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Haematopoietic Stem Cell Transplantation (HSCT) in children

Dr. Li Chi-Kong

January 2008

The principle of HSCT in children is same as adult HSCT, however the disease spectrum and the choice of stem cells is quite different from adult patients. Children are not mini-adults and attaining normal growth and development after HSCT is of great concern to paediatric transplanters. Since the number of children receiving HSCT is still far less than that of adults, paediatric transplant units always have to learn from the experience of adult colleagues especially on the management of complications.

Diseases requiring HSCT in children

Haematological malignancy is the number one indication for HSCT in children. Acute leukaemia constitutes about 35% of all childhood cancer and chronic leukaemia is much less commonly encountered. Among acute leukaemia, about 75-80% of the cases are acute lymphoblastic leukaemia (ALL). The cure rate of ALL with chemotherapy is now approaching 80%, and thus HSCT, especially unrelated donor transplant, is not the first line treatment for ALL children. However those who relapsed are always having resistant diseases and HSCT offers better chance of cure. Some high risk ALL such as Philadelphia chromosome positive have <30% chance of cure by chemotherapy and they may benefit from earlier transplant before they relapse. ALL is the commonest indication of transplantation in most paediatric transplant units. The long term disease free survival for Acute myeloid leukaemia after chemotherapy is now approaching 50%. The indication for HSCT during first remission is also getting more strict and only limited to those with high risk features. The chance of cure after HSCT for acute leukaemia depends on the remission status and the underlying leukaemia subtype. The cure rate is about 40% for those received HSCT after relapse, while those transplanted in first remission may achieve 70% chance of cure.

Paediatric HSCT is characterized by a variety of hereditary diseases which are less commonly seen in adult population. Severe haematological diseases are not malignant condition but they are associated with shortened survival. The successful transplantation will lead to replacement of the pathological bone marrow by healthy marrow system. One common condition in our locality is thalassaemia major. Prince of Wales Hospital has now performed 52 HSCT thalassaemia major and the long term disease free survival is 85%. The ex-thalassaemia patients do not require further blood transfusion and the life long iron chelation therapy, the quality of life is excellent. Other severe haematological conditions include Fanconi anaemia, severe aplastic anaemia and other congenital bone marrow failure syndromes. Congenital severe immunodeficiency syndromes are hereditary and these children will develop severe and life threatening infection in early childhood. The principle of HSCT in these conditions is to replace the patients with a new healthy immune system which originates from the bone marrow. However these patients should be transplanted early before they develop severe infection which carries a higher complication rate after HSCT, early diagnosis and referral for transplant is the key factor for success.

Some hereditary metabolic diseases may also benefit from HSCT, such as mucopolysaccharidosis and adrenoleukodystrophy. The metabolic syndromes are inborn error of metabolism with enzyme deficiency. The principle of HSCT in these conditions works as enzyme replacement therapy. The deficient enzymes usually originate from the monocyte-macrophage system of the bone marrow. After successful HSCT, the donor cells repopulate to the reticulo-endothelial system and may produce adequate enzyme to correct the underlying defect. Some macrophages can even cross the blood-brain-barrier into the brain parenchyma and prevents the CNS damage, which may not be corrected by the new recombinant enzyme. However the success of HSCT in the metabolic diseases depends very much on the pre-transplant status, HSCT cannot correct the damaged nervous system. Early diagnosis and referral to transplant centre before the patient progress to have brain damage is of special importance.

Choice of donor

As the family size of our local population is getting smaller, most young families have only one child. It is rather difficult to find HLA identical siblings in children requiring HSCT. Unrelated donor or closely matched parents are alternative donors. As described by Dr. WY Au, the unrelated donor pool in various BM Registries in the world can now provide a good chance of successful search for most patients. However the unrelated donor HSCT is carrying a higher chance of treatment related complications and lower chance of cure as compared to sibling transplant. Graft versus host disease (GVHD) may be very difficult to control and even fatal. In the recent 10 years, unrelated umbilical cord blood transplant (UCBT) is more commonly performed especially in paediatric centres. The principle of transplant by UCBT is same as other forms of stem cell transplant. The advantages of UCBT include: (1) the ready availability of the stem cell since the cord blood has already been stored, HLA typed and infectious diseases screened, (2) less severe GVHD as the cord blood is immunologically naïve, thus less strict HLA matching is possible, (3) no risk to the donor. In Hong Kong, the Red Cross Blood Transfusion Service has set up the HK Cord Blood Bank (HKCBB) and is now providing free UCB units to our local transplant centres. Prince of Wales Hospital has now performed 23 unrelated UCBT with cord blood units provided by HKCBB, including the first successful UCBT for thalassaemia major in Hong Kong. The limitation of UCBT is the finite number of stem cells stored in each unit. The stem cell number may be insufficient for bigger size children and adults, and thus making the HLA compatible units not suitable for transplant. Recently there are studies of combining two UCB units for one transplant and thus achieve a higher stem cell dose, the preliminary result is encouraging. More centres are now also including adult patients for UCB transplant. There are now over 60,000 cord blood units stored in public cord blood banks, and the US Government is supporting a programme aiming at 150,000 cord blood units storage. On the other hand, most professional colleges and academy do not recommend the long term storage of UCB for autologous (self) donation because of the limited indication and lack of scientific evidence to support such practice.

With the expansion of unrelated bone marrow donor pool and the umbilical cord blood banks, the chance of finding a suitable donor for HSCT in children is very high. It is now also possible to find a better HLA matched donor, 10 antigens (A, B, C, DR, DQ) matched, and a better matched transplant is associated with a better outcome.

Prince of Wales Hospital Paediatric Transplant Centre

PWH started the first transplant in February 1991, initially with two beds and now expanded to 4 beds. Up to August 2007, 270 transplants have been performed, of which 225 were of allogeneic transplant. The common indications for transplant are: acute lymphoblastic leukaemia (56), acute myeloid leukaemia (40), chronic leukaemia and myelodysplastic syndrome (37), thalassaemia major (52) , aplastic anaemia (20), metabolic diseases (12), immunodeficiency (7). More recently umbilical cord blood is the main source of unrelated donor transplant, so far 35 UCBT were performed in our centre.

Liquid Nitrogen Tank storing cord blood units

Frozen Cord Blood Unit

A young baby receiving UCBT in a Lamellar Air Flow Room


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