Feasibility and cost analysis of day 4 granulocyte colony-stimulating factor mobilized peripheral blood progenitor cell collection from HLA-matched sibling donors.

BACKGROUND: Guidelines recommend treatment with 4-5 days of granulocyte colony-stimulating factor (G-CSF) for optimal donor peripheral blood progenitor cell (PBPC) mobilization followed by day 5 collection. Given that some autologous transplant recipients achieve adequate collection by day 4 and the possibility that some allogeneic donors may maximally mobilize PBPC before day 5, a feasibility study was performed evaluating day 4 allogeneic PBPC collection. METHODS: HLA-matched sibling donors underwent collection on day 4 of G-CSF for peripheral blood (PB) CD34+ counts ≥0.04 × 106/mL, otherwise they underwent collection on day 5. Those with inadequate collected CD34+ cells/kg recipient weight underwent repeat collection over 2 days. Transplant and PBPC characteristics and cost analysis were compared with a historical cohort collected on day 5 per our prior institutional algorithm. RESULTS: Of the 101 patient/donor pairs, 50 (49.5%) had adequate PBPC collection on day 4, with a median PB CD34+ cell count of 0.06 × 106/mL. Day 4 donors were more likely to develop bone pain and require analgesics. Median collected CD34+ count was significantly greater, whereas total nucleated, mononuclear and CD3+ cell counts were significantly lower, at time of transplant infusion for day 4 versus other collection cohorts. There were no significant differences in engraftment or graft-versus-host disease. Cost analysis revealed 6.7% direct cost savings for day 4 versus historical day 5 collection. DISCUSSION: Day 4 PB CD34+ threshold of ≥0.04 × 106/mL identified donors with high likelihood of adequate PBPC collection. Day 4 may be the optimal day of collection for healthy donors, without adverse effect on recipient transplant outcomes and with expected cost savings.

Successful peripheral blood stem cell mobilization with a cost-efficient single fixed-dose plerixafor schedule in poor mobilizers.

Plerixafor, although costly, is added to mobilizing chemotherapy and G-CSF to overcome poor stem cell mobilization. We demonstrate that it can be safely administered mostly once as a single dose in preemptive and rescue settings, leading to apheresis yields of >2 and >4×106 CD34 + cells/kg body weight (bw) in 83% and 48%, respectively. Of note, 35/46 (76%) patients showed a substantial benefit with increased peripheral blood (PB) CD34 + cells prior to apheresis (8.84 vs. 1.72/µl, p < .001), and 5-fold increased CD34 + cells collected per single apheresis (2.25 vs. 0.43 × 106 CD34+/kg bw, respectively, p < .001). Patients profiting most (76%) vs. less (24%) had >5 vs. <5/µl PB CD34 + cells before plerixafor application, respectively, thus careful patient selection in the latter group is advised. To the best of our knowledge, this is the first report demonstrating that favorable apheresis results can be obtained using this cost-efficient, single fixed-dose plerixafor schedule.

Long-active granulocyte colony-stimulating factor for peripheral blood hematopoietic progenitor cell mobilization.

INTRODUCTION: Peg-filgrastim (PEG-FIL), a polyethylene glycol-conjugated form of granulocyte colony-stimulating factor (G-CSF), has been introduced in clinical practice and is effective in shortening the time of neutropenia after cytotoxic chemotherapy. G-CSF has emerged as the preferred cytokine for hematopoietic progenitor cells' (HPC) mobilization. Nevertheless, data on the ability of PEG-FIL in this field have been published. AREAS COVERED: We review publications in the field with the goal of providing an overview of this approach. EXPERT OPINION: PEG-FIL may be able to mobilize CD34(+) cells in a more timely fashion than G-CSF, with the advantages of only a single-dose administration, an earlier start and a reduction in the number of apheresis procedures. The main controversies concern the dosage of the drug and the optimal dose. In the context of chemo-mobilization, a single dose of 6 mg PEG-FIL seems effective in terms of HPC's mobilization and there is no increase in this effect if the dose is doubled to 12 mg. Steady-state mobilization requires higher doses of PEG-FIL and this approach is not cost-effective when compared with G-CSF. The experiences with PEG-FIL in the healthy donor setting are very limited.

Outcome, toxicity profile and cost analysis of autologous stem cell mobilization.

Autologous stem cell mobilization (ASCM) is conventionally done using high-dose CY plus granulocyte colony-stimulating factor (G). It is important to examine the outcomes, toxicity profile and costs of ASCM associated with CY+G. A retrospective study was conducted in 236 patients with myeloma or lymphoma undergoing ASCM with CY+G. An ideal outcome was defined as 2 × 10(6) CD34+ cells/kg collected on the planned day of collection in 1 or 2 apheresis without a negative clinical event. The total cost of ASCM including clinical events, were reported based on Medicare part-B physician, laboratory and ancillary fee schedule. ASCM was successful in 213 (90%) patients, but an ideal outcome was seen in only 50 (20%) patients. Median (interquartile range, IQR) total cost of CY+G stem cells mobilization was $10,605 ($9,230-$14,540). Ideal outcomes were associated with lower costs compared with non-ideal outcomes (median (IQR), $9914 ($8,743-$11,168) versus $11232 ($9,292-$15,518) respectively, P<0.001). The median (IQR) cost of non-ideal outcome was higher among lymphoma patients ($12,293 ($9578-$16,268)) compared with myeloma patients ($10,388 ($9,355-$14,360) (P=0.04). Although mobilization success is eventually realized with CY+G, it has a low rate of ideal outcome, associated with significant adverse events and costs.

EPO in combination with G-CSF improves mobilization effectiveness after chemotherapy with ifosfamide, epirubicin and etoposide and reduces costs during mobilization and transplantation of autologous hematopoietic progenitor cells.

A successful stem cell harvest is a prerequisite for peripheral blood SCT. We investigated the number of CD34(+) cells mobilized, the number of leukaphereses needed and the expenses of treatment for 28 patients with multiple myeloma randomly assigned to receive either G-CSF alone or G-CSF+EPO for stem cell mobilization after chemotherapy with ifosfamide, epirubicin and etoposide. All patients treated with G-CSF+EPO reached the threshold of 6 x 10(6) CD34(+) cells per kg body weight (kgbw), with a mean of 1.3 leukaphereses. On average 15.4 x 10(6) CD34(+) cells/kgbw were collected. In the G-CSF-alone group, the mean number of leukaphereses was 1.8, and 12.6 x 10(6) CD34(+) cells/kgbw were collected, and two patients failed the threshold. Overall costs per patient for mobilization and leukaphereses were 8339 euro (G-CSF+EPO) and 8842 euro (G-CSF). After transplantation, fewer blood transfusions (0.6 versus 1.3, P=0.05), fewer days on antibiotics (2.3 versus 6.1, P=0.02) and a shorter hospital stay (15.2 versus 17.8, P=0.06) were noted in the G-CSF+EPO group resulting in a 19.2% reduction of costs for each transplant (P=0.018). In summary, EPO improves the mobilization efficiency of G-CSF and so reduces costs of mobilization and SCT.

Mobilization strategies for the collection of peripheral blood progenitor cells: Results from a pilot study of delayed addition G-CSF following chemotherapy and review of the literature.

OBJECTIVE: Given the potential to limit cost, we conducted a pilot study evaluating delayed, low-dose granulocyte colony-stimulating factor (G-CSF) following chemotherapy for the procurement of peripheral blood progenitor cells (PBPCs) for autologous transplantation and reviewed the relevant literature. PATIENTS AND METHODS: Twenty-eight patients with various malignancies received cyclophosphamide 4 gm/m(2) and paclitaxel 170 mg/m2 followed by G-CSF 300 microg/d or 480 microg/d starting day +5 until two to four daily large volume leukapheresis yielded > or =5.0 x 10(6) CD34+ cells. We searched MEDLINE, Pubmed, and EMBASE databases from 1990 to the present to identify papers on PBPC procurement using delayed G-CSF (starting day +4 or later) following chemotherapy. RESULTS: G-CSF was administered for a median of 9 days at an average cost of 1260 USD per 70-kg patient. Collection was initiated at a median of 12 days after chemotherapy. A median 2.5 (range 2-4) apheresis were performed yielding an average daily CD34+ collection of 6.9 x 10(6)/kg (range 0.35-56.7). After one apheresis, 82% and 57% of patients collected > or =2.5 x 10(6)/kg and > or =5.0 x 10(6)/kg, respectively. Ultimately, 89% collected > or =5.0 x 10(6)/kg. Febrile neutropenia and catheter-related infection developed in five and two patients, respectively. All patients proceeded to transplantation and engrafted successfully with a median of 14.9 x 10(6)/kg (range 1.05-113) cells infused. Eleven published reports were identified involving 590 patients of whom 498 received G-CSF at a dose range of 250 microg/d to 10 microg/kg/d starting day +4 to 15 for a period of 4 to 9 days for PBPC procurement. Among these reports, 62 to 100% and 33 to 96% of patients collected > or =2 to 2.5 x 10(6) and > or =5.0 x 10(6) CD34+ cells, respectively. CONCLUSION: The use of delayed, low-dose G-CSF plus chemotherapy for stem cell mobilization was feasible and provides further evidence supporting this potentially cost-effective strategy. A review of the literature supports our findings and emphasizes the need for larger studies to address this issue.

Clinical and economic comparison of allogeneic peripheral blood progenitor cell and bone marrow transplantation for acute lymphoblastic leukemia in children.

There is limited experience in the use of peripheral blood progenitor cells (PBPC) for allogeneic transplantation in children. In the present study we compared engraftment kinetics, incidence of acute and chronic graft-versus-host disease (GVHD) and the outcome and economic costs of allogeneic PBPCT vs BMT in children with ALL in a single institution. All children were transplanted in complete remission (CR) with a similar conditioning regimen and the same GVHD prophylaxis. Patients undergoing PBPCT achieved myeloid and platelet engraftment before patients undergoing BMT (P < 0.001). Platelet recovery was faster for the PBPCT group (P < 0.014 for 50 x 10(9)/l and P < 0.039 for 100 x 10(9)/l). Incidence and severity of acute and chronic GVHD were similar in both groups (acute grade 1-2: 9/13 for PBPCT vs 9/11 for BMT; chronic GVHD: 5/12 for PBPCT vs 3/8 for BMT). Hospital stay was shorter for the PBPCT than for the BMT group (28.8 days vs 42.9 days, respectively) and the PBPCT group used less clinical resources, resulting in overall lower cost for PBPCT (US $14,046) compared to BMT (US $19,840). There was no statistically significant difference in DFS between PBPCT and BMT (68.4% vs 50%, respectively).

The possible cost effectiveness of peripheral blood stem cell mobilization with cyclophosphamide and the late addition of G-CSF.

The purpose of this study was to develop a cost-effective protocol for the mobilization of peripheral blood stem cells (PBSC) in patients with malignancy. Thirty consecutive patients were randomized to mobilize PBSC with the late addition of a standard 250 microg dose of G-CSF (Neutrogen) from day 8 or early addition of the same dose of G-CSF from day 2, following cyclophosphamide (CY) 4 g/m2. The median yield of CD34+ cells from evaluated patients was 7.87 x 10(6)/kg (range, 2.06-27.25), collected in a median of four apheresis (range, 2-9). Target CD34 + cell doses > or = 2.0 x 10(6)/kg were achieved in all patients able to be evaluated. There were no statistically significant differences in CD34+ cell yields or toxicities. Overall engraftment occurred with median days to neutrophils > or = 0.5 x 10(9)/L or platelets > 20 x 10(9)/L of 11 and 17 days, respectively. However, the duration of G-CSF administration was markedly shorter in the late use of G-CSF group than in the early use of G-CSF group, with a median of 9 days compared with 15 days (p<0.001). PBSC harvesting after priming with CY plus delayed use of G-CSF made it a safe and cost-effective procedure.

Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors.

We analyzed data on 612 patients who had undergone high-dose chemoradiotherapy (HDT) with autologous stem cell rescue for Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the City of Hope National Medical Center, to evaluate the incidence of therapy-related myelodysplasia (t-MDS) or therapy-related acute myeloid leukemia (t-AML) and associated risk factors. A retrospective cohort and a nested case-control study design were used to evaluate the role of pretransplant therapeutic exposures and transplant conditioning regimens. Twenty-two patients developed morphologic evidence of t-MDS/t-AML. The estimated cumulative probability of developing morphologic t-MDS/t-AML was 8.6% +/- 2.1% at 6 years. Multivariate analysis of the entire cohort revealed stem cell priming with VP-16 (RR = 7.7, P = 0.002) to be independently associated with an increased risk of t-MDS/t-AML. The influence of pretransplant therapy on subsequent t-MDS/t-AML risk was determined by a case-control study. Multivariate analysis revealed an association between pretransplant radiation and the risk of t-MDS/t-AML, but failed to reveal any association with pretransplant chemotherapy or conditioning regimens. However, patients who had been primed with VP-16 for stem cell mobilization were at a 12. 3-fold increased risk of developing t-AML with 11q23/21q22 abnormalities (P = 0.006). Patients undergoing HDT with stem cell rescue are at an increased risk of t-MDS/t-AML, especially those receiving priming with VP-16 for peripheral stem cell collection. (Blood. 2000;95:1588-1593)