Photo by Clay Eals
Patients surviving 20 to 30 years post- transplant can have normal lives, free of frequent infections. That's the result of a Hutch study that, for the first time, evaluated the immunity of long-term bone-marrow and stem-cell transplant survivors.
Though compromised immunity immediately following transplant occurs in all patients, the duration of immunodeficiency had not been known, said Dr. Jan Storek, staff scientist in Dr. David Maloney's Clinical Research Division lab and lead author of the study.
"Because bone-marrow transplantation came into general practice only in the 1980s, there has been, up until now, no opportunity to observe the immunity of very long-term survivors," he said.
Results from this study are reported in the Dec. 15 issue of the journal Blood. Other major contributors were Drs. Juni Joseph and German Espino as well as research technician Monja Dawson, all of the Clinical Research Division.
Storek, also an acting assistant professor at the University of Washington, evaluated 72 former patients who have survived 20 to 30 years post-transplant - the longest-surviving bone-marrow and stem-cell transplant patients in the world.
Quality of life after bone-marrow transplantation has long been a concern, especially for those who underwent the procedure before it was commonplace. Today, bone-marrow or stem-cell transplantation is considered the best chance for cure for people with leukemia.
Transplants require destroying diseased or damaged marrow with high-dose chemotherapy and radiation and replacement with healthy marrow or stem-cells. High-dose therapy causes blood and immune cell counts to drop to low levels, resulting in a highly immune-compromised state.
Although a patient's neutrophil (white blood cell) counts reach normal level within weeks, it can take years for the immune system to function normally. In addition, to reestablish immunity, patients who have undergone a transplant must be re-vaccinated against disease. During the recovery period for immune-system restoration, patients are susceptible to infections that can be debilitating or even life-threatening.
To determine whether the immunity of former bone-marrow transplant patients can be restored to normal by 20 years after transplant, Storek and colleagues evaluated questionnaires sent to former patients and their physicians about the occurrence of infections. Storek also reviewed medical recordsfrom the patients' primary physicians.
Storek evaluated 591 patient-years for the 72 patients. He found a total of 41 infections were reported, an average of one infection every 14 years, discounting common colds.
Storek said infections were rare despite the fact that some patients suffered from conditions known to be associated with increased susceptibility to infections.
"We believe we captured a significant majority of serious infections," he said. "However, it is possible that minor infections were underreported due to the patients not recalling these infections."
Blood samples to study immune cells were taken from 33 of the 72 patients. For most of the patients, the laboratory parameters for immunity were normal. Storek concluded that their immunity recovered to normal or near-normal by the time they were 20 years post-transplant.
Another possible explanation
"We realize there may be another explanation of the results," Storek said. "Instead of a gradual improvement of their immunity over the first two decades after transplant, the studied patients may have had a good immune system already between one and five years after transplant.
"However, we know that their immunity was still very abnormal in the first year after transplant, because the rate of infections between the time of neutrophil engraftment and day 365 was 18-times higher than around 20 years post-transplant."
Storek said the study depended upon the willing contribution of patients. "These individuals live generally busy professional lives," he said. "Yet in the midst of their busy days, they were willing to fill out questionnaires and have blood drawn and sent to us."
He also noted that the willingness of the patients and some of their marrow donors, who also donated blood for the research, led to an important finding: "For the first time, it was proven that the transplanted hematopoietic cells and/or immune cells persist and are active after 20 to 30 years."