Stem Cell Transplants Are Not Just for Liquid Tumors Anymore

By Peter Emanuel, M.D.

The Hematopoietic Cell Transplantation for Benign Hematological Disorders and Solid Tumors Educational Session presented on Saturday morning and again today (9:45 a.m. - 11:30 a.m.) offers an exciting glimpse as to the vast array of pre-transplant diagnoses one might find on the list of patients on a transplant unit, say, in the year 2010. While autologous transplants for breast cancer have largely fallen by the wayside, new manipulations in both autologous and allogeneic hematopoietic cell transplantations offer new hope to patients with a variety of benign hematological disorders as well as to some solid tumor patients.

Dr. Rainer Storb discussed the continuing development of non-myeloablative conditioning strategies for patients with severe aplastic anemia who have a HLA-matched family donor. The incidence of graft rejection is decreasing, concomitant with the more widespread use of leuko-depleted blood products for transfusions, as well as the routine use of gamma irradiation of transfused units. Outcomes of grafts from unrelated donors have steadily improved, but are still hampered by acute and chronic GVHD. The least toxic current conditioning regimen for unrelated grafts consists of CY/ATG combined with 2 Gy TBI.

Dr. Lucarelli presented the current data for marrow transplantation in thalassemia major, including severity classes 1-3. He presented unpublished data, calculated as of March, 2003, which demonstrated excellent overall and thalassemia-free survival rates. He also gave a glimpse of the future using genetically modified stem cells and autologous transplantation. His “crystal ball” prediction was that this new technique might not increase cure rates beyond that currently achieved with allogeneic transplantation, but the advantage would be no limitations for any thalassemia patient, as opposed to the current strategy which depends on the availability of a matched donor.

Dr. McSweeney is investigating the use of high-dose immunosuppressive therapy (HDIT), both with and without autologous stem cell transplantation. While these maneuvers are being attempted in patients with any one of a long list of autoimmune disorders, the most experience to date has been in patients with multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and juvenile idiopathic arthritis. A number of parameters are being investigated for the best outcomes including the stem cell source, manipulation of the graft, and various conditioning regimens. G-CSF mobilization of stem cells can be very hazardous in these patients, yet chemo-mobilization also has problems. Contrary to hematological malignancies, accurate assessment of outcomes in these autoimmune diseases can be quite problematic. Five randomized, controlled trials are on the verge of opening to compare these new techniques to conventional therapy.

Finally, Dr. Childs presented efforts aimed at nonmyeloablative transplantation for patients with solid tumors. These renewed efforts are seeking to exploit the known graft-versus-leukemia reaction and apply it to known epithelial tumor antigens that induce T-cell mediated tumor rejection in vitro (e.g., MART-1, WT-1). Preliminary results were presented for some patients with renal cell carcinoma as well as metastatic melanoma. Certainly anecdotal reports keep alive the hope for patients with other solid tumors including breast, ovarian, neuroblastoma, colon, and lung that this type of immunomodulatory therapy might some day have wider application.