Acute lymphoblastic leukaemia (ALL), a cancer of the white blood cells, is the most common type of leukaemia, with about 3,930 new cases diagnosed each year in the United States¹. According to researchers, approximately 20 to 25 percent of all adults with ALL have a genetic abnormality in which some genetic material from chromosome 9 switches position with some genetic material from chromosome 22. This condition is known as Philadelphia chromosome-positive (Ph+) ALL, which is a rapidly progressive form of leukaemia. It is associated with a poor prognosis since induction chemotherapy alone does not produce prolonged remissions. Therefore, an allogeneic stem cell transplant, in which a patient receives stem cells from a sibling or unrelated matched donor, is often recommended after the first complete remission.


In 1993 researchers from the National Cancer Research Institute in the United Kingdom and the Eastern Cooperative Oncology Group in the United States initiated a study to evaluate whether allogeneic stem cell transplant is an effective treatment option for adult patients with Ph+ ALL. In this study, 266 patients received two phases of induction chemotherapy followed by an allogeneic stem cell transplant (“pre-imatinib” arm). Following the availability of imatinib, a targeted BCR-ABL inhibitor, the purpose of the study was modified in 2003 to include and evaluate the use of imatinib as part of consolidation therapy prior to an allogeneic stem cell transplant (“late-imatinib” arm) or as part of standard induction therapy prior to the transplant (“early-imatinib” arm). Results from the pre-imatinib cohort (Fielding, Blood 2009) were then used as a benchmark for use of imatinib in patients with Ph+ ALL.

In the late-imatinib arm of the study, 86 patients received imatinib 600 mg a day as part of consolidation therapy prior to undergoing an allogeneic stem cell transplant following two induction chemotherapy regimens. Those in the early-imatinib arm (89 patients) were given imatinib 600 mg earlier as part of the second chemotherapy induction phase prior to the allogeneic stem cell transplant. All patients who received an allogeneic stem cell transplant in the study were given imatinib for two years post-transplant. If a transplant was not feasible for any reason, imatinib could be given as a maintenance therapy for two years.

Results from this study, the largest international study of patients with Ph+ ALL evaluating allogeneic stem cell transplantation (control group) and the use of imatinib, show significant differences in outcomes between the three different groups after three years of follow-up. The researchers found that overall survival reached 25 percent in the pre-imatinib arm, 34 percent in the late-imatinib arm, and 48 percent in the early-imatinib arm. Event-free survival was 19 percent in the pre-imatinib arm, 29 percent in the late-imatinib arm, and 35 percent in the early-imatinib arm. Additionally, relapse-free survival reached 36 percent, 45 percent, and 62 percent respectively.

Prior to the introduction and availability of imatinib, only 28 percent of patients went on to receive an allogeneic stem cell transplant per the study protocol. In these pre-imatinib patients, five-year overall survival was 40 percent for those patients who received an allogeneic stem cell transplant compared with 19 percent for non-transplanted patients. Of patients in the “late” and “early” arms who received imatinib, 44 percent were able to undergo the allogeneic stem cell transplant. Three-year overall survival was 59 percent for these transplant patients compared with 28 percent for those who did not receive a transplant.

“The Philadelphia chromosome is the single most common chromosome abnormality for adults with ALL, and therefore it is important to know that a targeted therapy like imatinib can help improve outcomes in these patients,” said lead study author Adele K. Fielding, MBBS, PhD, FRCPath, FRCP, Senior Lecturer, University College London. “These study results demonstrate for the first time that there is a long-term survival advantage of being treated with imatinib earlier in the treatment protocol.”


1 The leukemia & Lymphoma Society. Acute Lymphocytic leukemia. Available at: http://www.leukemia-lymphoma.org/attachments/National/br_1164741209.pdf.