Reduced-Toxicity (BuFlu) Conditioning Is Better Tolerated but Has a Higher Second Transplantation Rate Compared to Myeloablative Conditioning (BuCy) in Children with Inherited Metabolic Disorders

Gupta, Ashish; Downey, Michael; Shanley, Ryan; Jennissen, Cathryn; Miller, Weston P.; Lund, Troy C.; Orchard, Paul J.; Smith, Angela R.

doi:10.1016/j.bbmt.2019.11.014

Cited by 12 publications

(19 citation statements)

References 25 publications

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“…Immunosuppressive agents administered early in the transplant process included cyclosporine A, as well as mycophenolate mofetil, methotrexate, or corticosteroids, all used on a short-term basis. 5 , 10 The cyclosporine was routinely tapered beginning 6 months after transplantation, with tapering of immunosuppression complete by 9 months post-transplantation.…”

Section: Methodsmentioning

confidence: 99%

Neurocognitive benchmarks following transplant for emerging cerebral adrenoleukodystrophy

et al. 2020

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ObjectiveTo quantify benchmark treatment outcomes that may be enabled by newborn screening surveillance for X-linked adrenoleukodystrophy (ALD), we report neurocognitive, neuropsychiatric, and MRI change for boys who underwent hematopoietic stem cell transplant (HSCT) at initial stages of demyelination, prior to neurocognitive signs of disease.MethodsRetrospective chart review identified 36 patients whose cerebral ALD was detected and treated early, with lesion severity less than 5 on the ALD-specific MRI scoring system. Median age at transplant was 7.3 years (range, 4.0–16.1). Progression of radiologic disease on MRI in the 2 years following HSCT was examined relative to the severity of the initial lesion for 33 patients, and longitudinal neurocognitive and neuropsychiatric outcomes were studied for 30 patients.ResultsPatients whose pretransplant lesion extended beyond the splenium of the corpus callosum and adjacent periventricular white matter (MRI severity score >2) demonstrated lower posttransplant neurocognitive scores, more neuropsychiatric symptoms, and more disease progression on MRI than patients with a less severe lesion. Changes from baseline neurocognitive functioning were greater at 2 years posttransplant as compared to 1 year. There was greater variance and risk of lesion progression as pretransplant MRI severity increased.ConclusionTo realize the full benefits of newborn screening, clinicians must detect very small demyelinating lesions during surveillance and intervene quickly. Novel interventions that reduce risks inherent in allogeneic transplantation are needed. Trial endpoints should include direct neurocognitive assessment and extend at least 2 years posttreatment to provide the greatest sensitivity to detect neurocognitive morbidity.

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Section: Methodsmentioning

confidence: 99%

Neurocognitive benchmarks following transplant for emerging cerebral adrenoleukodystrophy

et al. 2020

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“…A well-established alkylating agent, cyclophosphamide has maintained its role in HSCT due to its highly immunosuppressive properties and the relative resistance of hematopoietic stem cells to this agent even the highest doses (8,10,11). Recent studies have utilized cyclophosphamide post graft infusion to improve the outcomes of haploidentical transplant procedures (12)(13)(14).…”

Section: Cyclophosphamidementioning

confidence: 99%

“…One of the first agents to be utilized in non-TBI containing preparative regimens, the establishment of pharmacokinetic modeling to project optimal dosing for this drug has reduced rejections and hepatotoxicity (8,10,11,15). Seizures, a common complication of this agent has been minimized with prophylactic anti-epileptic drugs.…”

Section: Busulfanmentioning

confidence: 99%

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Considerations in Preparative Regimen Selection to Minimize Rejection in Pediatric Hematopoietic Transplantation in Non-Malignant Diseases

Hayashi

2020

Front. Immunol.

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The variables that influence the selection of a preparative regimen for a pediatric hematopoietic stem cell transplant procedure encompasses many issues. When one considers this procedure for non-malignant diseases, components in a preparative regimen that were historically developed to reduce malignant tumor burden may be unnecessary. The primary goal of the procedure in this instance becomes engraftment with the establishment of normal hematopoiesis and a normal immune system. Overcoming rejection becomes the primary priority, but pursuit of this goal cannot neglect organ toxicity, or post-transplant morbidity such as graft-versus-host disease or life threatening infections. With the improvements in supportive care, newborn screening techniques for early disease detection, and the expansion of viable donor sources, we have reached a stage where hematopoietic stem cell transplantation can be considered for virtually any patient with a hematopoietic based disease. Advancing preparative regiments that minimize rejection and transplant related toxicity will thus dictate to what extent this medical technology is fully utilized. This mini-review will provide an overview of the origins of conditioning regimens for transplantation and how agents and techniques have evolved to make hematopoietic stem cell transplantation a viable option for children with non-malignant diseases of the hematopoietic system. We will summarize the current state of this facet of the transplant procedure and describe the considerations that come into play in selecting a particular preparative regimen. Decisions within this realm must tailor the treatment to the primary disease condition to ideally achieve an optimal outcome. Finally, we will project forward where advances are needed to overcome the persistent engraftment obstacles that currently limit the utilization of transplantation for haematopoietically based diseases in children.

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“…Furthermore, there are no clear guidelines on the diagnosis and management of IMC after transplantation. Since IMD itself appears to be an independent risk factor for IMC or has a relatively higher incidence of IMC [10][11][12][13][14], a multinational panel of physician experts in the treatment of IMD was convened, with the primary aim to identify the strategies for effective and timely diagnosis and develop a management strategy for IMC in this patient population. The panel included experts in HCT for IMDs from centers with experience in treating these disorders as well experts in nonmalignant disorders and transplant immunology.…”

Section: Introductionmentioning

confidence: 99%

Consensus opinion on immune-mediated cytopenias after hematopoietic cell transplant for inherited metabolic disorders

Gupta

Boelens

Ebens

et al. 2021

Bone Marrow Transplant

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Reduced-Toxicity (BuFlu) Conditioning Is Better Tolerated but Has a Higher Second Transplantation Rate Compared to Myeloablative Conditioning (BuCy) in Children with Inherited Metabolic Disorders

Cited by 12 publications

References 25 publications

Neurocognitive benchmarks following transplant for emerging cerebral adrenoleukodystrophy

Neurocognitive benchmarks following transplant for emerging cerebral adrenoleukodystrophy

Considerations in Preparative Regimen Selection to Minimize Rejection in Pediatric Hematopoietic Transplantation in Non-Malignant Diseases

Consensus opinion on immune-mediated cytopenias after hematopoietic cell transplant for inherited metabolic disorders

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