Increased overall and bacterial infections following myeloablative allogeneic HCT for patients with AML in CR1

Author:

Ustun Celalettin1ORCID,Kim Soyoung23ORCID,Chen Min2,Beitinjaneh Amer M.4,Brown Valerie I.5,Dahi Parastoo B.6,Daly Andrew7,Diaz Miguel Angel8,Freytes Cesar O.9ORCID,Ganguly Siddhartha10,Hashmi Shahrukh1112ORCID,Hildebrandt Gerhard C.13ORCID,Lazarus Hillard M.14ORCID,Nishihori Taiga15ORCID,Olsson Richard F.1617ORCID,Page Kristin M.18,Papanicolaou Genovefa19,Saad Ayman20ORCID,Seo Sachiko21,William Basem M.20,Wingard John R.22,Wirk Baldeep23,Yared Jean A.24ORCID,Perales Miguel-Angel25,Auletta Jeffery J.262728,Komanduri Krishna V.4ORCID,Lindemans Caroline A.2930,Riches Marcie L.31ORCID

Affiliation:

1. Division of Hematology/Oncology/Cell Therapy, Rush University, Chicago, IL;

2. Center for International Blood and Marrow Transplant Research, Department of Medicine, and

3. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI;

4. Department of Hematology, University of Miami, Miami, FL;

5. Division of Pediatric Oncology/Hematology, Department of Pediatrics, Penn State Hershey Children’s Hospital and College of Medicine, Hershey, PA;

6. Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY;

7. Tom Baker Cancer Center, Calgary, AB, Canada;

8. Department of Hematology/Oncology, Hospital Infantil Universitario Nino Jesus, Madrid, Spain;

9. Texas Transplant Institute, San Antonio, TX;

10. Division of Hematological Malignancy and Cellular Therapeutics, University of Kansas Health System, Kansas City, KS;

11. Department of Internal Medicine, Mayo Clinic, Rochester, MN;

12. Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;

13. Markey Cancer Center, University of Kentucky, Lexington, KY;

14. Stem Cell Transplant Program, Division of Hematology and Oncology, Department of Medicine, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH;

15. Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;

16. Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden;

17. Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden;

18. Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, NC;

19. Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY;

20. Division of Hematology, The Ohio State University, Columbus, OH;

21. Department of Haematology and Oncology, Dokkyo Medical University, Tochigi, Japan;

22. Division of Hematology & Oncology, Department of Medicine, University of Florida, Gainesville, FL;

23. Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, WA;

24. Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD;

25. Adult Bone Marrow Transplant Services, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;

26. Blood and Marrow Transplant Program and

27. Host Defense Program, Division of Hematology, Oncology, and Blood Marrow & Transplant, and

28. Division of Infectious Diseases, Nationwide Children’s Hospital, Columbus, OH;

29. Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;

30. Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands; and

31. Division of Hematology/Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC

Abstract

Abstract Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT–comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range, <1-99 days]; RIC/NMA, 21 days [range, <1-100 days]; P < .001). Patients receiving MAC were more likely to experience at least 1 bacterial infection by day 100 (MAC, 46% [95% confidence interval (CI), 43-49]; RIC/NMA, 37% [95% CI, 34-41]; P = .0004), whereas at least a single viral infection was more prevalent in the RIC/NMA cohort (MAC, 34% [95% CI, 31-37]; RIC/NMA, 39% [95% CI, 36-42]; P = .046). MAC remained a risk factor for bacterial infections in multivariable analysis (relative risk, 1.44; 95% CI, 1.23-1.67; P < .0001). Moreover, the rate of any infection per patient-days at risk in the first 100 days (infection density) after alloHCT was greater for the MAC cohort (1.21; 95% CI, 1.11-1.32; P < .0001). RIC/NMA was associated with reduced infections, especially bacterial infections, in the first 100 days after alloHCT.

Publisher

American Society of Hematology

Subject

Hematology

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