ABSTRACT
In a single-center study, we analyzed the outcomes of 66 patients with advanced hematological malignancies receiving two reduced-intensity conditioning regimens for allogeneic transplantation: fludarabine and low-dose TBI (flu/TBI, n=25), or fludarabine, antithymocyte globulin and BU (flu/ATG/BU, n=41). The selection criteria were based on the hypothesis that flu/TBI patients were expected to achieve autologous recovery in the event of non-engraftment. Sixty-three patients (95%) engrafted. Regimen-related mortality at day 100 and 1 year was 6 and 15%, respectively. With median follow-up of 50.4 months, survival did not differ by regimen. Multivariate analysis confirmed that the type of regimen did not affect relapse. In patients achieving full donor chimerism by day 30, those conditioned with flu/TBI showed greater overall survival (P=0.02). Engraftment failure occurred in two patients (3%), both of whom received flu/TBI. We conclude that conditioning with flu/TBI or flu/ATG/BU yields comparable survival and remission outcomes. By contrast to our hypothesis, patients receiving flu/TBI who subsequently failed engraftment did not achieve autologous recovery. Yet, rapid attainment of full donor chimerism after flu/TBI is associated with greater survival than after flu/ATG/BU. Further, larger prospective randomized studies are required to define the advantage of one regimen over the other.
Subject(s)
Antilymphocyte Serum/administration & dosage , Busulfan/administration & dosage , Hematopoietic Stem Cell Transplantation/methods , Myeloablative Agonists/therapeutic use , Transplantation Conditioning/methods , Vidarabine/analogs & derivatives , Whole-Body Irradiation/methods , Adolescent , Adult , Aged , Clinical Protocols , Female , Hematologic Neoplasms/therapy , Humans , Male , Middle Aged , Prospective Studies , Vidarabine/therapeutic useABSTRACT
Conventional cancer therapies are plagued by disease relapses due to incomplete eradication of cancer-initiating cells. Evidence for cancer-initiating cells originally arose from studies in hematology and leukemia. Lessons learned from hematopoietic stem cells laid the bedrock for understanding how leukemic cells self-renew and remain in immature states. Decades later, leukemia-initiating cell techniques are now being applied to the field of solid tumors such as brain, breast, bone, colon, pancreas, lung and prostate cancer, with several cancer-initiating cell efforts led by hematologists. Different isolation techniques enriching for primitive cancer-initiating cells have been developed and are described in this review. Although the concept of cancer-initiating cells arose from studies in normal tissue stem cells, differences exist between neoplastic-initiating clones and their normal counterparts. Several efforts have uncovered aberrant molecular pathways and niche interactions unique to cancer-initiating cells. Efforts to exploit these pathways and interactions could ultimately lead to complete eradication of cancers.
