J. Kapelushnik et al., Fludarabine-based protocol for haploidentical peripheral blood stem cell transplantation in Hurler syndrome, J PED H ONC, 22(5), 2000, pp. 433-436
To assess the feasibility of performing a haploidentical peripheral blood s
tem cell transplantation (PBSCT) in a child with Hurler syndrome after a no
vel conditioning regimen consisting of fludarabine monophosphate, anti-T-ly
mphocyte,globulin, low-dose busulfan, and single-dose total body irradiatio
n of 750 cGy. A 16-month old boy with Hurler syndrome underwent haploidenti
cal PBSCT from his 3/6 HLA-matched sister. Pretransplant conditioning consi
sted of fludarabine (30 mg/m(2) per day) from day -10 to day -5, busulfan (
4 mg/kg per day) on days -7 and -6, rabbit anti-T-lymphocyte globulin(10 mg
/kg per day) from day -4 to day -1, and total body irradiation of 750 cGy o
n day -1. In vitro T-cell depletion was carried out with rat antihuman CDw5
2 monoclonal antibody (Campath-1G). The fludarabine-based protocol was well
-tolerated, with mild toxicity and no major transplant-related complication
s or graft-versus-host disease. Engraftment was complete and stable. Chimer
ism was 100% donor origin, as determined by restriction fragment length pol
ymorphism. Cytogenetic and polymerase chain reaction-various number of tand
em repeats (PCR-VNTR) analyses of peripheral blood and bone marrow showed 1
00% reconstitution with female donor cells. The patient underwent the trans
plant 30 months ago and is in good clinical condition, with normal counts,
no signs of graft-versus-host disease, and no infectious episodes; neurolog
ic signs have stabilized. Haploidentical PBSCT, T-cell-depleted by means of
Campath-1G, may serve as a therapeutic alternative for patients with Hurle
r syndrome when a fully matched sibling is not available.