**1. Introduction**

Hematopoietic stem cell transplantation (HSCT) has become an established treatment for malignant hematological diseases, solid malignancies and non-malignant diseases **(**figure 1). Newer indications for HSCT have emerged because of better understanding of human immunology, tumor biology and immunotherapy (table 1). Novel approaches have resulted in increase number of transplants as well as significant reductions in the morbidity and mortality associated with HSCT. These include more suitable donors with the addition of unrelated cord blood units (single & double) and partially matched family members; and novel conditioning regimens (reduced & non-myeloablative) that allow patients with significant co-morbidities to undergo transplantation. On the other hand, the introduction of alternative therapies, such as imatinib (tyrosine kinase inhibitor) for chronic myelogenous leukemia (CML), has challenged well established indications. This chapter summarizes the current indications for HSCT in pediatrics and address recent clinical developments in the field of HSCT.

Fig. 1. Indications for HSCT

Hematopoietic Stem Cells Therapeutic Applications 349

Despite intensive chemotherapy, less than half of all patients with AML will survive in the long term (Creutzin, 2005; Gibson, 2005). Treatment outcome of pediatric AML is not as favorable as in ALL. AML treatment failure is due primarily to disease recurrence, although treatmentrelated mortality remains an important cause of treatment failure. Improvement in AML outcomes have been due primarily to intensification of therapy and improved supportive care guidelines. In AML, treatment intensity is an important determinator of outcome, and many studies have focused on the role of HSCT as post-remission intensification, utilizing both autologous as well as allogeneic HSCT. Allogeneic HSCT may provide a graft versus leukemia effect in pediatric AML. This is supported by a study from Bader et al that showed that preemptive immunotherapy following HSCT in patients with increasing (mixed chimerism) may lead to improved outcome. In another study Neudorf et al reported that children treated with allogeneic-HSCT in the children's cancer group 2891 study who developed acute graft

versus host disease (GVHD) had fewer relapses (Bader, 2004; Neudorf et al., 2004).

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. Recent AML trials (MRC-AML-12 & AML 0531) have shown that prognostic factors like cytogenetic and response to induction therapy are highly predictive of determining patients that are high risk at diagnosis and therefore would benefit from allogeneic-HSCT in CR1, while sparing lower risk patients the potential toxicities associated with an allogeneic-

Fig. 2. Major Key Steps of HSCT.

**2.1.1 Acute myeloid leukemia (AML)** 

**2.1 Leukemias** 


Abbreviations: ALL= acute lymphoblastic leukemia; AML= acute myeloblastic leukemia; CML= chronic myeloid leukemia; CR1, 2, 3= first, second and third complete remission; SCID= severe combined immunodeficiency.

aPatients at high risk of recurrence (that is, t (9; 22) or t (4; 11); T-ALL with poor prednisone response, high levels of minimal residual disease).

bStage IV neuroblastoma, renal cell carcinoma, very high risk Ewing sarcoma.

Table 1. Main Indications to allogeneic hematopoietic SCT in childhood
