Randomized Trial of Autologous Filgrastim-Primed Bone Marrow Transplantation Versus Filgrastim-Mobilized Peripheral Blood Stem Cell Transplantation in Lymphoma Patients

Abstract

Although a large amount of data is available on the effects of filgrastim (granulocyte colony-stimulating factor [G-CSF]) on the mobilization of stem cells in the circulation, data concerning its effects on bone marrow (BM) harvesting is scarce and controversial. We have designed a randomized trial comparing filgrastim-mobilized peripheral blood stem cell (PBSC) transplantation with filgrastim-primed autologous bone marrow transplantation (ABMT). Fifty-five patients affected by non-Hodgkin's (n = 38) or Hodgkin's (n = 17) lymphoma, selected for autologous transplantation over a 12-month period in a single institution, were randomized 2:1 to undergo BM or PB harvest/collection after priming for 3 days with filgrastim, 16 μg/kg body weight daily subcutaneously. BM priming with G-CSF allowed the harvest of a significantly higher number of mononuclear cells (MNC) (0.53 × 108/kg, range, 0.32 to 1.40), as compared with a historical control of unprimed BM harvests (0.43 × 108 MNC/kg, range, 0.15 to 0.72, P = .001). After high-dose ablative therapy, median time to neutrophil recovery above 0.5 × 109/L was 12 days for BM and 11 days for PB (P = .219); median time to platelet recovery above 20 × 109/L was 13 days for BM and 11 days for PB (P = .242). The same number of red blood cells, platelet transfusions, and posttransplant G-CSF doses were required in the two groups of patients. Less patients (50% v 70%) became febrile in the group transplanted with mobilized PB, but days of fever/patient and days on antibiotics were overlapping. The median time spent in the hospital after reinfusion was 16.5 and 15.5 days after primed BM and primed PB, respectively (P = .134). These data suggest that in patients with lymphoma submitted to autologous transplantation, the reinfusion of filgrastim-primed BM or filgrastim-mobilized PB leads to similar results, with an advantage of only 1 day in the neutrophil recovery and 1 day on the time spent in the hospital in favor of primed PB. Either option can be chosen on the basis of the availability of a surgery room or cell separator facilities and considering the patients' characteristics and wishes.

Comparison of rhG–CSF primed bone marrow and blood stem cell autografts: an analysis of engraftment in malignant lymphomas and solid tumours

“…However, the diagnoses of these patients were not mentioned in the paper and the time to PBSC engraftment was delayed compared to our data (11). In a recent randomized study in lymphoma patients, G-CSF primed BM was found to produce equally fast engraftment as G-CSF primed PBSC (12). This is in contrast to the findings in our study and may be due to different patient characteristics.…”

“…The engraftment data from 15 double BM transplants and 7 double PBSC transplants in testicular cancer patients are shown in Table 2. There was no (8)(9)(10)(11)(12)(13)(14)(15)(16) difference in time to neutrophil or platelet engraftment between first and second transplantation in neither BM nor PBSC transplantations.…”

Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation: the Hovon 22 study

“…The advantage in the granulocyte and platelet recovery in the PSCT arm was also reflected in a significant reduction in number of days with fever and intravenous antibiotics, and less transfusions, further underscoring the advantage of applying PSCT over ABMT. A recent study suggested that the results of ABMT could be improved by using G-CSF-exposed bone marrow cells for 3 d (Damiani et al, 1997). In this setting, the difference in engraftment between PSCT versus ABMT almost disappeared.…”

“…However, there is a great variability in neutrophil recovery in the setting of ABMT, which will be related to previous chemotherapy regimens and the number of (stem) cells collected. Damiani et al (1997) reported a median of 13 d for neutrophil engraftment in ABMT patients. In contrast, a recent study with recombinant interleukin 3 (IL-3) given in the setting of ABMT demonstrated a neutrophil ($ 0´5 Â 10 9 /l) and platelet ($ 20 Â 10 9 /l) engraftment in the placebo arm after a median of 25 and 28 d respectively (Brouwer et al, 1999).…”

Bioequivalence of two recombinant granulocyte colony-stimulating factor formulations in healthy male volunteers

“…Recombinant human G-CSF is mainly applied to reduce febrile neutropenia in patients with non-myeloid malignancies that receive myelosuppressor drugs [2,3]. It is also recommended for treating congenital, cyclic or idiopathic neutropenia [4], to accelerate neutrophils recovery in bone marrow transplantation [5], to minimize other neutropenia [6][7][8][9] and for the mobilization of hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis [10].…”