ABSTRACT
Not available.
ABSTRACT
The feasibility of unprocessed, granulocyte colony-stimulating factor (G-CSF)-mobilized whole blood (WB) as an alternative stem cell source for autologous stem cell transplantation was studied. Forty-seven relapsed non-Hodgkin's lymphoma (NHL) patients entered the study. After two or three ifosfamide, methotrexate and etoposide (IMVP) courses, 1 l of G-CSF-mobilized WB was collected and stored refrigerated for 72 h. Meanwhile, BAM conditioning was given: BCNU (carmustine) 300 mg/m(2), high-dose cytarabine 6000 mg/m(2) and melphalan 140 mg/m(2). Toxicity, haematological recovery and survival were assessed and compared with peripheral blood stem cell transplantation (PBSCT) and bone marrow transplantation (BMT) reference groups. High-dose G-CSF (2 x 12 microg/kg/d) gave the best mobilization results. Haematological recovery was related to the WB CD34+ content. A CD34+ threshold of >or= 0.3 10(6)/kg, obtained in 90% of patients using high-dose G-CSF, correlated with adequate recovery: absolute neutrophil count (ANC) > 0.5 x 10(9)/l: median 12 d (range 9-19). Platelet recovery > 20 and > 50 x 10(9)/l was 19 (11-59) and 30 d (14 not reached) respectively. Overall survival of patients < 60 years was 57% at 4 years and event-free survival was 32%. Survival was comparable with PBSCT and BMT after BEAM (BCNU, etoposide, cytarabine, melphalan). Remarkably, haematological recovery after BAM + WB was rapid and comparable (ANC) or slightly prolonged (platelets) in comparison with BEAM + PBSCT, despite a 10-20 times lower CD34+ cell dose in the WB graft. In conclusion, transplantation of WB containing >or= 0.3 x 10(6)/kg CD34+ cells after BAM conditioning is a safe procedure, and offers a fully equivalent and less costly alternative for PBSC.
Subject(s)
Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cell Transplantation , Lymphoma, Non-Hodgkin/surgery , T-Lymphocytes/immunology , Adult , Antigens, CD34 , Female , Humans , Male , Middle Aged , Recurrence , Transplantation Conditioning , Transplantation, AutologousABSTRACT
BACKGROUND: G-CSF-mobilized whole blood (WB) is a cost-reducing and simple alternative for peripheral blood progenitor cell transplantation. Recently, it was demonstrated that mobilized WB supplemented with Leibovitz's L15 medium permitted prolonged preservation of clonogenic cells at ambient temperature. In this study, an infusable-grade L15 medium (IG-L15) was developed, and the safety profile of mobilized WB after 7 days of storage was investigated. STUDY DESIGN AND METHODS: IG-L15 was manufactured in a closed system under good manufacturing practice conditions. Proinflammatory cytokine levels and hemolysis in mobilized WB were determined after 7 days of storage in different containers and were compared with current clinical mobilized WB values after 1 to 3 days of storage at 4 degrees C. RESULTS: IG-L15 and L15 maintained clonogenic cells equally. In the samples of mobilized WB that were returned to the patient, cytokine levels were not elevated in comparison with freshly collected mobilized WB. By using IG-L15 in polystyrene-coated cell culture bags, median (range) levels of 9.4 (2.2-69.8) pg per mL (IL-1beta), 31.6 (6.1-146.5) pg per mL (TNF-alpha), 76.9 (15.5-934.9) pg per mL (IL-6), and 7195 (104-205,600) pg per mL (IL-8) were found after 7 days. Higher cytokine levels were found with L15 and different containers. He- molysis was less than 0.5 g per dL in all cases. CONCLUSION: The storage of mobilized WB for 7 days in IG-L15 at ambient temperature is possible with adequate preservation of clonogenic cells, but cytokine levels may require plasma removal before return.
