Post-transplant events Combined administration of alpha-erythropoietin and filgrastim can improve the outcome and cost balance of autologous stem cell transplantation in patients with lymphoproliferative disorders A Olivieri 1 , I Scortechini 1 , D Capelli 1 , M Montanari 1 , M Lucesole 1 , G Gini 1 , M Troiani 1 , M Offidani 1 , A Poloni 1 , MC Masia 1 , GM Raggetti 2 and P Leoni 1 1 Clinica di Ematologia, Universita` Politecnica delle Marche, Italy; and 2 Facolta` di Economia e Commercio, Universita` Politecnica delle Marche, Italy Summary: We compared the use of G-CSF plus EPO in a group of 32 multiple myeloma and lymphoma patients with historical controls receiving G-CSF alone. Haemopoietic reconstitutionwassignificantlyfasterinpatientsreceiving G-CSF þ EPO(groupB),withamediantimeof10days to achieve an ANC count 40.5  10 9 /l, compared to 11 days in the historical group (A). The median duration of severe neutropenia (ANC count o100/ml) was signifi- cantly shorter in group B compared to group A; platelet counts 420  10 9 and 450  10 9 /lwereachievedatdays þ 13and þ 17,respectivelyingroupB,comparedtodays þ 14 and þ 24, respectively, in group A (P ¼ 0.015, 0.002) patients. The transfusion requirement was reduced in group B, with 0 (0–6) RBC units and 1 (0–5) platelet unit transfused in group B vs 2 RBC (0–9) and 2 platelet units (0–8) in group A. Median days of fever, antibiotic therapy and hospital stay were reduced in group B (9.5 days vs 22). The mean cost of autotransplantation per group A patient was 23988 Euro, compared with 18394 Euro for a group B patient. Our study suggests that the EPO þ G-CSF combination not only accelerates engraft- ment kinetics, but can also improve the clinical course of ASCT. Bone Marrow Transplantation (2004) 34, 693–702. doi:10.1038/sj.bmt.1704643 Published online 9 August 2004 Keywords: autologous transplantation; erythropoietin; engraftment kinetics Autologous stem cell transplantation (ASCT) has comple- tely replaced ABMT due to accelerated engraftment kinetics and reduction of costs of the high-dose therapy (HDT). 1 The use of growth factors (GFs) like G-CSF or GM-CSF for blood progenitor cell (BPC) mobilization (with or without chemotherapy) allows the collection of large amounts of CD34 þ cells in about 85% of patients with lymphoma or MM. The most used GF both for BPC mobilization and after transplantation is the human G-CSF (filgrastim or lenograstim) at doses ranging from 5 mg/kg, after chemotherapy, to 10–16 mg/kg as a single mobilizing agent. 2–5 Although BPCs accelerate engraftment kinetics compared to bone marrow (BM), the utility of adding GF after autotransplantation is still debated. 5–10 Some reports concerning the timing of G-CSF adminis- tration after BPC reinfusion suggest no clear clinical benefit of early vs delayed administration. 11,12 Consequently, in many centers the administration of G-CSF after transplantation is not performed routinely when the stem cell source is mobilized BPC, especially when the dose of CD34 þ cells reinfused is above the minimum safe threshold required for a rapid engraftment. While the BPC dose needed to ensure quick, sustained and complete engraftment should not be less than 2  10 6 /kg CD34 þ cells, 3,13 there is consensus that reinfusing a higher threshold (at least 5  10 6 /kg) of CD34 þ cells as an optimal target to warrant a safe transplant procedure in at least more than 90% of patients minimizes the risks of prolonged cytopenia and the costs of prolonged hospi- talization and/or supportive care. 14,15 Therefore, when the CD34 þ cell dose is optimal (45  10 6 /kg), the aplastic phase after HDT is unlikely to be further reduced. Moreover, the use of larger amounts of BPC is questionable and may increase the risks of reinfusing more clonogenic tumor cells. 16,17 The possibility of further reducing the aplastic phase after HDT has been explored by using ex vivo expansion of haemopoietic stem cells, but this approach is time- consuming and very expensive. The ability of erythropoietin (EPO), associated with G-CSF, to reduce life-threatening neutropenia after chemo- therapy, has been recently suggested by a randomized study of 50 patients with ovarian cancer, 18 and before 1995 at least three randomized studies evaluated the role of EPO administration after ASCT, but none was able to Received 20 February 2004; accepted 30 May 2004 Published online 9 August 2004 Correspondence: Dr A Olivieri, Clinica di Ematologia, Ospedale Torrette di Ancona, Via Conca 1 ZIP Code, 60020 Italy; E-mail: a.olivieri@ao-umbertoprimo.marche.it Bone Marrow Transplantation (2004) 34, 693–702 & 2004 Nature Publishing Group All rights reserved 0268-3369/04 $30.00 www.nature.com/bmt