Positive Selection and Transplantation of Autologous Highly Purified CD133+ Stem Cells in Resistant/Relapsed Chronic Lymphocytic Leukemia Patients Results in Rapid Hematopoietic Reconstitution without an Adequate Leukemic Cell Purging

Alessandro Isidori, Maria Rosa Motta, Monica Tani, Carolina Terragna, Pierluigi Zinzani, Antonio Curti, Simonetta Rizzi, Simona Taioli, Valeria Giudice, Alessandra D'Addio, Gabriele Gugliotta, Roberto Conte, Michele Baccarani, Roberto M. Lemoli

Research output: Contribution to journalArticlepeer-review

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 × 106 CD34+ cells/kg and of 3.14 × 106 CD133+ cells/kg were collected. Immunomagnetic selection resulted in the reinfusion of a median number of 2.45 × 106 CD133+ cells/kg (median purity: 94.8%; median recovery: 84%) and 2.4 × 106 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.

Original languageEnglish
Pages (from-to)1224-1232
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume13
Issue number10
DOIs
Publication statusPublished - Oct 2007

Keywords

  • Autologous stem cell transplantation
  • CD133 cells
  • CD34 cells
  • Chronic lymphocytic leukemia
  • Positive selection
  • Purging

ASJC Scopus subject areas

  • Transplantation

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