Haematopoietic cell transplantation with non-myeloablative conditioning in Denmark: disease-specific outcome, complications and hospitalization requirements of the first 100 transplants.

We analysed the outcome and hospitalization requirements of the first 100 patients (Hodgkin's disease (HD), N=13; multiple myeloma (MM), N=14; CLL, N=12; non-Hodgkin's lymphoma (NHL), N=17; myelodysplastic syndrome (MDS), N=18; AML, N=24 and CML, N=2) treated in Denmark with haematopoietic cell transplantation after non-myeloablative conditioning with TBI 2 Gy+/-fludarabine. The cumulative incidence of acute GVHD grade II-IV and extensive chronic GVHD was 67 and 49%. After a median follow-up of 534 days, the overall survival, PFS, relapse-related mortality and treatment-related mortality were 59, 50, 25 and 17%, respectively. Patients with CLL, NHL, AML and MDS with <5% blasts at any time had a favourable outcome with a PFS of 61-71%. Patients with MM, HD and MDS and a history of > or =5% blasts had a less favourable outcome with a PFS of 19-38% (P=0.001). The cumulative incidence of discontinuation of immunosuppression was 37%. During the first and second year post transplant, patients experienced a mean of 41 and 13 outpatient clinic visits, and 53 and 16 days of hospitalization. Sixteen patients were admitted to the intensive care unit, of whom eight are still alive. In conclusion, transplantation outcomes were encouraging, but complications requiring admission and outpatient clinic visits occur frequently post transplant.

Evidence for involvement of clonally expanded CD8+ T cells in anticancer immune responses in CLL patients following nonmyeloablative conditioning and hematopoietic cell transplantation.

We have analyzed the clonotype composition of CD8+ T cells following nonmyeloablative (NMA) conditioning and hematopoietic cell transplantation (HCT), of patients with chronic lymphocytic leukemia (CLL). Consecutive analyses of blood samples taken up to 2 years following HCT, demonstrated that CD8+ T-cell clonality was highly dynamic in the early phases after HCT, but became more stable after 4-5 months. Moreover, donor lymphocyte infusion (DLI) given for disease progression in one of the patients led to establishment of recurrent as well as new T-cell clonotypes. This coincided with disease remission, strongly suggesting that these T cells were engaged with anti-CLL cytotoxicity. To examine the functional capacity of stable clonally expanded T cells after HCT, CD8+ T cells isolated post-transplant from the recipients were stimulated ex vivo with CLL cells and subsequently analyzed by FACS for surface expression of the marker for cytotoxic activity, CD107a. Stimulation with CLL cells indeed led to surface expression of CD107a, and clonotype analyses of sorted cells demonstrated that CD107a positive T cells were stably expanded following HCT. Our data suggest that clonally expanded CD8+ T-cell clones participate in the ongoing T-cell response against CLL cells following HCT with NMA conditioning.

Occupational non-melanoma skin cancer.

Non-melanoma skin cancer is historically known to be associated with certain professions. Reporting is mandatory in Denmark when occupational exposure is suspected. In a retrospective register-based study of all cases of suspected occupational non-melanoma skin cancer reported to the Directorate of National Labour Inspection and the National Board of Industrial Injuries in Denmark in the period January 1, 1984 to December 31, 1994, we assessed the extent to which occupational exposures today are of importance in the occurrence of non-melanoma skin cancer. A total of 74 individuals (11 women and 63 men) aged 32-82 years (median 58 years) had been reported. Of these, 15 cases (20%) were approved as being occupational, 37 (50%) were rejected and 22 (30%) were either shelved or could not be further clarified. Most commonly approved were exposures such as asphalt, tar, and the like, and ionizing radiation, and localization on the arms or multiple tumours. Unexpected occupational exposure could not be identified but continued reporting is recommended in order to follow this in the future.

Survival among motherless children in rural and urban areas in Guinea-Bissau.

AIM: With the increasing incidence of HIV and TB, motherless children are becoming a rapidly growing problem in Africa. However, few studies describe the survival patterns of these children. The aim of this study was to investigate the mortality of motherless children in urban and rural areas of Guinea-Bissau. METHODS: A historical cohort study was set up in urban and rural areas in Guinea-Bissau. Motherless children were selected from two study cohorts under demographic surveillance since 1990. The relatives of 128 motherless children from the rural cohort and 192 from the urban area, as well as a total of 807 controls, were examined and interviewed. RESULTS: Controlling for significant background factors revealed that motherless children had a markedly higher mortality than that of controls in both urban (mortality rate ratio (MR) 2.32 (95% confidence interval 1.11-4.84)) and rural areas (MR = 4.16 (2.79-6.22)). Virtually all the excess mortality occurred among children under 2 y of age when their mother died. Few motherless children had been provided with surrogate breastfeeding. CONCLUSIONS: Since nearly all children in Guinea are breastfed until 2 y of age, premature weaning may be one of the major causes of the higher mortality rates observed among motherless children.