Question 1

Can you help us with the pathology of the stem cell, and what are the effects of the transplant? For example, one patient asked you in a consultation how their life would be after transplant, and you said it would be similar to the donor's.

Dr. Dharma Choudhary · Accepted Answer

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.

Question 2

Apart from transplantation, in symptomatic sickle cell patients, is there no antigen therapy for asymptomatic patients to prevent homozygous transmission?

Dr. Dharma Choudhary · Accepted Answer

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.

Question 3

What is the age at which patients can undergo bone marrow transplant? Is there an upper age cutoff after which the benefits no longer outweigh the risks?

Dr. Dharma Choudhary · Accepted Answer

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.

Question 4

What is the racial survival rate after transplant according to current statistics, and is race a factor in the success of transplant?

Dr. Dharma Choudhary · Accepted Answer

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.

Question 5

Are there any clinical nutritional considerations before and after transplant?

Dr. Dharma Choudhary · Accepted Answer

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.

Question 6

In some countries even HLA typing tests are not available. If a patient is travelling from elsewhere, how does a physician collect samples, what precautions should be taken, and how should the sample be transported so it can reach a transplant centre like yours for testing?

Dr. Dharma Choudhary · Accepted Answer

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.

Bone Marrow (Stem Cell) Transplant for Sickle Cell Disease

Questions Doctors Asked Dr. Dharma Choudhary