Conditioning Intensity, Pre-Transplant Flow Cytometric Measurable Residual Disease, and Outcome in Adults with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

Linde M Morsink; Brenda M Sandmaier; Megan Othus; Raffaele Palmieri; Noa Granot; Evandro D Bezerra; Brent L Wood; Marco Mielcarek; Gary Schoch; Chris Davis; Mary E D Flowers; H Joachim Deeg; Frederick R Appelbaum; Rainer Storb; Roland B Walter

doi:10.3390/cancers12092339

Conditioning Intensity, Pre-Transplant Flow Cytometric Measurable Residual Disease, and Outcome in Adults with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

Cancers (Basel). 2020 Aug 19;12(9):2339. doi: 10.3390/cancers12092339.

Authors

Linde M Morsink^{1

2}, Brenda M Sandmaier^{1

3}, Megan Othus⁴, Raffaele Palmieri¹, Noa Granot¹, Evandro D Bezerra⁵, Brent L Wood⁶, Marco Mielcarek^{1

3}, Gary Schoch¹, Chris Davis¹, Mary E D Flowers^{1

3}, H Joachim Deeg^{1

3}, Frederick R Appelbaum^{1

3}, Rainer Storb^{1

3}, Roland B Walter^{1

6

7

8}

Affiliations

¹ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
² Department of Hematology, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
³ Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
⁴ Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
⁵ Department of Medicine, Residency Program, University of Washington, Seattle, WA 98195, USA.
⁶ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.
⁷ Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
⁸ Department of Epidemiology, University of Washington, Seattle, WA 98195, USA.

Abstract

How conditioning intensity is related to outcomes of AML patients undergoing allografting in morphologic remission is an area of great ongoing interest. We studied 743 patients in morphologic remission and known pre-transplant measurable residual disease (MRD) status determined by multiparameter flow cytometry (MFC) who received a first allograft after myeloablative, reduced intensity, or nonmyeloablative conditioning (MAC, RIC, and NMA). Overall, relapse-free survival (RFS) and overall survival (OS) were longer after MAC than RIC or NMA conditioning, whereas relapse risks were not different. Among MRD^pos patients, 3-year estimates of relapse risks and survival were similar across conditioning intensities. In contrast, among MRD^neg patients, 3-year RFS and OS were longer for MAC (69% and 71%) than RIC (47% and 55%) and NMA conditioning (47% and 52%). Three-year relapse risks were lowest after MAC (18%) and highest after NMA conditioning (30%). Our data indicate an interaction between conditioning intensity, MFC-based pre-transplant MRD status, and outcome, with benefit of intensive conditioning primarily for patients transplanted in MRD^neg remission. Differing from recent findings from other studies that indicated MAC is primarily beneficial for some or all patients with MRD^pos pre-HCT status, our data suggest MAC should still be considered for MRD^neg AML patients if tolerated.

Keywords: acute myeloid leukemia (AML); adults; allogeneic; conditioning; hematopoietic cell transplantation; intensity; measurable (minimal) residual disease; multiparameter flow cytometry.

Abstract

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