autologous blood and marrow transplantation - Blog Science ...

Schlossman et al.
(sB2M), stage I disease at diagnosis, having received one line of previous treatment,
and being in CR prior to BMT. Of major concern, however is the 40% transplantrelated
mortality (50% in males) in the EBMT experience. 11
In a report of
allografting for MM in Seattle, actuarial probabilities of overall and event-free
survival (OS and EFS) for the 36% patients achieving CR were 0.50 + 0.21 and 0.43
+ 0.17, respectively, at 4.5 years. Adverse prognostic factors included: transplantation
>1 year from diagnosis, sB2M >2.5 at transplant, female patients transplanted
from male donors, having received >8 cycles of chemotherapy, and Durie Salmon
Stage ITJ disease at the time of BMT. Again, toxicity was common, with 35 (44%)
patients dying of transplant-related causes within 100 days of BMT. 12
Finally, there
were 15 deaths among 36 patients within the first 100 days after allografting in an
ongoing multigroup randomized trial of high-dose versus conventional therapy for
MM in the United States. As a result of this excessive toxicity, the allografting arm
of this study has been closed, and individual academic centers are encouraged to
develop strategies to achieve and maintain high remission rates, while avoiding
transplant-related morbidity and mortality.
High-dose chemoradiotherapy followed by transplantation of either autologous
BM or PBPCs has also achieved high (40%) CR rates, but the median duration of
these responses has unfortunately been only 24-36 months at best. 1314
Patients
with sensitive disease and who are less heavily pretreated have the most favorable
outcomes. The EBMT Registry has compiled data on 907 patients who underwent
autologous stem cell grafting for MM and reported that autografting is most
effective when applied early in the course of disease in younger, chemotherapyresponsive
patients. 15
The achievement of CR, a non-TBI containing preparative
regimen, and alpha IFN maintenance treatment is associated with more favorable
outcome. As in other settings, engraftment in patients with MM who receive PBSC
1 6
autografts is more rapid than in recipients of BM. Most importantly, a national
randomized trial in France of 200 patients with MM who received two courses of
vincristine, melphalan, cyclophosphamide, prednisone (VMCP) alternating with
vincristine, carmustine, doxorubicin, prednisone (VBAP) and then were
randomized to receive either conventional chemotherapy (eight additional courses
of VMCP/VBAP) or high-dose therapy (melphalan and TBI) followed by
autologous BMT has demonstrated significantly higher response rates, EFS, and
OS for those patients treated with high-dose compared with those receiving
conventional therapy. 17
Response rates in the high-dose and conventional arms
were 81 vs. 57%, respectively. The 5-year probability of EFS and OS was 28 and
52%, respectively, in recipients of high-dose therapy and only 10 and 12%, respectively,
in patients treated with conventional therapy; treatment-related mortality
was comparable between the two groups. However, with further follow-up, the 6year
postdiagnosis EFS in the high-dose arm was only 24%. 18
Therefore, although
this study is encouraging, and additional randomized trials in the United States,
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