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Immunologic Manipulations to Treat Blood and Bone Marrow Cancers

Patients receiving chemotherapy or transplants for hematologic malignancies unfortunately are not always cured of their disease. Most regimens used are close to the dose-limiting toxicity because of the side effects of these regimens. This suggests that simply giving more chemotherapy is not the solution to preventing relapse. More therapy is likely to result in more side effects. Likewise, the small increases in chemotherapy that are possible are unlikely to have significant effects since the remaining tumor cells are those that are the most resistant to chemotherapy. Thus, new approaches to preventing and/or treating are needed. We have been interested in using immunologic methods to address this problem. This type of approach makes sense because tumors that are resistant to chemotherapy are not necessarily resistant to immunologic therapy. Likewise, immunologic approaches usually have less toxicity than chemotherapy or radiotherapy approaches. One example of an immunologic approach is donor lymphocyte infusion (see next paragraph).

Donor Lymphocyte Infusions (DLI)

Another therapy which uses the immune system to try to fight the tumor is donor lymphocyte infusions or DLI. Patients relapsing after an allogeneic marrow transplant have few treatment options. Several groups have found that transfusion of donor white cells into patients, especially those with relapsed chronic myelogenous leukemia, is successful in re-inducing a remission in these patients. Many of these patients have Graft-versus-Host disease induced by this type of treatment. The toxicity seen with donor lymphocyte infusion can be significant if either severe Graft-versus-Host disease or marrow toxicity from the lymphocyte infusions occurs. However, this toxicity is milder than that seen with attempts at second marrow transplants. Currently we are exploring the use of donor lymphocyte infusion in patients who have relapsed after transplant. The dose of lymphocytes given and the schedule is dependent on the disease which has relapsed. Patients with rapidly progressing tumors may first need to be treated with chemotherapy. Depending on the disease, multiple infusions of white cells may be tried until a remission or significant side effects are obtained. Some patients receiving this type of treatment require a second marrow transfusion (without a preparative regimen) because of low count. Patients at high risk for relapse may also be offered DLI while they are still in remission after BMT.

 

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