Non-myeloablative hematopoietic cell transplant for treatment of nonmalignant disorders in children

Abstract

Hematopoietic stem cell transplantation (HCT) may offer the only curative therapy for certain life-threatening immune deficiency disorders. Conventional HCT poses a risk to patients for severe morbidity, mortality, and late sequelae resulting from myeloablative preparative regimens. This review summarizes the development of nonmyeloablative regimens that have the potential to reduce both short- and long-term risks of HCT. Results of NM-HCT in a small number of patients indicate that this procedure may play an important role in treatment of life-threatening immune deficiencies.

HEMATOPOIETIC CELL TRANSPLANTATION: A Curative Option for Sickle Cell Disease

“…Sustained engraftment and alleviation of clinical phenotype has been reported in patients with SCD and thalassemia with reduced intensity conditioning regimen [25][26][27][28][29][30]. HCTs using NMA regimens, although well tolerated, have generally not resulted in stable engraftment [31][32][33].…”

Primary immunodeficiency diseases

“…48 Regimens with 'reduced toxicity' (Fig. Recent reports have suggested that non-myeloablative (NM) SCT may be a suitable alternative to achieve stable engraftment of immunocompetent donor cells with reduced procedure-related morbidity and mortality.…”

Successful nonmyeloablative bone marrow transplantation in a corticosteroid-resistant infant with Diamond–Blackfan anemia

“…Nonmyeloablative BMT is likely to be safer in terms of long-term outcome and complications, although this remains to be demonstrated. 2,8 Our experience suggests that this approach is a safe alternative method for achieving hematopoietic chimerism in selected patients with DBA. …”

“…[1][2][3][4] Diamond-Blackfan anemia (DBA) is a childhood disorder characterized by normochromic-macrocytic anemia, reticulocytopenia and normocellular bone marrow with a selective deficiency of erythroid progenitors. 5 Most patients initially respond to corticosteroids, but about 60% of patients require chronic red cell transfusions and die from hemosiderosis in the second or third decade of life.…”

“…6,7 A conditioning regimen based on fludarabine and low-dose TBI (2 Gy) permits engraftment and full donor chimerism in both malignant and nonmalignant diseases, and can potentially avoid complications such as retarded growth and development, cataract formation and sterility in children. 2,8 We chose this regimen for a transfusion-dependent, 19-month-old boy with DBA.…”