Hematopoietic cell transplant leads to long-term risk of infection

From the Chow Group, Clinical Research and Public Health Sciences Divisions

Hematopoietic cell transplant (HCT) is a curative therapy for multiple cancers and non-malignant diseases. Before the HCT itself, the patient’s immune system is ablated with a preconditioning regime of chemotherapy and radiation, which allows the donor cells to grow in the patient and reconstitute a new immune system. However, complete immune reconstitution can take months, or even years, leaving HCT patients at risk for opportunistic infections. Additionally, acute or chronic graft-versus-host-disease (GVHD), a common complication of HCT, is managed with immunosuppressive drugs, leaving HCT patients with prolonged risk of infection. Though HCT patients are now commonly surviving longer, a comprehensive understanding of their long-term risks of infection was absent. Dr. Eric Chow (Clinical Research and Public Health Sciences Divisions) wanted to better understand the risk of infection for cancer patients who receive HCT compared to cancer patients who do not. He led a retrospective study that was recently published in Blood Advances.

To understand the relative risk of infection for cancer patients who undergo HCT, the authors needed a proper comparison group, which has limited previous studies. HCT patients included in the study were Washington state residents treated by Fred Hutch from 1992-2009 who survived at least two years post-transplant: 1,634 patients in total. The authors used the Washington State Cancer Registry to identify cancer patients diagnosed from 1992-2009 that survived at least two years but did not receive HCT therapy as part of their cancer treatment. This group (non-HTC) was matched demographically to the HCT group and consisted of 5,455 patients. For a general population comparison group, the authors used the Washington State Department of Licensing (DOL) files to randomly select demographically matched subjects, and records were cross compared to state death records to ensure subjects did not die within two years after licensing. The DOL group consisted of 16,340 subjects. With these groups, the authors then assessed hospitalization records using the Washington State Comprehensive Hospital Abstract Reporting System, a database with diagnosis codes for hospitalizations. This approach allowed the authors to track whether the subjects were hospitalized for infections from 1992-2011. In all, over 2,500 infections were tracked and analyzed, a wealth of information to allow the authors to identify infection risk for each group. 

Infection rate ratio of HCT cancer patients compared to non-HTC cancer patients (red circles) or compared to the general population (blue squares).
Infection rate ratio of HCT cancer patients compared to non-HTC cancer patients (red circles) or compared to the general population (blue squares). From Blood Advances

When looking at the overall infection rate regardless of infection type, the authors found that the infection rate in HCT patients was approximately twice the rate of non-HCT cancer patients and about ten times the rate in the general population. HCT patients experienced 70% more bacterial and fungal infections and 40% more viral infections than non-HTC patients. Respiratory infections, including all forms of pneumonia, were significantly higher in HTC patients than non-HTC patients. When the HTC group was compared to the DOL group, rates of all infections regardless of affected organ system were greatly increased, many exceeding ten times the infection rate in the general population. Additionally, the authors compared rates of vaccine-preventable infections and found that HTC patients had approximately 3 and 35 times the rate of infection compared to the non-HTC and DOL groups, respectively. Relapse of cancer was associated with an increased risk of infection; however, HTC subjects still had an increased rate of infection compared to non-HTC when patients who relapsed were removed from the analysis, indicating relapse was not the only risk factor. The authors wanted to understand whether patients who had survived longer after transplant would have a reduced risk of infection, possibly due to longer time for immune reconstitution. To understand this, the authors limited their analysis to subjects who survived 5+ years in each group; however, HCT patients still had an increased risk of infection compared to non-HTC cancer patients, indicating infection risk did not decrease with time. This trend held true for vaccine-preventable infection over 5 years, suggesting re-vaccination of HTC patients may be a potential strategy for long term health of patients. Dr. Foord, the first author of the article, explained the importance of their findings: “Vaccine preventable late infections were much higher in HCT patients, identifying a potential area for intervention and further investigation and strongly suggesting that patients and providers should maintain vigilance of infectious complications and the prolonged time it takes for the immune system to recover after HCT.  To our knowledge, this is the most comprehensive description and comparison of infectious complications occurring in long-term HCT survivors versus non-HCT cancer and noncancer populations in the literature.”

This work was supported by National Institutes of Health. A large portion of the data provided by the Washington State Cancer Registry were collected under NIH Surveillance, Epidemiology, and End Results (SEER) program contract.

UW/Fred Hutch Cancer Consortium members Michael Boeckh, Paul Carpenter, Mary Flowers, Stephanie Lee, Beth Mueller, Joshua Hill, and Eric Chow contributed to this work.

Foord AM, Cushing-Haugen KL, Boeckh MJ, Carpenter PA, Flowers MED, Lee SJ, Leisenring WM, Mueller BA, Hill JA, Chow EJ. 2020. Late infectious complications in hematopoietic cell transplantation survivors: a population-based study. Blood Adv. 4(7):1232-1241. doi: 10.1182/bloodadvances.2020001470