Abstract
High-dose chemotherapy (HDC) requires hematopoïetic stem cell support. Failure of mobilization was defined by CD34+ cells <20/μL, and failure of collection by CD34+ collected cells <2.106 cells/kg. In one center, 92 of 742 mobilization candidates in 5 years failed in mobilization/collection (classical parameters including age & previous line(s)-mean: 12.2%, range/year: 8.1–19.3%). In addition, 44/92 pts had an estimation of their CD34+ cell bone marrow (BM) content by a 2 to 3-site BM aspirate, allowing to subdivide pts with a defect of mobilization with persisting CD34+ in BM from pts with a lack of CD34+ cells in BM, corresponding to a true BM failure. Ancestim (r-metHuSCF, Amgen, CA) functions synergistically with filgrastim to mobilize progenitors to the peripheral blood. To evaluate a combination ancestim + filgrastim as rescue in the generation of a PBPC autograft in pts with prior failure to mobilize CD34+ cells, or from whom insufficient CD34+ cells had been collected, we performed the following analysis. Ancestim was delivered with the ATU (named pt French Temporary Authorization for Use) program to 372 pts (median age 53 yrs [1–70]; females 49%). Diseases categories were: lymphomas (Ly: 50%), multiple myeloma (MM,29%); CLL (6%), Ewing’s sarcoma (4%), neuroblastomas (4%), ovarian carcinoma (1%), other tumor (6%). 357 pts were analyzed: 339 pts having prior collection failure (number of prior failure of leukapheresis: 1 to 5), and 18 pts for whom stem cells mobilization failed and no prior leukapheresis. Ancestim (20μg/kg/d) was combined with filgrastim alone (10μg/kg/d; median 7 days) or with chemotherapy + filgrastim (5μg/kg/d, median 12 days). An autograft appropriate to support HDC (>2x106 CD34+ cells/kg) was obtained in 144/357 pts (40%) following an ancestim administration − 9 of 18 pts with prior mobilization failure(s) &135 of 339 pts with prior collection failure(s) (including 56% MM and 29% Ly) - The mean of CD34+ cells obtained was 3.26 x106/Kg. In the 339 pts with prior collection failure, the ancestim + filgrastim association was efficacious concerning the collection in 65% pts. To date, 115 pts have undergone transplantation (106 pts in the group of prior collection failure and 9 pts in the second group). Median times to platelet and neutrophil recovery were comparable to those obtained with filgrastim-mobilized PBPCs (platelets > 20 x 109/L-13 days; neutrophils > 0.5 109/L-12 days). Of the 22 evaluate pts with CLL who experienced mobilization failure, an adequate autograft was obtained in 10 pts, followed by an autotransplantation in 5 pts. Safety Amgen data report (459 pts with prior mobilization or collection failure have been exposed to ancestim) 2 experienced anaphylactoid symptoms with systemic histamine release, after inadvertant IV injection. In this population with prior failure for an autograft, an additional mobilization of progenitors using ancestim + filgrastim was tried to obtain an appropriate collection for an autograft and allow HDC progression, even in pts who failed previous mobilization(s). With an appropriate premedication, use of ancestim was safe in this large multicenter series.
Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients
