Gene Therapy vs Bone Marrow Transplant for Sickle Cell Disease: What the Evidence Shows

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.

No. Sickle cell disease is a gene defect — there are sickle cell carriers and sickle cell disease patients. Disease means both parents were carriers; a carrier has only one gene affected and can pass it to their children if their partner is also a carrier. Other than gene therapy, there is no treatment for asymptomatic carriers — no cure or treatment is needed, because they reach adulthood and live a normal life. Since there is no phenotypic expression of the genotypic disorder, no treatment is warranted, because every treatment carries a risk of morbidity and mortality.

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.

Five-year overall survival above 95% using a matched sibling donor and bone marrow as the stem cell source.

A review of 56 studies covering about 1,200 patients found the overall quality of evidence was low, with no randomised controlled trials comparing the two directly. Two-year overall survival for transplant patients was 91%, and both approaches reduced acute chest syndrome and vaso-occlusive episodes.

It is available only at a handful of centres, primarily in the US and Europe, making it inaccessible to the vast majority of African patients, unlike bone marrow transplant, which has decades of follow-up data and is available in India at a fraction of the cost.

Dr. Dharma Choudhary's unit has performed over 1,500 transplants in total, including 65 for sickle cell disease, using the same conditioning regimens and drugs as leading centres in the US and Europe.