Autologous Bone Marrow Transplantation - Blog Science Connections

326 Proposed International Adult Lymphoma Study
related and may also be related to the duration of infusion and the use of
hydration and mannitol (56). Myelosuppression from cytarabine is less severe
with shorter infusions than it is with 24-hour infusions or longer ones.
Tolerance so far has been acceptable, and the regimen can be administered
on an outpatient basis for young patients. Careful monitoring of fluid
intake and renal status will be performed during this study to keep urine output
at a minimum of 150 ml/hour during the cisplatin infusion.
Further expansion of these data has shown that the combination of
cisplatin and cytarabine in high doses has produced a 57% response rate in
the first 67 patients with diffuse lymphoma treated, of whom more than half
(30% of the total number of patients) are in CR. Seventeen patients with
diffuse large cell lymphoma who were less than 60 years of age with no bone
marrow or CNS involvement and good Karnofsky performance scores have
been treated at Cl.T. M. D. Anderson Hospital on dexamethasone, high-dose
cytarabine, and cisplatin. Of those, 35% achieved a CR and 41 % responded.
Fifty percent of the CR patients are still disease free (median follow-up, 9
months). Nine comparable patients have been treated at Omaha University,
and six responded, four having CRs. The response rate for the 25 patients
(Houston and Omaha) is 50%.
Radiotherapy
Results
The rationale for including irradiation in an autologous transplant program
is the known radiosensitivity of lymphomas. Radiobiologic studies
corroborate the clinical findings of significant radiosensitivity for this lymphoma
type. One study on large cell lymphoma of B-lymphocyte origin
showed that in vitro the radiation cell survival curve had a small shoulder (n =
1.2) and a steep slope (D 0
= 1.4 Gy) (57). From this it follows that the
radiotherapy schedule proposed in this study (see below) should result in 6-7
logs of additional cell killing (57-60). Previous experience with large cell
lymphoma in general (61) and with massive therapy in particular (W. Velasquez,
M.D., personal communication, 1986) has shown that initial sites of
bulky disease tend to be the sites of relapse and progression. Our review of
100 cases in adults (see Armitage, "Bone Marrow Transplantation in Relapsed
Diffuse Large Cell Lymphoma," in this volume) show that of 100
patients treated, 64 relapsed, and of these 48 (75%) had recurrences at sites
of initial bulky disease. This suggests that additional cytoreduction of bulky
disease is necessary. Because TBI was not able to overcome this problem in
our studies, because radiation is primarily a local-regional modality, and
because the probability of local control increases as dose increases, it is
logical to investigate in conjunction with the chemotherapy program the
effectiveness of involved-field (boost) radiation therapy (XRT) to sites of bulky
disease.