Reticular dysgenesis: HLA non-identical bone marrow transplants in a series of 10 patients

Abstract

Summary:Reticular dysgenesis is a very rare congenital immunodeficiency classified within the severe combined immunodeficiencies (SCID) and characterized by impairment of both lymphoid and myeloid cell development. We report our experience in 10 patients with RD, treated between 1979 and 1999 with HLA-haploidentical hematopoietic stem cell transplantation (HSCT). All children but one were symptomatic within the first days of their lives. Five patients required two HSCT. Five patients received conditioning therapy with busulfan (16 mg/kg) and cyclophosphamide. Three of them are alive and well with myeloid and T and B cell lymphoid reconstitution, whereas two patients died (one chronic graftversus-host disease, one pneumonitis). Transplantation without or with other conditioning regimens in the other five cases led to absent or incomplete engraftment and none of these cases survived. These results demonstrate the mandatory need for intensive conditioning before haploidentical HSCT in RD to achieve full lymphoid and myeloid engraftment.

Successful cord blood transplantation in a premature and dysmature neonate of 1700 g with reticular dysgenesis

“…There is only limited experience with SCT for RD, but the published cases favour the use of a myeloablative conditioning regimen prior to SCT. 7 Our patient is different from the patients described so far because she was extremely premature and dysmature at diagnosis. For this reason, we chose a reduced-intensity conditioning regimen using (1) treosulfan instead of busulfan, which is known for its toxic effects on liver and nervous system and (2) fludarabine instead of cyclophosphamide.…”

“…6 From the small number of cases described, it can be concluded that the use of a myeloablative conditioning regime before SCT is necessary for sustained stable engraftment. 7 Here, we describe a case of a premature and dysmature infant, weighing 1700 g at first SCT, with RD undergoing successful unrelated cord blood transplantation.…”

“…It was not observed in the follow-up of (only 4) patients successfully treated so far. 6,7 As our patient has a very rare disease and had two consecutive SCTs, the long-term follow-up, especially for late term effects, is essential. This is the first report on successful SCT for RD in a premature and dysmature neonate.…”

Hematopoietic stem cell transplantation for primary immunodeficiency disease

“…Bertrand et al 4 reported that their best outcomes follow a reduced intensity regimen utilizing 8 mg/kg of busulfan plus 200 mg/kg of cyclophosphamide, however other groups have reported that 8 mg/kg of busulfan is not sufficient to obtain myeloid chimerism. 24,28 Table 3 summarizes the survival rates in recent reports that indicate the type of conditioning regimen administered based on the stem cell source utilized.…”

“…Given the more global nature of the defect, it is not surprising that HSCT without conditioning results in treatment failure, while myeloablative conditioning can be successful. 28 For those patients requiring conditioning, the ideal regimen has not been defined. Many groups utilize a conventional 16 mg/kg of busulfan plus 200 mg/kg of cyclophosphamide.…”