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In order to assess the effect of Pegfilgrastim on the duration of neutropenia and clinical outcome of patients after autologous peripheral blood stem cell transplantation (PBSCT), we compared 20 consecutive patients with lymphoma or multiple myeloma receiving a single 6 mg dose of Pegfilgrastim on day 1 posttransplant to a historical control group of 60 patients receiving daily Filgrastim 5 μg/kg starting on day 1 posttransplant. There were 54 M and 26 F, 30 patients with lymphoma and 50 with myeloma, 26 in CR and 54 not in CR. Mean age was 55±10 yrs and 25 had already received a previous autologous transplant. The two groups were matched for disease and disease status, transplant number, age and sex. Cell dose infused tended to be higher in the Pegfilgrastim group (7.16±3.82 vs 10.03±6.25 x106 CD34+ cells/kg, p=0.0575). There were no differences (p>0.05) in time to 0.5 (8 vs 9 days) or 1 (9 vs 9 days) x109/L neutrophils; to 1 % reticulocytes (13 vs 15 days) or 9 (12 vs 14 days) or 10 (30 vs 25 days) g/dL Hb; to 20 (9 vs 9 days) or 100 (20 vs 31 days) x 109/L platelets. The number of days with fever (2.7±2.3 vs 2.3±2.4 days), incidence of infections (all infections; bacteremia; bacterial, fungal or viral infections; FUO), duration of antibiotic therapy (8.7±5.9 vs 8.4±5.9 days), RBC (1.1±1.6 vs 0.9±1.6) and platelet (1.0±1.7 vs 1.2±1.8) transfusions, and time to hospital discharge (14.5±5.3 vs 15.4±5.8 days) were similar in the Pegfilgrastim compared to the Filgrastim group. However, after initial hematopoietic recovery, several differences between the groups became apparent, with the group always showing higher counts compared to the Filgrastim group (p values <0.05 to <0.001). Neutrophils remained significantly higher in the Pegfilgrastim group between days 14–30, lymphocytes between days 56–90, monocytes between days 21–24, reticulocytes between days 17–42 and platelets between days 35–90, respectively. These differences had no impact on clinical outcome after day 30 due to the low incidence of infectious events after engraftment. We conclude that Pegfilgrastim administrated on day 1 posttransplant facilitates early hematopoietic reconstitution comparable to daily Filgrastim. However, despite a trend towards fewer CD34+ cells transplanted, the Pegfilgrastim group enjoyed higher trilineage cell counts for some time after initial engraftment. This should be further tested in prospective randomized trials.

The purpose of our study was to evaluate the capacities of cord blood (CB) CD34+ cells to proliferate and differentiate ex vivo into myeloid lineage in response to cytokines and to compare them with mobilized peripheral blood (MPB) cells. Briefly, 2.5 × 104 CD34+ cells, isolated from CB (n=10) and MPB (n= 9), were cultured in 5 ml MacoBiotech HP01 (Macopharma) with SCF, Flt3-L, IL-3 and G-CSF. At day 9, 106 cultured cells were replated for 5 additional days. Cells were counted and evaluated for their CD34, CD13 and CD15 expression. Differentiation into myeloid compartment was assessed by CD11b and CD16 coexpression on CD15+ cells. We observed that leucocyte expansion was significantly higher in CB than in MPB at day 9 (24.3±3.8 vs 15.2±1.9) and at day 14 (224.7±54.2 vs 72.9±20.0). A similar difference was observed for CD34+ cell expansion (8.7±1.4 vs 3.4±0.5 at day 9 and 31.3±4.6 vs 7.6±2.4 at day 14). at day 9, despite superior CB leucocyte expansion, CD13+ and CD15+ cell number produced per CD34+ cell seeded at day 0 were similar in CB and in MPB (18.5±2.4 vs 14.4±2.5 for CD13+ and 7.1±1.3 vs 6.0±1.2 for CD15+). Increasing the culture period led to higher numbers of CD13+ and CD15+ cells in CB than in MPB. This increase was due to a total leucocyte expansion rather than to high CD13+ and CD15+ cell percentage. The distribution of CD11b−CD16−, CD11b+CD16− and CD11b+CD16+ subpopulations in CD15+ cells was comparable in CB and in MPB after 9 days of culture, with a majority of relatively immature CD11b−CD16− myeloid progenitor cells. However, after 5 additionnal days of culture, MPB CD15+ cells expressed a more mature phenotype than CB CD15+ cells, with a dramatic increase of CD11b+CD16− cells (promyelocytes and myelocytes). In conclusion, our study suggests that, despite the high CB cell capacity of expansion in our culture conditions, CB CD34+ cell differentiation process into myeloid lineage appears to be slower. This difficulty of CB cells to reach maturation in vitro is likely to be related with the longer delay of neutrophil recovery after CB transplantation.

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