Allogeneic Stem Cell Transplantation with Sequential Melphalan-Based Conditioning in AML: Residual Morphological Blast Count Determines the Risk of Relapse

Katja Sockel; Friedrich Stölzel; Franziska Hönl; Henning Baldauf; Christoph Röllig; Martin Wermke; Malte von Bonin; Raphael Teipel; Cornelia Link-Rachner; Kalina Brandt; Frank Kroschinsky; Mathias Hänel; Anke Morgner; Christian Klesse; Gerhard Ehninger; Uwe Platzbecker; Martin Bornhäuser; Johannes Schetelig; Jan Moritz Middeke

doi:10.2147/CMAR.S339846

Allogeneic Stem Cell Transplantation with Sequential Melphalan-Based Conditioning in AML: Residual Morphological Blast Count Determines the Risk of Relapse

Cancer Manag Res. 2022 Feb 15:14:547-559. doi: 10.2147/CMAR.S339846. eCollection 2022.

Authors

Katja Sockel¹, Friedrich Stölzel¹, Franziska Hönl¹, Henning Baldauf², Christoph Röllig¹, Martin Wermke¹, Malte von Bonin¹, Raphael Teipel¹, Cornelia Link-Rachner¹, Kalina Brandt¹, Frank Kroschinsky¹, Mathias Hänel³, Anke Morgner³, Christian Klesse², Gerhard Ehninger¹, Uwe Platzbecker⁴, Martin Bornhäuser¹, Johannes Schetelig^#^{1

2}, Jan Moritz Middeke^#¹

Affiliations

¹ Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus and Medical Faculty of the TU Dresden, Dresden, Germany.
² Clinical Trials Unit, DKMS, Dresden, Germany.
³ Department of Medicine III, Chemnitz Hospital, Chemnitz, Germany.
⁴ Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany.

^# Contributed equally.

Abstract

Introduction: Allogeneic hematopoietic cell transplantation (HCT) during chemotherapy-induced aplasia may offer long-term survival in acute myeloid leukemia (AML) with otherwise poor prognosis including ELN adverse risk, relapsed or refractory disease. However, the value of residual morphologic disease prior HCT in this context has not been conclusively settled until yet. Therefore, we aimed to investigate variables predicting outcome in this unique setting of sequential conditioning therapy, with a focus on pretreatment morphologic blast count. In contrast to the most popular FLAMSA-RIC protocol, we used a melphalan-based conditioning regimen during aplasia.

Methods: We retrospectively analyzed data from 173 AML patients who underwent a sequential melphalan-based conditioning therapy between 2003 and 2015 at our centre. All patients participated either in the prospective Phase 2 BRIDGE trial (NCT01295307), the Phase 3 AML2003 study (NCT00180102) or were treated according to this protocol and underwent allogeneic HCT after melphalan-based conditioning in treatment-induced aplasia.

Results: Median bone marrow blast count prior to conditioning was 10% (range, 0-96%). Four year probabilities of EFS and OS were 34% (95% CI, 28-43%) and 43% (95% CI, 36-52%), respectively. In multivariate analysis, blast count >20% was associated with worse EFS (HR = 1.93; p = 0.009) and OS (HR = 1.80; p = 0.026). This effect was not significant anymore for HCT during 1st line therapy.

Conclusion: Allogeneic HCT in aplasia with a melphalan-based conditioning regimen has the potential to cure a subset of adverse risk AML patients, even with persistent morphological disease prior HCT. However, a high pre-transplant blast count still indicates patients with a dismal prognosis, especially in the relapsed patient group, for whom post-transplant strategies should be considered to further optimize post HCT outcome.

Keywords: AML relapse/refractory; ELN high risk; acute myeloid leukemia; blast count; early allogeneic transplantation in aplasia; melphalan-based conditioning; sequential conditioning.