VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

PATIENT SELECTION
RIT is in a developmental phase. Patient studies need to be designed carefully
to obtain answers on questions of RIT optimization. RIT itself should be
simple in the initial stages of analysis, i.e. consist of a single injection per treatment
cycle and not be combined with other treatment modalities (surgery, chemotherapy,
external beam irradiation). The most prominent theoretical advantage
of RIT is its selectivity. Therefore, the high therapeutic ratio of RIT needs to
be defined and maintained in initial clinical studies. Normal tissue damage can
be evaluated in most patients. However, therapeutic ratio can only be determined
if tumor responses are observed in the same patients. Tumor responses
can only be expected in patients whose malignancies have sufficient radiosensitivity
to respond to the doses of radiation that can be delivered by present day
RIT. Relapsed Hodgkin's disease, lymphoma, ovarian cancer, and breast cancer
patients are probably the best candidates for single agent RIT studies at this
time. Other malignancies will become candidates for study when improved RIT
delivers higher tumor doses.
BONE MARROW TRANSPLANTATION
Bone marrow transplantation can be utilized after high radioisotope activity
RIT to decrease the severe hematological side effects of such treatment. 1
' 3
' 5
Theoretically
RIT can be used to supplement or replace total body irradiation (TBI) in
the conditioning of bone marrow transplant patients. Previously we have shown
that dose homogeneity is not necessary for effective TBI schedules. Indeed, selectively
non-homogeneous TBI is expected to have a better therapeutic ratio. 12
RIT could deliver non-homogeneous TBI, with the highest doses delivered to
volumes containing the highest concentrations of the radiolabeled immunoglobulin.
Such volumes would be dependent on the specificity of the antibody
used and adapted to the problems presented by the patient.
Radioactivity in blood and bone marrow can interfere with the success of a
bone marrow transplant by inactivating the transplanted stem cells. Current recommendations
are to delay the transplant till the dose rate in bone marrow and
blood has decreased below 1 cGy per hour. 513
One study reports an improved
outlook for patients treated with poor prognosis relapsed Hodgkin's disease after
treatment with Yttrium 90 labeled antiferritin, high dose cyclophosphamide,
etoposide and carmustine followed by an autologous bone marrow transplant. 14
In general, activity escalation studies for RIT have shown a positive correlation
between intensity of treatment and severity of side effects in normal tissues. Unfortunately
dose-effect relationships for tumor responses have been less clear
cut. 1
- 3
We anticipate finding a positive correlation between tumor dose and response
when high tumor doses after RIT can be achieved on a regular basis. It is
our opinion that activity escalation with RIT reagents up to the level requiring
bone marrow transplant supportive care should be delayed until a good therapeutic
ratio has been obtained with the reagents in low activity studies.
NEW SEQUENTIAL PHASES FOR THE STUDY OF RIT REAGENTS
Chemotherapy and RIT are similar in several aspects. Both offer systemic
cancer treatment. Both will be tested in cancer patients for which other "older"
curative treatments are not available or have failed. Cancer chemotherapeutic
200 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION