Autologous Bone Marrow Transplantation - Blog Science Connections

336 International NHL Trial
THEORETICAL OBJECTIVES AND JUSTIFICATIONS
The main objective of this trial might be described as determining if a
high-dose chemotherapy regimen with ABMT can increase the survival rate
for patients with relapsed non-Hodgkin's lymphoma over that produced by
conventional chemotherapy. Other goals would be to compare toxicities,
response rate, and progression-free survival rate in ABMT and conventional
groups. However, the crude survival rate is not a valid criterion because other
therapeutics will be used after these therapies fail. So progression-free
survival should be taken as the main measure. To be valid, the study has to be
based on a solid understanding of the two therapeutic strategies.
Background of ABMT and Conventional Therapy
Few phase 11 trials of high-dose chemotherapy with ABMT have been
performed (1,2), but three conclusions may be drawn from these trials or
retrospective studies. First, results obtained with high-dose chemotherapy
and ABMT vary according to prior response to chemotherapy (complete
response or not). Second, patients who relapse after achieving a complete
response may be divided into two different groups: those whose disease
remains responsive though in relapse (sensitive relapse) and those whose
disease is resistant to therapy (resistant relapse). The former have a better
prognosis than the latter, even if high-dose chemotherapy is administered
later. Third, in a group of patients treated with high-dose chemotherapy and
ABMT after conventional therapy, the disease-free survival rate is 30% at 2
years.
On the other hand, good results can be obtained with conventional therapy
in terms of response and survival rates. In The University of Texas
M. D. Anderson Hospital and Tumor Institute at Houston's MIME (mitoguazone,
ifosfamide, methotrexate, etoposide) study (3), a 67% response rate was
obtained in a 52-patient group. With the DHAP protocol (dexamethasone,
cytarabine, cisplatin), similar results were obtained in 17 patients also at M. D.
Anderson Hospital. Findings about conventional therapy can be summarized
as follows: 1) a high response rate to a multidrug regimen can be obtained; 2)
evidence of prior complete response to chemotherapy is as important in
conventional therapy as it is in ABMT; and 3) the disease-free survival rate is
5-10% at 2 years.
Justification of a Randomized Trial
After several years of experience in high-dose chemotherapy with ABMT
in non-Hodgkin's lymphoma relapses, it is necessary to reevaluate this
treatment. Based upon the results of open cohort studies, ABMT appears to
have a higher response rate than does conventional therapy. However, ABMT
is an expensive treatment and sometimes induces severe toxicity (the toxic
death rate is estimated at 15%). Historical controls are not valid because of