Hydroxyurea and Other Medicines for Sickle Cell Disease: What They Can and Cannot Do

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.

It increases fetal haemoglobin, which reduces the number of pain crises and sometimes stroke risk, but it does not cure the disease. Patients unresponsive to hydroxyurea or with recurrent crises should be evaluated for bone marrow transplant.

L-glutamine, approved in 2017, crizanlizumab, approved in 2019, voxelotor, and gene therapy, approved in 2023. None of them replace the defective haematopoietic stem cells that produce abnormal blood.

Organ damage continues to accumulate. Strokes, pulmonary hypertension, kidney failure, and bone death are the eventual endpoint of a life managed on medicines alone.

No. The only treatment available today that is curative for everyone is haematopoietic stem cell transplant.