Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplant

Maxim Norkin, Bronwen E Shaw, Ruta Brazauskas, Heather R Tecca, Helen L Leather, Juan Gea-Banacloche, Rammurti Kamble, Zachariah DeFilipp, David A Jacobsohn, Olle Ringden, Yoshihiro Inamoto, Kimberly Kasow, David Buchbinder, Peter Shaw, Peiman Hematti, Raquel Schears, Sherif M Badawy, Hillard M Lazarus, Neel Bhatt, Biljana HornSaurabh Chhabra, Kristin Page, Betty Hamilton, Gerhard C Hildebrandt, Jean A Yared, Vaibhav Agrawal, Amer Beitinjaneh, Navneet Majhail, Tamila Kindwall-Keller, Richard F Olsson, Helene Schoemans, Robert Peter Gale, Siddhartha Ganguly, Ibrahim Ahmed, Harry C Schouten, Jane Liesveld, Nandita Khera, Amir Steinberg, Ami J Shah, Melhem Solh, David I Marks, Witold Rybka, Mahmoud Aljurf, Andrew C Dietz, Usama Gergis, Biju George, Sachiko Seo, Mary E D Flowers, Minoo Battiwalla, Bipin N Savani

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Abstract

BACKGROUND: We analyzed late fatal infections (LFI) in allogeneic stem cell transplant (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research.

METHODS: We analyzed the incidence, infection types and risk factors contributing to LFI in 10336 adult and 5088 pediatric subjects surviving ≥2 years after first HCT without relapse.

RESULTS: Among 2245 adult and 377 pediatric subjects who died, infections were a primary or contributory cause of death in 687(31%) and 110(29%) subjects, respectively. At 12 years post-HCT cumulative incidence of LFIs was 6.4 % (95% confidence interval[CI]:5.8-7.0%) in adults as compared with 1.8% (95%CI:1.4-2.3%) in pediatric subjects, p<0.001. In adults, the two most significant risks for developing LFI were increasing age (20-39, 40-54 and ≥ 55 vs 18-19 years) with hazard ratio (HR) of 3.12 (95%CI:1.33-7.32), 3.86 (95%CI:1.66-8.95) and 5.49 (95%CI:2.32-12.99) and a history of chronic GVHD (cGVHD) with ongoing immunosuppression 2 years post-HCT as compared to no history of GVHD with HR 3.87 (95%CI:2.59-5.78), respectively. In pediatric subjects, the three most significant risks for developing LFI were a history of cGVHD with (HR 9.49, 95%CI:4.39-20.51) or without (HR 2.7,95%CI:1.05-7.43) ongoing immunosuppression 2 years post-HCT as compared to no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function as compared to diagnosis of acute myeloid leukemia (AML) (HR 2.30, 95%CI:1.19-4.42) and age >10 years (HR 1.92, 95%CI:1.15-3.2).

CONCLUSION: This study emphasizes the importance of continued vigilance for late infections after HCT and support strategies aimed to decrease the risk of cGVHD.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StateE-pub ahead of print - Oct 1 2018

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Norkin, M., Shaw, B. E., Brazauskas, R., Tecca, H. R., Leather, H. L., Gea-Banacloche, J., Kamble, R., DeFilipp, Z., Jacobsohn, D. A., Ringden, O., Inamoto, Y., Kasow, K., Buchbinder, D., Shaw, P., Hematti, P., Schears, R., Badawy, S. M., Lazarus, H. M., Bhatt, N., ... Savani, B. N. (2018). Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplant. Biology of Blood and Marrow Transplantation. https://doi.org/10.1016/j.bbmt.2018.09.031