Universität zu Köln

Braun, Till, von Jan, Jana, Wahnschaffe, Linus and Herling, Marco (2020). Advances and Perspectives in the Treatment of T-PLL. Curr. Hematol. Malig. Rep., 15 (2). S. 113 - 125. PHILADELPHIA: CURRENT MEDICINE GROUP. ISSN 1558-822X

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Abstract

Purpose of Review T cell prolymphocytic leukemia (T-PLL) is a rare mature T cell tumor. Available treatment options in this aggressive disease are largely inefficient and patient outcomes are highly dissatisfactory. Current therapeutic strategies mainly employ the CD52-antibody alemtuzumab as the most active single agent. However, sustained remissions after sole alemtuzumab-based induction are exceptions. Responses after available second-line strategies are even less durable. More profound disease control or rare curative outcomes can currently only be expected after a consolidating allogeneic hematopoietic stem cell transplantation (allo-HSCT) in best first response. However, only 30-50% of patients are eligible for this procedure. Major advances in the molecular characterization of T-PLL during recent years have stimulated translational studies on potential vulnerabilities of the T-PLL cell. We summarize here the current state of classical treatments and critically appraise novel (pre)clinical strategies. Recent Findings Alemtuzumab-induced first remissions, accomplished in approximate to 90% of patients, last at median approximate to 12 months. Series on allo-HSCT in T-PLL, although of very heterogeneous character, suggest a slight improvement in outcomes among transplanted patients within the past decade. Dual-action nucleosides such as bendamustine or cladribine show moderate clinical activity as single agents in the setting of relapsed or refractory disease. Induction of apoptosis via reactivation of p53 (e.g., by inhibitors of HDAC or MDM2) and targeting of its downstream pathways (i.e., BCL2 family antagonists, CDK inhibitors) are promising new approaches. Novel strategies also focus on inhibition of the JAK/STAT pathway with the first clinical data. Implementations of immune-checkpoint blockades or CAR-T cell therapy are at the stage of pre-clinical assessments of activity and feasibility. The recommended treatment strategy in T-PLL remains a successful induction by infusional alemtuzumab followed by a consolidating allo-HSCT in eligible patients. Nevertheless, long-term survivors after this standard comprise only 10-20%. The increasingly revealed molecular make-up of T-PLL and the tremendous expansion of approved targeted compounds in oncology represent a never-before opportunity to successfully tackle the voids in T-PLL. Approaches, e.g., those reinstating deficient cell death execution, show encouraging pre-clinical and first-in-human results in T-PLL, and urgently have to be transferred to systematic clinical testing.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Braun, Till UNSPECIFIED UNSPECIFIED UNSPECIFIED von Jan, Jana UNSPECIFIED UNSPECIFIED UNSPECIFIED Wahnschaffe, Linus UNSPECIFIED UNSPECIFIED UNSPECIFIED Herling, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-345259
DOI:	10.1007/s11899-020-00566-5
Journal or Publication Title:	Curr. Hematol. Malig. Rep.
Volume:	15
Number:	2
Page Range:	S. 113 - 125
Date:	2020
Publisher:	CURRENT MEDICINE GROUP
Place of Publication:	PHILADELPHIA
ISSN:	1558-822X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL PROLYMPHOCYTIC LEUKEMIA; ALEMTUZUMAB THERAPY; KINASE ITK; TRANSPLANTATION; TRIAL; CD52; BENDAMUSTINE; PENTOSTATIN; PROGRESSION; VENETOCLAX Multiple languages Oncology; Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34525