TRANSPLANTATION AND CELLULAR ENGINEERING Long-term hematologic reconstitution after autologous peripheral blood progenitor cell transplantation: a comparison between controlled-rate freezing and uncontrolled-rate freezing at 80C Mauro Montanari, Debora Capelli, Antonella Poloni, Danilo Massidda, Marino Brunori, Luca Spitaleri, Massimo Offidani, Moira Lucesole, Maria C. Masia, Florinda Balducci, Cristina Refe, Mario Piani, Pietro Leoni, and Attilio Olivieri BACKGROUND: The most widely used system for pe- ripheral blood progenitor cell (PBPC) cryopreservation is controlled-rate freezing (CRF). Uncontrolled-rate freez- ing (URF) at –80°C has also been used, but its clinical impact has not been studied sufficiently yet. STUDY DESIGN AND METHODS: Two groups of pa- tients were compared: Group A consisted of 69 patients autotransplanted with PBPCs cryopreserved with CRF; Group B consisted of 192 patients autotransplanted with PBPCs cryopreserved with URF at –80°C. The same cryoprotectant solution and storage system were used. RESULTS: A significant delay of hematologic reconsti- tution (HR) in the URF group was observed for neutro- phils greater than 0.5 × 10 9 per L and for platelets greater than 20 × 10 9 per L and greater than 50 × 10 9 per L; we did not observe any differences in the clinical course. The long-term HR was comparable in the two groups, all patients showed stable engraftment, and no late graft failures were observed. CONCLUSION: Our study confirms that URF is safe and allows sustained long-term engraftment without in- creasing the risks of transplantation, even though the early engraftment after URF is slower. T he expanding indications of high-dose therapy (HDT) in hematologic 1,2 and nonhematologic malignancies 3 are associated with an increasing request for simplification and cost reduction of routine freezing procedures. Hematologic reconstitution (HR) after peripheral blood progenitor cell (PBPC) transplantation requires ef- ficient cryopreservation and storage techniques to reduce the loss and the functional damage of pluripotent HPCs. 4 Currently, the most widely used system for PBPC cryopreservation is controlled-rate freezing (CRF), but this technique is time consuming and increases the glob- al costs of transplantation. The cryogenic mixture is usu- ally composed of DMSO, as intracellular cryoprotectant at 10- to 2.2-percent concentrations, plus either human albumin serum, plasma, serum, or HES as extracellular cryoprotectant. CRF is generally followed by the storage of HPCs in either the liquid or vapor phase of nitrogen liquid. ABBREVIATIONS: ANC = absolute neutrophil count; CRF = controlled-rate freezing; CVC = central venous catheter; HDT = high-dose therapy; HR = hematologic reconstitution; MDS = myelodysplastic syndromes; PBPC = peripheral blood progeni- tor cell; TBI = total body irradiation; TRM = transplant-related mortality; URF = uncontrolled-rate freezing. From the Department of Haematology, University of Ancona, Torrette Hospital; and the Department of Transfusion Medi- cine, Torrette Hospital, Ancona, Italy. Address reprint requests to: Mauro Montanari, MD, De- partment of Haematology, University of Ancona, Ospedale Re- gionale Torrette, Via Conca, 60020 Ancona, Italy; e-mail: m.montanari@ao-umbertoprimo.marche.it. Financial support was received from the Associazione Italiana contro le Leucemie, Ancona, Italy. Received for publication February 25, 2002; revision re- ceived July 31, 2002, and accepted August 6, 2002. TRANSFUSION 2003;43:42-49. 42 TRANSFUSION Volume 43, January 2003