A Randomized Trial Comparing the Effectiveness of Peripheral Blood Stem Cell Mobilization with Chemotherapy and Early vs Delayed Initiation of Granulocyte Colony-Stimulating Factor (G-CSF) in Patients with Lymphoma and Multiple Myeloma.
Authors: Bence-Bruckler Isabelle A. , McDiarmid Sheryl , Atkins Harold L. , Sabloff Mitchell , Gauthier Isabelle , Huebsch Lothar B. 
Published: April 2020

The optimal dose and schedule of granulocyte colony-stimulating factor (G-CSF) for peripheral blood progenitor cell (PBPC) mobilization is unclear. When PBPC mobilization is performed using chemotherapy and growth factor priming, growth factors are often initiated early (day +1) upon completion of chemotherapy. Several small trials report safe and successful PBPC collection after delayed G-CSF initiation. We evaluated two schedules of G-CSF administration in patients with lymphoma and myeloma undergoing PBPC collection. We compared CD34+ cell yields obtained in each group and number of G-CSF doses required. Secondary end points were post-transplant neutrophil and platelet recovery and duration of febrile neutropenia, IV antibiotic administration and hospitalization.

We studied patients with lymphoma and myeloma referred for ASCT. Eligible patients had not received more than two prior chemotherapy regimens or pelvic irradiation. Priming chemotherapy was DHAP (lymphoma) or cyclophosphamide 2.5 gm/m2 (myeloma and lymphoma). Rituximab was combined with chemotherapy for certain lymphoma patients for purposes of in vivo purging. G-CSF was initiated either 24 hours (day +1) post completion of chemotherapy (Group 1), or on the 5th day (day +5) after chemotherapy (Group 2). The dose of G-CSF was 300 ug sc daily for patients weighing 70 kg or less, and 480 ug sc daily if &gt; 70 kg. Leukapheresis was initiated when the WBC count was &gt;2.0 x 109/l and the CD34+ count was &gt;10/microliter. Single or serial daily leukaphereses were performed until a minimum of 2 x 106 CD34+ cells/kg were obtained.

There were eighty-one consenting patients: 30 with nonHodgkin’s lymphoma, 37 with myeloma and 14 with Hodgkin’s lymphoma. Priming was done with DHAP in 33 and with cyclophosphamide in 46. Forty-two were randomized to day +1 G-CSF initiation (Group1) and 39 to day +5 (Group 2). Diagnosis, prior chemotherapy or priming regimen did not vary among the study groups. Three patients in Group 1 did not proceed to collection (two due to disease progression, the third withdrew consent). All patients in Group 1 were successfuly mobilized, while in group 2, two were not successfully mobilized (p=0.49). Of these patients, one underwent marrow harvest while the other was transplanted with a suboptimal CD34+ cell count. In Group 1, 32 of 39 were mobilized with a single leukapheresis and 7 required two; in Group 2, 25 of 37 were mobilized in 1 day, 11 in 2 days and one patient required 4 days (p=0.2).The median number of CD34+ cells collected was 10.6 x 106/kg in Group 1 versus 7.9 x 106/kg in Group 2 (p=.04). The median number of doses of G-CSF administered was 9 in Group 1 and 6 in Group 2 (p&lt;.0001).

The time to neutrophil and platelet recovery were 11 and 11.5 days respectively and did not differ amoung the groups. There was no difference in the number of platelet transfusions, duration of febrile neutropenia, antibiotic use or length of hospitalization. The number of units of RBC transfused in Group 1 was 4 (range; 0–11) versus 2 in Group 2 (range; 0–21; p=.04).

Stem cell mobilization using delayed G-CSF initiation was as effective as early initiation, and required a median of 9 vs 6 doses of drug. Despite lower CD34+ yields in the delayed G-CSF group, the outcome of mobilization was not compromised and post-transplant engraftment, infectious complications and hospitalization were comparable.