Paediatric stem cell transplantation challenges in South Africa

Professor Gita Naidu explains the various challenges that are faced in paediatric stem cell transplantation.

Stem cell therapy has become a very promising and advanced scientific research topic. Multi-potent haematopoietic stem cell transplantation (HSCT) is the most popular stem cell therapy and is used to eliminate blood diseases that infiltrate the bone marrow, such as leukaemia, or to correct congenital immunodeficiency disorders and metabolic defects. Haematopoietic stem cell transplantation is also used to enable cancer patients to receive higher doses of chemotherapy than the bone marrow is normally able to tolerate. 

Two types of stem cell transplantation

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) uses human leucocyte antigen (HLA)-matched cells from a donor, procured from bone marrow, peripheral blood, or the umbilical cord. 

Autologous haematopoietic stem cell transplantation (aHSCT) is the collection of the patient’s own stem cells prior to high-dose myeloablative chemotherapy, which are re-infused as a stem cell rescue to facilitate recovery of the marrow. 

Haematopoietic stem cells are responsible for the generation of all functional haematopoietic lineages in blood, including erythrocytes, leukocytes, and platelets. 

Autologous increases success rate

Conventional sources of haematopoietic stem cells pose important limitations as there is a limited number of transplantable cells, and an efficient way of improving their yield is still being investigated. 

A lack of antigen-matched donors for transplantation, viral contamination or immunoreactions also cause a reduction in efficiency in conventional haematopoietic stem cells transplantations. 

The use of a patient’s own stem cells provides the greatest immunological compatibility and significantly increases the success of the procedure.

Distributive justice

It was reported that 58% and 42% of all haematopoietic stem cell transplantations performed were autologous and allogeneic, respectively. The highest number of haematopoietic stem cell transplantations were performed in Europe, Americas, Southeast 

Asia and the Western Pacific and the lowest numbers were performed in Eastern Mediterranean countries and Africa. This raises ethical questions regarding distributive justice particularly as haematopoietic stem cell transplantation therapy is life-changing.

Challenges in South Africa

Haematopoietic stem cell transplantation in haematological malignancies allow the administration of haematopoietic stem and progenitor cells after myeloablative treatment, while using the donor stem cells to regenerate the haematopoietic system (stem cell rescue).

Before haematopoietic stem cell transplantation is undertaken, a suitable donor must be identified. 

For autologous haematopoietic stem cell transplantation, a patient’s stem cells may not adequately mobilise into the peripheral circulation, resulting in a low yield of stem cells while allogeneic haematopoietic stem cell transplantation may not be possible without a suitable donor, a challenge in the South African setting.

High-dose chemotherapy, prior radiation, extensive bone marrow infiltration, refractory disease, low bone marrow cellularity, and exposure to certain drugs, e.g. fludarabine, melphalan and lenalidomide, may all contribute to a low yield of stem cells.

Genetically diverse

Donor eligibility depends on matching human leukocyte antigen (HLA) alleles, which are heterogeneous between individuals and ethnic groups. Donors for allogeneic transplants may be sourced either from family members (HLA-matched related donors if they have identical HLA alleles, or haploidentical if they have half-matched HLA genotypes), or from unrelated HLA-matched donors. The South African population is genetically diverse with respect to HLA alleles, especially in people of African descent.

Cost

The cost of haematopoietic stem cell transplantation is an additional challenge in South Africa thus it can’t be provided to all patients in need of the treatment. Haematopoietic stem cell transplantations are predominantly performed in the private medical sector (17% of the SA population). The cost of accessing international donors is very expensive. 

Haploidentical transplantation

The South African Bone Marrow Registry (SABMR) has a shortage of African and mixed-ancestry groups. Additionally, those living with HIV are excluded from the donor pool. 

A haploidentical donor from first- or second-degree relatives has the advantage of immediate availability at a much-reduced cost. Haploidentical transplantation should be implemented by every haematopoietic stem cell transplantation centre in SA to ensure equitable and affordable access to stem cell transplantation for all patients, but especially for the ethnic subpopulations where other donor pathways are limited. 

Favourable outcomes have been observed with haploidentical transplantation, and this may offer a suitable alternative in the absence of fully-matched suitable donors.

Infectious complications

Infections contribute to high morbidity and mortality post-haematopoietic stem cell transplantations. Allogeneic transplant patients should be assessed to identify the potential risk of disease re-activation of dormant infections, such as syphilis, tuberculosis, Toxoplasmosis, and hepatitis viruses. Viral, fungal, and bacterial infections are common in patients post haematopoietic stem cell transplantation.

Encourage more South African donors

Recruitment of donors from South Africans is encouraged by the SABMR but the prevalence of HIV, and the high migration rate in South Africa adds to the challenges. 

It’s imperative to increase education and awareness regarding haematopoietic stem cell transplantation donation in South Africa as it may be the only curative options for a variety of blood disorders. 

We need to aim to establish a sustainable and cost-effective programme to enable all South Africans in need access to this curative modality of therapy. 

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