Autologous Bone Marrow Transplantation - Blog Science Connections

Proposed International Adult Lymphoma Study 327
Radiotherapy
Treatment in one arm of the study will integrate XRT and BEAC (BCNCI
[carmustine], etoposide, ara-C [cytarabine], cyclophosphamide). To limit
potential nonhematopoietic toxicities, we will employ a reduced XRT dose.
Assuming that cell survival statistics apply to the clinical situations included
in this study, we believe the proposed XRT schedule (26 Gy in 20 fractions of
1.30 Gy each that will be delivered twice daily over 2 weeks) will result in
approximately 7 logs of cell killing. Small doses will be employed to take
advantage of the relatively small shoulder on lymphoma cell survival curves
and should improve the therapeutic ratio relative to mucosal epithelial cells,
which generally have radiation survival curves with broad shoulders (62). To
allow for adequate normal tissue repair of sublethal damage, we will allow at
least 4 hours to elapse between each of the two daily treatments (62).
Bulky disease sites in this study are defined as sites of relapse in which a
mass measures 5 cm or greater prior to institution of DHAP therapy. In
extranodal head and neck sites, bulky disease is defined as any tumor falling
into a T3 or T4 category according to the International Onion Against Cancer
or the American Joint Committee criteria for epithelial cancers. Sites of bulky
relapse that have received prior irradiation to doses greater than 30.0 Gy or to
doses that would result in exceeding commonly accepted tolerances (63) if
XRT in our protocol were added will not receive involved-field XRT. Regardless
of disease status at relapse, the following sites will not receive systematic
XRT: bone marrow, lungs, heart, liver, and kidneys. It is admissible to
incidentally include up to 20% of the total volume of the lungs, heart, liver, and
kidneys during involved-field XRT to adjacent structures. The definition of an
XRT involved field is based on the Ann Arbor concept of a nodal region (64)
and is elaborated on in the section dealing with treatment methods.
Continued
DHAP
The considerations given previously relative to the potential benefits of
involved-field XRT also apply to conventional chemotherapy of intermediateand
high-grade lymphomas, and accordingly XRT will also be included in this
arm of the study. Since it is unlikely that XRT could be integrated early into the
DHAP-only arm without compromising the timing or dosage of chemotherapy
or both, XRT will be delivered after completion of six courses of
DHAP. Involved-field XRT will consist of conventional once-daily treatment of
1.50-2.00 Gy to a total of 35.0-40.0 Gy delivered to sites of initial bulky
disease as defined previously. However, patients showing disease progression
before the commencement of XRT will be regarded as patients whose
treatment failed, and their disease will be managed according to the discretion
of the investigator. The approach of DHAP-XRT is regarded as the best
conventional treatment, and against it XRT-BEAC-ABMT will be compared.