Article

Reduced intensity and non-myeloablative allogeneic stem cell transplantation in children and adolescents with malignant and non-malignant diseases.

Department of Pediatrics, Columbia University, New York, New York, USA.
Pediatric Blood & Cancer (Impact Factor: 2.35). 02/2008; 50(1):1-8. DOI: 10.1002/pbc.21303
Source: PubMed

ABSTRACT Allogeneic hematopoietic stem cell transplant (AlloSCT) from related or unrelated histocompatible donors has been well established as potentially curative therapy for children and adolescents with selected malignant and non-malignant diseases. In the malignant setting non-myeloablative (NMA)/reduced intensity (RI)-AlloSCT eradicates malignant cells through a graft versus malignancy effect provided by alloreactive donor T-lymphocytes and/or natural killer cells. In patients with non-malignant diseases NMA/RI AlloSCT provides enough immunosuppression to promote engraftment and correct underlying genetic defects. In children, myeloablative AlloSCT is not only associated with acute short-term toxicities but also long-term late complications such as growth retardation, infertility, and secondary malignancies. NMA/RI-AlloSCT in children may be associated with reduction in use of blood products, risk of infections, transplant-related mortality, and length of hospitalization. Despite the success of RI-AlloSCT in adults, large prospective and/or randomized multicenter studies are necessary in children and adolescent recipients to define the appropriate patient population, optimal conditioning regimens, cost-benefits, survival and differences in short-term and long-term effects compared to conventional myeloablative conditioning.

0 Bookmarks
 · 
82 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Conventional myeloablative conditioning (MAC) regimens often cause severe regimen-related toxicity (RRT). Furthermore, many patients suffer from poor quality of life in accordance with the increase in long-term survivors. We therefore devised a reduced-toxicity myeloablative conditioning (RTMAC) regimen consisting of 8-Gy total body irradiation (TBI), fludarabine (FLU) and cyclophosphamide (CY) for pediatric hematological malignancies. A retrospective single-center analysis was performed on patients with leukemia or myelodysplastic syndrome (MDS), aged ≤20 years, who had received an 8-Gy TBI/FLU/CY RTMAC regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thirty-one patients underwent first allo-HSCT after an RTMAC regimen. The diagnoses were acute lymphoblastic leukemia (n = 11), acute myeloid leukemia (n = 13), MDS (n = 4), juvenile myelomonocytic leukemia (n = 1) and acute leukemias of ambiguous lineage (n = 2). While 3 patients showed early hematological relapse, the remaining 28 patients achieved engraftments. None of the patients developed grade 4 or 5 toxicities during the study period. The 5-year overall survival and relapse-free survival were 80% [95% confidence interval: CI, 61-91%] and 71% [95% CI, 52-84%], respectively. Our RTMAC regimen would be less toxic and offers a high probability of survival for children with hematological malignancies.
    Scientific reports. 01/2014; 4:6942.
  • [Show abstract] [Hide abstract]
    ABSTRACT: With continuing improvements in the successful treatment of pediatric malignancies, long term survivors of pediatric cancers and their providers are faced with new oncologic issues regarding long-term morbidities. As pediatric cancer survivors have matured into adulthood, the development of secondary malignancies has become a significant issue for these patients. Whether a consequence of treatment for the patient's original cancer, such as chemotherapy, ionizing radiation, or hematopoietic stem cell transplantation, secondary malignancies now present patients and providers with new challenges regarding treatment, surveillance and counseling. We review the major risk factors for secondary malignancies in pediatric cancer survivors, with particular emphasis on important molecular and cytogenetic risk factors, both inherited and acquired. We conclude with a discussion of recommendations for surveillance and counseling of these patients.
    International Journal of Cancer 06/2014; · 6.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BU and CY (BU/CY; 200 mg/kg) before HLA-matched sibling allo-SCT in children with sickle cell disease (SCD) is associated with ~85% EFS but is limited by the acute and late effects of BU/CY myeloablative conditioning. Alternatives include reduced toxicity but more immunosuppressive conditioning. We investigated in a prospective single institutional study, the safety and efficacy of a reduced-toxicity conditioning (RTC) regimen of BU 12.8-16 mg/kg, fludarabine 180 mg/m(2), alemtuzumab 54 mg/m(2) (BFA) before HLA-matched sibling donor transplantation in pediatric recipients with symptomatic SCD. Eighteen patients, median age 8.9 years (2.3-20.2), M/F 15/3, 15 sibling BM and 3 sibling cord blood (CB) were transplanted. Mean whole blood and erythroid donor chimerism was 91% and 88%, at days +100 and +365, respectively. Probability of grade II-IV acute GVHD was 17%. Two-year EFS and OS were both 100%. Neurological, pulmonary and cardiovascular function were stable or improved at 2 years. BFA RTC and HLA-matched sibling BM and CB allo-SCT in pediatric recipients result in excellent EFS, long-term donor chimerism, low incidence of GVHD and stable/improved organ function.Bone Marrow Transplantation advance online publication, 5 May 2014; doi:10.1038/bmt.2014.84.
    Bone marrow transplantation 05/2014; · 3.00 Impact Factor

Full-text

Download
0 Downloads