transplantation, a larger number of protocols have explored 
autologous bone marrow or peripheral blood stem cell 
transplantation to facilitate the administration of very 
high-dose chemotherapy. Chemotherapy drugs, especially 
alkylating agents, have a steep dose-response tumor-killing 
curve in lymphoid malignancies, and various analyses have 
suggested that more dose-intensive regimens can increase the 
likelihood of disease-free survival, at least in lymphoma. 
18 The use of autologous bone marrow rescue may increase 
tolerated doses several fold. During the early 1980 's 
several investigators reported high response rates to single 
agent melphalan alone at doses of 80-140 mg/m2 even in 
patients refractory to all other therapy. 41, . However, the 
high morbidity and mortality resulting from prolonged 
neutropenia with this regimen was prohibitive. Thus 
autologous bone marrow rescue was added in an attempt to 
reduce toxicity and allow higher chemotherapy doses. 
Barlogie and coworkers initially gave refractory multiple 
myeloma patients high-dose melphalan alone as conditioning. 
The response rate (defined as a > 75% reduction in M 
component) in 27 patients was about 50%, but the median 
duration of response was < 6 months. 21 
The same group next added total body irradiation (TBI) to 
their conditioning regimen and increased the response rate 
to 86% in the initial 7 patients, with median duration of- 
response increased to > 15 months. 43 More recently their 
experience has been updated to include 21 patients 
refractory to MP and VAD. 44 All 21 showed > 75% decrease in 
M-component, but 5 patients with resistant relapse had early 
deaths (< 2 months post-transplant) . 
Based on these results in refractory patients and their own 
prior experience with high-dose melphalan without bone 
marrow rescue, a British group entered 50 patients at 
initial presentation into a sequential protocol. 2 Patients 
first patients received cycles of VAMP until a plateau in M- 
component was reached, then were harvested and given high- 
dose melphalan therapy (200. mg/m2) without TBI, followed by 
reinfpsion of marrow. 6/50 patients died during the VAMP 
phase, but 25 (or 50% of- the original patients) went into a 
complete remission, defined as complete absence of any M- 
component, and < 5% bone marrow plasma cells. During a 
'median follow-up of 14 months,- 5/25 CR patients have 
relapsed. This CR rate of 50% is unprecedented, and 
although follow-up is still brief, these results have 
generate' more interest in this type of approach. The vast 
majority of myeloma patients undergoing autologous 
transplant have been conditioned with melphalan alone or 
melphalan plus TBI. No other regimen has been fully 
studied, but as a single high-dose agent melphalan is more 
Recombinant DNA Research, Volume 16 
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