B and T cell prolymphocytic leukaemia

Cross, Matt; Dearden, Claire

doi:10.1016/j.beha.2019.06.001

Cited by 21 publications

(28 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Case reports have described the response of such patients treated with targeted drugs including ibrutinib, alemtuzumab, idelalisib, and venetoclax. 1,4,13,14 Although such regimens with superior efficacy are existent, the patient in our study was treated with bendamustine-rituximab, in view of the financial constraints.…”

Section: Case Reportmentioning

confidence: 99%

De novo chronic lymphocytic leukemia/prolymphocytic leukemia or B-cell prolymphocytic leukemia? The importance of integrating clinico-morphological and immunophenotypic findings in distinguishing chronic lymphoproliferative diseases with circulating phase

et al. 2021

View full text Add to dashboard Cite

Section: Case Reportmentioning

confidence: 99%

De novo chronic lymphocytic leukemia/prolymphocytic leukemia or B-cell prolymphocytic leukemia? The importance of integrating clinico-morphological and immunophenotypic findings in distinguishing chronic lymphoproliferative diseases with circulating phase

et al. 2021

View full text Add to dashboard Cite

“…Unfortunately clinical utility was limited by short durations of response and increased risk of opportunistic infections secondary to T cell depletion [ 35 , 36 ]. Alemtuzumab therapy of CLL has been largely superseded by targeted small molecule inhibitors but it remains an important treatment option for other rare B-cell malignancies such as B-cell prolymphocytic leukemia [ 37 ].…”

Section: Complement-activating Therapeutic Mabmentioning

confidence: 99%

Complement Activation in the Treatment of B-Cell Malignancies

et al. 2020

View full text Add to dashboard Cite

Unconjugated monoclonal antibodies (mAb) have revolutionized the treatment of B-cell malignancies. These targeted drugs can activate innate immune cytotoxicity for therapeutic benefit. mAb activation of the complement cascade results in complement-dependent cytotoxicity (CDC) and complement receptor-mediated antibody-dependent cellular phagocytosis (cADCP). Clinical and laboratory studies have showed that CDC is therapeutically important. In contrast, the biological role and clinical effects of cADCP are less well understood. This review summarizes the available data on the role of complement activation in the treatment of mature B-cell malignancies and proposes future research directions that could be useful in optimizing the efficacy of this important class of drugs.

show abstract

“…T-PLL patients typically present with exponentially rising blood lymphocyte counts, bone marrow infiltration, splenomegaly, and small lymphadenopathy. Their dismal prognosis is reflected in a median overall survival (OS) from diagnosis of < 3 years [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Advances and Perspectives in the Treatment of T-PLL

Braun

Jan

Wahnschaffe

et al. 2020

Curr Hematol Malig Rep

View full text Add to dashboard Cite

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 alemtuzumabbased 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 ≈ 90% of patients, last at median ≈ 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 CART cell therapy are at the stage of pre-clinical assessments of activity and feasibility. Summary 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-inhuman results in T-PLL, and urgently have to be transferred to systematic clinical testing.

show abstract

B and T cell prolymphocytic leukaemia

Cited by 21 publications

References 60 publications

De novo chronic lymphocytic leukemia/prolymphocytic leukemia or B-cell prolymphocytic leukemia? The importance of integrating clinico-morphological and immunophenotypic findings in distinguishing chronic lymphoproliferative diseases with circulating phase

De novo chronic lymphocytic leukemia/prolymphocytic leukemia or B-cell prolymphocytic leukemia? The importance of integrating clinico-morphological and immunophenotypic findings in distinguishing chronic lymphoproliferative diseases with circulating phase

Complement Activation in the Treatment of B-Cell Malignancies

Advances and Perspectives in the Treatment of T-PLL

Contact Info

Product

Resources

About