Myeloablative versus reduced intensity allogeneic stem cell transplantation for relapsed/refractory Hodgkin's lymphoma in recent years: a retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: To evaluate long-term outcome of myeloablative allogeneic stem cell transplantation (allo-SCT) (MAC) versus reduced-intensity allo-SCT (RIC) in patients with relapsed/refractory Hodgkin's lymphoma (HL) in recent years. PATIENTS AND METHODS: A total of 312 patients (63 MAC and 249 RIC) with relapsed/refractory HL who received allo-SCT between 2006 and 2010 and were reported to the EBMT Database were included in the study. RESULTS: With a median follow-up for alive patients of 56 (26-73) months, there were no significant differences in non-relapse mortality (NRM) between MAC and RIC. Relapse rate (RR) was somewhat lower in the MAC group (41% versus 52% at 24 months, P = 0.16). This lower RR translated into a marginal improvement in event-free survival (EFS) for the MAC group (48% versus 36% at 24 months, P = 0.09) with no significant differences in overall survival (73% for MAC and 62% for RIC at 24 months, P = 0.13). Multivariate analysis after adjusting for disease status at the time of allo-SCT showed that the use of MAC was of borderline statistical significance for predicting a lower RR and EFS [HR 0.7, 95% CI (0.5-1.0), P = 0.1] and [HR 0.7, 95% CI (0.5-1.0), P = 0.07], respectively, after allo-SCT. CONCLUSIONS: With modern transplant practices, the NRM associated with MAC for HL has strongly decreased, resulting into non-significant improvement of EFS because of a somewhat better disease control compared with RIC transplants. The intensity of conditioning regimens should be considered when designing individual allo-SCT strategies or clinical trials in patients with relapsed/refractory HL.

Assesment of non-relapse mortality (NRM) and long-term survival after autologous stem cell transplantation (ASCT) in patients with lymphoproliferative diseases.

A balanced risk-benefit approach to haematopoietic stem cell transplantation (HSCT) is the key for maximized chances of cure with acceptable quality of life for patients with advanced haematological malignancies. The aim was to try to assess the prognostic value of comorbidity and other independent variables concerning pretransplant mobilization strategies that affect auto SCT in patients with lymphoproliferative diseases.We stratified outcomes among 90 consecutive adult autologous recipients with lymphoproliferative diseases. 55% of patients were classified in the low index group for haematopoietic stem cell transplantation with comorbidity index (HCT-CI) scores between 0-1, 27% of patients with lymphoproliferative diseases had intermediate HCT-CI scores 1-2 and 12% of patients were in high HCT-CI group with a score≥3 and 6% undetermined. Two year NRM was 36% (95% CI: 17-36%), 26% (95% CI 15-39%) and 30% (95% CI: 22-39%) in the low, intermediate and high-risk HCT-CI groups respectively. The HCT-CI has been shown to sensitively capture organ comorbidities and provide valuable prognostic information for assignments of patients to clinical trials. Still, many questions remain to be answered, auch as good sample size, equal stratification of patients into risk groups, and also implementing better pretransplant assessment.

Iron overload in patients with transfusion dependent myelodisplastic syndrome.

The myelodisplastic syndrome is a heterogeneous group of diseases, characterised by ineffective and dysplastic haematopoesis and pancytopenia in the peripheral blood, followed by progressive disturbance of differentiation of the haematopoetic stem cell, resulting in evolution of the disease towards acute leukaemia. According to the latest WHO classification, the term myelodisplastic syndrome includes diseases with an indolent course, as well as diseases with a fast evolution towards acute leukaemia. Because of this diversity, haematologists base their therapeutic decisions on prognostic scoring systems which incorporate all the significant factors with an influence on survival in this group of patients with myelodisplastic syndrome. Bearing in mind that anaemia is the most frequent form of cytopenia in patients with myelodisplastic syndrome, it is common that at some point of the disease almost every patient with myelodisplastic syndrome is transfusion-dependent. Frequently applied transfusions secure the correction of anaemia in these patients, giving them a good quality of life, but at the same time endangering them with the potential threat of iron overload, when the physiological mechanisms of iron excretion from the organism become insufficient. There is a clear correlation between transfusion dependence and the overall survival in patients with myelodisplastic syndrome. Chelators secure the lowering of the iron surfeit and are indicated in transfusion-dependant patients with myelodisplastic syndrome ( need for two blood units monthly, during one year ), when the ferritin level increases over 1000, in patients who are candidates for transplantation as well as in patients from good prognostic groups with median survival over one year. The therapy with chelators lasts as long as the patient is transfusion-dependant.

Stem cell transplantation - new treatment approaches.

Stem cell research still remains one of the most controversial fields of science today on account cell plasticity and its capability of transdifferentiation or de-differentiations to certain tissue types, as well as the clinical application of this scientific concept. Stem cells derived from bone marrow, peripheral blood or the umbilical cords are a common therapeutic approach for treatment of haematological malignancies as part of established transplant procedures (allogeneic, autologous, syngeneic stem cell transplantation). But recent clinical data have revealed the potential role of stem cells in the treatment of other nonhaematological diseases, degenerative disorders, cardiovascular diseases and autoimmune diseases. The experience with stem cell transplantation in haematological malignancies at the Hematology Department, Skopje, has been established since it was set up 7 years ago, with more than 130 patients undergoing transplant procedures (87 autologous and 43 allogeneic recipients). Encouraging results were also reported from the Skopje Cardiology Clinic in the field of intracoronary application of bone marrow derived stem cells for the treatment of patients with acute myocardial infarction. But this new rout in tissue regeneration should still be further extended and evaluated in clinically randomized studies that will confirm the therapeutic potential of stem cells.