Hämatologische Rezidive akuter Leukämien nach allogener Stammzelltransplantation - Einflussfaktoren des Langzeitüberlebens in einer retrospektiven monozentrischen Analyse

Die allogene hämatopoietische Stammzelltransplantation (HSZT) ist als kurative Therapie­option für maligne und nicht-maligne Systemerkrankungen der Blutbildung und des lymphatischen Systems etabliert. Zu den wichtigsten Indikationen für einer allogene HSZT zählen die akute lymphatische Leukämie (ALL) und die akute myeloische Leukämie (AML). Ein hämatologisches Rezidiv stellt für Patienten mit AML und ALL die Hauptursache des Therapie­versagens nach allogener HSZT dar.

In die vorliegende retrospektive Analyse wurden 635 konsekutive Patienten der Klinik für Knochenmarktransplantation des Universitätsklinikum Essen eingeschlossen, die aufgrund einer AML oder ALL mit einer allogenen HSZT behandelt wurden und danach ein hämatologisches Rezidiv entwickelten. Ziel der Untersuchung war die Identifikation von Einflussfaktoren des Therapieansprechens, der Rezidiv- und Nicht-Rezidiv-bedingten Mortalität sowie des Langzeitüberlebens.

Als überragende unabhängige Einflussfaktoren der Rezidiv-bedingten Mortalität und des Langzeitüberlebens konnten das Krankheits­stadium bei allogener HSZT, das Zeitintervall bis zum hämatologischen Rezidiv und das Ansprechen auf die Rezidivtherapie identifiziert werden. Die Nicht-Rezidiv-bedingte Mortalität stieg bei Patienten, die eine hämatologische Remission erreichten und/oder eine zweite allogene HSZT erhielten, signifikant an. Die Applikation von DLI verbesserte hingegen das Langzeitüberleben auch unabhängig von den anderen Einflussfaktoren signifikant. Die vier unabhängigen Einflussfaktoren des Langzeit­überlebens wurden in einem stratifizierten Score-Punktewert zusammengefasst, der mit einer jeweils signifikant unterschiedlichen Langzeitüberlebenswahrscheinlichkeit assoziiert war (0 - 1: 23% [95 %-KI: 12 - 37]), 2: 7% [95 %-KI: 2 - 10]), 3 - 4: 3% [95 %-KI: 1 - 8]). Keiner der untersuchten Endpunkte wurde durch den Typ der akuten Leukämie beeinflusst.

Durch diese Untersuchung konnten somit Diagnose-unabhängige Einflussfaktoren identifiziert werden, die eine Prognoseabschätzung für Patienten mit hämatologischen Rezidiven akuter Leukämien nach allogener HSZT erlauben und somit auch das therapeutische Vorgehen beeinflussen können. Aufgrund der insgesamt sehr ungünstigen Langzeitprognose müssen Verfahren der Prävention und Früherkennung weiterentwickelt werden, die das Risiko von hämatologischen Rezidiven nach allogener HSZT vermindern.

 

Allogeneic haematopoietic stem cell transplantation (HSCT) is a curative therapeutic ­option for malignant and non-malignant diseases of the haematopoietic and lymphatic system. Major indications for allogeneic HSCT are acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Haematologic relapse represents the major cause of treatment failure in adult patients with AML und ALL after allogeneic HSCT.

In this retrospective analysis, 635 consecutive patients of the Department of Bone Marrow Transplantation at the University Hospital of Essen were included, who underwent allogeneic HSCT for the treatment of ALL or AML as the underlying disease and who developed haematologic relapse thereafter. The aim of this investigation was the identification of prognostic factors for complete response to further antileukaemic therapy, for relapse- and non-relapse-related mortality, and for long-term survival.

As the major prognostic factors for relapse-related mortality and long-term survival, the disease stage at allogeneic HSCT, the time interval between allogeneic HSCT and hematologic relapse, and complete response to therapy could be identified. Non-relapse-related mortality was significantly higher in patients, who achieved complete haematologic response and/or underwent a second allogeneic HSCT. Further, application of donor-lymphocyte infusions independently improved long-term survival.  The four prognostic factors of long-term survival were summarized into a stratified score-value, which was associated with significantly different long-term survival probabilities (0 - 1: 23% [95 %-KI: 12 - 37]), 2: 7% [95 %-KI: 2 - 10]), 3 - 4: 3% [95 %-KI: 1 - 8]). The type of acute leukaemia showed no influence on the evaluated clinical endpoints.

In conclusion, this investigation identified prognostic factors, which are independent of the type of acute leukemia and allow prognostic stratification of patients with haematologic relapse of acute leukaemia after allogeneic HSCT, which may guide therapeutic decision-making. In consideration of the overall unfavorable long-term prognosis in this clinical situation, strategies for the prevention and early detection of residual leukaemic disease have to be developed further, which can reduce the risk of haematologic relapse of acute leukaemia after allogeneic HSCT.

Allogeneic haematopoietic stem cell transplantation (HSCT) is a curative therapeutic ­option for malignant and non-malignant diseases of the haematopoietic and lymphatic system. Major indications for allogeneic HSCT are acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Haematologic relapse represents the major cause of treatment failure in adult patients with AML und ALL after allogeneic HSCT.

In this retrospective analysis, 635 consecutive patients of the Department of Bone Marrow Transplantation at the University Hospital of Essen were included, who underwent allogeneic HSCT for the treatment of ALL or AML as the underlying disease and who developed haematologic relapse thereafter. The aim of this investigation was the identification of prognostic factors for complete response to further antileukaemic therapy, for relapse- and non-relapse-related mortality, and for long-term survival.

As the major prognostic factors for relapse-related mortality and long-term survival, the disease stage at allogeneic HSCT, the time interval between allogeneic HSCT and hematologic relapse, and complete response to therapy could be identified. Non-relapse-related mortality was significantly higher in patients, who achieved complete haematologic response and/or underwent a second allogeneic HSCT. Further, application of donor-lymphocyte infusions independently improved long-term survival.  The four prognostic factors of long-term survival were summarized into a stratified score-value, which was associated with significantly different long-term survival probabilities (0 - 1: 23% [95 %-KI: 12 - 37]), 2: 7% [95 %-KI: 2 - 10]), 3 - 4: 3% [95 %-KI: 1 - 8]). The type of acute leukaemia showed no influence on the evaluated clinical endpoints.

In conclusion, this investigation identified prognostic factors, which are independent of the type of acute leukemia and allow prognostic stratification of patients with haematologic relapse of acute leukaemia after allogeneic HSCT, which may guide therapeutic decision-making. In consideration of the overall unfavorable long-term prognosis in this clinical situation, strategies for the prevention and early detection of residual leukaemic disease have to be developed further, which can reduce the risk of haematologic relapse of acute leukaemia after allogeneic HSCT.

Allogeneic haematopoietic stem cell transplantation (HSCT) is a curative therapeutic ­option for malignant and non-malignant diseases of the haematopoietic and lymphatic system. Major indications for allogeneic HSCT are acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Haematologic relapse represents the major cause of treatment failure in adult patients with AML und ALL after allogeneic HSCT.

In this retrospective analysis, 635 consecutive patients of the Department of Bone Marrow Transplantation at the University Hospital of Essen were included, who underwent allogeneic HSCT for the treatment of ALL or AML as the underlying disease and who developed haematologic relapse thereafter. The aim of this investigation was the identification of prognostic factors for complete response to further antileukaemic therapy, for relapse- and non-relapse-related mortality, and for long-term survival.

As the major prognostic factors for relapse-related mortality and long-term survival, the disease stage at allogeneic HSCT, the time interval between allogeneic HSCT and hematologic relapse, and complete response to therapy could be identified. Non-relapse-related mortality was significantly higher in patients, who achieved complete haematologic response and/or underwent a second allogeneic HSCT. Further, application of donor-lymphocyte infusions independently improved long-term survival.  The four prognostic factors of long-term survival were summarized into a stratified score-value, which was associated with significantly different long-term survival probabilities (0 - 1: 23% [95 %-KI: 12 - 37]), 2: 7% [95 %-KI: 2 - 10]), 3 - 4: 3% [95 %-KI: 1 - 8]). The type of acute leukaemia showed no influence on the evaluated clinical endpoints.

In conclusion, this investigation identified prognostic factors, which are independent of the type of acute leukemia and allow prognostic stratification of patients with haematologic relapse of acute leukaemia after allogeneic HSCT, which may guide therapeutic decision-making. In consideration of the overall unfavorable long-term prognosis in this clinical situation, strategies for the prevention and early detection of residual leukaemic disease have to be developed further, which can reduce the risk of haematologic relapse of acute leukaemia after allogeneic HSCT.

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Böger, Y., 2021. Hämatologische Rezidive akuter Leukämien nach allogener Stammzelltransplantation - Einflussfaktoren des Langzeitüberlebens in einer retrospektiven monozentrischen Analyse. https://doi.org/10.17185/duepublico/74167
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