ORIGINAL ARTICLE Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients ML Grazziutti 1 , L Dong 1 , MH Miceli 1 , M Cottler-Fox 2 , SG Krishna 1 , A Fassas 1 , F van Rhee 1 , BM Barlogie 1 and EJ Anaissie 1 1 Myeloma Institute of Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA and 2 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA The duration of neutropenia (absolute neutrophil count (ANC) p100/ll) identifies cancer patients at risk for infection. A test that precedes ANCX100/ll would be of clinical value. The immature reticulocyte fraction (IRF) reflects erythroid engraftment and hence a recovering marrow. We evaluated the IRF as predictor of marrow recovery among 90 myeloma patients undergoing their first and second (75 patients) melphalan-based autologous stem cell transplantation (Mel-ASCT). The time to IRF doubling (IRF-D) preceded ANCX100/ll in 99% of patients after the first Mel-ASCT by (mean7s.d.) 4.2371.96 days and in 97% of the patients after the second Mel-ASCT by 4.1171.95 days. We validated these findings in a group of 117 myeloma patients and 99 patients with various disorders undergoing ASCT with different conditioning regimens. We also compared the time to hypophosphatemia and to absolute monocyte countX100/ll to the time to ANCX100/ll. These markers were reached prior to this ANC end point in 55 and 25% of patients but were almost always preceded by IRF-D. We conclude that the IRF-D is a simple, inexpensive and widely available test that can predict marrow recovery several days before ANCX100/ll. Bone Marrow Transplantation (2006) 37, 403–409. doi:10.1038/sj.bmt.1705251; published online 9 January 2006 Keywords: neutropenia; autologous stem cell transplant; immature reticulocyte fraction; bone marrow engraftment Introduction Infectionisaseriouscomplicationofantineoplastictherapy particularly in the setting of profound and prolonged myelosuppression. 1 The severity of myelosuppression has been evaluated as absolute neutrophil count (ANC)p100/ ml, absolute monocyte count (AMoC)p100/ml, 2,3 expected resolution of neutropenia in o10 days and ‘early evidence of marrow recovery. 4 Unfortunately,itisdifficulttopredict time to resolution of neutropenia, and ‘early evidence of marrow recovery’ 4 is not a clearly defined end point. A test that can predict marrow recovery in an individual patient earlier than ANCX100/ml would be of clinical value. An increase in oral mucosal neutrophils precedes neutrophil recovery by 3 days 5 but is time consuming. Otherpredictivetestsofmarrowrecoveryincludehypophos- phatemia 6 and hypouricemia, 7 both of which develop in approximately60%ofpatientsuponmarrowrecovery 6,7 but precede ANCX500/ml by only 2–3 days and can be altered by phosphate replacement, renal failure and/or allopurinol therapy. Increasing numbers of circulating immature reticulocytes has been proposed as a marker of marrow recovery. 8,9 During erythropoiesis, reticulocytes are released into the circulation where they gradually lose their RNA, mature and evolve into erythrocytes. A higher proportion of circulating immature reticulocytes (high RNA content) indicates recovering marrow activity and is quantitated by automated hematology cell analyzers. 8,9 The fluorescence intensity of the entire reticulocyte population was initially reported as the reticulocyte maturation index or the mean fluorescent index. 10,11 Reticulocyteshavenowbeengrouped into low, middle (MFR) or high fluorescent region (HFR) corresponding to the lower, middle and higher RNA content, respectively. The immature reticulocyte fraction (IRF) measures the MFR and HFR populations and is more reproducible than the HFR. 12 We compared the time to doubling of IRF (IRF-D) to time to ANCX100/ml in 90 consecutive myeloma patients undergoing melphalan-based tandem autologous stem cell transplantation (Mel-ASCT). The IRF-D was found to be a reliable predictor of ANC recovery and preceded Received 16 September 2005; revised and accepted 11 November 2005; published online 9 January 2006 Preliminary results of this manuscript have been presented in abstract form at the 43rd Annual meeting of the Infectious Disease Society of America. San Francisco, October 6–9, 2005 Correspondence: Dr EJ Anaissie, Myeloma Institute of Research and Therapy, University of Arkansas for Medical Sciences, 4301 West Markham Slot 776, Little Rock, AR 72205, USA. E-mail: anaissieeliasj@uams.edu Bone Marrow Transplantation (2006) 37, 403–409 & 2006 Nature Publishing Group All rights reserved 0268-3369/06 $30.00 www.nature.com/bmt