Allogeneic hematopoietic stem cell transplants (HCT) have been used to treat various diseases of the blood, often with great success. Among the hematologic diseases treated are non-malignant disorders, including immune deficiencies, metabolic diseases, and bone marrow failure syndromes. Despite its curative ability, allogeneic HCT carries risks of toxicity from conditioning chemotherapy and post-transplant complications such as graft-versus-host-disease or infections. Patients with hematologic diseases frequently suffer from other disorders, such as pulmonary or hepatic disease, known as comorbidities. These comorbidities might make allogeneic HCT riskier for the patient. In order to better predict risk for patients who could benefit from allogeneic HCT, Dr. Mohamed Sorror and colleagues at Clinical Research Division of Fred Hutch developed the HCT comorbidity index (HCT-CI), which weights and totals these comorbidities in each patient. The HCT-CI has been studied so far mainly in patients with malignant diseases.
Drs. Mohamed Sorror and Monica Thakar (Clinical Research Division) wanted to fill in the gaps by studying the ability of the HCT-CI to predict overall survival (OS) in patients with non-malignant hematologic diseases. The study, recently published in Blood, was done using the Center of International Blood and Marrow Transplantation (CIBMTR) database that collects transplant information from all US transplant institutions.
Over 4000 patients with non-malignant disease treated with allogeneic HCT were included in the study. These patients were grouped according to comorbidity score. The data showed that very similar OS between patients with zero and patients with one to two comorbidities (82.7% and 80.3% respectively). However, survival was lower in patients with three to four (74%) and five or more comorbidities (55.8%). These results provide evidence that patients with some organ damage would be less able to tolerate allogeneic HCT, even if their primary disease is non-malignant hematologic disease.
The authors then stratified the groups further and looked at the OS of patients with each individual disease for which they were receiving the HCT. Many of the groups, such as those with acquired aplastic anemia, immune deficiencies, and bone marrow failure syndromes, followed the same pattern of lower OS in patients with HCT-CI scores of three or more. Surprisingly, those patients with hemoglobinopathies, a category which includes sickle cell anemia, did not follow the trend. Those with hemoglobinopathies and a score of three or more had similar OS (91.1%) when compared with those who had one to two (92.8%) or zero comorbidities (86.5%). When asked about these surprising results, Sorror said, “The prediction of survival worked in most of the diagnoses with the exception of hemoglobinopathies. I didn’t think that the impact would differ based on diagnosis, I think it’s more of a statistical issue. We need to study a different cohort with a larger sample size and maybe also look at other types of comorbidities.” The comorbidities not currently scored in HCT-CI could include symptoms of vascular disease common among patients with hemoglobinopathies.
On the importance of the findings, Sorror said, “This information will be important when counseling patients in the clinic about the benefits of transplant. The benefits of transplant for someone who has no or very low burden of comorbidities would be different from someone who is loaded with comorbidities. In some cases, alternative therapy could provide similar survival advantages.”
Sorror also commented about how the information gleaned from this study would aid in a new randomized trial. “Here at the Hutch, in collaboration with other institutions, we developed a trial where we take the patients who score three or more, with malignant or non-malignant disease, and we are going to study in a randomized fashion novel interventions how we can minimize the morbidities and mortalities,” Sorror said. “One of these approaches is supportive palliative care before and after transplant. The other approach is targeting their specific comorbidities with some lifestyle modifications and other types of interventions. Hopefully that can improve the resilience and tolerability to the transplant and by that improve their survival.”
Thakar M, Broglie L, Logan B, Artz A, Bunin N, Burroughs LM, Fretham C, Jacobsohn DA, Loren AW, Kurtzberg J, Martinez CA, Mineishi S, Nelson AS, Woolfrey A, Pasquini MC, Sorror ML. 2018. The Hematopoietic Cell Transplant Comorbidity Index predicts survival after allogeneic transplant for non-malignant diseases. Blood. 2018-09-876284. doi: https://doi.org/10.1182/blood-2018-09-876284
This study was funded by the National Center for Advancing Translational Sciences and the Midwest Athletes Against Childhood Cancer Fund.
Fred Hutch/UW Cancer Consortium members Mohamed Sorror (FH/UW), Lauri Burroughs (FH), and Ann Woolfrey (FH/UW) contributed to this work.