Hematopoietic Stem Cell Transplantation for Adults with Acute Lymphoblastic Leukemia

A Special Authors Introduction by Zuckerman and Rowe

The estimated number of new patients with acute lymphoblastic leukemia (ALL) in 2009 in the USA is 5,760, of which about 40 % are adults > age 20. Among pediatric patients a cure rate in the range of 80-90% is now within reach. In contrast, in adult patients, although a complete remission rate of 90% is achievable following induction therapy, most patients will relapse and the long term leukemia free survival is only in the range of 30-40%. In patients older than 60 years the data are even more devastating with a long term remission rate of only 5-10%.

A potent anti-leukemic approach is achieved by performing allogeneic stem cell transplantation which introduces not only high dose chemotherapy but also the very potent graft-versus-leukemia effect. However, this is offset by significant treatment related mortality which may abrogate the benefit of transplant.

The last few years have witnessed a risk adapted approach to the treatment of adults with ALL trough better understanding of the key factors in the decision making in the treatment of these patients. These include new molecular markers conferring different prognosis and other parameters such as epigenetic changes leading to silencing of important genes preventing leukemia development and incorporating the determination of minimal residual disease at different time points as a prognostic factor. In addition, the adoption of pediatric aggressive protocols to adults may have improved the outcome in young adults.

Results of prospective randomized trials have a major role in directing patient management. The international collaboration between the ECOG in the USA and MRC in the United Kingdom (the ECOG 2993 /MRC UKALL XII study) has yielded a large prospective database which for the first time was able to demonstrate that allogeneic stem cell transplantation is superior to conventional chemotherapy in standard risk ALL in first complete remission. In addition, it has shown no benefit of autologous transplantation. One other most important observation is that patients who relapse have a dismal prognosis and hence patients should be offered the best anti-leukemic treatment in first remission.

Recent information regarding the use of alternative donor transplantation (for example, matched unrelated donors, cord blood or haploidentical donors) for patients lacking a matched sibling show promising results with a long term survival approaching that of matched related donor transplant. The use of reduced intensity transplant may be one of the most important therapeutic advances in ALL, enabling older and sicker patients the opportunity of this modality. Finally, no less important, the incorporation of tyrosine kinase inhibitors in the treatment of Ph positive ALL has shown encouraging results and has altered the standard of care, especially among older B-lineage patients with this genetic abnormality.

This Article was published in Current Opinion in Hematology
The Full Article is available in the Registered Area