Bone Marrow Transplantation in Sickle Cell Disease

revised April 16, 1998

Bone Marrow Transplantation for Sickle Cell Disease

Sickle cell disease results from an abnormality in hemoglobin, the protein in red blood cells that carries oxygen. Because the disorder involves cells produced in the bone marrow, replacement of the defective bone marrow with normal marrow will cure sickle cell disease. This information has been available for a number of years (Abboud et al., 1994). The New England Journal of Medicine published a report on the largest series of patients undergoing bone marrow transplantation for sickle cell disease in the United States (Walters et al., 1996). Adults were not eligible for the study. Children tolerate transplantation better in general. Also, in sickle cell disease, children often have less organ damage from their sickle cell disease, which improves their chances of survival.

Patients chosen for bone marrow transplantation must be carefully selected. The bone marrow is almost always donated by a brother or sister who meet strict criteria for immune matching (Mentzer et al., 1994). Bone marrow transplantation carries significant risks, including the chance that about one child in ten will die from the procedure itself (Apperley, 1993). Bone marrow transplantation is recommended when the disease being treated carries a high probability of death. Examples include malignancies, such as certain forms of childhood leukemia and lymphoma. Bone marrow transplantation is also used in some diseases that are not frankly malignant, but where a predictable progression to illness and death occurs. This is the case with some forms of severe thalassemia (Lucarelli et al., 1993).

The clinical course of sickle cell disease is extremely variable (Platt et al., 1991). Some patients have nearly no symptoms. Others are severely incapacitated. Our ability to tell in advance which of two children will have severe disease and which will have mild disease is very limited (Bray et al., 1994). The nature of sickle cell disease in a particular child often is not clear until the child has suffered severe injury on the one hand, or lived a relatively normal childhood on the other. The risks of bone marrow transplantation are higher in older children and adults. Further, people who have suffered severe problems from their sickle cell disease, such as advanced kidney disease, are less likely to survive a bone marrow transplantation procedure. This is the difficulty with bone marrow transplantation in sickle cell disease.

The ideal time to transplant a child who will have severe disease is when s/he is young, and before advanced injury has occurred. Since we have no oracle that predicts the future of any child, a large risk exists for any transplant procedure. Transplantation would be the correct course for a child who in the future will suffer a series of strokes. Transplant would be wrong for a child who will lead an essentially normal life.

In the study reported in the New England Journal of Medicine, children were selected for transplantation if they had certain problems that were severe, or problems that suggested possible severe complications in the future. Some patients who underwent bone marrow transplantation were cured of their sickle cell disease. Some patients who underwent bone marrow transplantation suffered severe problems related to the procedure:

2 of 22 patients died of complications related to transplantation.
7 of 22 patients had severe neurological injury, including bleeding into the brain or seizures.
3 of 22 patients had their sickle cell disease return after transplantation.
1 of 22 patients suffered complete bone marrow failure after transplantation.

Some of the children suffered more than one of the complications listed above. Consequently, adding up the number of complications does not tell you home many individuals did poorly with transplantation. Nonetheless, bone marrow transplantation is no miracle cure for sickle cell disease. The authors of the article in the New England Journal of Medicine were carefully circumspect regarding this treatment for patients with sickle cell disease. Some news reports that appeared later in the lay press have been misleading, and proclaimed "a cure for sickle cell disease." This is not true.

Bone marrow transplantation has a role for a small, and very select group of patients with sickle cell disease. Extensive discussions with physicians and even outside consultations by other experts are reasonable steps before starting on such a potentially perilous journey.

References

Abboud, M., Jackson, S., Barredo, J., Beatty, J., and Laver, J. (1994). Bone marrow transplantation for sickle cell anemia. Am J Pediatr Hematol Oncol 16, 86-9.

Apperley, J. (1993). Bone marrow transplant for the haemoglobinopathies: past, present and future. Baillieres Clin Haematol 6, 299-325.

Bray, G., Muenz, L., Makris, N., and Lessin, L. (1994). Assessing clinical severity in children with sickle cell disease. Preliminary results from a cooperative study. Am J Pediatr Hematol Oncol 16, 50-4.

Lucarelli G, Galimberti M, Polchi P, Angelucci E, Baronciani D, Giardini C, Andreani M, Agostinelli F, Albertini F, Clift RA (1993) Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. N Engl J Med 329, 840-844.

Mentzer, W., Heller, S., Pearle, P., Hackney, E., and Vichinsky, E. (1994). Availability of related donors for bone marrow transplantation in sickle cell anemia. Am J Pediatr Hematol Oncol 16, 27-9.

Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, Kinney TR. (1991). Pain in sickle cell disease. Rates and risk factors. N Engl J Med 325, 11-16.

Walters MC, Patience M, Leisenring W, Eckman JR, Scott JP, Mentzer WC, Davies SC, Ohene-Frempong K, Bernaudin F, Matthews DC, Storb R, Sullivan KM. (1996). Bone marrow transplantation for sickle cell disease. N Engl J Med 335, 369-376.