Autologous Bone Marrow Transplantation - Blog Science Connections

594 BEAM: Cytoreductive Regimen for Lymphomas
approach is to combine a chemotherapy regimen with involved-field radiotherapy
(see Armitage "Bone Marrow Transplantation in Relapsed Diffuse
Large Cell Lymphoma," and T. Philip et al. "Autologous Bone Marrow
Transplantation in Burkitt's Lymphoma: 50 Cases in the Lyons Protocol,"
both in this volume).
The overall toxicity of the chemotherapy conditioning regimen until now
was in the range of 15% to 20% (4). In 1983, in an attempt to decrease the
conditioning regimen's toxicity without decreasing the response rate we set
up a new regimen, the BEAM protocol (BCNCI, etoposide, aracytine,
melphalan) derived from the BACT regimen (5-7). Carmustine and
cytarabine, proved to be efficient in NHL, were kept, whereas 6-thioguanine
was replaced by etoposide (5). Cyclophosphamide, found to be responsible
for fatal congestive heart failure, was deleted and replaced by melphalan as
the alkylating agent (6). For the BEAM regimen, in order to replace 6-
thioguanine, we decided to use etoposide (VP-16-213) because of a 40%
response rate in phase II studies of patients with NHL (7). With the
introduction of melphalan, no cardiotoxicity was observed, and a good
response rate has been reported in acute lymphocytic leukemia (ALL) (8) and
NHL. This report is a review of 52 patients treated with this protocol during the
period of 1983-1986, with particular reference to response rate and toxicity.
PATIENTS AND METHODS
Between January 1984 and January 1986, 52 BEAM conditioning
regimens were administered in a multicentric study to patients with NHL or
Hodgkin's disease. Institutions that entered patients in the study were: Centre
Leon Berard (Lyons, France, 26 patients), University College Hospital
(London, England, 11 patients), Centre Hospitalier de Tours (France, 7
patients), Hopital Saint-Antoine (Paris, France, 4 patients), and Institut Paoli
Calmettes (Marseilles, France, 3 patients).
Patients were children and adults ranging in age from 1 to 65 years with a
median age of 30.4 years. Thirteen patients were younger than 16 years
(range, 1-15 years; median, 9.5 years), and 39 were adults (range, 18-65
years; median, 37.4 years). Thirty-eight patients were male. As is shown in
Table 1, of 45 patients with NHL, 23 had high-grade, 18 had intermediategrade,
and 4 had low-grade NHL. Seven patients had Hodgkin's disease.
All patients with NHL had previously received a doxorubicin-containing
regimen. Twelve patients were in first complete remission (CR), five in first
partial remission (PR), and two were in primary refractory condition after
first-line therapy. Twenty-six patients were in relapse; among these, 19 were
still sensitive to a second-line chemotherapy (so-called sensitive relapse
[SR]), and 7 were resistant to this salvage chemotherapy (resistant relapse
[RR]). All patients with Hodgkin's disease were in relapse (two in RR and five
in SR), but only four of them had received a doxorubicin-containing regimen.