autologous blood and marrow transplantation - Blog Science ...

Elias et al.
selection of patients possessing chemosensitive tumors for subsequent intensification,
and diminution of micrometastases in the marrow and/or PBPCs as
discussed below. On the other hand, chemoresistant tumor cells might proliferate
or even be induced across treatment and may outweigh tumor burden reduction.
Indeed, the Arriagada trial suggests that initial intensification of induction may
improve disease-free and overall survival. 17
Administration of multicycle doseintensive
combination therapies supported by cytokines and PBPCs using either
repeated cycles of the same regimen 76-79
or a sequence of different agents 80-83
is a
logical extension of this concept. Thatcher and colleagues explored different
methods to collect hematopoietic stem cells to achieve greater dose intensity with
the ICE regimen for the treatment of good performance status SCLC patients.
Conventional-dose ICE was supported by autologous whole blood cells given on
day 3 of chemotherapy for six cycles. 78
Cycle length was 3 weeks using cryopreserved
apheresis products or 2 weeks using either apheresis products or 750 cc
whole blood stored at 4°C, thus increasing dose intensity. Cycles were repeated on
platelet recovery to 30,000/uL. In this phase I trial of 25 patients, the full planned
dose intensity for each of the arms was reached across the first three cycles,
although only 56% completed all six. Mortality was 12% and complete response
rate was 64%, but the longer-term outcomes are unknown as the median follow-up
was 10 months. The authors note that the collection of whole blood without
cryopreservation reduced the cost and complexity of cellular support for
nonablative therapy substantially. 78
In a subsequent randomized phase II study, 50
"good prognosis" patients were given ICE every 2 or 4 weeks. 77
The median dose
intensity delivered over the first three cycles was 1.8 (0.99-1.97) vs. 0.99
(0.33-1.02) on the 2-week vs. 4-week cycles, respectively. More hematopoietic
and infectious events occurred on the standard-dose 4-week arm.
In the EBMT study, 47 patients underwent mobilization with epirubicin and G-
CSF followed by three cycles of moderately intensive ICE. 79
Radiation to chest and
head was recommended. Of 35 évaluable, the complete and near complete response
rate was 69%. Mortality was 14%.
Humblet et al. treated 37 limited-stage patients with four intensive alternating
cycles of etoposide with either ifosfamide or carboplatin with stem cell support. 83
TRT (10 Gy) in five fractions was given .concurrently with each chemotherapy
administration. Mortality was 3%. The median event-free survival was 18 months,
and 80% remain alive at 30 months. Perhaps due to the fact that no PCI was given,
eight of 13 relapses occurred in the brain.
Minimal residual tumor/autograft involvement
Autograft contamination by tumor cells may cause relapse. Gene marking
studies have definitively proven that residual tumor cells do directly contribute to
407