Transplant

BOSTON — Long-term outcomes of hand transplant patients show that recipients can have good graft functionality and quality of life if they comply with immunosuppressive regimens, according to speakers at the 2006 World Transplant Congress.

Worldwide experience with hand transplants now includes 24 hands in 18 patients with “excellent results,” said Dr. Suzanne T. Ildstad, director of the Institute for Cellular Therapeutics at the University of Louisville (Ky.).

Patients are reluctant to undertake a hand transplant “until we modify or reduce the intensity of immunosuppression,” said Dr. Ildstad. “There are discussions right now with our group and other groups of using steroid-sparing protocols as well as attempts to induce tolerance,” she noted.

Dr. Ildstad presented the 7-year results of a 37-year-old, left-hand-dominant man (patient No. 1, currently the recipient of the longest-surviving hand transplant in the world) and the 4-year results of a 36-year-old, right-hand-dominant man (patient No. 2). Both men lost their left hands in fireworks accidents.

On measurements with the United Kingdom Medical Research Council strength scale, patient No. 1 had an excellent return of function of intrinsic muscles whereas patient No. 2 had an improved, but somewhat delayed, return of function because of a period of noncompliance with his immunosuppressive regimen.

Sensation gradually improved in patient No. 1 to the point where it has become “essentially normal” after 7 years of follow-up, Dr. Ildstad said. Patient No. 2 also experienced gradual improvement in sensation, but it was slightly delayed in comparison with patient No. 1.

In skin biopsy specimens from both patients, low-grade cellular infiltrates have been detected. The patients did not have rejections treated unless they were severe, she said.

When patient No. 2 decided to stop taking his immunosuppressive medications, he subsequently had a grade 3 rejection episode that was “relatively readily reversed” with antithymocyte globulins (Thymoglobulin), increased doses of tacrolimus (Prograf), and corticosteroid boluses, which is contrary to what Dr. Ildstad and many transplant immunologists would have predicted because of the presumed antigenicity of the skin.

In a study of two men who received bilateral hand transplants, improvement in function was accompanied by changes in brain function and good quality of life, reported Dr. Palmina Petruzzo of the department of transplantation at Hôpital Edouard Herriot, Lyon, France.

Functional MRI shows that the patients' representation of their hands in their brains progressively shifted from lateral to medial regions of the motor cortex.

By 2 years following transplantation, hand motor coordination had improved in both patients to the point where they could perform complex movements involving intersegmental coordination, which were assessed while the patients wore a CyberGlove containing 22 sensors that monitor hand movement, according to Dr. Ildstad.

A recipient of a transplant of a left hand demonstrated his manual dexterity and control by tying his shoe at his 4-year checkup. Courtesy Jewish Hospital/Kleinert, Kutz and Associates Hand Care Center/University of Louisville

BOSTON — Long-term outcomes of hand transplant patients show that recipients can have good graft functionality and quality of life if they comply with immunosuppressive regimens, according to speakers at the 2006 World Transplant Congress.

Worldwide experience with hand transplants now includes 24 hands in 18 patients with “excellent results,” said Dr. Suzanne T. Ildstad, director of the Institute for Cellular Therapeutics at the University of Louisville (Ky.).

Patients are reluctant to undertake a hand transplant “until we modify or reduce the intensity of immunosuppression,” said Dr. Ildstad. “There are discussions right now with our group and other groups of using steroid-sparing protocols as well as attempts to induce tolerance,” she noted.

Dr. Ildstad presented the 7-year results of a 37-year-old, left-hand-dominant man (patient No. 1, currently the recipient of the longest-surviving hand transplant in the world) and the 4-year results of a 36-year-old, right-hand-dominant man (patient No. 2). Both men lost their left hands in fireworks accidents.

On measurements with the United Kingdom Medical Research Council strength scale, patient No. 1 had an excellent return of function of intrinsic muscles whereas patient No. 2 had an improved, but somewhat delayed, return of function because of a period of noncompliance with his immunosuppressive regimen.

Sensation gradually improved in patient No. 1 to the point where it has become “essentially normal” after 7 years of follow-up, Dr. Ildstad said. Patient No. 2 also experienced gradual improvement in sensation, but it was slightly delayed in comparison with patient No. 1.

In skin biopsy specimens from both patients, low-grade cellular infiltrates have been detected. The patients did not have rejections treated unless they were severe, she said.

When patient No. 2 decided to stop taking his immunosuppressive medications, he subsequently had a grade 3 rejection episode that was “relatively readily reversed” with antithymocyte globulins (Thymoglobulin), increased doses of tacrolimus (Prograf), and corticosteroid boluses, which is contrary to what Dr. Ildstad and many transplant immunologists would have predicted because of the presumed antigenicity of the skin.

In a study of two men who received bilateral hand transplants, improvement in function was accompanied by changes in brain function and good quality of life, reported Dr. Palmina Petruzzo of the department of transplantation at Hôpital Edouard Herriot, Lyon, France.

Functional MRI shows that the patients' representation of their hands in their brains progressively shifted from lateral to medial regions of the motor cortex.

By 2 years following transplantation, hand motor coordination had improved in both patients to the point where they could perform complex movements involving intersegmental coordination, which were assessed while the patients wore a CyberGlove containing 22 sensors that monitor hand movement, according to Dr. Ildstad.

A recipient of a transplant of a left hand demonstrated his manual dexterity and control by tying his shoe at his 4-year checkup. Courtesy Jewish Hospital/Kleinert, Kutz and Associates Hand Care Center/University of Louisville

BOSTON — Long-term outcomes of hand transplant patients show that recipients can have good graft functionality and quality of life if they comply with immunosuppressive regimens, according to speakers at the 2006 World Transplant Congress.

Worldwide experience with hand transplants now includes 24 hands in 18 patients with “excellent results,” said Dr. Suzanne T. Ildstad, director of the Institute for Cellular Therapeutics at the University of Louisville (Ky.).

Patients are reluctant to undertake a hand transplant “until we modify or reduce the intensity of immunosuppression,” said Dr. Ildstad. “There are discussions right now with our group and other groups of using steroid-sparing protocols as well as attempts to induce tolerance,” she noted.

Dr. Ildstad presented the 7-year results of a 37-year-old, left-hand-dominant man (patient No. 1, currently the recipient of the longest-surviving hand transplant in the world) and the 4-year results of a 36-year-old, right-hand-dominant man (patient No. 2). Both men lost their left hands in fireworks accidents.

On measurements with the United Kingdom Medical Research Council strength scale, patient No. 1 had an excellent return of function of intrinsic muscles whereas patient No. 2 had an improved, but somewhat delayed, return of function because of a period of noncompliance with his immunosuppressive regimen.

Sensation gradually improved in patient No. 1 to the point where it has become “essentially normal” after 7 years of follow-up, Dr. Ildstad said. Patient No. 2 also experienced gradual improvement in sensation, but it was slightly delayed in comparison with patient No. 1.

In skin biopsy specimens from both patients, low-grade cellular infiltrates have been detected. The patients did not have rejections treated unless they were severe, she said.

When patient No. 2 decided to stop taking his immunosuppressive medications, he subsequently had a grade 3 rejection episode that was “relatively readily reversed” with antithymocyte globulins (Thymoglobulin), increased doses of tacrolimus (Prograf), and corticosteroid boluses, which is contrary to what Dr. Ildstad and many transplant immunologists would have predicted because of the presumed antigenicity of the skin.

In a study of two men who received bilateral hand transplants, improvement in function was accompanied by changes in brain function and good quality of life, reported Dr. Palmina Petruzzo of the department of transplantation at Hôpital Edouard Herriot, Lyon, France.

Functional MRI shows that the patients' representation of their hands in their brains progressively shifted from lateral to medial regions of the motor cortex.

By 2 years following transplantation, hand motor coordination had improved in both patients to the point where they could perform complex movements involving intersegmental coordination, which were assessed while the patients wore a CyberGlove containing 22 sensors that monitor hand movement, according to Dr. Ildstad.

A recipient of a transplant of a left hand demonstrated his manual dexterity and control by tying his shoe at his 4-year checkup. Courtesy Jewish Hospital/Kleinert, Kutz and Associates Hand Care Center/University of Louisville

Although nerve transplantations are rarely performed, they can provide an alternative to amputation, and some surgeons say they should be considered for seriously injured patients.

Surgeons interviewed for this article identified a total of nine neurosurgeons and plastic surgeons, including themselves, who have transplanted nerves from living donors for more than 10 years.

The surgeons believe that thousands of patients—including soldiers returning from Iraq—could benefit from transplantations and similar procedures. Soldiers who suffer blunt injuries to an isolated spot of nerve would be especially good candidates, said Dr. Andrew Elkwood in an interview.

Dr. Susan Mackinnon, a plastic surgeon at Washington University in St. Louis, performed the first nerve transplantation from a live donor in 1989 in Canada. Transplantation is used as a last resort if patients do not have enough of their own nerve tissue for a graft, she said.

Grafts of patients' own nerve tissues have been around for years, said Dr. Elkwood, a plastic surgeon who practices in New Jersey.

Both surgeons prefer live donors over cadavers for transplantations because family members usually are willing to donate nerve tissue immediately and such tissue is less likely to be rejected than cadaver tissue. It can take several months to find an appropriate cadaver, they added.

The ideal time for a transplantation is 3 months after injury, according to Dr. Elkwood.

In November, Dr. Allan Belzberg, a neurosurgeon at Johns Hopkins University, performed his first allograft transplantation of nerves from a 40-year-old mother to her 19-year-old son, to restore the use of his hand 1 year after an automobile accident left him with left leg amputation and 14-cm gaps in the median and ulnar nerves of the left arm going to the hand.

Dr. Belzberg opted against an autologous graft of expendable leg nerves because the patient had already lost one leg and the other had been broken in seven places. Nor did he want to remove nerves from the patient's one good arm.

Dr. Belzberg harvested nerves from the mother's legs and arms.

Within 3 months, Dr. Belzberg should know if the patient's nerves have regenerated. If all goes well, he will regain motion in his fingers within 8 months and, within 2 years, bend his elbow, grasp with his fingers, and feel protective sensations such as pain, cold, and heat, Dr. Belzberg said. He estimated the chances of achieving these outcomes as 50%–75%.

The patient will take the immunosuppression drug tacrolimus (FK 506) for about 2 years. One side effect of the drug is nerve growth, but Dr. Belzberg said he and a team of other doctors believe the drug is unlikely to spur tumor formation.

Dr. Mackinnon and other surgeons are now using another technique, nerve transfer, to treat patients in whom part of the brachial plexus has been torn. Nerve transfer consists of sacrificing the function of expendable portions of a patient's healthy nerves to revive function in a seriously injured, more crucial nerve.

Bundles of a healthy nerve near the motor end plate of the damaged muscle are teased apart and redirected to revive function in the recipient nerve and muscle. No grafting is necessary.

The technique changes the nerve injury from a proximal injury to a distal one, so nerves—which regenerate only about an inch a month—have less distance to grow, Dr. Mackinnon said.

For example, an injury to the ulnar nerve in the upper arm can require 2 years of recovery after grafting. But “stealing” nerve fibers from the pronator quadratus would require only a few months of recovery, Dr. Mackinnon said.

“There's a strong need for these procedures [transplantations and transfers],” Dr. Elkwood said, adding that too many physicians are unaware they are being done successfully. “We need massive education [about these procedures]. They need to become more mainstream in the lay and medical communities,” he said.

Although nerve transplantations are rarely performed, they can provide an alternative to amputation, and some surgeons say they should be considered for seriously injured patients.

Surgeons interviewed for this article identified a total of nine neurosurgeons and plastic surgeons, including themselves, who have transplanted nerves from living donors for more than 10 years.

The surgeons believe that thousands of patients—including soldiers returning from Iraq—could benefit from transplantations and similar procedures. Soldiers who suffer blunt injuries to an isolated spot of nerve would be especially good candidates, said Dr. Andrew Elkwood in an interview.

Dr. Susan Mackinnon, a plastic surgeon at Washington University in St. Louis, performed the first nerve transplantation from a live donor in 1989 in Canada. Transplantation is used as a last resort if patients do not have enough of their own nerve tissue for a graft, she said.

Grafts of patients' own nerve tissues have been around for years, said Dr. Elkwood, a plastic surgeon who practices in New Jersey.

Both surgeons prefer live donors over cadavers for transplantations because family members usually are willing to donate nerve tissue immediately and such tissue is less likely to be rejected than cadaver tissue. It can take several months to find an appropriate cadaver, they added.

The ideal time for a transplantation is 3 months after injury, according to Dr. Elkwood.

In November, Dr. Allan Belzberg, a neurosurgeon at Johns Hopkins University, performed his first allograft transplantation of nerves from a 40-year-old mother to her 19-year-old son, to restore the use of his hand 1 year after an automobile accident left him with left leg amputation and 14-cm gaps in the median and ulnar nerves of the left arm going to the hand.

Dr. Belzberg opted against an autologous graft of expendable leg nerves because the patient had already lost one leg and the other had been broken in seven places. Nor did he want to remove nerves from the patient's one good arm.

Dr. Belzberg harvested nerves from the mother's legs and arms.

Within 3 months, Dr. Belzberg should know if the patient's nerves have regenerated. If all goes well, he will regain motion in his fingers within 8 months and, within 2 years, bend his elbow, grasp with his fingers, and feel protective sensations such as pain, cold, and heat, Dr. Belzberg said. He estimated the chances of achieving these outcomes as 50%–75%.

The patient will take the immunosuppression drug tacrolimus (FK 506) for about 2 years. One side effect of the drug is nerve growth, but Dr. Belzberg said he and a team of other doctors believe the drug is unlikely to spur tumor formation.

Dr. Mackinnon and other surgeons are now using another technique, nerve transfer, to treat patients in whom part of the brachial plexus has been torn. Nerve transfer consists of sacrificing the function of expendable portions of a patient's healthy nerves to revive function in a seriously injured, more crucial nerve.

Bundles of a healthy nerve near the motor end plate of the damaged muscle are teased apart and redirected to revive function in the recipient nerve and muscle. No grafting is necessary.

The technique changes the nerve injury from a proximal injury to a distal one, so nerves—which regenerate only about an inch a month—have less distance to grow, Dr. Mackinnon said.

For example, an injury to the ulnar nerve in the upper arm can require 2 years of recovery after grafting. But “stealing” nerve fibers from the pronator quadratus would require only a few months of recovery, Dr. Mackinnon said.

“There's a strong need for these procedures [transplantations and transfers],” Dr. Elkwood said, adding that too many physicians are unaware they are being done successfully. “We need massive education [about these procedures]. They need to become more mainstream in the lay and medical communities,” he said.

Although nerve transplantations are rarely performed, they can provide an alternative to amputation, and some surgeons say they should be considered for seriously injured patients.

Surgeons interviewed for this article identified a total of nine neurosurgeons and plastic surgeons, including themselves, who have transplanted nerves from living donors for more than 10 years.

The surgeons believe that thousands of patients—including soldiers returning from Iraq—could benefit from transplantations and similar procedures. Soldiers who suffer blunt injuries to an isolated spot of nerve would be especially good candidates, said Dr. Andrew Elkwood in an interview.

Dr. Susan Mackinnon, a plastic surgeon at Washington University in St. Louis, performed the first nerve transplantation from a live donor in 1989 in Canada. Transplantation is used as a last resort if patients do not have enough of their own nerve tissue for a graft, she said.

Grafts of patients' own nerve tissues have been around for years, said Dr. Elkwood, a plastic surgeon who practices in New Jersey.

Both surgeons prefer live donors over cadavers for transplantations because family members usually are willing to donate nerve tissue immediately and such tissue is less likely to be rejected than cadaver tissue. It can take several months to find an appropriate cadaver, they added.

The ideal time for a transplantation is 3 months after injury, according to Dr. Elkwood.

In November, Dr. Allan Belzberg, a neurosurgeon at Johns Hopkins University, performed his first allograft transplantation of nerves from a 40-year-old mother to her 19-year-old son, to restore the use of his hand 1 year after an automobile accident left him with left leg amputation and 14-cm gaps in the median and ulnar nerves of the left arm going to the hand.

Dr. Belzberg opted against an autologous graft of expendable leg nerves because the patient had already lost one leg and the other had been broken in seven places. Nor did he want to remove nerves from the patient's one good arm.

Dr. Belzberg harvested nerves from the mother's legs and arms.

Within 3 months, Dr. Belzberg should know if the patient's nerves have regenerated. If all goes well, he will regain motion in his fingers within 8 months and, within 2 years, bend his elbow, grasp with his fingers, and feel protective sensations such as pain, cold, and heat, Dr. Belzberg said. He estimated the chances of achieving these outcomes as 50%–75%.

The patient will take the immunosuppression drug tacrolimus (FK 506) for about 2 years. One side effect of the drug is nerve growth, but Dr. Belzberg said he and a team of other doctors believe the drug is unlikely to spur tumor formation.

Dr. Mackinnon and other surgeons are now using another technique, nerve transfer, to treat patients in whom part of the brachial plexus has been torn. Nerve transfer consists of sacrificing the function of expendable portions of a patient's healthy nerves to revive function in a seriously injured, more crucial nerve.

Bundles of a healthy nerve near the motor end plate of the damaged muscle are teased apart and redirected to revive function in the recipient nerve and muscle. No grafting is necessary.

The technique changes the nerve injury from a proximal injury to a distal one, so nerves—which regenerate only about an inch a month—have less distance to grow, Dr. Mackinnon said.

For example, an injury to the ulnar nerve in the upper arm can require 2 years of recovery after grafting. But “stealing” nerve fibers from the pronator quadratus would require only a few months of recovery, Dr. Mackinnon said.

“There's a strong need for these procedures [transplantations and transfers],” Dr. Elkwood said, adding that too many physicians are unaware they are being done successfully. “We need massive education [about these procedures]. They need to become more mainstream in the lay and medical communities,” he said.