Stem Cell Transplantation (SCT)

Stem cell transplantation involves the introduction of donor (allogeneic) or the patientís own treated (autologous) stem cells into the patient in the hope that the procedure will replace the damaged stem cells causing the CML (chronic myeloid leukaemia). It is the only currently available therapy able to cure patients with CML. In this procedure, the patient is first treated with high doses of chemotherapy and/or radiation to destroy all bone marrow cells (cells used for autologous transplant are withdrawn prior to this step). This step is called the preparative regimen or conditioning. Stem cells from the donorís marrow or peripheral blood are then transfused into the patient, with the intent of repopulating the patientís marrow. In the case of CML, autologous transplantation has generally been unsuccessful because many of the patientís stem cells contain the genetic defect causing the disease. However, SCT can be curative for CML. Advances in SCT techniques in the past two decades have made CML the most frequent indication for allogeneic stem cell transplantation. It has been shown that:


  • The projected survival rates with SCT range from 40% to 80% in chronic phase CML.
  • Disease-free survival (DFS) is achieved in 30% to 70% of patients. Relapses occur in 15% to 30% of patients, and plateaus in survival curves are reached 5 years after transplantation.
  • SCT is not particularly effective as a salvage therapy (after initial failure of SCT) or as a treatment for CML in blast crisis.
  • The transplant-related mortality (TRM) can be quite high, ranging from 15% to more than 70%.
  • Only about 35% of patients under the age of 50 undergo this treatment, primarily because of the lack of an appropriate tissue-compatible related donor.

The outcome of SCT (stem cell transplantation) for CML is influenced by several host-, disease-, and treatment-associated factors:


  • Age: Most studies show an inverse relation between age and prognosis. This is due to a higher TRM in older patients. SCT is typically reserved for patients ≤ 50 years of age, although physically fit older patients may be considered. The median age for SCT in CML is around 40 years in most centres.
  • CML phase: DFS decreases from 40%Ė60% in patients with CML in chronic phase to less than 15% in those with CML in blast crisis. In the advanced phases of CML, SCT is generally unsuccessful and is associated with increased rates of leukaemic relapse and increased TRM.
  • Chronic phase duration: The duration of the chronic phase prior to SCT has been considered a prognostic factor for SCT success. However, recent studies have not confirmed this.
  • Degree of donor-host matching: Generally patients with complete six-antigen matches (usually from HLA-identical siblings) have the best response to SCT. Those with less than a five-antigen match are not generally considered for SCT except in experimental protocols.
  • Preparative regimen: The combination of busulfan and cyclophosphamide seems to be as effective as cyclophosphamide and total body irradiation, but with less toxicity.
  • Treatment before transplant: Prior treatment with hydroxyurea does not affect the success rates of SCT. Prior treatment with busulfan seems to decrease the post-transplant DFS rate. Prior treatment with IFN-α does not appear to affect the chances of successful SCT, though there remains some controversy on this issue.
  • Graft-versus-host disease (GVHD) prophylaxis: GVHD can increase post-transplant mortality and occurs when the donor cells react to host tissues. The usual practice to prevent GVHD is post-transplant immunosuppression with two agents, such as methotrexate and cyclosporine. T-cell depletion of donor marrow or blood prior to transplant reduces treatment-related mortality rates due to GVHD, but increases the rate of CML relapse, suggesting that donor T cells (and a degree of GVHD) may have a direct anti-leukaemic effect.
  • Source of stem cells (related versus unrelated): Historically, related donors have been associated with a more successful SCT outcome, but improvements in matching and donor recruitment have altered this picture, such that similar rates between related and unrelated donors are now reported.
  • Prior exposure to cytomegalovirus (CMV): CMV is a double-stranded DNA virus, similar to herpes, that can cause a mild mononucleosis-like syndrome in healthy adults. In immunosuppressed persons, however, it can lead to devastating disease and is the most important viral disease complicating transplantation. SCT is more successful if neither the donor nor patient has evidence of prior CMV infection.

The long-term DFS rates following allogeneic SCT have ranged from 80% (young patients, matched related donors, CMV negative, appropriate GVHD prophylaxis, and supportive care) to less than 30% (older patients, unrelated donor transplants, CMV positive). If patients relapse following SCT, there are several treatment options:


  • Donor lymphocyte infusions (DLIs): DLI is the most effective salvage therapy for chronic phase relapse after SCT. The infusion of HLA-matched lymphocytes may induce a "graft-versus-leukaemia" (GVL) response. Cytogenetic responses and complete haematological remission rates range from 60% to 80% with DLI. Responses, however, are infrequent and short lasting during CML in accelerated phase or blast crisis. The activity of DLI is limited by the occurrence of marrow suppression and GVHD.
  • Second transplant: The outcome from a second SCT from HLA-identical siblings depends on the time from initial SCT to relapse. This procedure is effective only in patients with prolonged first remissions. Patients who experience a relapse within 6 months of SCT have a DFS of less than 10%, a TRM of 69%, and a probability of relapse of more than 70%. In contrast, in patients with longer first remissions, the DFS may reach up to 30%.
  • IFN-α: IFN-α may induce long-lasting cytogenetic remissions in 20% to 40% of patients.