1. ¹Department of Clinical Hematology, Institut Curie, Paris, France
2. ²Department of Clinical Hematology, Institut Gustave Roussy, Villejuif, France
3. ³Inserm U362, Hématopoiëse et Cellules Souches, Institut Gustave Roussy, Villejuif, France
4. ⁴Cell Therapy Unit, Translational Research and Cell Therapy Laboratories, Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France
5. ⁵Department of Transfusion, Institut Curie, Paris, France
6. ⁶Laboratoire d'Hématologie, Department of Clinical Biology, IGR, Villejuif, France
7. ⁷Department of Pediatric Oncology, Institut Curie, Paris, France

Correspondence: Dr AG Turhan, Cell Therapy Laboratory, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif 94805, France. E-mail: turali@igr.fr

⁸Equal contribution as first authors

⁹Equal contribution as last authors

Received 29 April 2004; Accepted 12 July 2004; Published online 18 October 2004.

Abstract

To evaluate the impact of ex vivo expanded megakaryocyte (MK) progenitors on high-dose chemotherapy-induced thrombocytopenia, we conducted a phase II study in 10 patients with relapsed lymphoma. Two fractions of peripheral blood progenitor cells (PBPC) were cryopreserved, one with enough cells for at least 2 10⁶ CD34+ cells/kg and a second obtained after CD34+ selection. Ten days before autologous stem cell transplantation, the CD34+ fraction was cultured with MGDF+SCF for 10 days. After BEAM (BCNU, cyclophosphamide, cytarabine, and melphalan) chemotherapy, patients were reinfused with standard PBPC and ex vivo expanded cells. No toxicity was observed after reinfusion. The mean fold expansion was 9.27 for nucleated cells, 2 for CD34+ cells, 676 for CD41+ cells, and 627 for CD61+ cells. The median date of platelet transfusion independence was day 8 (range: 7–12). All patients received at least one platelet transfusion. In conclusion, ex vivo expansion of MK progenitors was feasible and safe, but this procedure did not prevent BEAM-induced thrombocytopenia. Future studies will determine if expansion of higher numbers of CD34+ cells towards the MK-differentiation pathway will translate into a functional effect in terms of shortening of BEAM-induced thrombocytopenia.