Transplantation of allogeneic CD34-selected stem cells after fludarabine-based conditioning regimen for children with mucopolysaccharidosis 1H (M. Hurler)

Abstract

Summary:Hurler syndrome (MPS1H) is a progressive inborn error of mucopolysaccharide metabolism leading to premature death. Allogeneic hematopoietic cell transplantation (HCT) can achieve stabilization and improve long-term survival. However, large studies have shown that preparative regimen-related toxicity (RRT) and graft failure rates have been relatively high. We transplanted five Hurler children with a fludarabine-based conditioning regimen, consisting of fludarabine/busulphan/ATG for matched family donor (MFD), with the addition of melphalan for mismatched family donor and matched unrelated donor (MUD) transplantations. Median age at HCT was 27 months (range 10-36). The source of stem cells was bone marrow in one MFD and CD34-selected PBSC in four patients. Median CD34 þ cell dose was 25 Â 10 6 /kg (range 11.5-54). No RRT 4grade II was observed. All patients are surviving at a median of 32 months (range 14-41) and show sustained donor engraftment with 3/5 having full donor chimerism, and 2/5 mixed chimerism (485%). We conclude that this regimen is feasible and has low toxicity in Hurler children. In combination with high doses of CD34 þ selected cells (410 Â 10 6 /kg) and donor lymphocyte infusions, stable engraftment could be achieved in unrelated and mismatched related transplantations. Bone Marrow Transplantation (2005) 35, 265-269.

Developmental outcome in five children with Hurler syndrome after stem cell transplantation: a pilot study

“…6 After a mean follow-up time of 43.6 months (range 32-59mo), all of our children showed progression of psychomotor development. Similarly to the findings of Staba et al, 13 we observed a more pronounced increase of psychomotor skills with a latency of several months after SCT.…”

“…The SCT relevant details have been communicated elsewhere. 6 Informed consent was obtained from the parents for the publication of case details.…”

“…Using a new regimen consisting of a combination of fludarabine, intravenous busulphan, and anti-thymocyte globulin, we found a sustained engraftment after allogeneic SCT but only limited RRT. 6 The aim of this study was to assess the developmental outcome of the first five children with MPS1H treated with this new regimen. In addition, we evaluated neuroradiological findings and head circumference measurements before and after SCT.…”

Allogeneic blood SCT for children with Hurler's syndrome: results from the German multicenter approach MPS-HCT 2005

“…6 As a phase 2 study, the protocol was approved by the institutional review board and then distributed to other German centers willing to transplant children with inborn errors of metabolism. A total of 12 consecutive children were enrolled.…”

Hematopoietic stem cell transplantation in patients with Hurler syndrome – myeloablative conditioning efficiency

“…Кроме того, в большинстве протоколов циклофосфамид заменен на флударабин с целью снижения токсичности, а для дополнительной миелоаблации (учитывая высокий потенциал отторже-ния) в терапию был добавлен мелфалан. Мелфалан и флударабин, в свою очередь, не обладают кардиоток-сичностью [11].…”