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
a

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

b

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

c

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

d

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

e

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

f

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

g

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

h

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

i

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

j

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

k

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

l

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

m

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

n

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

o

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

p

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

q

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

r

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

s

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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