The Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Therapy of Acute Myeloid Leukemia in Children: An Evidence-Based Review

Abstract

Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in the therapy of acute myeloid leukemia (AML) in children is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented in the table entitled "Summary of Treatment Recommendations Made by the Expert Panel for Pediatric Acute Myeloid Leukemia" and were reached unanimously by a panel of experts in AML. The identified priority areas of needed future research in pediatric AML include: What is the role of risk group stratification, including the role of cytogenetics, in selection of patients for allogeneic SCT, especially those in first CR? What is the appropriate timing and use of alternative donor SCT, given that matched unrelated donor SCT appears to yield outcomes equivalent to matched related donor SCT? What is the role of reduced intensity SCT (including the use of fludarabine-based preparative regimens) and/or other immunomodulatory approaches to maximize the graft-versus-leukemic effect? and What is the role of biologically targeted agents (ie, tyrosine kinase inhibitors, farnesyl transferase inhibitors, Flt-3 inhibitors, etc) in the treatment of AML, including induction, consolidation, conditioning regimens, and after SCT?

Are there roles for observational database studies and structured quantification of expert opinion to answer therapy controversies in transplants?

“…Examples include expert panels from the National Cancer Center Network (NCCN), American Society of Blood and Marrow Transplantation (ASBMT). [60][61][62][63][64][65] These panels performed structured evidence-based reviews and made consensus recommendations of graded strength. 20 Mechanisms of panel selection and process for quantifying consensus were not specified.…”

Place of HSCT in treatment of childhood AML

“…However, most experts in this field would prefer as post-remission treatment allogeneic HSCT in particular in early (o1 year after diagnosis) relapse. 1 For evaluating the role of haploHSCT and of unrelated cord blood as stem cell source for the treatment of AML, too few data are available. For the future, controlled studies in this field are needed.…”

“…For more details there are excellent overviews such as the recently published systematic review of the American Society of Blood and Marrow Transplantation. 1 It is a challenge for the responsible physician to select for each patient the best post-remission treatment applicable in the particular patient's situation.…”

Hematopoietic Stem Cells Therapeutic Applications

“…In addition, HSCT is also not indicated for acute promyelocytic leukemia (APL) due to excellent cure rates with conventional chemotherapy. However, for the few patients with APL who relapse or have persistent minimal residual disease, the prognosis is less favorable and HSCT might be a recommended choice (Oliansky et al, 2007). Allogeneic-HSCT from an HLA-identical sibling is an option for patients defined as intermediate risk.…”

“…The American society of bone marrow transplant position statement for the treatment of AML in children indicates that allogeneic HSCT should be recommended in the first complete remission because transplant has better overall survival and leukemia-free survival compared with chemotherapy alone (ASBMT, 2007;Oliansky, 2007). However, the role of allogeneic-HSCT in complete remission one (CR1) is declining because of the better outcome with modern multiagent chemotherapy and better methods of identifying patients that have low risk features at diagnosis and therefore are more likely to be cured with conventional chemotherapy.…”