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Summary:We studied the effect of the CD34 ؉ cell dose on transplant-related mortality (TRM) and survival in 39 patients randomized to receive lenograstim-mobilized PBSCT (n = 20) or BMT (n = 19) from HLA-identical siblings. Both marrow and blood were harvested, and one infused in a double-blind fashion. The median nucleated

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Summary:OS yet to reach a median at 8 years and a PFS of 44 months, significantly better than non IFN high-dose A single centre series of 195 consecutive newly diagpatients (P Ͻ 0.0036). However, although we showed nosed untreated myeloma patients under 70 years, seen benefit for selected patients in studies and trials between September 1986 and March 1994, were ana-(particularly with IFN) during the 8-year period of the lysed to assess the impact of current intensive treatment series, this did not translate into overall PFS benefit in methods upon remission rate, response rate and subour study for unselected cohorts of patients for 1986-sequent outcome. They were predominantly an unselec-1988 (64 patients) 1989-1992 (100 patients) and 1992-ted population based group of patients (other than by 1994 (31 patients) in spite of progressive increases in age) that could be used by purchasers of health care the proportion of patients receiving IFN (respectively 6, as a model for outcome assessment. All patients were 35 and 58%). This is likely to be due to the dilution scheduled to receive a care plan which included a of benefit to specific patients by the overall number of sequential package of treatment consisting initially of patients involved. Outcome data from unselected courses of infusional chemotherapy using vincristine, patients are now expected by purchasers and presented adriamycin and methyl prednisolone (VAMP) and 90 of in this way, help qualify the activity impact of advances these also received cyclophosphamide (C-VAMP).made from research trials for the treatment of popuThirty-eight patients received verapamil in addition to lation-based cancer problems. C-VAMP(V-C-VAMP). After VAMP all patients wereKeywords: myeloma; induction; autologous transplanplanned to receive high-dose treatment with melphalan tation; interferon; outcome assessment; population based and an autograft (marrow or blood) and 112 received this treatment; a further 29 patients received modified high-dose treatment with melphalan alone (23) or busulfan (6) and 54 (28%) did not proceed to high-dose treatSince 1980, three important and entirely different treatment because of refusal, resistant disease, poor performments for myeloma have been developed in phase II studies ance or treatment-related death. The patients who and then been shown in controlled trials to markedly received melphalan or busulfan alone instead of highimprove outcome for selected patients with myeloma; dose melphalan/autografts did so because of increasing namely infusional induction chemotherapy, 1-3 high-dose age (P = 0.001) and a raised creatinine (P = 0.05). The consolidation chemotherapy 4,5 with autologous bone marcomplete remission rate was 53% for the whole group row rescue, 6,7 and maintenance interferon. 8,9 However, the and 74% for those receiving high-dose melphalan and nature of controlled trials, with strict entry criteria, usually an autograft. From July 1988, the sequential therapy requires that patients are selected, and further selection package in...

Summary. SCID mice were inoculated intravenously with cells from the human HL60 myeloblastic leukaemia cell line and then treated with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, simvastatin, by subcutaneous continuous infusion. The effect of the drug was measured by subsequent colony formation of surviving HL60 cells in vitro and flow cytometry. The number of clonogenic HL60 cells was reduced in the bone marrow of mice that received simvastatin compared with control mice by 65% and 68% in two separate experiments. The number of clonogenic, normal, murine, bone marrow progenitor cells concomitantly exposed to simvastatin in vivo, was not affected in either experiment. Flow cytometric analysis of bone marrow and spleen cells confirmed these results by showing that simvastatin had reduced the percentage of human leukaemia cells in these tissues by 70% and 88% respectively.The data show that the reported selective effect of simvastatin against acute myeloid leukaemia cells in vitro, can be extended to this in vivo model. HL60 bears an Nras mutation. In further in vitro studies, ketoconazole, an inhibitor of cholesterol biosynthesis post farnesyl pyrophosphate synthesis, had a similar effect to simvastatin on HL60 colony development. Furthermore, the clonogenicity of a population of N-ras mutated, primary acute myeloid leukaemia (AML) cells was no more sensitive to simvastatin than a population without the mutation. The data suggest that the inhibition of AML cell proliferation by simvastatin may be independent of the RAS signalling pathway.

Summary:Forty healthy adult donors underwent marrow (BM) as well as peripheral blood (PBSC) stem cell collections for their HLA-identical adult siblings with hematologic malignancies. BM was harvested on day 1 (target 3 ؋ 10 8 nucleated cells/kg, 10 g/kg lenograstim (glycosylated G-CSF) administered on days 2-6, and a single leukapheresis performed on day 6. The blood volume processed was the higher of 200% donor blood volume or 10 liters. The total nucleated cell (TNC) yields from PBSC were 1.1-to 4.3-fold higher than BM (median 7.0 vs 3.1 ؋ 10 8 /kg, P Ͻ 0.0001). Although BM contained a higher proportion of CD34 + cells (1.3% vs 0.7%, P Ͻ 0.0001) and a comparable proportion of CD3 + cells (median 29% vs 26%, P = 0.4), the absolute numbers of CD34 + and CD3 + cells and their subsets were several times higher in PBSC. There was a poor correlation between BM and PBSC CD34 and TNC numbers, but a significant correlation between BM and PBSC CD3 numbers. Only five of 40 BM harvests contained у2 ؋ 10 6 CD34 + cells/kg compared with 35 of 40 PBSC harvests (P Ͻ 0.0001). We conclude that the numbers of progenitor and immunocompetent cells in PBSC are several times higher than in BM. It is possible to collect adequate numbers of progenitor cells from blood after lenograstim stimulation more frequently than from marrow, and donors yielding low quantities of progenitor cells from BM usually deliver better quantities from PBSC. Bone Marrow Transplantation (2000) 25, 501-505.

Summary. In a sequential nonrandomized study, 204 consecutive unselected patients aged < 70 years received induction chemotherapy with infusional vincristine and adriamycin with oral methyl prednisolone (VAMP; n ¼ 75) or with additional cyclophosphamide, C-VAMP (n ¼ 129). 38/129 C-VAMP patients also received verapamil during induction as part of a controlled trial with the aim to overcome drug resistance. A median of five courses (range 1-11) of chemotherapy were required before maximal response was attained and this was similar in both groups. An over-all response rate of 71% was noted at the end of induction. The complete remission (CR) rate with C-VAMP was 24%, which was significantly higher ( P ¼ 0 . 04) than the CR rate with VAMP alone (8%). The addition of verapamil did not alter the response rate of C-VAMP. Compliance to VAMP was overall 83% and not affected by the addition of cyclophosphamide. The proportion of patients going on to receive high-dose chemotherapy and an autograft was the same for VAMP and C-VAMP treated patients (71%). The median overall survival (OS) and progression-free survival (PFS) for the whole group were 4·4 years and 2·0 years and no difference in outcome was observed between the different treatment groups. Therefore the addition of weekly cyclophosphamide to VAMP induction therapy has significantly improved the response rates of previously untreated myeloma patients. C-VAMP was not more toxic and did not compromise the chances of receiving an autograft. Verapamil was without influence on any parameters in this study.