Allogeneic BMT has generally been limited to patients younger than age 50 to 55 years, and to those with good performance status and renal function. Several approaches are being evaluated to allow these poorer-risk patients to safely undergo transplantation. The successful use of submyeloablative (mini) transplants has previously been reported by groups from Israel (Slavin et al: Blood 91:756-73, 1998) and M. D. Anderson (Khouri et al: J Clin Oncol 16:2817-2824, 1998). A moderately myelosuppressive agent, such as cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar), and an immunosuppressive drug, such as fludarabine (Fludara), are used as the preparative regimen. Following BMT, allogeneic donor leukocytes may be used to eliminate residual disease or mixed chimerism. Further study of this interesting approach is ongoing.
At the ASH meeting, Childs et al (abstract #1173) reported another approach for reducing transplant-related toxicity. They described their experience with T-celldepleted allogeneic BMT, which permits older patients to undergo this procedure because of a reduction in graft-vs-host disease GVHD). The authors felt that their results supported preservation of the graft-vs-lymphoma (GVL) effect. This approach may also be applicable to patients undergoing an unrelated donor transplant, and infusions of small numbers of donor leukocytes could reduce the high incidence of severe opportunistic infections (Small et al: Blood 93:467-480, 1999).
Patients with indolent NHL may undergo a transformation to an aggressive, high-grade NHL. This event is usually accompanied by molecular findings of p53 mutations and clinical drug resistance. The only form of therapy that has been associated with a prolonged disease-free survival in these patients has been high-dose therapy with stem-cell support. Friedberg et al (abstract #2982) provide an update of their experience with autologous transplantation in 27 patients with follicular NHL whose tumors had undergone histologic transformation. The 5-year disease-free survival was 46% and overall survival was 58%. It is important to reinforce the point that, at transplantation, 12 patients had been reinduced into a complete remission and 15 had achieved a good partial response. These results confirm previous data that high-dose therapy with stem-cell support may benefit carefully selected patients whose NHL has undergone histologic transformation.
Bruce D. Cheson, MD