Sickle Cell Disease And Cancer Risk

TL;DR

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Research on cancer risk in people with sickle cell disease (SCD) has produced mixed results, with some studies suggesting higher rates of blood cancers and others finding no increase in overall risk. Newer laboratory studies of clonal hematopoiesis may help explain the findings, but they do not establish that SCD causes cancer or quantify an individual patient’s risk.

Studies of cancer risk in people with sickle cell disease have reached conflicting conclusions, while newer laboratory findings point to a possible role for clonal hematopoiesis, according to a MedPage Today report published October 15. Researchers say the evidence does not yet establish how much, if at all, SCD raises overall cancer risk, though some studies report higher rates of blood cancers.

Population-based studies have not produced a consistent picture. A study of more than 7,500 patients in Britain reported about twice the risk of any malignancy compared with the general population. A California study of 6,400 patients found a lower overall cancer risk, alongside a 72% higher risk of leukemia and a 38% lower risk of solid cancers. A case-control study of about 1,300 patients found no increase in overall or solid cancers, but a marginal increase in blood cancers.

A systematic review covering roughly 24,000 people worldwide also found highly variable estimates. Its findings pointed to an overall increase in malignancy in SCD and thalassemia, particularly hematologic cancers and, for SCD, myeloid leukemia. But another analysis described the relative cancer risk in SCD as much lower than in established cancer-predisposition syndromes. The findings do not settle the risk for individual patients.

Attention to the issue rose after clinical trials of the gene therapy lovotibeglogene autotemcel, or lovo-cel, were paused following reports of leukemia in one patient and myelodysplastic syndrome in another. The manufacturer, Bluebird Bio, said an investigation found the therapy was “very unlikely” to have caused the cases. The FDA later lifted the hold and approved lovo-cel and exagamglogene autotemcel, or exa-cel. Lovo-cel’s labeling includes a boxed warning about potential malignancy risk.

How Risk Affects SCD Care

The uncertainty matters to patients weighing treatment options and to clinicians explaining possible long-term risks. A cancer concern associated with a particular treatment should not be treated as proof that SCD itself causes cancer: the evidence discussed in the report distinguishes baseline disease risk from exposures such as high-dose chemotherapy used in gene therapy and stem cell transplantation.

For people with SCD, the current findings do not support a simple conclusion that cancer is expected or that every patient faces the same risk. A clinician’s discussion should account for the patient’s treatment history and the specific therapy under consideration. The report also underscores that absolute risk may remain low even when some studies find an elevated relative risk.

Earlier Studies and Treatment Concerns

Early reports, often based on case reports and surveys, generally suggested higher cancer rates in SCD. Later population studies produced conflicting results, partly because they examined different populations and cancer types. The report also notes that a separate study found no significant overall association between sickle cell trait and cancer, though it suggested a possible trend toward higher kidney cancer risk. Trait and SCD are distinct conditions, so those results should not be treated as interchangeable.

Gene therapy trials renewed public attention to malignancy concerns after the reported blood cancers. The FDA subsequently approved both lovo-cel and exa-cel for SCD, while lovo-cel’s warning remains part of its prescribing information. A specialist quoted in the report also said earlier concerns that hydroxyurea causes cancer had been refuted; that statement reflects the clinician’s assessment, not a new finding from the report.

One proposed biological avenue is clonal hematopoiesis, in which acquired mutations allow some blood stem cells to multiply more than others. Earlier work by Vijay Sankaran and colleagues found no difference in its frequency between people with SCD and controls. More sensitive tests in later studies have reported different results, including higher odds in two cohorts of children with SCD compared with matched controls.

““There appears to be an increased malignancy risk in sickle cell disease,” but “the extent to which there is an increased malignancy risk remains not so well established.””

— Vijay Sankaran, MD, PhD, of Harvard Medical School and Boston Children’s Hospital

Why Cancer Estimates Still Differ

The studies vary in design, populations, follow-up and cancer categories, and their results do not establish a single risk estimate. It remains unclear whether SCD independently raises overall cancer risk, which patients might face greater risk, or how much observed risk relates to treatment exposures rather than the disease.

The newer clonal hematopoiesis findings are a possible research lead, not proof that the condition causes cancer in SCD. The report provides no final results from the additional study comparing 3,885 people with SCD and 3,398 people with sickle cell trait or neither condition; the source text ends before those findings are given. The relationship between gene therapy and malignancy also remains a treatment-specific issue, despite the manufacturer’s assessment and the FDA’s decision to lift the hold.

More Sensitive Blood-Cell Studies

Researchers are continuing to use more sensitive assays to detect clonal hematopoiesis and compare its frequency across people with SCD, sickle cell trait and control groups. Further studies with larger cohorts and longer follow-up may clarify whether the laboratory findings track with later cancers and help separate disease-related risk from treatment-related risk.

For now, patients considering gene therapy or stem cell transplantation can discuss the risks and benefits of the specific treatment with their care team, including the warning attached to lovo-cel. The available evidence does not resolve the broader question of baseline cancer risk in SCD, so additional population research and follow-up will be needed.

Key Questions

Does sickle cell disease increase cancer risk?

Research is mixed. Some studies report higher overall or blood-cancer rates, while others find no increase in overall cancer risk. The available evidence does not establish a definitive individual risk.

Which cancers have been linked to SCD in studies?

Some studies have reported higher rates of hematologic cancers, particularly leukemia and myeloid leukemia. Findings for solid cancers differ, with one California study reporting a lower rate of solid malignancies.

Did gene therapy cause the cancer cases reported in trials?

After leukemia and myelodysplastic syndrome were reported during lovo-cel trials, Bluebird Bio said an investigation found the therapy was “very unlikely” to be the cause. The FDA later lifted the trial hold. The broader question of treatment-related risk remains under study.

What is clonal hematopoiesis?

It is a process in which acquired mutations allow some blood stem cells to multiply faster than others, forming cell populations called clones. Researchers are studying whether it helps explain cancer patterns in SCD; current findings do not prove a causal link.

Source: rss