Second malignancies with autologous stem cell transplantation

Myeloablative chemo or radiochemotherapy followed by autologous stem cell transplantation (ASCT) is used for relapsed aggressive lymphoma and first or second line consolidation therapy in indolent lymphoma. Retrospective studies have suggested that it is associated with increased risk of therapy related myelodysplastic syndrome (t-MDS) or acute myeloid leukaemia (t-AML) and reported incidences have ranged from 1% to 12%. This randomised trial included previously untreated patients with stage III and IV follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma or lymphoplasmacytic lymphoma. All patients received between four and six cycles of CHOP like induction therapy consisting of cyclophosphamide, doxorubicin, vincristine and prednisone or mitoxantrone, chlorambucil and prednisone or CHOP and rituximab. Those with a partial remission or more were randomly assigned to either myeloablative radiochemotherapy and stem cell collection followed by conditioning high-dose therapy with total body irradiation and cyclophosphamide (the ASCT group, with 195 patients) or to 2 cycles of CHOP-like consolidation and interferon alpha maintenance (236 patients).Progression free survival was 83.7% after 2 years and 60.2% after 5 years in the ASCT group compared to 56.8% and 31.6% in the interferon alpha arm (p After a median follow-up of 44 months, there were five cases of t-MDS in the ASCT arm and none in the maintenance group. The estimated cumulative five-year risk of secondary haematologic neoplasia was 3.8% in the ASCT group and 0% in the interferon alpha group (p = 0.0248). The authors noted that the risk of t-MDS should be assessed in the context of the initial lymphoma chemotherapy, as 5.1% of patients receiving MCP compared to 1% of patients receiving CHOP developed secondary haematologic neoplasias, although this was not statistically significantly different.The authors concluded, "currently there is no evidence that the moderate increase in the instance of secondary t-MDS or t-AML will substantially diminish the long-term benefits of myeloablative radiochemotherapy and ASCT." Reference...