For years, researchers have tried to pin down whether sickle cell disease raises the risk of cancer, but the population-level data have not delivered a clear answer. A British study of more than 7,500 patients found a twofold higher risk of any malignancy, while a California study of 6,400 patients saw a lower overall cancer risk but a 72% higher risk of leukemia. A case-control study of 1,300 patients found no overall increase and only a marginal rise in blood cancers.
These conflicting results have left experts cautious. Vijay Sankaran of Harvard Medical School and Boston Children's Hospital says the burden of proof is still unmet, while Sana Saif Ur Rehman of Washington University in St. Louis does not think patients are at higher baseline risk than the general population. Concerns around gene therapy were raised after two patients developed blood cancers in a lovo-cel trial, but investigation found the therapy was "very unlikely" to be the cause, and the FDA later lifted the hold.
New laboratory work points to clonal hematopoiesis as a possible mechanism. Using more sensitive assays, researchers found a fourfold higher odds of clonal hematopoiesis in two large cohorts of children with sickle cell disease compared with matched controls. The overall evidence still shows "highly variable" risk estimates, but a recent systematic review of 24,000 patients found an overall increased risk of malignancy in both sickle cell disease and thalassemia, especially hematologic cancers.