Unmanipulated HLA-haploidentical bone marrow transplantation for the treatment of fatal, nonmalignant diseases in children and adolescents.
Fetomaternal microchimerism has been demonstrated, and immunologic tolerance to unshared HLA antigens between mother and offspring may be suggested. We used T-cell-repleted bone marrow transplantation (BMT) from their HLA-haploidentical mothers to treat 6 patients with fatal nonmalignant diseases. The number of mismatched HLA loci in the graft-versus-host disease (GVHD) direction was 3 in 4 patients and 2 in 2 patients. The number in the host-versus-graft direction was 3 in 4 patients, 2 in 1 patient, and 1 in 1 patient. Microchimerism of inherited paternal antigens was demonstrated in 5 donors, and microchimerism of noninherited maternal antigens was detected in 3 recipients. GVHD prophylaxis consisted of short-course methotrexate, tacrolimus, and mycophenolate mofetil (3 patients) or short-course methotrexate, tacrolimus, and methylprednisolone (1 patient). Engraftment was achieved in 5 patients who had received preconditioning, and T-cell engraftment was confirmed in 1 patient with severe combined immunodeficiency. Acute GVHD developed in 3 patients: grade 1 in 2 patients and grade 2 in 1 patient. Chronic GVHD was observed in 5 patients: localized type in 3 patients and extended type in 2 patients. Five patients were alive 11 to 30 months after BMT and 1 patient died of chronic GVHD. Unmanipulated haploidentical BMT from a maternal donor may be the treatment of choice of poor-prognosis nonmalignant diseases.
Specialized Clinical Science, Pediatrics, Tokai University School of Medicine, Shimokasuya, Isehara, Japan. yabeh@is.icc.u-tokai.ac.jp
Hiromasa
H
Yabe
Hiroyasu
H
Inoue
Masae
M
Matsumoto
Satoshi
S
Hamanoue
Aiko
A
Hiroi
Takashi
T
Koike
Masahiro
M
Sako
Mitsuhiro
M
Fujiwara
Yasunori
Y
Ueda
Etsuko
E
Maruya
Hiroh
H
Saji
Shunichi
S
Kato
Miharu
M
Yabe
D000015:Abnormalities, Multiple / Q000628:therapy; D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000628:therapy; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002678:Chimera; D005199:Fanconi Anemia / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D006238:Haploidy; D006650:Histocompatibility Testing; D006801:Humans; D007231:Infant, Newborn; D007239:Infections / Q000209:etiology; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D008363:alpha-Mannosidosis / Q000628:therapy*