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Although high-dose therapy followed by allo-Stem-cell transplantation is considered the only curative treatment for chronic myelogenous leukemia, the

procedure’s toxicity has always restricted its use to younger (generally younger than 55), fitter patients. The number of patients receiving allo-Stem-cell transplantation is further limited by the number of available matched donors. As previously noted, although long-term survival rates are higher for allo-Stem-cell transplantation than for interferon-a, the high early mortality associated with transplantation means that the survival benefit does not become apparent until five to ten years after transplantation.

Allo-Stem-cell transplantation is more successful if it is performed in the chronic phase rather than in the accelerated or blastic phases (long-term disease-free survival rates are 50-60%, 30-40%, and 20-25%, respectively). Aside from the phase in which allo-Stem-cell transplantation is performed, several other factors can increase the risk of mortality. TABLE . Prognostic Scoring System for Allogeneic Progenitor Stem-Cell Transplantation in Chronic Myelogenous Leukemia summarizes these factors, which can be used to calculate an overall risk score that may help determine whether allo-Stem-cell transplantation should be undertaken.

Survival appears to be best among patients who receive their transplant within one year of diagnosis, are less than 40 years of age, have a male donor, and, along with their donor, are cytomegalovirus-seronegative. For such a cohort, five-year disease-free survival is 70% to 80%, and the relapse rate is 10% to 20%.

TABLE . Prognostic Scoring System for Allogeneic Progenitor Stem-Cell Transplantation in Chronic Myelogenous Leukemia

Note: A patient’s overall risk score for allo-Stem-cell transplantation (allogeneic stem-cell transplantation) in chronic myelogenous leukemia is calculated by combining the individual risk scores above. If the total score is 1 or less, the patient is a good candidate for allo-Stem-cell transplantation (treatment-related mortality [TRM] of approximately 20%). If the total score is 5 or more, the patient is a poor candidate for transplantation (TRM > 70%). For patients with a score of 2-4 (which accounts for 71 % of patients), the choice of transplantation would be made on an individual basis depending on the Sokal score. HLA = Human leukocyte antigen.

The details of transplant procedure and the source of stem cells (marrow versus peripheral) also influence outcome. Engraftment appears to be more rapid following a peripheral blood stem-cell transplant, though the incidence of chronic graft-versus-host disease may be increased.

Acute and chronic graft-versus-host disease is a significant cause of transplant-related mortality. A combination of cyclosporine and methotrexate is the usual prophylaxis treatment, but controversy surrounds the question of what is the best approach. Researchers have demonstrated that T-cell depletion of the graft substantially reduces the incidence of chronic graft-versus-host disease but also increases the risk of relapse. Allo-Stem-cell transplantation using T-cell depletion with the CD52 monoclonal antibody Campath results in an actuarial relapse rate of 60% to 70%. Other methods of T-cell depletion include the use of other antibodies and E-rosette formation/soybean lectin agglutination. They also reduce the incidence of chronic graft-versus-host disease while increasing the incidence of relapse to varying degrees.

A study involving 22 patients showed that transplantation of highly purified CD34+ peripheral blood stem cells with T-lymphocyte add-back does not appear to be associated with an increased risk of relapse; this strategy is being tested further.

Studies have suggested that prior treatment with interferon-a is associated with inferior survival, although reports conflict on the matter. However, preliminary data from the European Group for Blood and Marrow Transplantation (EBMT) suggest that treatment with interferon-a’s successor, imatinib, does not have a deleterious effect on subsequent transplantation. This phenomenon requires further observation.

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