Treatment success varies widely from cancer to cancer, but for one cancer, acute lymphoblastic leukemia (ALL), we have a really good track record. The cure rate for ALL has, over the last 40 years, climbed to nearly 90 percent.
Less comforting is the fact that the disease comes back in about 10 to 20 percent of children who are initially cured. That’s what Michelle Fineberg found out when her daughter Sarah Levin relapsed nearly six years after her last treatment.
“Sarah’s color wasn’t right, and then she started running a fever, so I took her in for a blood test. I just knew deep down that the cancer was coming back,” Michelle recalls. “When the call came that we had to go back to the hospital, we were devastated. We knew we were going back into hell.”
What Michelle didn’t yet know was that Sarah’s leukemia would prove resistant to the drugs at her care team’s disposal, drugs that generally aren’t very good to begin with at helping children whose leukemia returns.
“We have standard treatment regimens for newly diagnosed and relapsed ALL, both of which rely heavily on steroids like prednisone and dexamethasone,” says Lewis Silverman, MD, who directs the Pediatric Hematologic Malignancy Service at Dana-Farber/Children’s Hospital Cancer Center (DF/CHCC) and has been part of Sarah’s care team from day one. “But we know that leukemias with any level of steroid resistance are more likely to relapse.
“Anything we can do to overcome that resistance,” he continues, “would let us help many children.”
With a new clinical trial, Silverman is trying a strategy that could help punch holes in the barriers relapsed ALL cells put up against steroids.
That strategy centers on a drug called everolimus. Silverman thinks it might help overcome steroid resistance because lab studies suggesting that drugs like it could make the steroids that he and his team use in patients with relapsed ALL work better.
Silverman tested those lab results in a very small clinical trial a few years ago by giving rapamycin (an older relative of everolimus) and steroids to children and adults with relapsed ALL for a few days. They then started the patients on the standard treatment program.
“We saw the numbers of cancer cells in the patients’ blood drop dramatically while they took rapamycin and, in some cases, rise again when they stopped taking it, even though they continued on steroids and other drugs,” says Silverman.
With the new trial—which is currently recruiting patients—Silverman wants to see whether adding everolimus to the standard regimen for relapsed ALL is safe for children like Sarah. “Might there be too many side effects?” he asks. “We don’t yet know, but everolimus and similar drugs have been used on their own in children and adults for many years, and have good safety profiles.”
Silverman has high hopes for everolimus, should it earn its salt in this trial. “If it works as we think, then we would want to test it in children with newly diagnosed ALL. It might also let us reduce the amount of steroids we have to give ALL patients, which could help children avoid some of the side effects of long-term steroid treatment like weight gain, bone and joint problems and increased infection risk. And it might prevent some relapses from ever happening,” he says.
This trial wasn’t open yet when Sarah had her relapse, but luckily she had an option available to her when the drugs failed to put her leukemia back into remission: She was able to receive a new drug combination that had just been tested in another clinical trial at DF/CHCC and other centers nationwide. That drug combination did the trick, knocking her leukemia back into remission and making her eligible for a bone marrow transplant.
She had the transplant in July of 2010, and had to live in isolation for a year. But so far all is well. “We are going in for a checkup this summer,” Michelle says, “and if everything is okay, she can go back to being a regular kid.”
Sarah is now 11, and she and her family see the bone marrow transplant as having given her a second chance at life. “We now celebrate two birthdays for her,” Michelle notes. “Her real birthday, and her re-birthday, the day she got the transplant.”