Pocket Drug Guide

Nonmyeloablative transplants (NM-allo-SCTs; also known as mini transplants or reduced-intensity-conditioning hematopoietic stem-cell transplantation) are allo-generic stem-cell transplants (allo-Stem-cell transplantation) that are preceded by a low-dose conditioning regimen. This regimen is not as intensive, nor as life-threatening, as traditional transplant regimens, which use high-dose chemotherapy.

In nonmyeloablative transplants, the aim of the conditioning regimen is to destroy a sufficient number of the patient’s T cells to reduce the patient’s immune response and thereby prevent the donor bone marrow from being rejected. To this end, conditioning regimens containing immunosuppressive drugs such as fludarabine and cyclophosphamide are used. The success of the transplant relies on the transplanted cells mounting an immunologic graft-versus-leukemia effect against the patient’s leukemic cells. Candidates for these transplants are those deemed at high risk of transplant complications (e.g., relatively older patients or those with compromised organ function).

A study by P.A. McSweeney and colleagues used reduced total-body irradiation as the allo-Stem-cell transplantation conditioning regimen and included nine patients with chronic myelogenous leukemia. Of the six chronic-phase patients receiving transplants, four achieved cytogenetic and molecular responses studied by real-time PCR. The molecular responses lagged behind cytogenetic responses by several months. In three accelerated-phase patients, two had progressive disease, and one achieved a molecular response.

Two small studies reported on the outcome of patients following nonmyeloablative transplants. In the larger trial, 21 chronic myelogenous leukemia patients in the first or stable second chronic phase underwent NM-allo-Stem-cell transplantation. An evaluation of the first 17 patients with a median follow-up of 33 months provided a four-year probability of survival of 87%. Only one patient had a molecular recurrence, which was treated successfully with donor lymphocyte infusion (DLI).

In the second trial, 12 patients with chronic myelogenous leukemia were treated in a group of 88 patients with hematologic malignancies. Sixty-eight percent of patients were still alive after a median follow-up of 244 days (range 100-842).

Although nonmyeloablative therapy has yet to be tested in a randomized controlled trial, it is already being used in the clinic. Graft rejection has been observed more frequently in nonmyoablative than in myoablative transplant, especially in patients with chronic myelogenous leukemia and myelodysplastic syndrome. This rejection is most likely the result of a relatively active donor immune system, which in chronic myelogenous leukemia has been spared exposure to cytotoxic and immunosuppressive therapy.

Nonetheless, early results suggest that the nonmyeloablative approach may be quite useful in chronic myelogenous leukemia, especially for treating chronic-phase disease. Many lines of evidence suggest that chronic myelogenous leukemia is especially sensitive to immunologic effects (including the high relapse rates in syngeneic and T-cell-depleted transplants, the beneficial effects of DLI, and the effects of interferon). However, the question of whom to apply the nonmyeloablative approach to is problematic. Restricting the procedure to those patients who fail imatinib or to those who have a related or unrelated donor but are too old or too ill for conventional transplantation would confine the treatment to a very small patient population. One possible approach might be to add nonmyeloablative transplants as an immunologic adjuvant after initial therapy with imatinib, followed by the addition of imatinib after transplant to clear out any residual disease.

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