Summary:Unrelated donor (UD) transplantation is the only potentially curative therapy for many leukaemia patients but is associated with a high mortality and morbidity. We sought to identify factors that could be optimised to improve outcome following UD transplantation in adults. Data was retrospectively analysed on 55 patients sequentially receiving UD transplants for CML or acute leukaemia (AL), all of whom received serotherapy for the prevention of GVHD and rejection. All patients received standard conditioning regimens. The first 28 patients transplanted also received combined pre-and post-transplant serotherapy with Campath 1G (days ؊5 to ؉5) and standard dose CsA plus MTX as GVHD prophylaxis (protocol 1). The subsequent 27 patients received a 5-day course of pre-transplant serotherapy alone either with ATG (CML patients) or Campath 1G (AL patients) on days ؊5 to ؊1 inclusive, with highdose CSA plus MTX (protocol 2). The incidence of acute GVHD was low with no patient receiving either protocol developing Ͼgrade 2 disease. The use of protocol 2 and the administration of a bone marrow cell dose above the median (2.17 ؋ 10 8 /kg) were the most important factors predicting engraftment (P ‫؍‬ 0.03 and P ‫؍‬ 0.001, respectively) but this only remained significant for cell dose in multivariate analysis (P ‫؍‬ 0.03). Overall survival for the group was 45% at 3 years and was influenced by both age (P ‫؍‬ 0.02) and disease status at transplantation (P ‫؍‬ 0.001). Receiving a cell dose above the median was also associated with a trend towards better survival (P ‫؍‬ 0.08), due primarily to a reduction in the TRM to 8.2% compared with 54.5% in those receiving a lower cell dose (P ‫؍‬ 0.002). We conclude that pretransplant serotherapy alone is highly effective at preventing acute GVHD following UD BMT and that additional post-transplant serotherapy does not confer any benefit. Furthermore, a high marrow cell dose infused has a major effect in reducing transplant-

Longer follow-up duration is required to determine the significance of these findings, but we have confirmed the feasibility of CD34+ selected cells to deplete peripheral-blood stem cells of tumor cells from patients undergoing high-dose therapy for follicular lymphoma.

Summary Two hundred and seventy-eight adult chemonaive patients receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eighty-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone.As single agents the 5HT3 antagonists granisetron (Marty, 1992;Chevallier, 1993) ondansetron (De Mulder, 1990) and tropisetron (De Bruijn, 1992) have been shown to be at least as effective as conventional treatments in controlling the acute nausea and vomiting experienced by patients receiving highly emetogenic chemotherapeutic regimens. Furthermore, they have an improved safety profile. There is now evidence indicating that the addition of a corticosteroid to ondansetron further enhances its efficacy in the acute phase (Roila, 1991;Smyth, 1991), although to date there are no similar data for granisetron.The management of delayed emesis, however, remains less than satisfactory with existing therapies, with around 50% of patients remaining uncontrolled (Kris, 1989). The combination of metoclopramide and dexamethasone has been shown to be better than either dexamethasone or placebo (Kris, 1989;Moreno, 1992). However, the place of 5HT3 antagonists in the management of delayed emesis is as yet unclear. Indeed, oral ondansetron alone has not been demonstrated to be superior to either dexamethasone (Jones, 1991) or metoclopramide (De Mulder, 1990). The objective of this study was therefore to compare the safety and efficacy of intravenous granisetron plus dexamethasone phosphate with that of intravenous granisetron alone in the prevention of both acute and delayed emesis induced by moderately emetogenic cytotoxic chemotherapy. Patients and methods Study designThe study was a double-blind, randomised, parallel group study carried out at 18 centres in the UK. Patients gave their witnessed written or verbal informed consent to participate in the study and were informed that they were free to withdraw at any time. The Cytotoxic chemotherapy regimens Patients received at least one of the following cytotoxic drugs: carboplatin > 300 mg m2, cisplatin 20-50 mg dacarbazine 350-500 mg m-2, cyclophosphamide > 500 mg m 2 (in combination), doxorubicin>40 mg m2 (single agent), doxoru...

Summary: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 уgrade 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.