Successful reduced‐intensity bone marrow transplantation in a patient with bone marrow failure associated with Seckel syndrome

Abstract

the patient maintains full donor chimaerism with normal blood counts and immune function. This patient's transplant conditioning regimen was designed to limit exposure to agents that may cause adverse effects in children with chromosomal breakage syndromes. Use of alemtuzumab (CAMPATH-1H) and fludarabine provided the required immune suppression, while the lowest considerable dose of the alkylator melphalan was adequate to provide modest myeloablation and to ensure successful engraftment.To our knowledge, this is the first account of a reducedintensity HSCT from an unrelated donor in a patient with Seckel syndrome. One prior report described the use of a conventional transplant regimen in a Seckel syndrome patient (Esperou-Bourdeau et al, 1993). Reduced-intensity HSCT conditioning regimens have been successfully used in other bone marrow failure syndromes (Shenoy et al, 2005; Gruhn et al, 2007) and metabolic disorders (Hansen et al, 2007).Selecting an appropriate conditioning regimen for a child with Seckel syndrome is particularly challenging due to the heterogeneity of the disorder and the lack of prior reports to guide the choice. There is a high likelihood that Seckel syndrome patients will exhibit some degree of increased sensitivity to DNA damaging agents, even with normal mitomycin C or DEB chromosomal breakage studies. The preparative regimen that we selected, with emphasis on immune suppression and minimal use of DNA-damaging agents, is an attractive option for additional children with this disorder, in the absence of an available test to quantify increased sensitivity.

A case of severe growth retardation, probably Seckel syndrome

“…This was not confirmed in 2 arabic patients, who presented no abnormalities during this test (17) or in all three patients from a consanguineous family (18). Hematological abnormalities include pancitopenia or aplastic anemia (19,20), but successful reduced-intensity bone marrow transplantation has been reported (20,21). A case of acute myeloid leukaemia has been described, with unfavorable evolution under treatment (22).…”

Successful outcome of allogeneic stem cell transplantation in Seckel syndrome

“…The literature has reported HSCT as treatment for disorders associated with defective DNA repair; however, it still remains a challenge . In 1993, Esperou‐Bourdeau et al.…”

“…The literature has reported HSCT as treatment for disorders associated with defective DNA repair; however, it still remains a challenge (6,7,12). In 1993, Esperou-Bourdeau et al reported a female with severe growth retardation and microcephaly, Seckel-like facies, and mental deficiency who became pancytopenic at 15 yr of age, presenting with a hypoplastic bone marrow and spontaneous chromosome breakage.…”

“…Reports of hematological disorders in some patients with SCKL, including pancytopenia with hypoplastic marrow, myelodysplasia, and acute myelogenous leukemia, indicate that this disorder may be part of a group of hereditary syndromes with hematological defects and cancer predisposition (6,10,11). As far as we are concerned, only two HSCT in SCKL patients with concomitant hematological diseases have been described (6,7). We report the results of HSCT in one patient with SCKL and aplastic Abbreviations: ATR, ataxia telangiectasia and Rad3 related; CENPJ, centromere protein J; DEB, diepoxybutane; HSCT, hematopoietic stem cell transplants; SCKL, Seckel syndrome; VNTR, variable number tandem repeats.…”

“…There is some likelihood that patients present some degree of increased sensitivity to DNA damaging agents, even with normal mitomycin C or DEB chromosomal breakage evaluations . The syndrome is part of a group of genome instability disorders collectively referred to as DNA damage response and repair defective syndromes .…”