At Last a Cure for Sickle Cell?
Date: April 1, 2013
For patients with a chronic disease, a cure unfailingly cleaves time in two. Life splits into before and after. Until now, precious few adult sickle cell patients have known that. Most who have the genetic disease die before age 50.
A new Johns Hopkins study should change that, though, as Maya White-Simmons* fully realizes.
The Maryland woman's sickle cell disease was "manageable" until high school, when ischemia-based pain crises became increasingly frequent. White-Simmons was sidelined by leg and arm pain that, she says, "felt like someone dropped me from a second story." Available treatment was but short-time palliative.
Then came a second insult: In her senior year, White-Simmons was diagnosed with lupus after nephritis and resulting edema kept her from walking. Each disease aggravated the other; doctors couldn't distinguish between her lupus and sickle cell as a cause of her severe joint pain.
She graduated from college, with a minor in persistence. But the next year was a blur of pain, pain narcotics, transfusions and pneumonia, forcing the young woman to revisit a possibility she'd earlier tabled: bone marrow transplant.
BMT has long offered intractable lymphoma and leukemia patients a therapy that includes high-dose chemotherapy and whole-body irradiation. Bone marrow stem cells die, as do key white cells, making way for the transplant which engrafts and reboots hematopoiesis. The procedure walks a line between raising infection risk and damping the immune response that can cause rejection or prompt graft-versus-host disease.
"It's never been a therapy for the weak," says Robert Brodsky, White-Simmon's transplant physician.
That's one reason BMT hasn't applied to adult sickle cell disease, despite its potential to replace flawed red cells with healthy ones. "The standard BMT regimen would be demanding for this population," says Brodsky, who directs Hematology at Johns Hopkins. Adults sick enough to need transplant often suffer damaged kidneys, brain, lungs and bones as well as anemia.
The main problem, however, is making transplant donor matches. "Though patients may want a transplant, incompatibility has kept BMT from being an option," says oncologist Javier Bolaños Meade. Even half-matched (haploidentical) donors were considered too dangerous, says Brodsky.
But this fall, the two clinicians reported a clinical trial that skirts the drawbacks. They found significant benefit in a traditional BMT protocol that's immune-tailored for sickle cell patients. "Our use of high doses of the immunosuppressant cyclophosphamide shortly after transplant now makes using half-matched donors safe," Brodsky says. The tactic so broadened the donor pool that 90 percent of patients had a suitable donor.
Also, the protocol is gentler. Because there's no cancer, the rigorous "myoablative" pretreatment was scrapped, lowering chemotherapy and radiation dosage.
For two weeks in 2009, White-Simmons underwent that milder "conditioning" for her transplant-one that let stem cells from her marrow survive in case the graft from her teenaged brother failed.
Now, three years later, she reports normal energy and no sickle cell symptoms. Her prednisone is still tapering. And her red cells are 100 percent donor.
All patients aren't cured. Graft rejection, at 43 percent, is too high, says Bolaños Meade, who hopes tactics like transplanting more stem cells will help.
White-Simmons, however, describes herself as "a new person. I can actually go places without wondering Am I going to get sick here?" The kicker is that her lupus has practically gone. That's two cures-two clear before-and-afters-for the price of one.