patients with OAC are relatively iron replete compared with those presenting with GAC. Iron parameters were not significantly altered by standard neoadjuvant chemotherapy.

Conclusions

Patients presenting with resectable or advanced OAC could be considered as candidates for a clinical trial of iron chelation therapy as an addition to standard neoadjuvant or palliative treatments.     

Incidence Patterns of Primary Bone Cancer in Taiwan (2003–2010): A Population-Based Study

Background

Primary bone cancer (BC) incidence by age has not been surveyed in Asia.

Methods

The incidence patterns of nine subtypes of primary BCs registered between 2003 and 2010 were analyzed from Taiwan cancer registry data. More specific analyses were conducted within age groups (Group I: 0–24 years; Group II: 25–59 years; and Group III: 60–85+ years).

Results

A total of 1,238 newly diagnosed subjects were registered with an age-standardized incidence rate (ASR) of 6.70 per million person-years. Overall, osteosarcoma (OS: 45 %) was the most common, followed by chondrosarcoma (CS: 18 %), and Ewing sarcoma (ES: 8 %). The percentages of cases and ASRs for age groups I, II, and III were 36.3, 43.0, and 20.7 %, and 7.00, 5.48, and 10.28 per million, respectively. Significant male predilections were observed for all BCs combined, and the CS, chordoma, and malignant ameloblastoma subtypes. Our findings demonstrated an upward trend of 4.8 % per year over the study period, and was more significant for females (6.7 %). A significant increase in trend existed in the incidence of BC among females in Group II, and the incidence of OS and ES among females in Group I.

Conclusions

This population-based study has allowed us to confidently define the incidence rates among three age groups of Taiwanese. Despite overall low rates, the upward trend in BC incidence among females may invoke a concern. The results suggest areas for further study into the underlying causes for these cancer trends.     

Efficient detection of factor IX mutations by denaturing high-performance liquid chromatography in Taiwanese hemophilia B patients,and the identification of two novel mutations

Hemophilia B (HB) is an X-linked recessive disorder characterized by mutations in the clotting factor IX (FIX) gene that result in FIX deficiency. Previous studies have shown a wide variation of FIX gene mutations in HB. Although the quality of life in HB has greatly improved mainly because of prophylactic replacement therapy with FIX concentrates, there exists a significant burden on affected families and the medical care system. Accurate detection of FIX gene mutations is critical for genetic counseling and disease prevention in HB. In this study, we used denaturing high-performance liquid chromatography (DHPLC), which has proved to be a highly informative and practical means of detecting mutations, for the molecular diagnosis of our patients with HB. Ten Taiwanese families affected by HB were enrolled. We used the DHPLC technique followed by direct sequencing of suspected segments to detect FIX gene mutations. In all, 11 FIX gene mutations (8 point mutations, 2 small deletions/insertions, and 1 large deletion), including two novel mutations (exon6 c.687–695, del 9 mer and c.460–461, ins T) were found. According to the HB pedigrees, 25% and 75% of our patients were defined as familial and sporadic HB cases, respectively. We show that DHPLC is a highly sensitive and cost-effective method for FIX gene analysis and can be used as a convenient system for disease prevention.