Haploidentical Transplant for Sickle Cell Disease: Why the Outcomes Have Changed

We advise the youngest age should be more than two years — doing a transplant very early, at 6 months to 1 year after only one crisis episode, children cannot tolerate the required immunosuppression properly, though on an emergency basis it is sometimes done for leukaemia. For sickle cell disease and thalassemia, transplant should be offered after 2 years of age. There is no upper age cutoff — every patient has the right to live, whatever the outcome percentage; the decision to go for transplant depends on the patient and family, weighed against quality of life.

Race does not affect the outcome. African sickle cell patients present with more severe sickling compared to Indian sickle cell patients, but the transplant outcome is the same — leukaemia treated in Africa versus leukaemia treated in India has the same outcome. Transplant outcome is mainly affected by patient factors (disease stage and comorbidity), donor factors (full match, half match, or mismatch), and treatment factors (right conditioning, right immunosuppression, right supportive care). Get those right and outcomes across the globe are similar, whether the transplant is done in America, Tokyo, or India.

We encourage good nutrition — patients can eat whatever they like, there is no prohibition, other than avoiding street food. Any hygienic food eaten at home, with good nutrition and a good amount of protein, is good for transplant outcome — the same as for any ordinary healthy human being.

I will circulate full information from my lab on the prerequisites for an HLA sample — what temperature it should be kept at, how many hours it can take to transport, and how many ml of blood sample or a buccal swab is required, so the sample can safely reach India for testing. Laboratory networks such as Metropolis and Lancet already exist in Kenya, Ghana and Uganda, though coverage is patchier in countries such as Nigeria and the DRC.

The stem cell itself has no pathology — it is the mother cell present in every human being that produces blood, the haematopoietic stem cell. Sickle cell disease is a defect in a single gene, a single base-pair defect in the beta-haemoglobin chain, so it is the haematopoietic stem cell that is defective, and we need to replace it with a healthy one. As for effects: about 70% of patients have no major complications and 30% will have graft-versus-host disease. In the acute phase there can be neutropenia leading to sepsis, mucositis (mouth ulceration causing pain, vomiting, diarrhoea), and haemorrhagic cystitis (blood in urine from the conditioning chemotherapy or radiation), which usually recovers with hydration and prevention. Veno-occlusive disease of the liver can also occur. The two most important complications are acute and chronic graft-versus-host disease — chronic GVHD causes dry eyes, dry skin, dry mouth and lung problems, and impairs quality of life. Infertility is another complication, meaning inability to reproduce, not sexual dysfunction — sexual and social life are not affected after transplant, only ovarian or testicular failure affecting spermatogenesis and ovulation.

Post-transplant cyclophosphamide. It made haploidentical donor transplant a standard of care, and the number of haploidentical transplants has increased exponentially worldwide since 2010.

Overall survival of 80 to 90%, close to matched sibling donor results, for both malignant and non-malignant diseases including sickle cell disease.

African patients have disproportionately low representation in international donor registries, making matched unrelated donors hard to find. Haploidentical transplant bypasses this problem, because every patient has a biological parent who is by definition a haploidentical match.

35 of 65 sickle cell transplants performed have been haploidentical, with overall survival of 83%, despite many patients arriving with late-stage disease and alloimmunisation.