title: Role of CD34+ cells in engraftment after high-dose melphalan in multiple myeloma patients given peripheral blood stem cell rescue.
abstract: During the period December 1992 to June 1995, 95 patients were treated with high-dose melphalan (HDM) with peripheral blood stem cell rescue (PBSCR). Sixty-five had received previous treatment and 28 had relapsed. Among patients who had relapsed 21/28 had received HDM previously including one who received HDM twice during the course of the study. Seventy-five patients were given HDM/PBSCR for the first time. Comparisons have been made between engraftment times for platelets and neutrophils among patients who received less than or greater than 2 x 10(6) CD34+ cells at rescue. Analyses have also been done to evaluate the effect of previous HDM on recovery. Mobilization of progenitor cells was done with granulocyte colony-stimulating factor (G-CSF). Patients received only PBSCR. No growth factors were given to the PBSCR recipients during the recovery period. The percentage of patients from whom the number of CD34+ cells mobilized was > 2 x 10(6)/kg was similar in patients who received HDM for the first time (23%) compared with those who had had it previously (19%). The yield of CD34+ cells correlated with the number of granulocyte-macrophage colony forming units (CFU-GM). Although the number of CD34+ cells infused was < 2 x 10(6)/kg in 77% of patients, all engrafted for neutrophils to > 0.5 x 10(9)/l. This was delayed in patients who had had previous HDM (P < 0.02). Platelet recovery to > 25, 50 and 100 x 10(9)/l was delayed in all patients who received < 2 x 10(6) CD34+ cells/kg infused (P < 0.02). In patients who had had previous HDM both neutrophil (P < 0.05) and platelet recovery (P < 0.007) were delayed compared with recovery in patients who had not had HDM. In patients who had had previous HDM and received < 2 x 10(6) CD34+ cells/kg infused only 3/17 regained platelets to > 100 x 10(9)/l compared with 3/4 who had > 2 x 10(6) CD34+ cells/kg infused (P < 0.05 Fisher's exact test). There was no evidence that low numbers of CD34+ cells in the PBSCR were associated with early death. The data show that previous treatment with HDM had adverse effects on the subsequent engraftment of platelets among patients given HDM/PBSCR. The data suggest that additional measures are needed to achieve platelet reconstitution in these heavily pre-treated patients.
authors.affiliation: Section of Academic Haematology, McElwain Laboratories, Sutton, Surrey, UK.
authors.forename: B C
authors.initials: BC
authors.lastname: Millar
authors.forename: J L
authors.initials: JL
authors.lastname: Millar
authors.forename: J B
authors.initials: JB
authors.lastname: Bell
authors.forename: N
authors.initials: N
authors.lastname: Raje
authors.forename: S
authors.initials: S
authors.lastname: Milan
authors.forename: J
authors.initials: J
authors.lastname: Mehta
authors.forename: S
authors.initials: S
authors.lastname: Singhal
authors.forename: G W
authors.initials: GW
authors.lastname: Middleton
authors.forename: V
authors.initials: V
authors.lastname: Sheperd
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
authors.forename: R L
authors.initials: RL
authors.lastname: Powles
mesh_terms: D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001772:Blood Cell Count; D003131:Combined Modality Therapy; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage*; D009101:Multiple Myeloma / Q000097:blood / Q000628:therapy*
chemical_list: D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan