Nordic Myeloma Study Group, the first 15 years: scientific collaboration and improvement of patient care.

The accomplishments of the Nordic Myeloma Study Group (NMSG) during its first 15 yr are briefly surveyed, together with a discussion of principles guiding the group's clinical trials and of problems that need to be addressed in coming years. The group has so far carried out 12 clinical trials, comprising more than 2500 patients, spanning from minor phase II to large randomised phase III trials. At the time of writing, two randomised trials are running (comparing two doses of i.v. pamidronate, and melphalan-prednisone (MP) vs. MP-thalidomide to elderly patients). The group has strived for a simple organisation with much responsibility delegated to regional coordinators (Denmark 3, Norway 5, Sweden 5). With regard to trial design, the group has considered it important that studies are based on sound scientific questions, are simple to handle for the participants, population based, investigator initiated, include quality of life and health resources assessment as end-points, and can be used as basis for diverse scientific spin-off projects. Like other clinical trial groups, NMSG faces a number of challenges in coming years. The financial situation for independent investigator-initiated trials is far from satisfactory, especially with regard to the resource-consuming implementation of more stringent good clinical practice rules and ethical committee demands. NMSG has also encountered increasing difficulties in recruiting patients to recent trials, partly because of problems related to participating physicians (lack of support, laborious paper work, insufficient credit for participation). Solutions to these problems have to be found if industry-independent clinical trial groups are to survive.

Serum erythropoietin (EPO) levels correlate with survival and independently predict response to EPO treatment in patients with myelodysplastic syndromes.

Treatment with recombinant erythropoietin (EPO) can alleviate anaemia in patients with myelodysplastic syndromes (MDS). The present study, based on a long-term follow-up of 68 MDS patients (26RA, 16 RAS, 26 RAEB) treated with EPO alone, pinpoints pre-treatment variables associated with response induction, response duration and overall survival. Response, defined as an increase in haemoglobin >15gL1 or eliminated erythrocyte transfusion requirements, was observed in 22 of 66 (33%) evaluable patients. The median response duration was 15 (range 3-64+) months. Using univariate logistic regression models, responders displayed significantly lower baseline serum EPO levels (S-EPO), more often normal bone marrow blast cell content (RA/RAS vs. RAEB), normal cytogenetics and no need for erythrocyte transfusion. In a multiple logistic regression model, S-EPO (P=0.009), marrow blast content (P=0.031) and erythrocyte transfusion need (P=0.024) remained associated with response induction. The probability of response for a patient with S-EPO >50UL1, RA/RAS and no transfusion need was 0.79 (0.53-0.93, 95% CI). The median overall survival time from start of EPO treatment was 26 months, significantly longer for responders than for non-responders (49 vs. 18 months, P=0.018). Survival was also predicted by baseline S-EPO; patients with S-EPO >50UL1 (n=50) had a median survival of 17 months, as compared to 65 months for those with S-EPO >50UL1 (n=14, P=0.024). The international prognostic scoring system (IPSS) for MDS predicted survival (P=0.003) and progression to acute leukemia (P<0.001) but not response to EPO treatment. Furthermore, in a logistic regression model with S-EPO and IPSS, S-EPO (but not IPSS) was again a significant predictor for response (P=0.007). Our data facilitate the optimal selection of MDS patients suitable for EPO treatment and pinpoint S-EPO as a powerful predictor of response and overall survival in MDS.