"By the time yearold Ava Christianson got to the National Institutes of Health this summer she had lost several grueling rounds to leukemia and was bracing for the next one. Intensive chemotherapy which cures up to  percent of children with the most common type of leukemia hadnt kept her cancer from coming back. Neither had a painful bonemarrow transplant nor an experimental treatment. Her careworn father cried in the shower to hide his anguish. Her mother couldnt help but wonder Why is this happening to our child But Ava was fortunate in one respect. Discoveries in the burgeoning field of immunotherapy are offering lifelines to desperate patients who previously had none. Five years ago said her mother Bethany Christianson our doctor would have just had to tell us to go home. Instead in a fiveminute procedure at the NIH Clinical Center in late July the freckleface girl got another chance to beat the acute lymphoblastic leukemia ALL that has stalked her since age . She was infused with  million of her own T cells a key part of the immune system that had been genetically modified to track down and kill her cancer like a pack of crazed dogs. Avas treatment called CAR Tcell therapy is one of the new immunotherapies that attempt to rally the bodys own defenses to fight malignancies. Unlike other cancer advances it is being tested widely in children because of its stunning effectiveness in ALL the most common pediatric cancer. In earlystage trials many patients who had repeatedly relapsed saw their leukemia disappear. Some remain cancerfree. Yet big questions surround the therapy and many scientists are urging caution. Theres very real promise with this approach but the immune system is complicated said Terry Fry the National Cancer Institute NCI scientist who is running Avas trial. Theres a lot that still needs to be worked out. Heres what you need to know about immunotherapy https  Complications can be lethal one clinical trial was briefly halted in July after three young adults died of brain swelling. It is also far from clear that such a personalized approach  possibly costing hundreds of thousands of dollars  is economically viable on a large scale or will produce the lasting remissions that everyone hopes to see. U.S. researchers running CAR Tcell trials for children and adults with leukemia and lymphoma have reported remission rates up to  percent in some cases. Thats a major achievement in a group whose cancer is emboldened by every treatment failure. But rates in other trials are considerably lower and many patients eventually relapse. The treatment is great about getting people into remission but not at keeping everyone in remission said Rebecca Gardner a pediatric oncologist at Seattle Childrens hospital. She ran an earlystage trial using CAR Tcell therapy in which  of  patients went into complete remission. By a year about half had relapsed either because their T cells had inexplicably disappeared or their cancer had changed so that the T cells could no longer recognize it. Leukemia is really smart she said. Avas family understands that better than most. She underwent her first CAR Tcell procedure in Minnesota last year but her leukemia returned within six months. Her treatment at NIH involved a nextgeneration version developed by NCI that used a different target for her marauding T cells. In this firstinhumans trial she is Patient No. . In late August the Christiansons learned that Ava had gone into remission. She and her mother who were still at the Clinical Center in Bethesda Md. gleefully rushed home to Wisconsin so Ava could start third grade.  Her parents so frequently disappointed remain guardedly optimistic. Hope is all you have said her father Jay Christianson. Her mother added We just need this to work and to stay working. NCIs Fry is careful not to make any promises about an extended remission. I cant say thats going to be the case he said because we just dont know. Its too soon. Scientists have wanted for decades to marshal the immune system to vanquish cancer but their attempts have mostly been frustrated. In the past few years however breakthroughs have led to the development of two types of immunotherapy  checkpoint inhibitors and CAR T cells  that are generating enormous excitement. Checkpoint inhibitors are offtheshelf therapies aimed at unleashing the immune systems power to see and attack the disease. Used mostly in adults to date they are producing impressive results albeit in a minority of cases. The most prominent Jimmy Carter. The former president became the poster patient when he was successfully treated last year with a checkpoint inhibitor called Keytruda along with surgery and radiation for his advanced melanoma. Much of the earliest research for customized CAR Tcell therapy was conducted at NCI the University of Pennsylvania the Memorial Sloan Kettering Cancer Center and Seattle Childrens. The technology of CAR T cells is really a breakthrough especially for children said Michael Jensen director of the Ben Towne Center for Childhood Cancer Research at Seattle Childrens Research Institute. Almost all the initial work focused on CD a protein found on the surface of Bcell acute lymphoblastic leukemia. Scientists figured out ways to use a chimeric antigen receptor or CAR to reprogram T cells to recognize the protein and kill the cancer. Immunotherapy is showing benefits in an increasing number of cancers https  Zane Esposito a yearold from Plano Tex. calls himself the TCell Explorer. He was diagnosed with ALL in June . I just thought my back hurt he said. I couldnt walk up the steps very well. Almost three years of treatment including punishing chemotherapy provided a couple of years of remission. His leukemia returned in January and this time it did not respond to treatment. Soon after Zane relapsed he and his father bumped into friends in a local doughnut shop who told them about a TV segment on CAR Tcell therapy. Paul Esposito searched online and found Gardners clinical trial in Seattle. Zane signed on got the treatment went back into full remission and gained  pounds.  His Texas doctors have talked about a bonemarrow transplant to increase the chance of a true cure but the Espositos have resisted. The Seattle doctors say it is not clear yet whether that is necessary or whether there would be still other options should Zanes cancer recur. Zane is moving on with dreams of competing on Chopped Junior to show off his homemade pasta and pizza. On July  the day that Ava got her T cells he celebrated his th birthday. Ava was  when she started having leg pains then trouble standing up. Her mother suspected Lyme disease. You never think of cancer with a child she said eyes filling as she recalled her daughters cancer diagnosis in November . The doctors assured the family that it was typical leukemia  and curable. Like most children Ava quickly went into remission after starting the prescribed  months of chemotherapy. But at home in Prescott a small Wisconsin city at the confluence of the Mississippi and St. Croix rivers things did not get easier for the Christiansons. In early  Ava was hospitalized in Minneapolis for a lung infection. About the same time the couples second daughter Audrey was born  weeks premature and hospitalized in a neonatal intensive care unit in St. Paul. Bethany who manages occupational therapists for a nursinghome chain and Jay a rural mail carrier shuttled between the Twin Cities visiting their daughters. I would be with Ava during the day and then when Jay got home he would stay with Ava and I would spend time with Audrey she said. No matter what you do you feel like a bad mom. A year or so after treatment began Ava relapsed. Now she was in a much more dangerous category children whose leukemia no longer responds to chemo. Her doctors arranged for a bonemarrow transplant with her baby sister as the donor. The transplant made her sick and the whole family miserable. Ava spent months in the hospital and then a year at home. Because of fears of infection she couldnt go out much. She missed all of first grade. But her parents had hope that the transplant would keep her cancer at bay. Brain cancer now the leading cause of cancer deaths in children https  At a sixmonth checkup tests showed that the leukemia was back again. There were no more conventional treatments to try. But because of her two relapses Ava was now eligible for a CAR Tcell trial at the University of Minnesota Masonic Childrens Hospital. Her T cells would be genetically altered to go after CD.The number of cells then would be vastly increased and reinfused. It sounded like science fiction but Bethany Christianson found comfort in talking to the father of Emily Whitehead. In  the yearold Pennsylvania girl became the first child to be treated with reprogrammed T cells for leukemia. She has been in remission ever since. Ava got her treatment in April   after her cells were extracted via a tube inserted into her neck  and five days later had a massive immune reaction with a high fever and intense pain. While that is typical some patients become dangerously ill. Yet Ava recovered fast went into remission and attended summer school where she learned how to make pigsinablanket and wrote her own cookbook. By then her parents had gotten used to living in the midst of remissions and relapses. When she felt better we would do everything we could Bethany said. They visited Robot World a scientifically themed attraction a few hours from Prescott. You dont put things off because you are always thinking What if Last fall doctors delivered the bad news. Avas cancer had changed. It was no longer producing the CD protein which meant her modified T cells could no longer recognize the disease. But the leukemia was still producing another common protein called CD and that offered an opportunity.  As it happened Fry head of the bloodcancer section in NCIs pediatric oncology branch had already launched the worlds first trial using CAR Tcell therapy to focus on CD. It seemed an equally promising target that could broaden the therapys impact researchers thought. At the time they did not realize that a significant percentage of patients in the other trials might relapse because of changes in their cancer. Fry insisted as he designed the study that children be included despite everpresent concerns about exposing them to safety risks. He wanted to avoid a delay in testing what could be a lifesaving pediatric treatment. I didnt want to take two to three years on adults and then go back and do children he said. For a yearold with cancer a future staked on medicines hottest field http_story.html  The clinical trial already has treated nearly two dozen leukemia and lymphoma patients through age . The majority have gone into remission although some have had their cancer return. While it is far too early to know longterm outcomes Fry said he is convinced the CD treatment holds much potential. He is planning another trial next year with the Stanford University School of Medicine. It will target both proteins  CD and CD  simultaneously.  Once Ava relapsed after the Minnesota trial Frys study at the NIH Clinical Center appeared to be the only option. But there was no slot immediately available. With Ava deteriorating doctors put her on an experimental treatment that sent her into remission but had serious side effects. They immediately stopped the medication when they learned Ava might get her Tcell therapy in January  she actually needed a high level of leukemia in her body to participate. But on this wrenching roller coaster of research and treatment it turned out that she still had to wait several more months. Avas cancer returned in June. Her T cells were extracted in preparation for the trial even as she got sicker and sicker. She was admitted to the Clinical Center in midJuly to a room with dancing penguins painted on the windows. The day before her therapy an ebullient Audrey burst into the room and the two sisters ran down the hall to a play space. Her mother was ready this time for the intense immune reaction that followed treatment although she still found it hard to watch Ava spike a fever of . When you see that temperature on the thermometer every bone in your body says its wrong to let it get that high Bethany said. Then suddenly its over. If his daughters cancer returns yet again I have no idea what well do Jay said. Were kind of up against the edge. Fry thinks she might be able to undergo a second round of her latest immunotherapy as long as her cancer is still producing CD proteins. Doctors in Minnesota also might recommend a second bonemarrow transplant  something her parents dread saying it was the roughest treatment of all. For now Ava is happily back in school. I just want her to be a kid Bethany Christianson said. She has missed out on a lot of that."