HSCT for Fanconi anemia in children: factors that influence early and late results

Abstract

Fanconi anemia (FA) is a rare autosomal recessive disease characterized by congenital abnormalities, cancer predisposition and progressive BM failure. FA patients present spontaneous and induced chromosome breakage. Hematopoietic SCT (HSCT) represents the unique therapeutic option to restore normal hematopoiesis when marrow failure or clonal hematopoietic abnormality occurs. Conventional myeloablative conditioning regimen, especially including a high dose of irradiation, appeared strongly toxic for FA patients. Then, reduced-intensity conditioning regimens were developed successfully for those patients. However, TRM still remained higher than for other HSCT indications. The development of fludarabine containing a non-myeloablative conditioning regimen appears to be a major progress. Long-term follow-up is absolutely necessary.

Interleukin-22 Protects Intestinal Stem Cells from Immune-Mediated Tissue Damage and Regulates Sensitivity to Graft versus Host Disease

“…However, specific mechanistic etiologies for the susceptibility of older adults to GVHD are unclear, and acute GVHD susceptibility can be difficult to separate from toxicity due to pre-transplant conditioning (Jagasia et al, 2011). Factors such as DNA repair mechanisms may regulate damage from conditioning (Dalle, 2008), and Indoleamine 2,3-dioxygenase may regulate repair mechanisms as well as immune effects (Jasperson et al, 2008), but specific regulation of GVHD susceptibility remains poorly understood. In our study, host IL-22 deficiency led to increased GVHD morbidity and mortality.…”

Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin

“…Additionally, the enhanced stability and cost-effective production of protein-based immunotoxins compared to radioimmunotherapy may facilitate their widespread use. Finally, as protein-based immunotoxins such as CD45–SAP do not induce DNA damage, they may be better suited to condition pre-malignant Fanconi anemia patients, who are genetically predisposed to be hypersensitive to DNA damaging agents and conventional conditioning 51 .…”

Combined umbilical cord blood and bone marrow transplantation from a sibling in a patient with Fanconi anemia

“…Fanconi anemia (FA) is an inherited rare autosomal recessive aplastic anemia associated with developmental anomalies, for the first time described in 1927 [1][2][3]. The disease more often affects boys (the ratio of boys to girls is 1.2 : 1).…”

“…In 2006, the fourth report of the European Group for Blood and Marrow Transplantation (EBMT) summarized the clinical management of Fanconi anemia [4,5]. Hematopoietic stem cell transplantation from an HLA-matched donor is the only treatment with a curative potential [1][2][3]. Among different options as well umbilical cord blood (CB) stem cells can be transplanted as well.…”

“…Among different options as well umbilical cord blood (CB) stem cells can be transplanted as well. It is always necessary to carry out clinical, hematological and cytogenetic tests to exclude FA in related donors [1][2][3]6]. Impaired DNA repair mechanisms in FA result in excessive toxicities after chemotherapy and FA patients must be prepared for transplantation with an appropriate conditioning regimen [7,8].…”