The treatment of hairy cell leukemia with a focus on long lasting responses to cladribine: A 30‐year experience

Broccoli, Alessandro; Argnani, Lisa; Nanni, Laura; Terragna, Carolina; Sabattini, Elena; Gabrielli, Giulia; Stefoni, Vittorio; Pellegrini, Cinzia; Casadei, Beatrice; Morigi, Alice; Lolli, Ginevra; Carella, Matteo; Coppola, Paolo Elia; Zinzani, Pier Luigi

doi:10.1002/ajh.26287

Cited by 12 publications

(15 citation statements)

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“…T A B L E 1 Genomic alterations in hairy cell leukemia (HCL), hairy cell leukemias variant (HCL-v), splenic diffuse red pulp lymphomas (SDRPL), and splenic marginal zone lymphoma (SMZL) of patients requiring first-line treatment. 63 In large retrospective series [64][65][66][67][68] including both agents, 76%-83% of patients receiving chemotherapy achieved complete response (CR) and 31%-33% partial response (PR), with no significant difference in CR or PR observed between both agents.…”

Section: Recurrent Genetic Alterations In Sdrplmentioning

confidence: 99%

“…In a large representative US database including 749 HCL patients, cladribine was utilized in more than 75% of patients requiring first‐line treatment 63 . In large retrospective series 64–68 including both agents, 76%–83% of patients receiving chemotherapy achieved complete response (CR) and 31%–33% partial response (PR), with no significant difference in CR or PR observed between both agents.…”

Section: Update On Hcl Treatment and Hcl‐like Disordersmentioning

confidence: 99%

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Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

2021

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Disease Overview: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders characterized by the identification of hairy cells, a specific genetic profile, a different clinical course, and the need for appropriate treatment. Diagnosis: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation. Risk Stratification: Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood, and the immunoglobulin heavy chain variable region gene mutational status. VH4-34-positive HCL cases are associated with a poor prognosis. Treatment: Patients should be treated only if HCL is symptomatic. Chemotherapy with risk adapted therapy purine analogs (PNAs) are indicated in first-line HCL patients. The use of chemo-immunotherapy combining PNAs and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/ refractory disease is based on the use of BRAF inhibitors (BRAFi) plus rituximab or MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22 or BrutonTyrosine Kinase inhibitors (BTKi). However, the optimal sequence of the different treatments remains to be determined. The Bcl2-inhibitors (Bcl-2i) can play a major role in the future. | INTRODUCTIONHairy cell leukemia (HCL) is recognized as an entity by the World Health Organization since 2008 1 and in the last 2017 revision of the WHO classification of lymphoid neoplasms. 2 HCL, four to five times more frequent in men than women, accounts for 2% of all leukemias with approximately 1.100 new HCL cases in the United States. 3 The few available population-based studies are limited. [4][5][6][7][8] When including HCL and HCL-like disorders, the overall age-adjusted to the 2000 US population incidence rate is 0.7 per 100 000 in men and 0.3/100 000 in women. When adjusting to the worldwide population, the incidence rate of HCL is 0.3 and 0.1/100 000, respectively, and remains relatively stable over time. 8 It is lower in non-Hispanic/black, Hispanic, or Asian/pacific Islander. Despite an improvement of overall (OS) and relative survival (RS), a significantly lower OS is observed among African American individuals compared with other ethnic groups. 6 The mortality rates for patients with HCL is similar to those of the general population 5 years after diagnosis. 9 HCL must be differentiated from other

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Section: Recurrent Genetic Alterations In Sdrplmentioning

confidence: 99%

Section: Update On Hcl Treatment and Hcl‐like Disordersmentioning

confidence: 99%

Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

2021

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“…The Consensus Resolution criteria, along with recently updated guidelines for the diagnosis and management of HCL patients, rely on the resolution of all peripheral cytopenias and organomegaly, as well as on the disappearance of marrow lymphoid infiltration with hematoxylin‐eosin staining, to establish the status of CR 14,15 . Immunohistochemistry may be a strategy to assess the persistence of a minimal marrow infiltrate: however, neither thresholds for positivity, nor the most appropriate immunohistochemical markers have been validated or widely acknowledged 13,17,20,21 . Likewise, flow cytometry appears a useful tool, but no consensus is established on which antibody panel needs to be used 12,22,23 .…”

Section: Discussionmentioning

confidence: 99%

“…We have implemented a molecular assay based on the use of ddPCR on PB and/or BM in patients with HCL at different phases of their disease, which may individuate a minimal disease burden in patients achieving a CR and that allows monitoring of all CR patients in the post‐treatment phase. Here we present the preliminary results of this exploratory analysis on patients recently treated at our Institution because of a new diagnosis of HCL or relapse, as well as followed‐up after having obtained a CR several years before 17,18 …”

Section: Introductionmentioning

confidence: 99%

Droplet digital polymerase chain reaction for the assessment of disease burden in hairy cell leukemia

Broccoli

Terragna

Nanni

et al. 2021

Hematological Oncology

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BRAFV600E mutation is the pathogenic driver of hairy cell leukemia (HCL) found in the vast majority of cases both at onset and during recurrences. The identification of the mutated allele in blood and marrow correlates with the presence of neoplastic cells and can be considered a marker of active disease. Likewise, the absence of the mutation after treatment may indicate a state of deep response. The BRAFV600E burden was measured by droplet digital polymerase chain reaction (ddPCR) and expressed as fractional abundance in 35 HCL patients at different stages of disease (onset, relapse, complete response [CR] after treatment, long‐term remission) in peripheral blood and/or bone marrow (when available). Mean values of fractional abundance for patients at diagnosis, relapse and response, respectively, were 12.26%, 16.52% and 0.02% in peripheral blood and 23.51%, 13.96% and 0.26% in bone marrow. Four patients out of 6 evaluated at response were molecularly negative for BRAFV600E in peripheral blood. Mean fractional abundance in peripheral blood tested in 14 patients with long lasting CR was 0.05%, and 10 patients were BRAFV600E negative. These preliminary results suggest that ddPCR permits to assess the active tumor burden in HCL at different disease phases and support the hypothesis that some patients in CR qualify for a molecular CR.

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“…Although a head-to-head comparative, prospective clinical trial has not been performed, long-term follow-up studies indicate similar clinical efficacies of pentostatin and cladribine in terms of the quality and duration of responses achievable, and both purine analogues can be equally considered front-line treatments of choice in HCL [ 6 ]. Although studies with the longest follow-up indeed suggest indefinite remissions in about half of patients in CR and point towards a possibly curative potential of purine analogues in HCL [ 20 ], there is a non-diminishing risk of relapse in the long run, particularly for patients achieving partial remission (PR) only. PFS curves do not show a plateau, and patients in PR tend to relapse early within only 5 years [ 6 ].…”

Section: Purine Analoguesmentioning

confidence: 99%

Treatment of Classic Hairy Cell Leukemia: Targeting Minimal Residual Disease beyond Cladribine

Bohn

Dietrich

2022

Cancers

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Classic hairy cell leukemia (HCL) is a rare indolent B-cell lymphoproliferative disorder characterized by profound pancytopenia and frequent infectious complications due to progressive infiltration of the bone marrow and spleen. Lacking effective treatment options, affected patients were confronted with a dismal survival prognosis of less than 5 years when the disease was first described in 1958. Tremendous therapeutic advances were accomplished with the introduction of purine analogues such as cladribine in the 1990s, facilitating a near-normal life expectancy in most HCL patients. Nevertheless, nearly all patients eventually relapse and require successive retreatments, while drug-associated myelotoxicity may accumulate and secondary malignancies may evolve. Detection of minimal residual disease (MRD) in a substantial portion of treated patients has become a surrogate for this still limited treatment efficacy. In the last decade, novel biologic insights such as identification of the driver mutation BRAF V600E have initiated the development and clinical investigation of new, chemotherapy-free, targeted drugs in HCL treatment, with encouraging efficacy in early clinical trials aimed at boosting eradication of MRD while optimizing drug tolerability. This review summarizes current clinical trials investigating treatment strategies beyond purine analogues in HCL and discusses clinically relevant obstacles still to overcome.

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The treatment of hairy cell leukemia with a focus on long lasting responses to cladribine: A 30‐year experience

Cited by 12 publications

References 35 publications

Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

Droplet digital polymerase chain reaction for the assessment of disease burden in hairy cell leukemia

Treatment of Classic Hairy Cell Leukemia: Targeting Minimal Residual Disease beyond Cladribine

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