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Background: The use of cytokine-mobilised peripheral-blood-derived progenitor cells (PBPC) has resulted in a significant improvement in the safety of autologous transplantation. Collections of PBPC contain large numbers of haemopoietic progenitors and T-lymphocytes when compared with bone marrow (BM). Aims: To assess the clinical effects and safety of filgrastim-mobilised allogeneic PBPC, in particular whether PBPC would alter the kinetics of engraftment or the incidence and severity of graft-versus-host disease (GVHD). Methods: Twenty-seven patients undergoing allogeneic transplantation were randomised to receive BM or BM supplemented by PBPC. Patients were conditioned with busulphan 16 mg/kg and cyclophosphamide 120 mg/kg. GVHD prophylaxis was with methotrexate and cyclosporin. Ganciclovir prophylaxis was administered to all cytomegalovirus seropositive patients. No haemopoietic growth factor was used after BMT. Donors of PBPC underwent a single, seven litre apheresis after four days of filgrastim, 10 μg/kg/day by subcutaneous injection. Results: Donor toxicity was mild, with the most frequently reported being bone pain in the cytokine-treated donors. The patients transplanted with BM+PBPC received an eight-fold increase in CD3+ T-lymphocytes (1.65×10 8 kg vs 0.22×10 8 /kg, p=0.04) and the cytokine product contained a median of 5×10 6 CD34+ cells/kg. BM+PBPC patients had more rapid engraftment of neutrophils to 0.5×10 9 /L (17 days vs 19 days, p=0.02) and platelets to 50×10 9 /L (22 days vs 35 days, p=0.04). BM megakaryocyte numbers were significantly enhanced at days 14 and 28 after BMT (both p=0.04), however platelet transfusions were not significantly different. The incidence, organ distribution, severity and time to onset of acute and chronic GVHD were not different between the treatment groups and there was no difference in overall survival or event-free survival. Conclusions: Allogeneic PBPC from HLA-identical siblings may speed engraftment of neutrophils and platelets without detrimental effects on GVHD or survival.

Background: Much research has been conducted into the pathobiology, diagnosis, and management of acute myeloid leukaemia (AML) since 1980, with major contributions from Australian studies in this period. Aims: To determine whether advances in basic and clinical research into AML have translated into improved survival for patients in the community. Methods: A retrospective survey of records of all patients with AML presenting to the Royal Melbourne Hospital (RMH) over a 16 year period, analysed according to induction therapy and established prognostic factors. Between 1980 and December 1996 223 (98%) of 227 patients were evaluable. Results: The probability of survival at five years for patients treated since 1990 has improved significantly compared to the cohort treated between 1980-89 (34±5% vs 4 ± 2%; mean ± standard error). This benefit is most evident in patients less than 60 years of age (50±7% vs 11 ±4%). Successive induction protocols in the context of clinical trials conducted since 1985 contributed to improved outcomes. The selective application of bone marrow transplantation, and use of retinoic acid as induction therapy for acute promyelocytic leukaemia has also improved survival. Despite increases in dose-intensity, early death rates for patients undergoing induction therapy fell during the study period. Conclusions: Participation in clinical and basic research with the development of more intense and specific treatments for patients with AML has contributed to better outcomes, underpinned by improvements in supportive care.

Background: The lengthy period of neutropenia which follows allogeneic bone marrow transplantation (BMT) results in significant morbidity and some mortality. Recombinant human granulocyte colony-stimulating factor (rhuG-CSF) effectively reduces neutropenia and morbidity when given after autologous BMT, but has not been adequately investigated in allografts. Aims: To assess the tolerability, safety and efficacy of rhuG-CSF after allogeneic BMT. Methods: rhuG-CSF was administered to 13 adult patients with haematological malignancies after HLA-identical sibling BMT. Five μg/kg of rhuG-CSF was given daily by subcutaneous bolus injection, commencing four hours after marrow infusion and continuing until the neutrophil count was ≥ 1.0 × 109/L on three consecutive days. Graft-versus-host disease (GVHD) prophylaxis was cyclosporin and short-course methotrexate (days 1, 3, 6 and 11). Prophylactic intravenous (IV) antibiotics were administered from the onset of neutropenia. The control group consisted of patients with comparable diagnoses, transplanted before and after the current study using identical supportive care and GVHD prophylaxis policies. Results: Although time to recovery of the neutrophil count to >0.1 × 109/L was similar, the rhuG-CSF-treated patients experienced accelerated recovery to > 0.5 × 109/L, which occurred at a median of 15 days (range 11–21) after marrow infusion in study patients compared to 18.5 days (range 14–41) in the controls (p = 0.04). No significant differences were detected in any of the indices of transplant-related morbidity examined, including the number of days of fever, the incidence of culture-positive infections, the usage of antibiotics, the requirement for parenteral nutrition and IV morphine, the maximum severity of mucositis and GVHD, and the day of discharge. Conclusion: Within the context of this study, rhuG-CSF had limited impact on the clinical outcome of HLA-identical sibling BMT. (Aust NZ J Med 1994; 24: 541–546.)

BACKGROUND The administration of granulocyte colony-stimulating factor (G-CSF) increases the granulocyte count in normal donors and enables the collection of large numbers of mature myeloid cells by leukapheresis. This has potential value in the treatment of sepsis unresponsive to antibiotics in patients with severe neutropenia. AIM To evaluate the tolerability of granulocyte collections in normal donors receiving G-CSF, the optimal method of collection and the clinical factors influencing the efficacy of granulocyte infusions. METHODS Analysis of the outcome of 55 granulocyte collections from 26 donors for progressive bacterial or fungal sepsis in neutropenic patients (n = 8) or as prophylaxis in patients with recent fungal infections undergoing allogeneic bone marrow transplantation (BMT) (n = 3). RESULTS G-CSF was well tolerated in most donors. Fatigue occurred commonly after the second collection. The median WCC per 200-220 mL bag was 351 x 10(9)/L. Collections were optimised with the use of a sedimenting agent (dextran) and a deepened interface setting on the cell separator. There was only a weak correlation between the number of granulocytes infused and the increment in the patient, but levels were usually maintained > or = 0.5 x 10(9)/L for the next 24 hours. The infusions were successful in three septic patients without multi-organ dysfunction and prophylactically, in two patients with localised fungal infections undergoing MBT. The infusions were not beneficial in patients with septicaemia and established organ dysfunction or with extensive pulmonary aspergillosis. CONCLUSIONS G-CSF mobilised granulocyte collections are feasible and the preliminary evidence suggests that the infusion of these cells may be useful early in the prophylaxis or treatment of severe neutropenic sepsis.

While most patients with disseminated non-seminomatous germ cell tumours (NSGCT) are cured by treatment with cisplatinum-based chemotherapy, a subset die from refractory or relapsing disease. Poor prognostic factors at diagnosis include bulky disease, visceral involvement, high serum marker levels and an inadequate rate of fall in these markers in response to treatment. There are a number of approaches to poorer risk patients. One is to use conventional induction chemotherapy followed by second-line salvage regimens in those who fail induction. Results with this approach have been disappointing. A second approach is to use more intensive induction regimens, in some cases with growth factor support; whether these are superior to standard treatment has yet to be established by randomised studies. A third approach, based on the chemotherapy-dose responsiveness of NSGCT, consists of the administration of very high dose chemotherapy followed by haematological rescue with autologous marrow to patients failing initial therapy. Review of autograft studies suggest that durable remissions can be obtained in most patients with responsive disease, but not if the disease is chemotherapy-refractory. A new approach may be elective early autografting in patients identified at diagnosis to have very poor prognosis disease. (Aust NZ J Med 1992; 22: 679ndash;684.)

Factor V inhibitors are uncommon, bleeding manifestations variable and recommendations for management are unclear. We present a patient with non-Hodgkins lymphoma who developed gastrointestinal bleeding and was found to have a Factor V inhibitor. The inhibitor was active against both plasma Factor V and platelet associated Factor V, and was associated with a five-fold increase in platelet associated IgG. Fresh frozen plasma was ineffective in preventing bleeding. Resolution of bleeding was associated with a fall in the levels of the inhibitor and of platelet associated IgG. The patient had no further bleeding episodes nor evidence of progression of his lymphoma, but six months later died as a result of metastatic adenocarcinoma.