Cost-effectiveness of alternative changes to a national blood collection service.

OBJECTIVES: To evaluate the cost-effectiveness of changing opening times, introducing a donor health report and reducing the minimum inter-donation interval for donors attending static centres. BACKGROUND: Evidence is required about the effect of changes to the blood collection service on costs and the frequency of donation. METHODS/MATERIALS: This study estimated the effect of changes to the blood collection service in England on the annual number of whole-blood donations by current donors. We used donors' responses to a stated preference survey, donor registry data on donation frequency and deferral rates from the INTERVAL trial. Costs measured were those anticipated to differ between strategies. We reported the cost per additional unit of blood collected for each strategy versus current practice. Strategies with a cost per additional unit of whole blood less than £30 (an estimate of the current cost of collection) were judged likely to be cost-effective. RESULTS: In static donor centres, extending opening times to evenings and weekends provided an additional unit of whole blood at a cost of £23 and £29, respectively. Introducing a health report cost £130 per additional unit of blood collected. Although the strategy of reducing the minimum inter-donation interval had the lowest cost per additional unit of blood collected (£10), this increased the rate of deferrals due to low haemoglobin (Hb). CONCLUSION: The introduction of a donor health report is unlikely to provide a sufficient increase in donation frequency to justify the additional costs. A more cost-effective change is to extend opening hours for blood collection at static centres.

Preliminary experience of allogeneic stem cell transplantation for lymphoproliferative disorders using BEAM-CAMPATH conditioning: an effective regimen with low procedure-related toxicity.

Autologous transplantation has an established role in the treatment of lymphoproliferative disorders, but allogeneic transplantation remains controversial. In an attempt to reduce the high procedure-related mortality reported with allografting in lymphoma, we have used BEAM (BCNU, etoposide, cytarabine and melphalan), a standard conditioning regimen for autologous transplantation. As BEAM may be insufficiently immunosuppressive to permit durable engraftment in the allogeneic setting, patients received additional pretransplant immunosuppression with the anti-CD52 antibody CAMPATH-1G from day -5 to day -1. Twelve patients (median age 46 years) underwent allogeneic transplantation for lymphoma (n = 11) or chronic lymphocytic leukaemia (n = 1) from HLA-identical (n = 9) or mismatched (n = 3) sibling donors. Cyclosporin A and methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. One patient died of progressive lymphoma at day +12, the remaining 11 patients engrafted rapidly, with eight demonstrating full donor chimerism. One patient had an episode of rejection and received a further stem cell infusion with sustained recovery. Only one patient developed GVHD (grade I). The low incidence of acute GVHD may be in part related to persisting levels of in vivo CAMPATH-IG at the time of transplantation. Of 11 evaluable patients, nine achieved complete remission (CR), and a further patient achieved CR after donor lymphocyte infusion at 5 months. Our preliminary experience is that this regimen was well tolerated with a low risk of GVHD and appears no more toxic than a BEAM autograft. Further follow-up is required to see whether the low incidence of GVHD impacts upon relapse risk.

An analysis of the effect of chronic GvHD on relapse and survival following allogeneic PBSC transplantation.

BACKGROUND: PBSC are increasingly being used as the source of stem cells in allogeneic transplantation. An increased incidence of chronic GvHD has been suggested following unmanipulated allogeneic PBSC transplantation (PBSCT), however, how this affects overall survival is not yet clear. Our aim was to study the impact of chronic GvHD on survival and relapse following allogeneic PBSCT. METHODS: We have analyzed data from 73 patients undergoing HLA-matched allogeneic PBSCT. GvHD prophylaxis was with CYA and MTX in 97% of patients. We have studied the incidence of chronic GvHD and its affect on relapse and survival in these patients. All patients were at least 100 days post-transplant at the time of analysis. RESULTS: Seventy-three patients were evaluable for analysis of chronic GvHD. The overall incidence of chronic GvHD was 55% (limited in 18% and extensive in 37%). Overall median survival was 991 days, with a 4 year survival rate of 48%. Twelve patients relapsed. Patients with chronic GvHD had a significantly lower incidence of disease relapse (p = 0.005) with a relapse probability of 8% at 3 years, compared with 40% in patients with no chronic GvHD. In addition, the extent of chronic GvHD had a marked effect on survival, patients with limited chronic GvHD had a 4 year survival rate of 83%, compared with 45% in patients with extensive chronic GvHD and 38% in patients with no chronic GvHD. This difference was primarily due to the low incidence of relapse and low mortality seen in patients with limited chronic GvHD. DISCUSSION: The presence and extent of chronic GvHD is an important predictor of outcome following allogeneic PBSCT, in that patients who developed either limited or extensive chronic GvHD had a low risk of disease relapse.

Comparative serial quantitative measurements of chimaerism following unmanipulated allogeneic transplantation of peripheral blood stem cells and bone marrow.

Serial samples were collected from 38 patients following allogeneic transplantation using either unmanipulated peripheral blood stem cells (PBSC) (n = 18) or bone marrow (BM) (n = 20) to assess the incidence of mixed chimaerism using PCR amplification of five VNTR regions. After amplification, products were analysed using the Applied Biosystems ABI PRISM 377 Automated DNA Sequencer and GeneScan software GenoTyper program to determine a quantitative measure of chimaerism. The sensitivity of detection using this method was 0.1%. In the immediate post-transplant period (up to day 30) a significantly lower incidence of mixed chimaerism (MC) occurred in recipients of PBSC compared to BM (P < 0.0005). Between 1 and 6 months there was a significantly lower incidence of low-level MC in patients receiving PBSCT compared to BMT (4/14 v 8/11 respectively, P = 0.04) in patients who had not rejected their grafts or relapsed. Similarly, beyond 6 months 0/9 PBSCT patients compared to 4/9 BMT patients showed MC (P = 0.02). Beyond day 30 13/33 (39%) patients showed intermittent low-level MC, but this was not predictive for subsequent relapse. A rapidly increasing proportion of recipient haemopoiesis was predictive of graft rejection or relapse. Stable continuous MC without relapse was seen in one patient transplanted with PBSC for severe aplastic anaemia. These results suggest that the incidence of intermittent low-level MC is relatively high in the first 6 months following unmanipulated haemopoietic stem cell transplantation but reduces with time and is significantly lower in recipients of PBSC.

Low incidence of acute graft-versus-host disease and recurrent leukaemia in patients undergoing allogeneic haemopoietic stem cell transplantation from sibling donors with methotrexate and dose-monitored cyclosporin A prophylaxis.

One of the major aims of allogeneic haemopoietic stem cell transplantation has been the effective suppression of graft-versus-host disease (GVHD) without loss of a graft-versus-leukaemia effect. For GVHD suppression, one of the most frequently used regimens has been the combination of cyclosporin (CsA) and a short course of methotrexate (MTX) although the optimal usage of these agents remains unclear. Here, we report the results of 55 patients with standard risk leukaemia who have undergone allogeneic transplantation using either bone marrow (n = 48) or G-CSF mobilised peripheral blood stem cells (n = 7) using CsA and MTX for GVHD prophylaxis where the dosage of CsA was regularly adjusted to maintain a trough whole blood level of 95-205 ng/ml for the first 50 days post-transplant. To achieve this level of CsA in the immediate post-transplant period, over 40% of patients required dose adjustments of CsA as a result of sub-therapeutic levels on day +1 post-transplant. The achievement of CsA levels within the therapeutic range was expedited following the introduction of a sliding scale for dose adjustment. With this regimen we have observed a low incidence of acute GVHD with only 11% of patients developing > or =grade II disease. With a median follow-up of 66 months (range 8-132) the probability of relapse is only 6.6%. The disease-free survival probability for all patients was 72% at 5 years. These results demonstrate that effective GVHD prevention with CsA and MTX can be achieved without a high risk of recurrent leukaemia provided that rapid attainment of therapeutic CsA levels is achieved and maintenance within a low therapeutic range may help to maximise this effect.

A comparison of two different systems for CD34+ selection of autologous or allogeneic PBSC collections.

This study compared CD34 selection procedures using the CellPro CEPRATE and the Baxter Isolex 300 systems. Thirty-two procedures were performed, 19 CEPRATE and 13 Isolex. Median starting CD34 percentages were (CEPRATE/Isolex) 0.80% (range 0.24%-7.73%) and 0.85% (range 0.27%-10.17%), respectively (p = 0.788). After selection, there was a highly significant difference in purity of the product (CEPRATE/Isolex), 54% and 82% respectively (p < 0.0001). There was no significant difference in median recovery (CEPRATE/Isolex), 43% and 50%, respectively (p = 0.383). The starting CD34 percentage influenced the purity of the final product, and at high and low starting percentages, the Isolex produced superior purity. Improved efficacy of T cell depletion was observed with the Isolex, a median log depletion of 3.4 compared with 2.9 for the CEPRATE system (p = 0.012). In conclusion, the Isolex 300i produced a significantly higher purity CD34+ fraction, even at starting CD34+ levels of <0.5%, with no significant difference in recovery when compared with the CEPRATE system. The associated log T cell depletion is significantly improved with the Isolex system, with possible implications for use in CD34-selected allogeneic transplants.

Allogeneic peripheral blood stem cell transplantation for haematological malignancies--an analysis of kinetics of engraftment and GVHD risk.

We have carried out an analysis of 44 patients undergoing allogeneic PBSC transplants from fully HLA-matched related donors with particular emphasis on engraftment kinetics and the incidence and severity of GVHD. The recipients had a median age of 37 years (range 5-56 years), 16 patients had standard-risk disease and 28 had poor-risk disease. GVHD prophylaxis was with cyclosporin A and methotrexate (n = 41), cyclosporin A alone (n = 2) or cyclosporin A and methyl-prednisolone (n = 1). Stem cells were mobilised using G-CSF, collecting a median of 5.75 x 10(6) CD34+ cells/kg recipient weight (range 0.94-35 x 10(6) CD34+ cells/kg). Engraftment times to a neutrophil count > 0.5 x 10(9)/1 and platelets > 20 x 10(9)/1 were achieved at a median of day +14 (range 10-25) and day +14 (range 9-130) respectively. Patients receiving > or = 4 x 10(6) CD34+ cells/kg had significantly accelerated neutrophil and platelet engraftment and this number of CD34+ cells would appear to be a prerequisite for maximum engraftment using PBSC. Acute GVHD occurred in 25 of 43 evaluable patients although in only 12 was this clinically significant (grades II-IV). Chronic GVHD has occurred in 17 out of 36 evaluable patients, there was no significant difference between the standard- and poor-risk groups in incidence of either acute or chronic GVHD. In conclusion, these results confirm the feasibility of using PBSC for allogeneic transplantation without evidence for increased risk of either acute or chronic GVHD and provide further evidence supporting the potential of PBSC to replace bone marrow as the major source of haemopoietic cells for allogeneic transplantation.

Stem cell mobilization in normal donors for allogeneic transplantation: analysis of safety and factors affecting efficacy.

The use of peripheral blood stem cells instead of bone marrow as the source of haemopoietic cells for allogeneic transplantation is being increasingly explored. We have analysed data from 17 normal donors who underwent stem cell mobilization for allogeneic transplantation with an identical protocol using G-CSF at a dose of 10 micrograms/kg/d, with the first leukapheresis (LP) on the day following the fourth dose of G-CSF. Both G-CSF administration and leukapheresis were well tolerated. Donors under-went a median of two leukaphereses (range one to three) and a median of 6.80 x 10(6) CD34+ cells/kg recipient weight (range 2.4-15.6 x 10(6)) were collected. The median number of CD34+ cells per kg donor weight was 6.05 x 10(6), when corrected for a 12 litre leukapheresis, this gave a median total of 3.89 x 10(6) CD34+ cells/kg donor weight. When analysed with respect to factors which might influence the efficacy of mobilization, male donors were associated with a superior yield. The median number of CD34+ cells/kg/LP harvested was 4.96 x 10(6) in males and 2.79 x 10(6) in females (P < 0.05). The results suggested that, given a recipient of 75 kg, in a male donor a single 12 litre leukapheresis should yield sufficient CD34+ cells (4 x 10(6)/ kg), whereas a female donor would be likely to need two leukaphereses. Age was not found to affect donor yield. In summary, these data confirm that leukapheresis is a safe procedure in normal donors and suggest that males may be more efficient mobilizers of stem cells than females.