Abstract
We assessed the capacity of positively selected autologous CD133 + hematopoietic stem cells (HSCs) to reconstitute lymphomyelopoiesis in chronic lymphocytic leukemia (CLL) patients receiving myeloablative chemotherapy. Ten resistant/relapsed CLL patients underwent HSC mobilization with chemotherapy and granulocyte-colony stimulating factor (G-CSF). Positive selection of circulating CD133 + HSCs was performed by immunomagnetic technique. Highly purified HSCs were reinfused after busulphan/melphalan myeloablative treatment. A median number of 4.2 × 10 6 CD34 + cells/kg and of 3.14 × 10 6 CD133 + cells/kg were collected. Immunomagnetic selection resulted in the reinfusion of a median number of 2.45 × 10 6 CD133 + cells/kg (median purity: 94.8%; median recovery: 84%) and 2.4 × 10 6 CD34 + cells/kg (median purity: 93%; median recovery: 71%). HSC selection resulted in a median T cell and CD19 +/CD5 + cell depletion of 3.85 log and 2.8 log, respectively. At the molecular level, however, 7 of 8 valuable purified HSC fractions were contaminated by leukemic cells. All CLL patients showed rapid and sustained myeloid engraftment after reinfusion of purified CD133 + cells. Immunologic reconstitution was comparable to that routinely observed in patients reinfused with unmanipulated leukapheresis products and no late infectious complications were observed. With a median follow-up of 28 months for transplanted patients, 5 patients are in clinical complete remission, 3 are in partial remission, and 1 is in progression. In conclusion, the reinfusion of highly purified CD133 + HSCs allowed the rapid and sustained recovery of hematopoiesis after myeloablative treatment in resistant/relapsed CLL patients. However, the purging potential of positive selection of CD133 + cells is not adequate to achieve tumor-free autografts.
Published Version
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