VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

HIGH DOSE INTERCALATOR BASED THERAPY WITH MARROW
SUPPORT IS EFFECTIVE FOR REFRACTORY HODGKIN'S DISEASE (HD).
Hughes P., Swan F. Jr, Hagemeister F., Cabanillas F., Samuels B., Champlin
R.C., and Andersson B.S.
From
The Department of Hematology, Box 65,
University of Texas M.D. Anderson Cancer Center,
1515 Holcombe Blvd.
Houston, Texas 77030.
INTRODUCTION
Hodgkin's disease is usually regarded as a curable malignancy, even in advanced
stages. However, as many as one third of the patients with advanced
stage disease may fail to achieve a complete remission (CR) with initial combination
therapy and up to 40% of those who initially respond will eventually suffer
a relapse 0). A significant number of patients with relapsed Hodgkin's disease
who had a long initial CR (lasting at least 1 year) can achieve a durable second
remission with salvage chemotherapy. In contrast, patients with a short initial
CR (less than 1 year) and those who never achieved a CR only rarely achieve a
durable response to salvage therapy ( 2
).
Several hundred patients with recurrent advanced Hodgkin's disease
havebeen treated with high-dose chemotherapy or chemoradiotherapy, followed
by autologous bone marrow (ABMT) or peripheral stem cell support. The
results show convincingly that this is a safe treatment modality that offers longterm
progression-free survival to a large fraction of the patients. Thus, Jagannath
et al demonstrated that patients responding to conventional salvage chemotherapy
prior to receiving high-dose cyclophosphamide, BCNU, and etoposide
(CBV) with ABMT had a major survival advantage over patients resistant to
conventional salvage therapy prior to receiving CBV with ABMT ( 3
). Based on
this notion, we evaluated a novel high-dose chemotherapy program designed
for patients with recurrent Hodgkin's disease resistant to conventional salvage
therapy or for patients relapsing after having received a previous high-dose (i.e.
autologous transplant) regimen. This program consists of a combination of
mitoxantrone, etoposide and thiotepa (MVT). None of our patients had previously
been exposed to mitoxantrone or thiotepa. Mitoxantrone has shown activity
in Hodgkin's disease both when used alone and in combination with other
cytotoxic agents, and response rates as high as 50% have been reported C" 6
).
Mitoxantrone causes less mucositis and less cardiac toxicity than doxorubicin ( 7
~
n
). Etoposide has been used extensively in high-dose regimens and is very active
in HD, the dose-limiting side effect being mucositis, even at doses above 1,000
mg/m 2
( 12
). When high dose thiotepawith ABMT was evaluated in clinical
phase I-II studies, it was very active against lymphoma, and mucositis was the
only serious side effect at total doses up to about 1,100 mg/m 2
( 13
).
304 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION