CD34 positive PBPC expanded ex vivo may not provide durable engraftment following myeloablative chemoradiotherapy regimens

• Published in: Bone marrow transplantation (Basingstoke) Vol. 19; no. 11; pp. 1095 - 1101
• Main Authors: HOLYOAKE, T. L, ALCORN, M. J, RICHMOND, L, FARRELL, E, PEARSON, C, GREEN, R, DUNLOP, D. J, FITZSIMONS, E, PRAGNELL, I. B, FRANKLIN, I. M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.06.1997
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens, CD34 - analysis; Biological and medical sciences; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Busulfan; CD34 antigen; Cell culture; Chemoradiotherapy; Chemotherapy; Conditioning; Cyclophosphamide; Granulocyte Colony-Stimulating Factor - pharmacology; Hematopoietic Stem Cell Transplantation; Hemopoiesis; Humans; Irradiation; Leukocytes (neutrophilic); Lymphoma; Lymphoma, Non-Hodgkin - therapy; Medical sciences; Melphalan; Middle Aged; Multiple myeloma; Multiple Myeloma - therapy; Non-Hodgkin's lymphoma; Peripheral blood; Platelets; Progenitor cells; Radiation; Radiation therapy; Stem cell transplantation; Stem cells; Toxicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation Conditioning; Antineoplastic agent; Cell proliferation; Transfusion; Stem cell; Hematopoietic cell; Myeloma; Cell surface; Blood; Autograft; Immunoglobulinopathy; Ex vivo; Lymphoproliferative syndrome; Melphalan; Graft; Busulfan; Human; Immunopathology; Alkanediol; Malignant hemopathy; Non Hodgkin lymphoma; Radiotherapy; Long term; Cell subpopulation; Antigen; Alkanesulfonic acid; Oxazaphosphinane derivatives; Alkylating agent; Chemotherapy; Cyclophosphamide; Treatment; Nitrogen mustard; Engraftment; Combined treatment
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1700799

We have previously demonstrated that CD34+ cells, selected from peripheral blood progenitor cells (PBPC), can be expanded in ex vivo culture and can be infused in tandem with unmanipulated PBPC with little or no toxicity. In this study, four patients (two non-Hodgkin's lymphoma (NHL), two multiple myeloma (MM)) received myeloablative conditioning prior to stem cell rescue using ex vivo expanded cells alone. The two patients with NHL received cyclophosphamide and total body irradiation (CY/TBI) and the two patients with MM, busulphan and melphalan (Bu/M). One case received an inadequate CFU-GM dose, despite expansion, and in one case the expanded cells were contaminated. No definitive conclusions may therefore be drawn concerning engraftment in these two cases. However, the other two cases received high doses of committed progenitors. Following infusion of the expanded material, all four patients failed to show sustained neutrophil engraftment and none showed evidence of platelet engraftment. Back-up, unmanipulated PBPC were therefore infused on days 14, 34, 32 and 28 and subsequently all four cases achieved satisfactory engraftment of both neutrophils and platelets. In conclusion, we feel that, CD34+ cells, expanded ex vivo using the conditions described in this report, may not provide durable engraftment following fully myeloablative conditioning.