Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia

Oscier, David; Dearden, Claire; Erem, Efrem; Fegan, Christopher; Follows, George; Hillmen, Peter; Illidge, Tim; Matutes, Estella; Milligan, Don; Pettitt, Andrew R.; Schuh, Anna; Wimperis, J. Z.

doi:10.1111/bjh.12067

Cited by 130 publications

(156 citation statements)

References 177 publications

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“…great progress in cancer diagnostics and treatment has been made, but this type of leukemia remains incurable. the simultaneous coexistence of two populations of quiescent and cycling cells in cll treatment represents a special challenge (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia

Rogalińska

Błoński

Góralski

et al. 2015

International Journal of Oncology

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Abstract. to improve the efficacy of therapeutic options in chronic lymphocytic leukemia (cll) an in vitro system to determine the response of mononuclear blood cells from blood of patients was elaborated. the study combines four approaches, i.e., cell viability, apoptosis rate, differential scanning calorimetry (DSc), and immunoblotting to develop personalized therapy protocols based on the cell sensitivity to drug exposure of individual cll patients. the complementary analyses were performed on 28 peripheral blood samples from previously untreated cll patients before therapy. the induction and progress of apoptosis in cll cells exposed in vitro to purine analogs combined with mafosfamide, i.e., cladribine + mafosfamide (CM) and fludarabine + mafosfamide (fM) were assessed using the above approaches. the changes in thermal profiles (decrease/loss of transition at 95±5˚C) coincided with an accumulation of apoptotic cells, a decrease in the number of viable cells, and differences in the expression of the apoptosis-related protein ParP-1. no significant changes were observed in the thermal profiles of nuclei isolated from cll cells resistant to the treatment. the complementary assays revealed a strong relationship between both the in vitro sensitivity of leukemia cells to drugs and the clinical response of the patients, determined usually after the sixth course of treatment (after ~6 months of therapy). as a summary of studies followed by complementary tests, our findings demonstrate the value of in vitro exposure of cll cell samples to drugs intended to treat cll patients, before their administration in order to recommend the most suitable and effective therapy for individual patients.

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Section: Introductionmentioning

confidence: 99%

Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia

Rogalińska

Błoński

Góralski

et al. 2015

International Journal of Oncology

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“…15 The third recommendation of ASH's 2014 Choosing Wisely ® campaign advises against baseline or surveillance CT scans in patients with asymptomatic, early-stage chronic lymphocytic leukemia (CLL). 19,20 Unlike in other lymphoproliferative diseases, CT scans are not necessary to fully stage patients with CLL. Both the Rai and Binet staging systems are based on physical examination findings and complete blood counts.…”

Section: Discussionmentioning

confidence: 99%

“…23 There is no evidence that baseline or surveillance CT scans improve survival in patients with asymptomatic, early-stage CLL. 19,20 CT scans can also contribute to harm to patients. CTs are associated with a small, but cumulative, risk of radiation-induced malignancy.…”

Section: Discussionmentioning

confidence: 99%

Five hematologic tests and treatments to question

et al. 2014

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“…Rossi integrált prognosztikus modelljében a 10 éves OS szempontjából nagy rizikójú csoport TP53-és/ vagy BIRC3-abnormalitásokat, a közepes rizikójú csoport NOTCH1-és/vagy SF3B1-mutációkat és/vagy 11q-deletiót, az alacsony rizikójú csoport 12-es triszó-miát vagy normális karyotypust, míg a nagyon alacsony rizikójú csoport 13q-deletiót hordoz [14]. Az 1. táblá-zat a ma prognosztikus, illetve prediktív értékkel rendelkező genetikai eltéréseket és azok vizsgálatának ajánlott idejét tartalmazza [1,[15][16][17][18].…”

Section: Főbb Mutációs Célpontok a Cll-genomunclassified

A krónikus lymphocytás leukaemia korszerű molekuláris diagnosztikája és kezelése az új célzott terápiák korszakában

et al. 2017

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A krónikus lymphocytás leukaemia (CLL) heterogén klinikai lefolyású lymphoproliferativ betegség, amelyben számos klinikai és molekuláris prognosztikai marker nyújt segítséget a leghatékonyabb terápia megválasztásában. Eddig a TP53-defektus bizonyult kulcsfontosságú prognosztikai és prediktív faktornak, amely befolyásolja a terápiás döntést, különösen az új célzott kezelések érájában. A tünetmentes, korai stádiumú betegek nem igényelnek kezelést, követé-sük javasolt (úgynevezett "watch and wait"). Első vonalban a standard rizikójú CLL-es betegek többségében a standard kezelés továbbra is a kemo-immuno terápia. Az új orálisan alkalmazható kis molekulájú gyógyszereknek, mint a kinázinhibitorok (KI) és a Bcl-2-gátlók (ibrutinib, idelalisib és venetoclax), elsősorban relabáló/refrakter CLL kezelésében van helyük, ez alól kivétel az ibrutinib-monoterápia, amely a nagy rizikójú (TP53-defektust hordozó) betegek első vonalbeli kezelésére is javasolt. A nem túl távoli jövőben az új generációs szekvenálás diagnosztikába történő integrálása támogathatja majd a CLL-es betegek személyre szabott ellátását és az optimális kezelési stratégia megvá-lasztását. Orv Hetil. 2017; 158(41): 1620-1629.Kulcsszavak: krónikus lymphocytás leukaemia, prognosztikai marker, TP53-defektus, kemo-immuno terápia, célzott kezelés, ibrutinib, venetoclax State of the art molecular diagnostics and therapy of chronic lymphocytic leukaemia in the era of new targeted therapiesChronic lymphoid leukaemia (CLL) has a heterogeneous clinical course depending on many clinical and molecular prognostic markers, which play an important role in the selection of the best treatment option. So far, TP53 disruption is the key prognostic and predictive factor assisting treatment decisions, especially in the era of novel therapies. Asymptomatic patients in early stages of the disease will still benefit from watchful waiting. In the frontline setting, chemoimmunotherapy is still the standard care in the majority of standard risk CLL patients. New classes of drugs like kinase inhibitors and BCL-2 inhibitors (ibrutinib, idelalisib and venetoclax) are the treatment of choice in CLL patients with relapsed/refractory disease, with the exception of high risk disease, where the optimal treatment is frontline ibrutinib monotherapy. In the near future, integrating next generation sequencing into the routine diagnostics would help the development of individual CLL patient management and to choose an optimal treatment strategy.

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Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia

Cited by 130 publications

References 177 publications

Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia

Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia

Five hematologic tests and treatments to question

A krónikus lymphocytás leukaemia korszerű molekuláris diagnosztikája és kezelése az új célzott terápiák korszakában

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