Amazing Treatment Options For Sickle Cell Disease

I was surprised when chatting recently with Leslie Lehmann, MD, clinical director of the Stem Cell Transplantation Program at Dana-Farber/Children’s Hospital Cancer Center (DF/CHCC). She turned to me and asked, “Did you know there’s been a cure for sickle cell disease for nearly 40 years?”

I had to admit that I didn’t. I’ve always thought of sickle cell—a painful and debilitating disease caused by an inherited mutation that makes red blood cells stiffen into a characteristic sickled shape—as a chronic disease to be managed, not one that could be cured.

I’m not alone in that belief. Lehmann often asks this question when she give talks for medical students, residents and other physicians. Their reaction is puzzlement, then a shaking of heads.

The cure is there, though. It’s a stem cell (aka bone marrow) transplant. The catch is that it’s not available to everyone—but for reasons that Lehmann thinks can be overcome.

Children and adults with the condition often receive treatment that alleviates symptoms or prevents complications (e.g., transfusions for anemia or strokes, penicillin to prevent infections, hydroxyurea to decrease pain crises and acute chest syndrome).

sickle cell disease
The malformed red blood cells of sickle cell disease can get stuck in small blood vessels, damaging organs and causing great pain. (NHLBI)

But none of these treatments address sickle cell’s root cause: the inherited mutation, which scrambles the gene for the adult form of hemoglobin. Hydroxyurea can force the body to stop making adult hemoglobin and instead make fetal hemoglobin (the form we produce during development and shortly after birth, and which never carries the sickle cell mutation). But it needs to be taken for life and it doesn’t work for everyone.

A stem cell transplant cures the disease by removing its source. Patients are “conditioned” with chemotherapy to completely destroy the hematopoietic (blood forming) stem cells in their bone marrow (including the ones that produce the malformed red blood cells). Doctors then rebuild their blood with healthy stem cells from a matched donor that doesn’t have the sickle cell mutation.

Stem cell transplants are often employed in blood and other cancers, but in sickle cell they’re currently available to a limited number of patients with truly severe disease. One reason is that they’re complicated and risky; many patients are too sick to tolerate the conditioning process, or their bodies don’t accept the donor cells.

A less intense form of stem-cell transplant may make cures possible for more children.

Then there’s the awareness issue. “Many physicians who see children with sickle cell don’t know if their patients are candidates for transplant,” Lehmann notes. “In turn, most families aren’t aware that it could be an option.”

Third is the “matched donor” requirement. “The matching requirements for a transplant in sickle cell are different from those in cancer,” Lehmann explains. “Right now only children with a sibling with identical but non-sickled red blood cells can qualify for a transplant. Only about 14 percent of patients are likely to have a match like that.”

But that may not always be the case. Lehmann is running the DF/CHCC arm of a clinical trial that could make non-related donations possible, as they can for many other kinds of transplants. Called the SCURT (Sickle Cell UnRelated Transplant) study, the trial tests the combination of a less intense (and therefore potentially safer) conditioning regimen and stem cells from unrelated donors.

“In cancer, less intense or ‘minimally ablative’ techniques let us eliminate just enough of a patient’s immune cells to avoid transplant rejection,” Lehmann says. “We think that we can achieve the same results for patients with sickle cell.

Amazing Treatment Options For Sickle Cell Disease
Leslie Lehmann, MD

“Also, we know that we don’t need to completely replace a patient’s red blood cells to achieve better health and quality of life,” she continues. “If we can get them to the point where just 15 or 20 percent of the hemoglobin they produce is normal, we can correct the disease. We shouldn’t need to completely replace their stem cells to achieve that.”

Lehmann thinks the SCURT study could help make stem cell transplantation a more widely accepted option. “We’ve been doing transplants for sickle cell since 1975,” she says. “The sickle cell community needs to know that it’s a choice available to families coping with SCD.”

To learn more about what it’s like for a child with sickle cell disease to undergo a stem cell transplant, read the story of Maryam Idan, a young Iraqi girl with sickle cell disease who came to Boston Children’s last year.

While Lehmann’s work on stem cell transplantation could help cure more children with sickle cell disease, DF/CHCC doctors are also developing ways to manage sickle cell disease better. Learn more about what DF/CHCC is doing to stop sickle cell pain crises and how flipping one genetic switch offcould be a new way to stop the body from producing sickled cells in the first place.