Knee replacement surgery works, but so can nonsurgical techniques

Total knee replacement can usually relieve pain and improve function, but a nonsurgical regimen can also be effective in some people without posing the complication risks that can plague people who choose surgery, according to a new study.

The test found that while 85 percent of patients who underwent surgery showed clinically-significant improvement after one year, so did 67 percent assigned to a combination of supervised exercise, use of insoles, pain medication, education and dietary advice.

"It won't do any harm trying the nonsurgical treatment," chief author, Dr. Soren Skou of the University of Southern Denmark in Odense, told Reuters Health. "I hope this will give a more balanced discussion of whether or not to have the surgery."

There's little debate that knee replacement helps many people, and the new test of 100 patients—the first randomized controlled trial ever done on the technique—confirms it. Surgery patients didn't show just some improvement. They registered far less pain and disability than those assigned to the non-surgery group.

Yet the study was needed because as many as 1 percent of surgery patients die within 90 days of their operation and about 1 in 5 have residual pain at least six months after the procedure, said Dr. Jeffrey Katz of Harvard Medical School in Cambridge, Massachusetts, in an accompanying editorial in the New England Journal of Medicine. "Until now, we have lacked rigorously controlled comparisons between total knee replacement and its alternatives."

"People need to understand and respect that knee replacement is not without complication. Knee replacement is a big surgical procedure and there are risks associated with it," Dr. Andrew Pollak, chairman of orthopedics at the University of Maryland School of Medicine in Baltimore, told Reuters Health.

The study "really emphasizes what we suspected all along—total knee replacement works. It will be obvious to many of us who take care of patients. But for patients with significant symptoms and evidence of arthritis, total knee replacement is a very effective way of improving quality of life," said Pollak, who was not associated with the research. "Therapy alone has a role. It does help certain patients. It can certainly prolong the time to when knee replacement is necessary."

More than 670,000 total knee replacements are done in the US each year at a cost of $36.1 billion.

All of the patients in the study had moderate-to-severe knee osteoarthritis. The team measured symptoms, pain and quality of life over a one year period.

Volunteers in the surgery group gained an average of 32.5 points versus 16.0 points for people who received nonsurgical therapy. All started off with a score of about 48 on a 101-point assessment scale.

Individual measures of pain, symptoms, activities of daily living, quality of life, and sports and recreation all showed significant improvement with surgery.

But while there were just six instances of serious adverse events in the 50 patients who didn't receive surgery, there were four times as many among the 50 assigned to have a knee replaced. One third of the problems involved the replaced knee, including three cases each of unacceptable stiffness and deep vein thrombosis requiring anticoagulation, and one case each of deep infection and leg fracture.

Thirteen of the 50 patients assigned to the no-surgery group ended up having their knee replaced anyway during the 12-month follow-up period.

"We've had some patients who had the surgery who did not improve in pain and, in some cases, had worse pain," Skou said. They may improve with longer followup, but, he said, "what struck me is, if you do not go through surgery, you could always have the surgery later." —Reuters

Last-resort leukemia treatment produces dramatic remission rate

NEW YORK - Ninety percent of people facing death because conventional treatments had failed to destroy their leukemia have responded to an experimental therapy that trains their cells to kill out-of-control blood cells, doctors in Philadelphia report.

Twenty seven of the 25 children and 5 adults initially responded to the new therapy. Nineteen - including a 9-year-old treated two and a half years ago - have remained cancer-free and 15 of those 19 have not receive any subsequent therapy.

"We're astonished how well it turned out," senior author Dr. Stephan Grupp of Children's Hospital of Philadelphia told Reuters Health. Doctors are often happy if a treatment can improve the remission rate by 3 percent to 5 percent. "In our wildest dreams, we didn't think it would work as well as it did for the patients we've treated so far," Grupp said.

"It's equally impressive in both the adult and pediatric population," said Dr. Noelle Frey of the University of Pennsylvania, who directed the adult portion of the study.

"These are patients where the chances of cure are close to zero, if not zero," she said. "This is a therapy that not only gives hope, but is also correlated with tremendous success."

The treatment results, reported in the New England Journal of Medicine, are part of a broader effort to reprogram the cells of cancer patients so they reproduce rapidly and attack the rogue cells responsible for tumors.

"If this has curative potential - which we don't know yet, but seems to be the case - it's a game changer," said Dr. Michael Sadelain of Memorial Sloan Kettering Cancer Center, part of a separate team that previously used the technique to produce complete remissions in 14 out of 16 adults who had acute lymphoblastic leukemia (ALL) of a stage "where nobody would go into complete remission."

"The good news is, this therapy can work just as well in children as it was reported to do in adults," he told Reuters Health.

In the Philadelphia study, other treatments - as many as four - had failed in the 30 patients. Conventional therapy typically cures 80 percent to 85 percent of children with ALL and those children "don't need this," said Grupp. "The other 15 percent or so are candidates for this."

Adults with ALL are tougher to treat, "so 50 percent or more might need this," he said.

In July, the U.S. Food and Drug Administration gave the treatment, known as CTL019, a Breakthrough Therapy designation designed to expedite its development for ALL.

The Philadelphia researchers have also been experimenting with CTL019 for chronic lymphocytic leukemia and Hodgkin's lymphoma,. The remission rates in those tests have been high, but not nearly as high as with ALL, Frey told Reuters Health. Those findings have not been published.

The ALL treatment involves training disease-fighting blood cells known as T-cells. Once removed from a patient's body, they are programmed to hunt cancer cells that have a telltale protein on their surface. The specially-trained cells are then re-injected into the patient. The re-engineering process currently costs about $25,000.

Of the initial 30 patients, 27 were in complete remission by the one-month mark, but seven relapsed over a period ranging from 6 weeks to 8.5 months after treatment. Twenty three were alive at the six-month mark. Five of the 23 left the study to receive other treatments, including stem cell transplantation.

The treatment is not without serious risks. The most common is cytokine release syndrome, where the body appears to react to the mass killing of tumor cells.

Patients "become tired, achy and nauseous," said Frey. "You can also get low blood pressure and breathing difficulties. Unfortunately, it can be life-threatening. But we have, in most cases, been able to reverse it. Yet in most situations it’s very manageable."

“For our patients who have already relapsed after stem cell transplants, or don’t have any options for donors," she said, "this option has provided new hope.”

In eight of the 27 cases where there was a response, cytokine release syndrome was judged to be severe and the patients ended up in intensive care.

At least part of the technique involved in the Philadelphia study has been licensed to Novartis. Sloan Kettering has teamed up with a start-up company, Juno Therapeutics, which will conduct a multicenter study of adults with ALL, Sadelain said.

"That's a sea change in the field because, until now, this realm of cell therapy was almost exclusively in the hands of academic centers," he said. "Now you see a whole host of companies moving into this space. Investors have been impressed by these results and will take them far beyond what academic centers will do." — Reuters