Search

High-dose chemotherapy followed by CD34+ enriched peripheral blood progenitor cell (PBPC) transplantation is used for the treatment of primary refractory or relapsed Hodgkin’s and non-Hodgkin’s lymphomas. The CD34+ enrichment procedure, while reducing tumor burden, may compromise immunological reconstitution in the transplanted patient and result in increased rates of post-transplant infection. We compared infectious complications in patients with lymphoma who were treated with high-dose chemotherapy and supported either with CD34+ enriched PBPC (n = 19) or unmanipulated PBPCs (n = 24). Analysis was limited to patients discharged from initial hospitalization for transplantation with a minimum of 1 year follow-up and free of lymphoma recurrence. We found a statistically significant increase in the number of patients with one or more infectious events in the CD34+transplant group (14/19) compared with the unmanipulated PBPC group (9/24, P < 0.01). Greater numbers of patients with two or more infectious events were observed in the CD34+ group (7/19 vs 2/24, P < 0.03) and an increased incidence of bacterial infections was observed in the CD34+ group (10/19 vs 5/24, P < 0.05). Two deaths due to infectious complications were observed in the CD34+ group. There was no significant difference in blood lymphocyte or monocyte recovery between the groups. These data demonstrate a significant increase in the long-term incidence of infectious events in lymphoma patients transplanted with autologous CD34+ enriched PBPCs compared to unmanipulated PBPCs. Thus, patients who undergo CD34+ enriched PBPC transplantation should be followed closely for infectious complications and prolonged infectious prophylaxis should be considered. Bone Marrow Transplantation (2000) 26, 831–836. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate whether storing mobilized peripheral blood progenitor cell (PBPC) collections overnight before CD34+ selection may delay platelet count recovery after high-dose chemotherapy and CD34+-enriched PBPC re-infusion. Lymphoma patients underwent PBPC mobilization with cyclophosphamide 4 g/m2 i.v. and G-CSF 10 μg/kg/day subcutaneously. Patients were prospectively randomized to have each PBPC collection enriched for CD34+ cells with the CellPro CEPRATE SC System either immediately or after overnight storage at 4°C. Thirty-four patients were randomized to overnight storage and 34 to immediate processing of PBPC; 15 were excluded from analysis due to tumor progression or inadequate CD34+ cell mobilization. PBPC from 23 patients were stored overnight, while 30 subjects underwent immediate CD34+selection and cryopreservation. Median yield of CD34+ enrichment was 43.6% in the immediate processing group compared to 39.1% in the overnight storage group (P = 0.339). neutrophil recovery >500 × 109/l occurred a median of 11 days (range 9–16 days) in the overnight storage group compared to 10.5 days (range 9–21 days) in the immediate processing group (P = 0.421). Median day to platelet transfusion independence was 13 (range 7–43) days in the overnight storage group vs 13.5 (range 8–35) days in those assigned to immediate processing (P = 0.933). We conclude that storage of PBPC overnight at 4°C allows pooling of consecutive-day collections resulting in decreased costs and processing time without compromising neutrophil and platelet engraftment after infusion of CD34+-selected progenitor cells. Bone Marrow Transplantation(2000) 25, 559–566. [ABSTRACT FROM AUTHOR]

In order to demonstrate the feasibility of mobilization, enrichment and engraftment of autologous peripheral blood CD34+ cells in patients with relapsed lymphoma, 59 peripheral blood progenitor cell (PBPC) collections from 21 patients were enriched for CD34+ cells using CEPRATE SC (CellPro, Bothell, WA, USA) immunoaffinity column. Following high-dose chemotherapy, a mean of 17 × 108 (range, 3–34) nucleated cells/kg containing 8.7 × 106 (0.3–26) CD34+ cells/kg were re-infused. Blood cell recovery in these patients was compared to engraftment capacity of unenriched PBPCs in a cohort of lymphoma patients treated with an identical high-dose chemotherapy regimen. Neutrophil and platelet engraftment was rapid in both groups including five patients who received 1 × 106 CD34+ cells/kg. After infusion of CD34+ enriched cells, neutrophils exceeded 0.5 × 109/l in 11 (8–14) days and platelets exceeded 20 × 109/l (untransfused) in 15 (9–39) days. In order to optimize the immunoaffinity column utilization we stored the first PBPC collections overnight at 4°C and combined them with the next day’s collection prior to the CD34+ enrichment procedure in 11 patients. This maneuver resulted in a significant decrease in the CD34+ cell recovery (resulting in reinfusion of a mean of 42% less CD34+ cells). Although overnight storage did not affect neutrophil engraftment, platelet engraftment was prolonged in this group of patients even when >2.0 × 106 CD34+ cells/kg were re-infused. The overnight storage procedure should be further evaluated for its effects on the CD34+ immunoaffinity enrichment procedure, megakaryocyte progenitors and platelet engraftment. We conclude that CD34+ cells enriched from peripheral blood result in... [ABSTRACT FROM AUTHOR]

We evaluated induction of lymphomas by the methylating carcinogen, N-methylnitrosourea [MNU], in transgenic mice expressing both LMO1 and the DNA repair gene, MGMT, in the thymus. The goal was to determine whether environmental mutagens shorten the latency or increase the incidence of LMO1+lymphomas and whether mice transgenic for both LMO1 and MGMT, and thereby able to repair O6-methylguanine DNA adducts induced by MNU, would be protected. Mice heterozygous for LMO1 or MGMT were crossed and offspring treated with MNU at 6 weeks of age. MNU induced lymphoma incidence was highest in the LMO1 mice, 91% and lowest in the hMGMT+mice, 15%. MNU induced K-ras mutations in codon 12 in non-MGMT transgenics resulted in a shorter latency of tumors and accounting for half of the early lymphomas in LMO1 mice. The effect of MNU was abrogated in the LMO1/hMGMT transgenic mice, indicating the ability of MGMT expression to block the carcinogenic effect of MNU even in cancer prone mice. Thus, methylating agents potentiate lymphomagenesis of LMO1, in part through activation of K-ras and the MAPK pathway, a process which appear to synergize with LMO1 mediated transcription activation. O6-alkylguanine DNA-alkyltransferase mediated DNA repair effectively blocks chemical carcinogenesis in mice carrying the LMO1 oncogene. [ABSTRACT FROM AUTHOR]