76
In order to achieve a quicker hematopoietic recovery and prevent infectious and
bleeding complications after HDchemotherapy, ABMT was introduced in 1986.
Sixteen refractory myeloma patients were treated with 80–100 mg/m^2 melphalan
solely, and seven patients with 140 mg/m^2 melphalan with ABMT. A reduction of
the tumor mass by more than 75% was noted in 14 patients, including four who died
of bone marrow aplasia. In six out of seven patients who received HDmelphalan
with ABMT serious infections were prevented [ 9 ]. In 1987 Barlogie et al. applied
HDmelphalan (140 mg/m^2 ) with total body irradiation (TBI) supported by ABMT
in seven patients with advanced MM who were refractory to VAD (vincristine, adri
amycin, dexamethasone). A very rapid response with larger than 90% reduction of
tumor mass was accomplished in six patients with a median remission duration of
15 months, and five patients remained alive and well without further cytotoxic treat
ment for a median of more than 9 month [ 29 ].
Later on in 1990 the concept of Total Therapy was established by Bart Barlogie
applying two ASCT (tandem) successively as backbone treatment for MM embed
ded in a treatment regimen consisting of induction (prior to ASCT), consolidation
and maintenance therapy (after ASCT) [ 30 ]. Until now, tens of thousands of
myeloma patients have been successfully treated with HDchemotherapy and ASCT
worldwide.
5.2.2 Chemotherapy Versus ASCT
It is general agreement among myeloma experts that HDchemotherapy and ASCT
is recognized as effective standard consolidative treatment in patients with MM. In
1996 the Intergroupe Francais du Myeloma (IFM) research group presented the first
randomized study in 200 newly diagnosed myeloma patients receiving either con
ventional chemotherapy (CC) or HDchemotherapy and ASCT as consolidation
treatment. The response rate in the CC group was 57%, compared to 81% in the
ASCT group with CR and very good partial remission (VGPR) rates of 5% and 9%
only, compared and 22% and 16% (p < 0.001), respectively. The probability of
eventfree survival (EFS) for 5 years was 10% in CC, and 28% in ASCTpatients
(p = 0.01). The estimated 5year OS rate was 12% in the CC group, and 52% in the
ASCT group (p = 0.03) while exhibiting similar treatment related mortality (TRM)
rates in both groups [ 31 ]. Child et al. came to a very similar finding in the MRC
Myeloma VII Trial where myeloma patients (<65 years) either received standard
conventional chemotherapy or HDchemotherapy and ASCT: CR (8% vs. 44%,
p < 0.001), OS (42.3% vs. 54.1%) and progressionfree survival (PFS) rates were
significantly in favor of the intensively treated myeloma patients [ 32 ].
After publication of these clinical trials, several highly effective antimyeloma
agents have been introduced for treatment of newly diagnosed and relapsed myeloma
patients, ushering a new era of antimyeloma treatment and questioning the
S. Thanendrarajan and T.K. Garg