4.6 Article

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

Journal

BLOOD ADVANCES
Volume 3, Issue 17, Pages 2525-2536

Publisher

AMER SOC HEMATOLOGY
DOI: 10.1182/bloodadvances.2019000226

Keywords

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Categories

Funding

  1. Public Health Service from National Cancer Institute [5U24CA076518]
  2. National Heart, Lung, and Blood Institute
  3. National Institute of Allergy and Infectious Diseases of the National Institutes of Health
  4. National Institues of Health, National Heart, Lung, and Blood Institute [4U10HL069294]
  5. National Cancer Institute
  6. Health Resources and Services Administration (Department of Health and Human Services) [HHSH250201200016C]
  7. Office of Naval Research [N00014-17-1-2388, N0014-17-1-2850]
  8. Actinium Pharmaceuticals, Inc.
  9. Amgen, Inc.
  10. Amneal Biosciences
  11. Angiocrine Bioscience, Inc.
  12. Astellas Pharma US
  13. Atara Biotherapeutics, Inc.
  14. Be the Match Foundation
  15. bluebird bio, Inc.
  16. Bristol-Myers Squibb Oncology
  17. Celgene Corporation
  18. Cerus Corporation
  19. Chimerix, Inc.
  20. Fred Hutchinson Cancer Research Center
  21. Gamida Cell Ltd.
  22. Gilead Sciences, Inc.
  23. HistoGenetics, Inc.
  24. Immucor
  25. Incyte Corporation
  26. Janssen Scientific Affairs, LLC
  27. Jazz Pharmaceuticals, Inc.
  28. Juno Therapeutics
  29. Karyopharm Therapeutics, Inc.
  30. Kite Pharma, Inc.
  31. medac GmbH
  32. MedImmune
  33. Medical College of Wisconsin
  34. Mediware
  35. Merck Co., Inc.
  36. Mesoblast
  37. MesoScale Diagnostics, Inc.
  38. Millennium
  39. Takeda Oncology Co.
  40. Miltenyi Biotec
  41. National Marrow Donor Program
  42. Neovii Biotech NA, Inc.
  43. Novartis Pharmaceuticals Corporation
  44. Otsuka Pharmaceutical Co, Ltd.-Japan
  45. PCORI
  46. Pfizer Inc.
  47. Pharmacyclics, LLC
  48. PIRCHE AG
  49. Sanofi Genzyme
  50. Seattle Genetics
  51. Shire
  52. Spectrum Pharmaceuticals, Inc.
  53. St. Baldrick's Foundation
  54. Sunesis Pharmaceuticals, Inc.
  55. Swedish Orphan Biovitrum, Inc.
  56. Takeda Oncology
  57. Telomere Diagnostics, Inc.
  58. University of Minnesota

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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.

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