Autotransplants in Chronic Myeloid Leukemia

Abstract

INTRODUCTION: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease due to a unique gene rearrangement event occurring within a pluripotent stem cell. The main characteristic of this mutation is the formation of a fusion gene (BCR-ABL) with increased tyrosine kinase activity from which a transforming activity for myelopoiesis derives. Clinically, CML is characterized by an initial chronic phase, followed by inevitable progression to an accelerated phase, and then to a terminal blastic phase. Allografting represents the only therapeutic procedure capable of curing the disease. Most centers currently use HLA-identical sibling transplants for patients less than 55 years of age. However, the majority of patients do not have an HLA-matched sibling donor. Matched or partially matched unrelated donor transplants are associated with a high transplant-related mortality within the first 100 days following the procedure. This approach should be offered to patients less than 50 years of age. Conventional therapy for CML includes hydroxyurea, busulfan and interferon alpha (IFN-&agr;). Conventional chemotherapy is unable to modify the natural history of the disease. On the contrary, recent randomized studies suggest that IFN-&agr; produces cytogenetic conversions to Philadelphia (Ph)-negative in some cases and may prolong overall survival [1-5]. Considering that the majority of Ph-negative patients maintain evidence of BCR/ABL positivity after IFN-&agr; therapy, it is unlikely that IFN-&agr; can cure the disease. In upcoming years, we must evaluate whether the high cost of IFN-&agr;, the poor tolerance of it in about one-fourth of treated patients, and the small chance of long-term benefit will be justified by a higher overall survival than with hydroxyurea. About 70% of CML patients do not have a matched family donor, and unrelated transplantation may produce high morbidity, particularly in older patients. For these patients and for those who do not achieve a cytogenetic remission after IFN-&agr; therapy, alternative treatment strategies are needed to increase disease-free survival. Autologous stem cell transplantation (ASCT) has been explored as an option for the treatment of these patients. In this review, we will focus on the recent update of this procedure, particularly on the in vivo manipulation technique.