Hairy cell leukemia: Past, present and future

Getta, Bartlomiej; Park, Jae H.; Tallman, Martin S.

doi:10.1016/j.beha.2015.10.015

Cited by 13 publications

(16 citation statements)

References 26 publications

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“…Hairy cell leukemia is a rare B-cell, chronic and indolent lymphoproliferative disease characterized by the bone marrow and spleen/lymph nodes infiltration by pathological CD20+, CD103+, CD25+, CD11c, sIg+, CD5-, CD23-, CD10- lymphocytes ( Getta et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

The Droplet Digital PCR: A New Valid Molecular Approach for the Assessment of B-RAF V600E Mutation in Hairy Cell Leukemia

et al. 2016

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Hairy cell leukemia (HCL) is a chronic lymphoproliferative B-cell disorder where the B-RAF V600E mutation has been recently detected, as reported for solid neoplasias but not for other B-cell lymphomas. The digital droplet PCR (dd-PCR) is a molecular technique that, without standard references, is able to accurately quantitate DNA mutations. ddPCR could be an useful instrument for the detection of the B-RAF V600E mutation in HCL, where the minimal residual disease monitoring is fundamental for planning a patients-targeted treatment in the era of new anti-CD20 and anti-RAF compounds. This retrospective study enrolled 47 patients observed at the Hematology Unit of the University of Pisa, Italy, from January 2005 to January 2014: 27 patients were affected by “classic” HCL, two by the variant HCL (vHCL), and 18 by splenic marginal zone lymphoma (SMZL). The aim of the study was to compare dd-PCR to “classic” quantitative PCR (QT-PCR) in terms of sensitivity and specificity and to demonstrate its possible use in HCL. Results showed that: (1) the sensitivity of dd-PCR is about half a logarithm superior to QT-PCR (5 × 10-5 vs. 2.5 × 10-4), (2) the specificity of the dd-PCR is comparable to QT-PCR (no patient with marginal splenic lymphoma or HCL variant resulted mutated), (3) its high sensitivity would allow to use dd-PCR in the monitoring of MRD. At the end of treatment, among patients in complete remission, 33% were still MRD-positive by dd-PCR versus 28% by QT-PCR versus 11% by the evaluation of the B-cell clonality, after 12 months, dd-PCR was comparable to QT-PCR and both detected the B-RAF mutation in 15% of cases defined as MRD-negative by IgH rearrangement. Moreover, (4) the feasibility and the costs of dd-PCR are comparable to those of QT-PCR. In conclusion, our study supports the introduction of dd-PCR in the scenario of HCL, also during the follow-up.

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Section: Introductionmentioning

confidence: 99%

The Droplet Digital PCR: A New Valid Molecular Approach for the Assessment of B-RAF V600E Mutation in Hairy Cell Leukemia

et al. 2016

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“…Hairy cell leukaemia (HCL) is a rare B‐cell disease typified by somatic BRAF mutations (Grever et al , ; Leonard et al , ). Clinical features at presentation generally include splenomegaly, lymphocytosis and monocytopenia with an underlying immunocompromised state (Getta et al , ). Infectious complications have been a hallmark of the clinical course in HCL patients but to what extent the immunocompromised state is the result of the underlying disease or following immunosuppressive chemotherapy remains unclear (Grever et al , ).…”

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confidence: 99%

“…Many patients have an indolent course and no therapies are initially required (Dinmohamed et al , ). Therapies based on purine analogues were developed in 1990, which achieve good response rates, and, more recently, targeted treatments have become available, including inhibition of the mutated BRAF kinase (Grever et al , ; Getta et al , ). Since 1990, relative survival has been similar to that of the background population among patients diagnosed before the age of 60 years, and has now improved to some 90%, even among elderly people (Dinmohamed et al , ).…”

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Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia

et al. 2019

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Summary Improvement of survival in lymphocytic leukaemia has been accompanied by the occurrence of second primary cancer (SPCs). Based on Swedish Family Cancer Database, we applied bi‐directional analyses in which relative risks (RRs) were calculated for any SPCs in patients with chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL) and hairy cell leukaemia (HCL) and the risks of these leukaemias as SPCs. After CLL, RRs were significant for 20 SPCs, and high for skin squamous cell cancer (24·58 for in situ and 7·63 for invasive), Merkel cell carcinoma (14·36), Hodgkin lymphoma (7·16) and Kaposi sarcoma (6·76). Conversely, 15 CLL cancer pairs were reciprocally increased. The increased risks were reciprocal for ALL and four cancers. RR for ALL was 15·35 after myeloid neoplasia. HCL showed reciprocally increased RRs with non‐Hodgkin lymphoma and melanoma. The concordance between RRs for bi‐directional associations between CLL and different cancers, and HCL and different cancers was highly significant. For CLL (also for HCL), the bi‐directional risks with skin cancers and other immune‐related cancers suggest the probable involvement of immune dysfunction. For ALL, treatment may contribute to risks of multiple SPCs. Increased risk of ALL after haematological neoplasms may indicate bone marrow dysfunction. These findings may help guide treatment decisions and prognostic assessment.

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“…Purine analogues (cladribine or pentostatin) are the standard of care for initial treatment and are associated with durable remissions that last for years; however, many patients relapse and require additional therapy [ 2 ]. Subsequent treatment is usually with purine analogues, although treatment efficacy is reduced, patients have shorter remissions and are ultimately refractory to treatment [ 3 ]. Moreover, purine analogues have been associated with neurotoxicity [ 4 ] and are very immunosuppressive, which may increase the risk of opportunistic infections [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Moxetumomab Pasudotox: First Global Approval

Dhillon

2018

Drugs

119

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Moxetumomab pasudotox-tdfk (LUMOXITI™), an anti CD22 recombinant immunotoxin, has been developed by MedImmune and its parent company AstraZeneca for the treatment of hairy cell leukaemia. The product, discovered at the National Cancer Institute, is an optimised version of immunotoxin CAT-3888. Moxetumomab pasudotox is composed of the Fv fragment of an anti-CD22 monoclonal antibody fused to a 38 kDa fragment of Pseudomonas exotoxin A, PE38. The Fv portion of moxetumomab pasudotox binds to CD22, a cell surface receptor expressed on a variety of malignant B-cells, thereby delivering the toxin moiety PE38 directly to tumour cells. Once internalised, PE38 catalyses the ADP ribosylation of the diphthamide residue in elongation factor-2 (EF-2), resulting in the rapid fall in levels of the anti-apoptotic protein myeloid cell leukaemia 1 (Mcl-1), leading to apoptotic cell death. This article summarizes the milestones in the development of moxetumomab pasudotox leading to this first approval for the treatment of adults with relapsed or refractory hairy cell leukaemia who received at least two prior systemic therapies, including treatment with a purine nucleoside analogue. Development of moxetumomab pasudotox for non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia and precursor cell lymphoblastic leukaemia/lymphoma was discontinued.

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Hairy cell leukemia: Past, present and future

Cited by 13 publications

References 26 publications

The Droplet Digital PCR: A New Valid Molecular Approach for the Assessment of B-RAF V600E Mutation in Hairy Cell Leukemia

The Droplet Digital PCR: A New Valid Molecular Approach for the Assessment of B-RAF V600E Mutation in Hairy Cell Leukemia

Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia

Moxetumomab Pasudotox: First Global Approval

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