BY STEVE KOHLER

IN JUNE OF 2012, 6-year-old Gabby Carter reached a watershed moment in her young life. Having lived with sickle cell disease and its debilitating effects since the time of her first medical crisis at 10 months of age, she arrived at transplant day.

Gabby needed more than 30 blood transfusions and made 50 trips to St. Louis Children’s Hospital from her Cape Girardeau, Mo., home to manage her condition. Sickle cell disease (SCD) is marked by a host of symptoms, including sudden pain throughout the body. Although Gabby never suffered a stroke, many SCD patients do, and the threat is always present.

The transplant itself must have seemed eerily anticlimactic. Right there in her all-too-familiar hospital room, a bag of what appeared to be oddly colored blood hung next to her, and, under the direction of Shalini Shenoy, MBBS, MD, its contents flowed into Gabby’s veins. No operating room, nary a scalpel, and the next day, Gabby was up and moving around.

If all went as planned, these donated cord blood stem cells would find their way to Gabby’s bone marrow and begin producing normal, oxygen-carrying red blood cells, replacing her defective sickle cells.

Although the procedure was less than dramatic, Gabby’s pre-conditioning to receive it was finely tuned. And the 18 months post-transplant have been a closely monitored “tightrope walk,” according to Shenoy.

Today, Gabby’s sickle cell disease (SCD) is gone — cured. Now, her mom, Debbie, says Gabby’s a vibrant 7-year-old who has played in the snow, gone swimming and attends second grade with her classmates.

5 things to know about sickle cell disease

· About 100,000 Americans live with SCD. It is the most common inherited blood disorder in the U.S.

· Sickle cell affects those with African, Spanish, Mediterranean and Indian ancestry. In the U.S., about one in 500 African Americans and one in 1,200 Hispanic Americans are born with SCD.

· SCD occurs when a child inherits two sickle hemoglobin genes, one from each parent. People are born with sickle cell; it doesn’t develop later in life and it’s not contagious.

· The dysfunctional genes produce red blood cells with a distinctive sickle shape, jagged edges and a brittle structure. These cells clump together, and intense pain results as blocked and damaged arteries starve organs and systems of oxygen. Anemia is the No. 1 symptom.

· SCD is a chronic illness, but with new therapies, many people are living more productive lives. Life expectancy has increased from 14 years to 50 and older.

Gabby is among the earliest sickle cell patients in the country to be cured via an umbilical cord blood transplant from an unrelated donor using a reduced-intensity conditioning procedure refined at Washington University School of Medicine.

The novel procedure is remarkable for two primary reasons: It is much gentler on patients than earlier procedures; and it dramatically will expand an extremely limited donor pool.

upping the odds

A renowned leader in pediatric stem cell transplantation, Shenoy is the Teresa J. Vietti, MD Scholar in Pediatrics and directs the Pediatric Bone Marrow Transplant Program at St. Louis Children’s Hospital and the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

Shenoy is leading a 20-center pilot study focused on reduced-intensity cord blood transplants from unrelated donors. The study has a safety restriction: three patients must have successful transplants before three more can be performed. Following the completion of nine patients, Shenoy is hopeful that the pilot study will extend to a fully funded national trial by the end of 2014.

Since Gabby’s transplant, two other children — Caitlyn Hill and Judah Wilks — have undergone the procedure at St. Louis Children’s Hospital.

Up until now, treatment options for children were limited. One option was to find an exact bone marrow match, but that’s difficult. African Americans, who make up the majority of the sickle cell population, are vastly underrepresented in national marrow registries. The other option was to use umbilical cord blood from a tissue-matched sibling free from the disease.

Nimble newborn cord blood offers significant benefits over bone marrow, requiring a less stringent match and fewer cells to effect a cure. Even so, tissue-matched sibling donors often are not available. Unrelated cord blood is easier to find because many public banks have made minority cord blood donation a priority. However, unrelated cord blood transplants simply weren’t very successful.

“You have better chances of finding a cord match than a marrow,” Shenoy said. “It was important for us to find a successful way.”

ABOVE: Checking in post-transplant, Caitlyn Hill and her mom, Lena, review progress with nurse practitioner Monica Hente.

BELOW: Some of the meds Caitlyn was taking to help her body readjust as the transplant takes hold.

PHOTOS BY ROBERT BOSTON

improving the process

Cord blood transplants — regardless of source — carried an important drawback: they required that all of a recipient’s blood-producing cells first be eliminated via high-dose chemotherapy, a toxic pre-transplant process known as myeloablative conditioning. Despite this, many patients rejected cord blood cells from unrelated donors. Even if the cells engrafted successfully, curing the disease, patients often had unwanted collateral organ damage, a high incidence of sterility and liver dysfunction. A less toxic option using cord blood was needed.

Shenoy’s reduced-intensity conditioning avoids major organ damage. It forces the patient’s immune system to accept the new cells — a balancing act that requires judgment and experience. Too little conditioning will cause the donor cells to be rejected, but too much can cause prolonged immune suppression.

In particular, to prevent rejection, the T-cells of the recipient’s immune system must be depleted, making it possible to slip in the new cells. This is done via low-dose chemotherapy and monoclonal antibodies.

In this method, the donated cord blood still must be tissue-matched for compatibility, but importantly, can come either from a sibling or from the widely available unrelated donor pool.

watching the risks

For the critical month following the cord blood transplant, the patient is sustained by transfused red blood cells and platelets. Over time, the new cells begin to work. SCD patients need as much as a year of recovery as the new cells become prolific and establish an operative immune system.

Shenoy monitors what she calls the “big three” risks. First is infection. With a downsized old immune system and a new one not yet fully functional, infection is a constant threat and must be treated promptly.

The second is rejection. Rejection can occur when the patient’s remaining immune system identifies the transplant as foreign and attacks the new cells. Shenoy uses DNA tests to determine the source — new or old — of the gradual increase in red blood cells. She says some mixed chimerism — carrying two DNA sets (patient and donor) — is acceptable, even long term, but she stays alert to any drop in productivity of the new cells.

The third is rejection’s sneaky counterpart: graft versus host disease (GVHD), which can quickly ruin everything. In GVHD, the transplanted cells’ immune components identify the patient’s body as foreign and attack it. The results are difficult to treat, and treatment causes further immune suppression resulting in a cycle of infection and GVHD.

Judah Wilks with Megan Holtmann (left), stem cell transplant nurse coordinator at St. Louis Children’s Hospital. The conditioning already underway, Judah played with Megan, read books with his brother, hugged his mom, Maryl (right), and mugged for the camera — testimony to the general mildness of the transplant preparations.

PHOTO BY ROBERT BOSTON

expecting the best

For many, Gabby included, the year post-transplant is tough. She needed 50 medications, including 15 IVs for blood pressure control, diabetes regulation and steroids to manage GVHD.

It wasn’t easy avoiding crowds and eating a healthful diet. But she followed the regimen and came through, with the benefits afforded by reduced-intensity conditioning: no cognitive impairment, no liver or kidney dysfunction and no discernible fertility damage. Not surprisingly, mom Debbie now struggles to maintain the tight control she adopted to protect her daughter.

Because strokes often recur with SCD and damage accumulates over time, Shenoy said it’s advantageous to intervene early. But only when the risk-to-benefit ratio with transplant has been shown to be positive.

That’s why 2-year-old Judah Wilks underwent a transplant last fall. Whereas the average age of first stroke for a SCD patient is 9 years, Judah suffered his first stroke 10 months ago.

Judah’s parents, Bryce and Maryl Wilks of Marshfield, Mo., adopted him and his brother, David, from the Democratic Republic of the Congo. The family learned of Judah’s SCD only when the standard tests that all U.S. infants receive were run upon his arrival in this country.

People of deep faith, the Wilks firmly believe it is no accident that they found Judah and that he is now part of their Missouri family and close to Shenoy’s groundbreaking program. Bryce said of the post-transplant future, “We expect the best.” That fervent belief — along with Shenoy’s attention to balance in applying her novel approach to transplant — suggests they will get nothing less.

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