Cancer Treatment Today

Despite improvement of treatment with Gleevec, Sprycel and Tasigna, allogeneic stem cell transplantation remains the only curative treatment for patients with CML. This form of treatment is only available for a small minority of patients due to the advanced age of most patients at the time of diagnosis and the lack of a suitable related or unrelated allogeneic stem cell donor. Despite significant progress, allogeneic transplants are associated with significant early mortality and morbidity. Until the advent of Gleevec, “young” patients with an HLA-matched related or unrelated donor were advised to undergo a transplant without a trial of IFNa. Older patients and patients with high-risk factors for failure of transplantation were advised to have an allogeneic transplant only after failure of IFNa. The definition of who is “young” and who is at “high” risk of transplant failure varies from center to center and is evolving over time. Advising selected patients to have an immediate transplant was based on the observation that the results of transplant were worse for patients transplanted after one or two years than for patients transplanted within one year of diagnosis. Until recently, a major criterion for delay of transplant was a good initial response to IFNa treatment. Now all patients with newly diagnosed CML are receiving initial treatment with Gleevec or other newer drugs before combination with other agents or a transplant is considered. However, clinicians should identify a donor early for younger patients without significant co-morbidities since, sooner or later, the disease will progress despite Gleevec and other therapies.NCCN recommends allogeneic tansplant in blast crisis, after obtaining a remission.

Transplantation should be done sooner when there are poor-risk features, such as presentation in blast crisis.Age has consistently been an important factor for outcome of allogeneic stem cell transplantation, but the exact upper age limit for performing an allogeneic transplant in early chronic phase is controversial, with ranges from 40-65 years, depending on the institution performing the procedure. In general, treatment-related deaths increase with age in most centers. In one clinical study, no patients under age 20 died. Patients 30-40, 40-50 and 50-60 years were 1.24, 2.30 and 2.54 times more likely to die of the procedure, respectively. Patients over age 40 had a significant increase in the risk of dying of the transplant compared to younger individuals. Thus, patients under the age of 40 had a 5-year survival of 85%, compared to 65-70% for patients over 40 years of age.

Delay of transplant can also affect outcomes of patients transplanted in chronic phase. In one study, patients transplanted from HLA-matched unrelated donors while in chronic phase within one year of diagnosis had a 5-year survival of 85% while those transplanted between 1 and 2 years from diagnosis had a survival of 78%. Patients transplanted in chronic phase more than 2 years from diagnosis had a survival 50%, with the excess deaths all being related to complications of the transplant. However, these data were generated in the era of INF alfa treatment and the impact of Gleevec on survival from a subsequent transplant is unknown. This will be very important since patients will be coming to transplant after years of Gleevec treatment.Allogeneic stem cell transplantation can cure up to 80-85% of patients with newly diagnosed CML but can be associated with significant morbidity and mortality. There have been attempts to define risk factors associated with failure to assist in decision making concerning the appropriate timing of allogeneic stem cell transplantation for an individual patient with CML. However, these risk factor analyses may be dated and may not be relevant to patients being treated in the Gleevec era and an era of improving results of allogeneic stem cell transplantation.