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transient BCR-ABL positivity in the first year post-transplant in patients who are ultimately destined not to relapse. Two consecutive samples with increasing numbers of BCR-ABL transcripts are ideally required. Options for treatment are the withdrawal of immunosuppression (i.e., stop cyclosporin), consideration of IFN, donor lymphocyte infusions, or contemplation of a second allograft procedure. Chemotherapeutic methods are now a viable option with the advent of imatinib, but hydroxyurea or other forms of chemotherapy have been shown to be unsatisfactory.

DLI therapy has had a major impact on the treatment of relapse postallograft in CML, more so than in other hematological malignancies. DLI therapy relies on exploiting the GVL effect of the original transplant to "mop up" small amounts of recurrent disease, and hence is most effective when performed in the earliest stage of relapse. The two major side effects are GVHD and marrow aplasia, but no pretreatment parameters can reliably predict which patients may suffer these complications. The typical schedule of escalating dose given every 3 months until recurrent disease is eradicated is described in Table 5-7.

"Mini" Transplants

Over the past 3 to 4 years there has been a vogue for nonmye-loablative stem cell transplants (NSTs), so-called mini-transplants, the intention of which is to minimize the morbidity and mortality of the transplant-conditioning regimen so that the procedure might be available to older patients.133-135 NSTs are based on the hypothesis that transient immunosuppression allows eradication of disease by alloreactive immune cells over time, and hence continuous cell-mediated immunotherapy with donor cells.136 It is hypothesized that NST can induce transient mixed chimerism that may protect from severe GVHD. One of the earliest regimens from Seattle137 was to use only minimal immunosuppression [200 cGy-one fraction and oral mycophenolate mofetil (Cellsept)]. Thereafter donor lymphocyte infusions are used to alter the ratio of donor/recipient chimerism in order to eradicate host leukemia.138 Although the toxicity profile of such procedures has been impressive,139 there have been considerable problems with failed engraftment, and immunosuppression is being increased. It is suggested that NSTs are not sufficiently cytoreductive in patients with advanced malignancy.140,141 A number of regimens contain flu-darabine and/or Campath, but as yet there are no clear data to

Table 5-7.

Donor Lymphocyte Infusion:

Escalating Doses

Usually Given at Three Month Intervals

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