Table 29Treatment benefits and harms for Gaucher Type I, Niemann-Pick Type B, Krabbe disease, and metachromatic leukodystrophy

DiseaseTreatmentSource, Evidence TypeIndicationsClinical BenefitsClinical Harms
Gaucher Disease Type IERTJmoudiak and Futerman 2005,296
literature review

all cases, as first line therapy


rapid and sustained improvements in anemia for about 90% of pts over 2 year perioda - among pts with bone pain, 52% pain free and 94% report no additional crises after 2 yearsa - hepatomegaly decreased by 30-40% and splenectomy decreased by 50-60%, but liver and spleen remain larger than normal sizea


intravenous catheterization in children can be difficult, causing pain and apprehension in ptsb - infusion-related adverse events can be expected, including nausea, headache, rash, malaise, chest pain, vomiting; most can be managed through slower infusion rates or pretreatment with antihistaminesc

Allogeneic HSCTPeters 2004,270
literature review

recommended for more severe cases


increase in enzyme activity level, though still below normald,e - decrease in liver size, though liver still enlarged, 3-6 months post HSCTd,e,f,g - growth pattern returned to normal by 3 years post HSCTe,f,g - psychological development normalf


1 treatment-related mortality due to aspergillosis reported, out of 6 in case seriesg - 5 of 6 had mild acute GVHDg (- 2 of 2 had grade I acute GVHDf - 1 of 2 developed septicemiaf

Niemann-Pick Disease Type BAllogeneic HSCTPeters 2004,270
literature review

recommended for pts with early severe liver disease or pulmonary symptoms


considered experimental therapy for pts with neurological symptoms


reduction in liver size, though liver still enlargedh,i,j - enzyme level increasedij - interstitial lung disease resolved, though mild restrictive lung disease persistsi,j - 5.5 years post transplant, either stable or improved in cognitive function, verbal skills, performance skills, receptive vocabulary, and expressive vocabularyi - 10 yrs post transplant, pt can perform majority of activities of daily living without assistance, though mild gross motor delay persistsj


acute and chronic GVHDh,I,j - septicemia and pneumonitish - veno-occlusive diseasei - mild to moderate respiratory distressi


deficits in memory, but not known if underlying disease or transplant are responsiblei,j - engraftment decreasing with time, so disease progression continued several yrs post transplant; pt now severely mentally and physically disabledk

Schuchman 2007,306
literature review
Globoid Cell Leukodyst rophy (Krabbe Disease)Allogeneic HSCTPeters 2004,270
literature review

recommended for severe early onset form if disease is diagnosed antenatally, so that HSCT can be performed during neonatal period, prior to onset of symptoms


recommended for late onset form of disease if symptoms are not severe


enzyme activity levels in pts reached donor levels after 1 year post-transplantl - 2 pts with late onset form and neurologic disability: tremors and ataxia resolved by 6 months, motor incoordination resolved by 1 year, and gait dysfunction resolved slowly over 7 years post-transplantl - 3 late onset pts developed normally in: cognition, language, and memoryl - asymptomatic newborns survival better compared to untreated controls (p=0.001) and better than treated symptomatic patients (p=0.01)m - early onset pts with no symptoms prior to transplantation maintained normal vision, hearing, and cognitive development; variable motor function was maintainedm - central nervous system deterioration reversed in 4 out of 4 ptsn


3 of 5 pts had graft-vs.-host disease, grade I-IIl


complications among 25 transplant pts: 17 graft-vs.-host disease grades I-IV, 3 brief episodes of autoimmune hemolytic anemia, 1 catheter-related silent brain infarct, 2 asymptomatic hypertrophic cardiomyopathies, 1 symptomatic hypertrophic cardiomyopathym - treatment-related mortality among 25 transplant pts: 1 GVHD, 1 aspiration pneumonia, 1 adenoviral infection, 1 complication from liver biopsy for GVHDm

Pastores 2009,307
literature review
Metachromatic LeukodystrophyAllogeneic HSCTPeters 2004270,
literature review

not recommended if neuro-psychologic and/or neurologic symptoms are advanced


recommended in pre-symptomatic pts (usually diagnosed early post-natally or prenatally) or pts with good neuropsychologic function


enzyme activity reaches donor levelso,p


no further deterioration of white matter in the brain following transplanto - some mental capabilities preserved (well-developed language, for example), but physical limitations persisted (difficulty with gross and fine motor skills)o


nerve sensory velocities improved from abnormal to normal, 2 years post transplantq - serial MR findings support neuropsychological and neurophysiological tests that show disease stabilization 2-6 years post-transplantr - disease progression halted for over 11 years post-transplant, based on clinical, electrophysiological, and neuroradiological data: wheelchair bound, IQ stable at mild mental retardation, auditory evoked responses stable, nerve conduction velocities stables


3 of 4 pts experienced acute GVHDp; 1 of 2 pts experienced chronic GVHDr - 4 pts with mild to moderate symptoms at time of transplant deteriorated mentally and physically post-HSCTp

Biffi et al. 2008,308
literature review

Weinreb et al. 2002,299 1028 Gaucher I pts, 2-5 yrs followup of ERT


Charrow et al. 2003,297 ERT consensus recommendations for Gaucher type I


Starzyk et al. 2007,300 review of adverse event reports from 1994-2004 for ERT


Chan et al. 1994,302 Gaucher type I case report, 2.8 yrs post HSCT


Yen et al. 1997,304 Gaucher I case report, 3 yrs post HSCT


Ringden et al. 1995,303 case series of 2 Gaucher type I pts, 3-8 yrs post HSCT


Hobbs et al. 1987,305 case series of 6 Gaucher type I pts, 1-3.3 yrs post HSCT


Vellodi et al. 1987,309 Niemann-Pick Type B case report, 9 months post HSCT


Shah et al. 2005,310 Niemann-Pick Type B case report, 5.5 yrs post HSCT


Schneiderman et al. 2007,311 Niemann-Pick Type B case report, 10 yrs post HSCT


Victor et al. 2003,312 Niemann-Pick Type B case report 16 yrs post HSCT


Krivit et al. 1998,313 case series of 5 GLD pts, 1-9 yrs post HSCT


Escolar et al. 2005,314 case series of 25 GLD pts, 11 asymptomatic and 14 symptomatic, 4 months - 6 yrs post HSCT


Kurtzberg et al. 2002,315 case series of 5 GLD pts, 1-9 yrs post HSCT


Krivit et al. 1990,316 MLD case report, 5 yrs post HSCT


Malm et al. 1996,317 case series of 4 MLD pts, 2-3 yrs post HSCT


Pierson et al. 2008,318 case series of 3 MLD siblings, 2 yrs post HSCT


Stillman et al. 1994,319 case series of 2 MLD pts, 2-6 yrs post HSCT


Gorg et al. 2007,320 case report of 1 MLD pt, 13-yrs post HSCT

From: Narrative Reviews

Cover of Hematopoietic Stem-Cell Transplantation in the Pediatric Population
Hematopoietic Stem-Cell Transplantation in the Pediatric Population [Internet].
Comparative Effectiveness Reviews, No. 48.
Ratko TA, Belinson SE, Brown HM, et al.

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