Genetic prognostic factors and the outcome of autologous stem cell transplantation in plasma cell disorders

Between December 1999 and May 2008 104 autologous stem cell transplantations were performed in 103 patients with plasma cell disorders in our transplant center in Hungary. The patients mean age was: 54.48 years. Sex distribution: 56 males, 47 females. The diagnosis was multiple myeloma in 98, multiple plasmocytomas in 4, acute plasma cell leukemia in 1 patient. The conditioning regimen was 200 mg/[m.sup.2] melphalan in 100 cases, 120-160 mg/[m.sup.2] melphalan in 3 patients with kidney failure and in 1 case with a second transplantation. We administered the median of 4.9 x [10.sup.6]/kg CD34 positive cells on transplantation. Neutrophil engraftment (ANC>1.0 G/l) occurred on day +10, platelet engraftment (PLT > 20.0 G/l) on day +13. According to bone marrow morphology on day 100 and immunofixation CR rate was 76%, VGPR occurred in 21%, 2 patients were considered as non-responders. 80% of the 103 patients are still alive. The median observation time from diagnosis was 38.4 months and from transplantation 28.9 months. The day 100 non-relapse mortality was 0%. The progression free survival according to Kaplan-Meier analysis was 63.17 ± 6.1 (95% CI: 51.0-75.3) months, the overall survival was 83.2 ± 5.7 (95% CI: 71.9-94.5) months. The results of interphase cytogenetical examinations (FISH) were available in 45 patients. In 74% of them genetical abnormalities have been identified. Del(13q) was proved in 41.9%, del(17p) in 9.7%, abnormalities in the IgH gene in 58% of the cases (overlaps). Among IgH gene abnormalities t(11;14) occurred in 16.7%, t(4;14) in 22.2% and t(14;16) in 5.6%, in 55.5% of the cases no partner gene has been identified. Three prognostic categories were distinguished: good prognosis (t(11;14)), intermedier prognosis (normal FISH results, IgH gene abnormalities without identification of a partner gene, t(11;14) + the presence of a poor prognostic marker) and poor prognosis (the presence of any unfavorable genetic prognostic marker). 22% of the patients belonged to the good, 33% to the poor and 45% to the intermedier prognostic category. There were significant survival differences (p= 0.01) between the different genetic prognostic groups of patients. Autologous stem cell transplantation definitely improves survival in patients with multiple myeloma. Cytogenetical examinations play an important role in the definition of different prognostic categories that represent significant survival differences of these patients.