Stephen J. Forman, MD

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Graft Purging in Autologous Bone Marrow Transplantation: A Promise Not Quite Fulfilled

June 1st 2004

Clonogenic tumor cells contained within hematopoietic stem cell(HPC) grafts may contribute to relapse following autologous transplantation.Graft purging involves either in vivo or ex vivo HPC manipulationin order to reduce the level of tumor cell contamination.Some phase II trials suggest that patients who receive purged productsmay have a superior transplant outcome. Phase I trials demonstratethe feasibility of purging methods including ex vivo graft incubationwith chemotherapeutic drugs, monoclonal antibodies and complement,and CD34+ cell selection. A phase II trial in follicular non-Hodgkin’slymphoma demonstrates that patients who receive HPC products purgednegative for bcl-2 gene rearrangements have a superior outcome, comparedwith patients who receive polymerase chain reaction (PCR)-positiveproducts. This finding, however, has not been confirmed in a randomizedtrial. HPC purging has demonstrated no benefit in a phase IIItrial in myeloma. Phase II trials in acute myelogenous leukemia showcomparable outcomes for patients who receive either purged orunpurged HPC grafts. Limitations of purging include possible progenitorcell loss, delayed engraftment, and qualitative immune defects followingtransplant. Data to justify routine use of HPC graft purging areinsufficient. Phase I and II data support development of phase III trialsof both in vivo and in vitro purging methods.