Outcomes of haematopoietic stem cell transplantation for inherited metabolic disorders: A report from the Australian and New Zealand Children's Haematology Oncology Group and the Australasian Bone Marrow Transplant Recipient Registry

Abstract

We report a retrospective analysis of 53 haematopoietic stem cell transplants for inherited metabolic disorders performed at ANZCHOG transplant centres between 1992 and 2008. Indications for transplant included Hurler syndrome, ALD, and MLD. The majority of transplants utilized unrelated donor stem cells (66%) with 65% of those being unrelated cord blood. Conditioning therapy was largely myeloablative, with Bu plus another cytotoxic agent used in 89% of recipients. Primary graft failure was rare, occurring in three patients, all of whom remain long-term survivors following the second transplant. The CI of grade II-IV and grade III-IV acute GVHD at day +100 was 39% and 14%, respectively. Chronic GVHD occurred in 17% of recipients. TRM was 12% at day +100 and 19% at one yr post-transplant. OS at five yr was 78% for the cohort, 73% for patients with ALD and 83% for patients with Hurler syndrome. There was no statistically significant difference in overall survival between unrelated marrow and unrelated cord blood donor groups. The development of interstitial pneumonitis was an independent variable shown to significantly impact on TRM and OS. In summary, we report a large cohort of patients with inherited metabolic disorders with excellent survival post-allogeneic transplant.

Hematopoietic SCT in Iranian children 1991–2012

“…39 As for patients with IEM, patients in our center had 5-year OS of around 70% compared with 78% in a report from the Australian and New Zealand Children's Haematology Oncology Group. 40 OS for patients with IEM in our center was consistent with findings of other studies. 41,42 In a study of HSCT in pediatric patients with leukemia in Italian centers, probability of survival at 24-month interval for patients with matched sibling donors was between 60 and 70%.…”

Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy

“…Among patients with cerebral adrenoleukodystrophy and other inherited metabolic disorders, allogeneic transplantation has been associated with a 100-day mortality rate of 8%, a 1-year mortality rate of 18%, a rate of graft failure of 6 to 14%, a rate of serious infection of 29%, a rate of acute grade 2, 3, or 4 GVHD of 8 to 45%, and a rate of chronic GVHD of up to 21%. 5,10,22–24 Among patients in our study, who underwent gene therapy with an autologous approach, no GVHD or life-threatening infections were noted.…”

Newborn screening for X-linked adrenoleukodystrophy: evidence summary and advisory committee recommendation

“…HSCT has been reported to slow or even arrest the progression of leukodystrophy, 15–26 but it does not modify the course of adrenal insufficiency or other types of myelopathy and neuropathy.…”

“…However, among studies reporting transplant follow-up at 1 year or later, the overall 1-year risk of mortality following HSCT appears to be approximately 15% or less. 15,19,21–23,27–29 The mortality rate is a function of several factors, including the health of the child at the time of HSCT, the type of transplantation performed, the degree of match between donor and recipient, and the treatment regimen used by those performing the HSCT. Due to lack of data, the Condition Review Workgroup was unable to assess the potential availability of well-matched donors if newborn screening were adopted.…”