autologous blood and marrow transplantation - Blog Science ...

Leyvraz et al. 397
Table 1. Results of four randomized trials (2-year survival data)
Author DI No. No. No. CR RR OS 2-year
(year) Regimen (%) patients LD ED (%) (%) (months) survival (%)
Arriagada CAEP — 50 50 — 54 13 26
(1993) CAEP 25-33* 50 50 — 67 17 43
Woll V-ICE — 31 28 3 58 93 16 15
(1995) V-ICE 7 34 32 2 56 94 17 32
Steward V-ICE — 153 85 68 51 77 12.5 18
(1998) V-ICE 26 147 93 54 51 90 16 33
Thatcher ACE — 202 86 11 39f
(1998) ACE 33 201 89 12.5 47t
*First cycle only. fAt I year. DI, increase in dose intensity; OS, median overall surviva
survival rate. It is not known yet if high-dose chemotherapy will have a significant
long-term impact, but the 2-year survival data of four randomized trials testing the
early intensification strategy all showed an improvement compared with the
standard regimen 6-9
(Table 1). Interestingly enough, neither the overall response
rate, the complete remission rate, nor the median survival were predictive of the 2year
survival improvement. Furthermore, these results were obtained by only a
small increase in dose intensity, from 7 to 33%. Within the EBMT, it was proposed
that a higher increase in dose intensity might lead to a higher increase in long-term
survival and that only a randomized trial could prove it. To prepare for such a trial,
a phase II study was designed to test a threefold intensification of dose and was
conducted from March 1994 until October 1997. It aimed to test the feasibility of
an intensive approach within a multicenter setting. 10
RESULTS
Sixty-nine patients were included in the study (Table 2). Median age was 53
years (range 35-65), and median performance status was 0 (range 0-1). There were
58 men and 11 women. Thirty patients (43.5%) were diagnosed as having limited
disease and 39 patients (56.5%) had extensive disease, of whom 27 had more than
two metastatic sites (69%). Abnormal lactate dehydrogenase (LDH) level was
observed in 30 patients. Twenty-five percent of patients with extensive disease had
metastases in liver, 15% in bone, 14% in distant lymph nodes, 13% in bone
marrow, 11% in adrenal glands, and 3% in brain.
Mobilization/collection phase
Mobilization of progenitor cells (PBPCs) was performed with high-dose
epirubicin (Farmorubicin) 75 mg/m 2
/d intravenous bolus on days 1 and 2, followed