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

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

doi:10.1016/j.bbmt.2007.07.004

« Previous Next »Biology of Blood and Marrow Transplantation
Volume 13, Issue 10 , Pages 1224-1232, October 2007

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
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
- Hematology and Bone Marrow Transplant Center, San Salvatore Hospital, Pesaro, Italy
- Correspondence and reprint requests: Alessandro Isidori, MD, Hematology and Bone Marrow Transplant Center, San Salvatore Hospital, Via Lombroso, 61100 Pesaro, Italy.
Maria Rosa Motta
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
Monica Tani
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
Carolina Terragna
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
Pierluigi Zinzani
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
Antonio Curti
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
Simonetta Rizzi
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
Simona Taioli
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
Valeria Giudice
- Immunohematology Service and Blood Bank, S. Orsola-Malpighi Hospital, Bologna, Italy
Alessandra D’Addio
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
Gabriele Gugliotta
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
Roberto Conte
- Immunohematology Service and Blood Bank, S. Orsola-Malpighi Hospital, Bologna, Italy
Michele Baccarani
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy
Roberto M. Lemoli
- Institute of Hematology and Medical Oncology, “L. & A. Seràgnoli,” University of Bologna, Bologna, Italy

Received 2 May 2007; accepted 10 July 2007. published online 28 August 2007.

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.