Treosulfan-Based Conditioning Regimen for Second Allograft in Patients with Myelofibrosis

Atagunduz, Isik Kaygusuz; Klyuchnikov, Evgeny; Wolschke, Christine; Janson, Dietlinde; Heidenreich, Silke; Christopeit, Maximilian; Ayuk, Francis; Kröger, Nicolaus

doi:10.3390/cancers12113098

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Treosulfan-Based Conditioning Regimen for Second Allograft in Patients with Myelofibrosis

Isik Kaygusuz Atagunduz

^1,2,

¹,

¹,

¹,

¹,

Maximilian Christopeit

¹,

Francis Ayuk

¹ and

Nicolaus Kröger

^1,*

Hematology Department, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany

Hematology Department, Marmara University Pendik Training and Research Hospital, 34899 Istanbul, Turkey

Author to whom correspondence should be addressed.

Cancers 2020, 12(11), 3098; https://doi.org/10.3390/cancers12113098

Received: 31 August 2020 / Revised: 15 October 2020 / Accepted: 21 October 2020 / Published: 23 October 2020

(This article belongs to the Special Issue New Insights into Myeloproliferative Neoplasms)

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Currently, the only curative therapy in myelofibrosis is allogeneic hematopoietic stem cell transplantation. Donor lymphocyte infusion and second stem cell transplantation are the two main treatment options for myelofibrosis patients who relapse after the first transplantation. The optimal conditioning regimen for the second transplantation in myelofibrosis patients is not well defined. Our study aimed to address this question and showed that treosulfan-based conditioning for second allograft in relapsed myelofibrosis patients resulted in longtime freedom from disease in about 50% of the patients. This data supports the second allogeneic hematopoietic stem cell transplantation with a less toxic treosulfan-based conditioning regimen that is effective in relapsed, donor lymphocyte infusion resistant myelofibrosis patients with long term low transplant-related mortality and relapse rates.

Abstract

Relapse after allogeneic hematopoietic stem cell transplantation (AHSCT) in myelofibrosis (MF) patients remains as a significant issue despite advances in transplantation procedures and significant prolongation in survival. Second AHSCT is a potential treatment option but associated with high treatment-related mortality and novel less toxic conditioning regimens are needed. In 33 MF patients with relapse after AHSCT and failure to donor lymphocyte infusion (DLI) we investigated treosulfan (36–42 g/m²) in combination with fludarabine and anti-thymocyte globulin (ATG) as conditioning regimen for a second AHSCT with matched related (n = 2), unrelated (n = 23), or mismatched unrelated (n = 8) donors. All patients achieved leukocyte engraftment after a median of 11 days, and 56 ± 13% experienced acute GVHD grade II–IV at day 100. The therapy-related mortality at day 100 and at 3 years was 16% and 31%, respectively. The cumulative incidence of relapse at 5 years was 16%, resulting in a 5-year disease-free and overall survival of 45% and 47%, respectively. Treosulfan-based conditioning for second allograft in relapsed MF patients resulted in about 50% of the patients in long-term freedom from disease. View Full-Text

Keywords: treosulfan; myelofibrosis; second allogeneic transplant; stem cell transplantation

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MDPI and ACS Style

Atagunduz, I.K.; Klyuchnikov, E.; Wolschke, C.; Janson, D.; Heidenreich, S.; Christopeit, M.; Ayuk, F.; Kröger, N. Treosulfan-Based Conditioning Regimen for Second Allograft in Patients with Myelofibrosis. Cancers 2020, 12, 3098. https://doi.org/10.3390/cancers12113098

AMA Style

Atagunduz IK, Klyuchnikov E, Wolschke C, Janson D, Heidenreich S, Christopeit M, Ayuk F, Kröger N. Treosulfan-Based Conditioning Regimen for Second Allograft in Patients with Myelofibrosis. Cancers. 2020; 12(11):3098. https://doi.org/10.3390/cancers12113098

Chicago/Turabian Style

Atagunduz, Isik K., Evgeny Klyuchnikov, Christine Wolschke, Dietlinde Janson, Silke Heidenreich, Maximilian Christopeit, Francis Ayuk, and Nicolaus Kröger. 2020. "Treosulfan-Based Conditioning Regimen for Second Allograft in Patients with Myelofibrosis" Cancers 12, no. 11: 3098. https://doi.org/10.3390/cancers12113098

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Treosulfan-Based Conditioning Regimen for Second Allograft in Patients with Myelofibrosis

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