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
Summary.We analysed the factors influencing the efficacy of peripheral blood stem cell (PBSC) collection in patients with lymphoma. Sixty-six patients underwent initial PBSC collection following mobilization with chemotherapy plus recombinant granulocyte colony-stimulating factor (300 mg/d). and the mobilization regimen were the only factors associated with high CD34 þ cell yield. However, in a multivariate analysis of factors affecting mobilization including age, lymphoma subtype, previous chemotherapy and radiotherapy, only the use of the IVE protocol was predictive of a high yield of CD34 þ cells. In 13 patients undergoing a second mobilization procedure the use of IVE was associated with a significantly higher yield of CD34 þ cells compared to cyclophosphamide; three patients who failed cyclophosphamide plus G-CSF mobilization were able to proceed to transplantation following successful mobilization with IVE þ G-CSF. These results demonstrate that IVE is a highly effective mobilization regimen which is superior to cyclophophamide and has the benefit of being effective salvage therapy for lymphoma patients.
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-
Summary. Myeloma cells produce immunoglobulin which is unique to the malignant clone and presents antigenic determinants, or idiotypes, which may function as a tumour-speci®c antigen. The availability of signi®cant quantities of idiotype protein in the serum makes immunotherapeutic strategies utilizing this protein to generate an anti-idiotype immune response an attractive prospect. We treated two patients with advanced refractory myeloma with a series of four vaccinations using autologous idiotypeprotein pulsed dendritic cells combined with adjuvant GM-CSF. The vaccinations were well tolerated with a mild fever post-vaccination in one patient. An idiotype-speci®c T-cell proliferative response developed in both patients. This T-cell response was associated with the production of g-interferon, indicating a TH-1-like response. Furthermore, one patient developed anti-idiotype IgM antibodies. However, no idiotype-speci®c cytotoxic T-cell response could be demonstrated. Further investigation is warranted to de®ne the optimal conditions for dendritic cell culture and priming to maximize the anti-tumour immune response.
Summary:A number of different regimens have evolved for the mobilisation of peripheral blood stem cells for autologous transplantation in patients with lymphoma or myeloma. A successful regimen could be defined as one which consistently resulted in the collection of an optimal number of CD34 ؉ cells with a minimum number of apheresis procedures with minimal toxicity. Initial protocols, which used chemotherapy alone as a mobilising agent, have now been replaced by regimens involving the use of haematopoietic growth factors either alone or in combination with variable doses of cyclophosphamide. Although there is good evidence that highdose cyclophosphamide (6-7 g/m 2 ) is an effective mobilising agent it is associated with significant toxicity and many groups have now utilised lower doses of cyclophosphamide with reduced toxicity which have still proven to be effective in the majority of patients. More recently a number of 'second generation' combined salvage chemotherapy and mobilisation regimens have been reported for use in the lymphomas which have the advantage of avoiding a specific stem cell mobilisation step and at the same time appear more consistently effective at mobilising stem cells than cyclophosphamide and G-CSF. These regimens are associated with fewer 'poor-mobilisers' and indeed some patients who have failed previous mobilisation with cyclophosphamide and G-CSF have been successfully re-mobilised. It is clear that in both lymphoma and myeloma patients the success of PBSC mobilisation is affected by the amount and type of previous chemotherapy and radiotherapy and probably other pre-treatment factors as exemplified by variability seen in normal donors mobilised with G-CSF alone. In myeloma most groups have utilised cyclophosphamide in variable doses in combination with G-CSF or GM-CSF. However, recent randomised studies have confirmed that G-CSF alone is an effective and nontoxic alternative although it appears that the efficacy of G-CSF as a single agent is related to the dosage used with daily doses of 16 g/kg/day or greater being most effective. Thus, disease-specific mobilisation strategies appear to be emerging and these will undoubtedly be Correspondence: Prof NH Russell, Department of Haematology, Nottingham City Hospital, Nottingham, NG5 1PB, UK Received 14 July 1998; accepted 19 July 1998 modified further as more is understood concerning the biology of blood stem cell mobilisation.
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