PMID- 7906103
OWN - NLM
STAT- MEDLINE
DCOM- 19940316
LR  - 20071114
IS  - 0192-8562 (Print)
IS  - 0192-8562 (Linking)
VI  - 16
IP  - 1
DP  - 1994 Feb
TI  - In utero hematopoietic stem cell transplants for inherited diseases.
PG  - 35-42
AB  - PURPOSE: The treatment of choice for many inherited diseases is bone marrow 
      transplantation (BMT). Limitations to using marrow transplants for inherited 
      diseases include (a) the toxicity associated with high doses of chemotherapy 
      necessary to obtain engraftment; (b) the complications associated with 
      graft-versus-host disease (GVHD); (c) the fact that only 20-25% of children will 
      have a human leukocyte antigen (HLA)-matched donor; and (d) the concern that, at 
      least for some inherited diseases, significant organ damage, especially to the 
      nervous system, has occurred by the time the child is diagnosed and evaluated for 
      possible BMT. In utero transplantation of hematopoietic stem cells (HSCs) offers 
      the possibility of overcoming many of these limitations. PATIENTS AND METHODS: 
      One of the biggest hurdles to a successful transplant is the ability of the 
      recipient to reject the donor marrow. Except in patients with severe combined 
      immunodeficiency disease (SCID), overcoming this hurdle requires high doses of 
      chemotherapy. Early in gestation, the fetus is significantly immunoincompetent. 
      Before 14-15 weeks of gestation, the human fetus appears to be similar to a child 
      with SCID in its inability to reject allogeneic cells. Potential sources for HSCs 
      are HLA-matched sibling marrow, fetal liver, parental bone marrow, and cord 
      blood. RESULTS: With fetal liver, only cells from fetuses < 10-12 weeks are 
      acceptable because of the high risk of GVHD. With parental marrow, the cells must 
      be T cell depleted in order to minimize the risk for GVHD. Problems in using 
      fetal liver include the inability to obtain sufficient numbers of cells and 
      inadequate supplies of donor tissue. The source and supply of parental bone 
      marrow is almost unlimited, but, because of the need for T-cell depletion, bone 
      marrow from a parent may have a lower engraftment rate in the child. CONCLUSIONS: 
      Studies in fetal murine and Rhesus models using fetal liver or T cell-depleted 
      bone marrow from adult animals suggest that engraftment can be successfully 
      obtained, providing the transplant is performed sufficiently early in gestation. 
      To date, at least a dozen in utero human transplants have been attempted 
      worldwide in fetuses diagnosed with a variety of inherited diseases. Because of 
      the small number of transplanted fetuses and the variety of diseases and 
      differing transplant conditions, it is difficult to draw any firm conclusions 
      regarding ultimate efficacy of the procedure and its risk. However, it does 
      appear that the age of gestation of the recipient, the dose of cells infused, and 
      possibly the route of administration of the HSCs will be critical factors in 
      determining success rates for this approach. The successful application of in 
      utero transplantation would allow treatment of a variety of inherited diseases 
      early in gestation while eliminating many of the risks associated with 
      conventional BMT.
FAU - Cowan, M J
AU  - Cowan MJ
AD  - Department of Pediatrics, University of California, San Francisco 94143-1278.
FAU - Golbus, M
AU  - Golbus M
LA  - eng
GR  - NIAID P01-AI29512/AI/NIAID NIH HHS/United States
GR  - RR01271/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Pediatr Hematol Oncol
JT  - The American journal of pediatric hematology/oncology
JID - 7908071
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation
MH  - Female
MH  - Fetal Diseases/*therapy
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Pregnancy
EDAT- 1994/02/01 00:00
MHDA- 1994/02/01 00:01
CRDT- 1994/02/01 00:00
PHST- 1994/02/01 00:00 [pubmed]
PHST- 1994/02/01 00:01 [medline]
PHST- 1994/02/01 00:00 [entrez]
PST - ppublish
SO  - Am J Pediatr Hematol Oncol. 1994 Feb;16(1):35-42.