Allogeneic Stem Cell Transplantation with Sequential Melphalan-Based Conditioning in AML: Residual Morphological Blast Count Determines the Risk of Relapse
Katja Sockel,1 Friedrich Stölzel,1 Franziska Hönl,1 Henning Baldauf,2 Christoph Röllig,1 Martin Wermke,1 Malte von Bonin,1 Raphael Teipel,1 Cornelia Link-Rachner,1 Kalina Brandt,1 Frank Kroschinsky,1 Mathias Hänel,3 Anke Morgner,3 Christian Klesse,2 Gerhard Ehninger,1 Uwe Platzbecker,4 Martin Bornhäuser,1 Johannes Schetelig,1,2,* Jan Moritz Middeke1,* 1Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus and Medical Faculty of the TU Dresden, Dresden, Germany; 2Clinical Trials Unit, DKMS, Dresden, Germany; 3Department of Medicine III, Chemnitz Hospital, Chemnitz, Germany; 4Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany*These authors contributed equally to this workCorrespondence: Jan Moritz Middeke, Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus and Medical Faculty of the TU Dresden, Fetscherstr. 74, Dresden, 01307, Germany, Tel +49-0351-458-15603, Fax +49-0351-458-4373, Email JanMoritz.Middekeuniklinikum-dresden.deIntroduction: 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: acute myeloid leukemia, ELN high risk, AML relapse/refractory, early allogeneic transplantation in aplasia, blast count, melphalan-based conditioning, sequential conditioning.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2022 |
|---|---|
| Enthalten in: |
Cancer Management and Research - (2022), Seite 547-559 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sockel K [VerfasserIn] |
|---|
| Links: |
doaj.org [kostenfrei] |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
DOAJ060075953 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ060075953 | ||
| 003 | DE-627 | ||
| 005 | 20230309000811.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230228s2022 xx |||||o 00| ||eng c | ||
| 035 | |a (DE-627)DOAJ060075953 | ||
| 035 | |a (DE-599)DOAJd911e82fe4a74930bdd5c5cb8cbefc69 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a RC254-282 | |
| 100 | 0 | |a Sockel K |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Allogeneic Stem Cell Transplantation with Sequential Melphalan-Based Conditioning in AML: Residual Morphological Blast Count Determines the Risk of Relapse |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Katja Sockel,1 Friedrich Stölzel,1 Franziska Hönl,1 Henning Baldauf,2 Christoph Röllig,1 Martin Wermke,1 Malte von Bonin,1 Raphael Teipel,1 Cornelia Link-Rachner,1 Kalina Brandt,1 Frank Kroschinsky,1 Mathias Hänel,3 Anke Morgner,3 Christian Klesse,2 Gerhard Ehninger,1 Uwe Platzbecker,4 Martin Bornhäuser,1 Johannes Schetelig,1,2,* Jan Moritz Middeke1,* 1Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus and Medical Faculty of the TU Dresden, Dresden, Germany; 2Clinical Trials Unit, DKMS, Dresden, Germany; 3Department of Medicine III, Chemnitz Hospital, Chemnitz, Germany; 4Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany*These authors contributed equally to this workCorrespondence: Jan Moritz Middeke, Medical Clinic and Policlinic I, University Hospital Carl Gustav Carus and Medical Faculty of the TU Dresden, Fetscherstr. 74, Dresden, 01307, Germany, Tel +49-0351-458-15603, Fax +49-0351-458-4373, Email JanMoritz.Middekeuniklinikum-dresden.deIntroduction: 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: acute myeloid leukemia, ELN high risk, AML relapse/refractory, early allogeneic transplantation in aplasia, blast count, melphalan-based conditioning, sequential conditioning | ||
| 650 | 4 | |a acute myeloid leukemia | |
| 650 | 4 | |a eln high risk | |
| 650 | 4 | |a aml relapse/refractory | |
| 650 | 4 | |a early allogeneic transplantation in aplasia | |
| 650 | 4 | |a blast count | |
| 650 | 4 | |a melphalan-based conditioning | |
| 653 | 0 | |a Neoplasms. Tumors. Oncology. Including cancer and carcinogens | |
| 700 | 0 | |a Stölzel F |e verfasserin |4 aut | |
| 700 | 0 | |a Hönl F |e verfasserin |4 aut | |
| 700 | 0 | |a Baldauf H |e verfasserin |4 aut | |
| 700 | 0 | |a Röllig C |e verfasserin |4 aut | |
| 700 | 0 | |a Wermke M |e verfasserin |4 aut | |
| 700 | 0 | |a von Bonin M |e verfasserin |4 aut | |
| 700 | 0 | |a Teipel R |e verfasserin |4 aut | |
| 700 | 0 | |a Link-Rachner C |e verfasserin |4 aut | |
| 700 | 0 | |a Brandt K |e verfasserin |4 aut | |
| 700 | 0 | |a Kroschinsky F |e verfasserin |4 aut | |
| 700 | 0 | |a Hänel M |e verfasserin |4 aut | |
| 700 | 0 | |a Morgner A |e verfasserin |4 aut | |
| 700 | 0 | |a Klesse C |e verfasserin |4 aut | |
| 700 | 0 | |a Ehninger G |e verfasserin |4 aut | |
| 700 | 0 | |a Platzbecker U |e verfasserin |4 aut | |
| 700 | 0 | |a Bornhäuser M |e verfasserin |4 aut | |
| 700 | 0 | |a Schetelig J |e verfasserin |4 aut | |
| 700 | 0 | |a Middeke JM |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Cancer Management and Research |d Dove Medical Press, 2009 |g (2022), Seite 547-559 |w (DE-627)DOAJ000125725 |x 11791322 |7 nnns |
| 773 | 1 | 8 | |g year:2022 |g pages:547-559 |
| 856 | 4 | 0 | |u https://doaj.org/article/d911e82fe4a74930bdd5c5cb8cbefc69 |z kostenfrei |
| 856 | 4 | 0 | |u https://www.dovepress.com/allogeneic-stem-cell-transplantation-with-sequential-melphalan-based-c-peer-reviewed-fulltext-article-CMAR |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/1179-1322 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 951 | |a AR | ||
| 952 | |j 2022 |h 547-559 | ||