Role of Stem Cell Transplant in Pediatric Cancers

In the June issue of ONCOLOGY, authors McGregor et al did an admirable job of reviewing childhood cancer advances and current issues in their article entitled "Pediatric Cancers in the New Millennium: Dramatic Progress, New Challenges" (21[7]:809-820, 2007). While the review by Arceci points out the notable lack of discussion about acute myelogenous leukemia (AML), another omission of great importance is the role of allogeneic transplant in the progress achieved in pediatric cancer treatment.

Passing mention is made of autologous rescue for Hodgkin's lymphoma, and of multiple autologous transplants in the treatment of neuroblastoma, but allogeneic transplant has played a major role in attaining the cure rates seen for other malignancies presented within the parent article. Allogeneic transplant is indicated for high-risk acute lymphoblastic leukemia (ALL) in the Total 15 protocol used at the authors' institution,[1] and has been moderately successful in treating various forms of chemorefractory leukemias.[2] If we are to improve upon existing outcomes, it will not come about without transplant, and not without giving as much attention to improved transplant methodologies as to the chemotherapeutic agents highlighted in the article.

-Name Withheld by Request

References

1. Pui CH, Evans WE: Treatment of acute lymphoblastic leukemia. N Engl J Med 354:166-178, 2006.

2. Chen X, Hale GA, Barfield R, et al: Rapid immune reconstitution after a reduced-intensity conditioning regimen and a CD3-depleted haploidentical stem cell graft for paediatric refractory haematological malignancies. Br J Haematol 135:524-532, 2006.

The Authors Respond

Dr. Arceci's comment on our review was entirely appropriate. The review was incomplete without a section on childhood AML, and we sincerely regret our oversight. The past 30 years have seen steady progress in understanding the biology of the AML stem cell, identifying factors associated with poor outcome, tailoring treatment to clinical and biologic features, optimizing the use of standard chemotherapeutic agents such as cytarabine, improving supportive care, and assessing the clinical benefits of stem cell transplantation (SCT) for children with AML. However, AML remains a therapeutic challenge-less than half of children with AML are cured of their disease.[1]

We also recognize that SCT is undoubtedly an effective curative therapy for certain hematologic malignancies such as AML and myelodysplastic syndrome, and for selected cases of acute lymphoblastic leukemia.[2] The selection of transplant candidates with childhood ALL and the optimal source of stem cells continue to evolve, especially in view of the increasing availability of targeted therapies.[3] For example, the role of SCT for children with Philadelphia chromosome–positive ALL is becoming less clear since the introduction of the signal transduction inhibitor imatinib (Gleevec).[4]

We should note that while the role of autologous and allogeneic SCT in childhood cancer is an interesting and deserving topic, our review was intended as a disease-focused discussion of progress and challenges rather than a comprehensive examination of specific therapeutic interventions. When appropriate, we briefly mentioned interventions such as surgery, radiation, or stem cell transplantation in the context of the progress and challenges of treating specific disease types. Exploratory pilot trials of innovative SCT approaches are promising and exciting, but their benefits have yet to be defined in the context of well designed and controlled clinical trials.

LISA M. MCGREGOR, MD, PhD
MONIKA L. METZGER, MD
ROBERT P. SANDERS, MD
VICTOR M. SANTANA, MD
St. Jude Children's Research Hospital and
University of Tennessee Health Science Center
College of Medicine
Memphis, Tennessee

References:

1. Meshinchi S, Arceci RJ: Prognostic factors and risk-based therapy in pediatric acute myeloid leukemia. Oncologist 12:341-355, 2007.

2. Miano M, Labopin M, Hartmann O, et al: Haematopoietic stem cell transplantation trends in children over the last three decades: A survey by the pediatric diseases working party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 39:89-99, 2007.

3. Hahn T, Wall D, Camitta B, et al: The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in children: An evidence-based review. Biol Blood Marrow Transplant 11:823-861, 2005.

4. Jones LK, Saha V: Philadelphia positive acute lymphoblastic leukemia of childhood. Br J Haematol 130:489-500, 2005.