Autologous Stem Cell Transplantation for CML


Currently, allogeneic stem cell transplantation is the only available treatment that is known to cure CML. All other therapies, including autologous stem cell transplantation (ASCT), aim to control the growth of abnormal cells or to delay the progression of leukemia from a chronic phase to acute myeloid leukemia. The current initial treatment of choice for patients with newly diagnosed CML is Gleevec® (imatinib), which has been shown to be a superior treatment to alfa interferon and cytarabine in randomized controlled trials.1,2,3 Treatment with Gleevec results in a complete cytogenetic response in two thirds of patients. (1) The success of Gleevec prompted a reassessment of the role of both allogeneic and autologous transplants for patients with CML.

The following is a general overview of the role of ASCT in the management of CML. For a general overview of the process of autologous stem cell transplant, select Autologous Stem Cell Transplant.

Background: The Development of ASCT in the Treatment of CML

The use of ASCT for the treatment of CML was developed more than 20 years ago, but has never been widely accepted outside academic transplant centers. This is likely due to the perceived complexity of collecting and freezing stem cells for present or future use. As well, since most patients feel well in the chronic phase, both the patient and the physician are often reluctant to plan early for the inevitable transformation to the blastic phase. Even though the role of ASCT in the chronic phase of CML is not yet firmly established, some patients with CML may want to consider this form of treatment.

The original concept of ASCT for CML was to collect and store stem cells while the patient is in chronic phase. Cells would then be used after high-dose chemotherapy treatment once the patient progressed to the accelerated, or blastic, phase of the disease. When blood counts recover after infusion of stored stem cells collected in chronic phase, they usually are 100 percent Philadelphia chromosome positive. In approximately 10 percent of cases, patients recover with all normal cells or, more frequently, a proportion of normal cells and leukemia cells. However, only a few long-term remissions are achieved by performing high-dose therapy with support of stem cells collected in chronic phase for patients treated in accelerated or blastic phase. This is because the chemotherapy rarely kills all CML cells and the infused stored stem cells typically contain leukemic cells from the chronic phase.

How does ASCT fit into the treatment of CML?

High-dose chemotherapy with allogeneic stem cell transplantation currently provides patients with CML the best chance of cure. Although some young patients are offered an allogeneic transplant as initial treatment, the majority will receive an allogeneic transplant only after failure of Gleevec. Patients too old to undergo allogeneic stem cell transplantation or those without an acceptable stem cell donor may also be treated with interferon and/or chemotherapy.

High-dose chemotherapy and ASCT may represent an attractive treatment option for some patients unable or unwilling to undergo allogeneic stem cell transplantation after failure of Gleevec. This therapy may also be an alternative for patients who cannot tolerate or do not respond to alfa interferon treatment. The rationale behind high-dose chemotherapy and ASCT is that patients with CML usually retain substantial numbers of Philadelphia chromosome-negative stem cells in their blood and bone marrow. These stem cells can be collected and stored early in the disease course and can be use to restore blood cell function after high-dose chemotherapy treatment.

Patients with CML not scheduled for an allogeneic transplant should consider having stem cells collected and preserved (cryopreserved) while their disease is still in chronic phase. These stem cells can be used to support treatment while the patient is in chronic phase or used after progression of leukemia to the accelerated or blastic phase.

ASCT for treatment of CML in Chronic Phase

Doctors from Italy reported that high-dose chemotherapy and autologous peripheral blood stem cell transplantation for chronic phase CML is safe and potentially superior to standard interferon treatment.

In their clinical trial, 30 patients with chronic phase CML had peripheral blood stem cells collected at or near the time of initial diagnosis. In 22 of 30 patients, there was no evidence of leukemia (Philadelphia chromosome) in the harvested stem cells. Stem cells were harvested after chemotherapy and treatment with Neupogen® (filgrastim). These patients were subsequently treated with high-dose chemotherapy and infusion of the previously collected peripheral blood stem cells while still in the chronic phase of CML. Over half of the patients (16) experienced bone marrow recovery with no evidence of the abnormal leukemia cells detected in the blood or bone marrow. All patients experienced full recovery following high-dose chemotherapy. Two years after initiation of treatment, 87 percent of patients were alive, and several patients survived between six months and four years with no evidence of leukemia recurrence.4

The results of this small clinical study suggest this treatment may be superior to standard interferon treatment and is clearly associated with fewer side effects than allogeneic stem cell transplantation.

Recent studies have shown that peripheral blood stem cells can be collected after mobilization with Neupogen in patients receiving Gleevec.5,6 Also, two studies suggest that Gleevec can be given safely after an autologous stem cell transplant.7 These data suggest that current and future studies of autologous transplants in chronic phase will involve pre and post-transplant treatment with Gleevec.

ASCT for Treatment of CML in Accelerated or Blastic Phase

In order to utilize high-dose chemotherapy for treatment of accelerated phase or blastic phase, patients must have had stem cells collected and stored (cryopreserved) while in chronic phase. Some patients in accelerated or blastic phase can achieve a “second remission” with chemotherapy and have stem cells harvested during their remission. Cryopreserved stem cells from the chronic phase are in essence an “insurance policy”, which allows the administration of higher than usual doses of chemotherapy to patients with advanced leukemia. This process offers the assurance that white blood cells and platelets counts can be recovered by infusing the previously collected stem cells.

Strategies to Improve Autologous Stem Cell Transplant

Reasons for treatment of CML with ASCT that does not result in remission may include leukemic cells not eradicated by the high-dose chemotherapy or leukemic cells present in the infused stem cells.  Researchers continue to investigate new ways to improve the results of ASCT.

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of chronic myeloid leukemia will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving autologous stem cell transplantation in the treatment of chronic myeloid leukemia include the following:

Treatment of minimal residual disease: Unfortunately, many patients who achieve a remission still experience a relapse of their cancer. This is because not all of the cancer cells were destroyed. Doctors refer to this as a state of "minimal residual disease". Many doctors believe that applying additional cancer treatments when only a few cancer cells remain represents the best opportunity to prevent the cancer from returning. Immunotherapy to activate the body's anti-cancer defense system or other agents including monoclonal antibodies, targeted therapies and chemotherapy drugs, can be administered over several weeks to months following high-dose chemotherapy and autologous stem cell transplantation in an attempt to eliminate any cancer cells remaining in the body or infused with the stem cells. For example, Gleevec or immunologic therapies such as Proleukin® (aldesleukin) could be administered with ASCT to eradicate minimal residual disease.

Cell processing: When stem cells are collected from a patient for infusion after high-dose chemotherapy, cancer cells may contaminate the stem cell collection. Although the majority of cancer relapses occurring after high-dose chemotherapy and ASCT happen because the high-dose chemotherapy did not kill all of the cancer cells, it is possible that some patients may also experience a cancer recurrence from infusion of the cancer cells with the stored stem cells. Many techniques are being evaluated that effectively remove cancer cells from the stem cell collection. It is currently unknown whether enough cancer cells can be removed to decrease relapse rates.

Expansion of stem cells outside the body: For the past two decades, many doctors have been working on ways to get small quantities of stem cells to grow outside the body. If small quantities of stem cells could be expanded in a culture system as they are in the body, then the problems of collecting stem cells from bone marrow or blood could be avoided. This culture system has an added advantage of not supporting the growth of cancer cells. Thus, one could take small numbers of stem cells, place these cells in a culture system and grow a lot of stem cells that are suitable for transplantation and do not contain cancer cells. To learn more about techniques for removing cancer cells from the stem cell product, go to Autologous Stem Sell Collection and Processing.

Increased dose intensity: More treatment typically kills more cancer cells.  Techniques for increasing the intensity of treatment delivered to the leukemia cells and potentially increasing cure rates include administering higher doses of anti-cancer therapies or delivery of multiple cycles of high-dose therapy. While increasing the intensity of treatment may kill more leukemia cells, this approach may also damage normal cells and increase the side effects of therapy.

Targeted therapy: A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes. Monoclonal antibodies are a type of targeted therapy that can locate cancer cells and kill them directly without harming normal cells. Monoclonal antibodies may be administered alone or with a radioactive material attached to them.  In this manner, radiation is targeted and delivered primarily to the bone marrow while the vital organs such as the liver and lungs are spared high doses of the radioactive material.


1 Hughes TP, Kaeda J, Branford S, et al. Frequency of Major Molecular Responses to Imatinib or Interferon Alfa plus Cytarabine in Newly Diagnosed Chronic Myeloid Leukemia. New England Journal of Medicine. 2003;349:1423-1432.

2 O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. New England Journal of Medicine. 2003;348:994-1004.

3 Lowenberg Bob, Perspective: Minimal Residual Disease in Chronic Myeloid Leukemia. New England Journal of Medicine. 2003;349:1399-1401.

4 Carella AM, Lerma E, Corsetti MT, et al. Autografting with Philadelphia Chromosome-Negative Mobilized Hematopoietic Progenitor Cells in Chronic Myelogenous Leukemia. Blood. 1999;93:1534-1539.

5 Filgrastim-Induced Stem Cell Mobilization in Chronic Myeloid Leukaemia Patients During Imatinib Therapy: Safety, Feasibility and Evidence for an Efficient In Vivo Purging. British Journal of Haematology. 2004;124:195-199.

6 Fisher T, Reifenrath C, Hess GR, et al. Safety and Efficacy of STI-571 (Imatinib Mesylate) in Patients with BCR/ABL-Positive Chronic Myelogenous Leukemia (CML) after Autologous Peripheral Blood Stem Cell Transplantation (PBSCT). Leukemia. 2002;16:1220-1228.

7 Imatinib Mesylate (STI571) Treatment in Patients with Chronic-Phase Chronic Myelogenous Leukaemia Previously Submitted to Autologous Stem Cell Transplantation. British Journal of Haematology. 2003;120:500-504.