Bone marrow transplantation for Fanconi anemia

Abstract

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Should chromosome breakage studies be performed in patients with VACTERL association?

“…Fanconi anemia (FA) is a complex recessive disorder characterized clinically by bone marrow failure leading to pancytopenia, diverse congenital abnormalities, and predisposition to malignancy, particularly acute myelogenous leukemia (AML) [Kutler et al, 2003; Tischkowitz and Hodgson, 2003]. Hematopoietic stem cell transplantation (SCT) is the only current treatment for the hematological complications [Gluckman et al, 1995]. The manifestations of FA are highly variable and include abnormalities in any major organ system.…”

Squamous cell carcinoma development in Fanconi anemia patients who underwent hematopoietic stem cell transplantation

“…Gluckman et al proposed the use of low‐dose CY and a single fraction of TAI (500 cGy) conditioning regimen, leading to markedly to reduced RRT with enhanced survival after related sibling donor HSCT 8 . Later, the use of low‐dose CY and LFI became the standard HCT preparative regimen for FA patients with related donors 15 . However; GVHD still remains a major problem and malignancy is seen as a late complication of HSCT.…”

“…HSCT is the standard treatment for FA patients with BM failure. Various conditioning regimens were used over time for FA patients, to reduced RRT, to reduced the risks of malignancy, GVHD and other late adverse effects with enhanced survival after HSCT 7‐11 . Malignancy is a late complication of HSCT for FA patients with inherently underlying genomic instability defects, the risk of malignancy is 48‐ to 500‐fold higher for FA patients than the non‐FA population 12‐14 …”

Allogeneic haemopoietic stem cell transplantation in children: what alternative donor should we choose when no matched sibling is available?

“…Allogeneic HSCT is the only curative therapy for bone marrow failure associated with Fanconi anaemia (FA). A matched sibling BMT is the recommended first line therapy in such patients, with a probability of overall survival at 2 years of around 70% (Gluckman et al , 1995; Gluckman & Wagner, 2008). FA patients have an inherently increased risk of a range of malignancies (Socie et al , 1998).…”

“…FA patients have an inherently increased risk of a range of malignancies (Socie et al , 1998). This is exacerbated in the context of HSCT, with the use of TBI and acute and chronic GVHD being important risk factors (Gluckman et al , 1995; Rosenberg et al , 2005).…”