RESUMO
Hairy cell leukemia (HCL) and HCL-like disorders have to be distinguished because of their different biology and treatment response. Thus, we conducted a retrospective study on patients with HCL and hairy cell leukemia variant (HCLv) to assess diagnostic algorithms and treatment outcomes in a real-world setting. We analyzed 225 HCL and 26 HCLv patients with median follow-up of 67.9 months (HCL) and 20.1 months (HCLv). Median age at diagnosis was 56.2 (HCL) and 69.5 years (HCLv), male predominance was observed in both groups (76.0% vs. 73.1%). Diagnostics was mostly based on morphological evidence of hairy cells in the peripheral blood and bone marrow. At diagnosis, BRAF V600E mutation was detected in 94.7% of examined HCL patients and in no HCLv patient. Front-line treatment was indicated in 205 (91.1%) HCL and 18 (69.2%) HCLv patients. The majority of HCL patients were administered a cladribine-based regimen (91.2%). Overall response rate (ORR) was higher in cladribine-treated patients compared to those given other treatments (97.7% vs. 81.3%), the same applied with achieving Complete remission (CR) (91.2% vs. 62.5%). HCLv treatment was heterogeneous, but cladribine remained the most frequent option (44.4%) with ORR 81.3% and CR rates 43.8%. Second-line treatment was indicated in 52 HCL and 8 HCLv patients, 25.4% and 44.4% of those treated in first-line. In the whole HCL group, median time to next treatment (TTNT) was not reached and 10-year TTNT was estimated at 74.1%. HCLv patients who underwent first-line treatment had a median TTNT of 56 months. The median overall survival (OS) in HCL patients was not reached compared to HCLv with a median OS of 9.5 years. These data confirm an excellent prognosis for HCL patients treated with cladribine-based therapy. On the contrary, HCLv with its aggressive behavior represents a group of patients in whom novel treatment approaches are needed.
Assuntos
Leucemia de Células Pilosas , Humanos , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/patologia , Leucemia de Células Pilosas/mortalidade , Leucemia de Células Pilosas/terapia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Resultado do Tratamento , Cladribina/uso terapêutico , Cladribina/administração & dosagem , Seguimentos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
BACKGROUND: Hairy cell leukemia (HCL) is a rare mature B-cell malignancy that is primarily treated with purine analogues. However, relapse remains a significant challenge, prompting the search for alternative therapies. The BRAF V600E mutation prevalent in HCL patients provides a target for treatment with vemurafenib. PATIENTS AND METHODS: This multicenter retrospective study included nine patients with relapsed/refractory (R/R) HCL from six different centers. Patient data included demographics, prior treatments, clinical outcomes, and adverse events. RESULTS: Patients received different treatment regimens between centers, including vemurafenib alone or in combination with rituximab. Despite the differences in protocols, all patients achieved at least a partial response, with seven patients achieving a complete response. Adverse events were generally mild with manageable side effects. The absence of myelotoxic effects and manageable side effects make BRAF inhibitors attractive, especially for patients ineligible for purine analogues or those with severe neutropenia. CONCLUSION: Single agent vemurafenib or in combination with rituximab appears to be a promising therapeutic option for R/R HCL. Further research is needed to establish standardized treatment protocols and to investigate long-term outcomes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia de Células Pilosas , Rituximab , Vemurafenib , Humanos , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/patologia , Vemurafenib/administração & dosagem , Vemurafenib/uso terapêutico , Vemurafenib/efeitos adversos , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Resultado do Tratamento , Idoso de 80 Anos ou mais , Resistencia a Medicamentos AntineoplásicosRESUMO
CONTEXT: Splenic B-cell lymphoma/leukemia with prominent nucleoli (SBLPN) aka hairy cell leukemia variant (HCL-v) is a rare B-cell chronic lymphoproliferative disorder. The main diagnostic challenge is to differentiate SBLPN from Classical hairy cell leukemia (HCL-c), as the former faces inferior responses to therapies and a poor prognosis. AIMS: The aim is to discuss the clinic-hematological and immunophenotyping findings of three cases of SBLPN. SETTINGS AND DESIGN: This is a retrospective observational study. METHODS AND MATERIAL: From the year 2011 to 2021, flow cytometry of all the cases with HCL diagnosis was reviewed, and three cases with negative or dim CD25 and hematological presentation matching with SBLPN were picked up. STATISTICAL ANALYSIS USED: Descriptive statistics is used. RESULTS: All the cases were male. The age ranges from 43 to 64 years. Median hemoglobin concentration, total leucocyte count, and platelet count were 8.6 g/dL, 6.9 × 109/L, and 53 × 109/L, respectively. The atypical cells were medium to large. All three showed prominent nucleoli. Bone marrow biopsies showed an interstitial pattern of infiltration in all the cases. The hairy cells were positive for CD20, CD11c, and CD103. CD25 was dim positive in one case. Annexin A1 was negative in all three cases. BRAF V600E mutation analysis was done in one case and turned out negative for the mutation. CONCLUSIONS: SBLPN is a rare entity, usually on-flow cytometry CD25 negative. However, in dim CD25-positive cases, BRAFV600E mutational analysis helps in discerning SBLPN diagnosis and differentiating it from HCL-c.
Assuntos
Leucemia de Células Pilosas , Linfoma de Células B , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Biópsia , Medula Óssea/patologia , Imunofenotipagem , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/patologia , Linfoma de Células B/patologia , Estudos Observacionais como Assunto , Baço/patologiaRESUMO
First-line purine nucleoside analogues (PNAs) in hairy cell leukaemia (HCL) allow deep and long-lasting responses. We retrospectively analysed 53 HCL patients treated frontline with cladribine and assessed for response at 2 and 6 months after treatment to evaluate the kinetics of response. The estimated median progression-free survival was significantly different according to the degree of residual HCL infiltrate detected by immunohistochemistry at the bone marrow biopsy at 2 months (≤5% vs. >5%, 247 vs. 132 months, respectively, p = 0.033), but not at 6 months (p = 0.79). Our data suggest a favourable prognostic impact of early marrow HCL clearance in patients treated with cladribine.
Assuntos
Antineoplásicos , Leucemia de Células Pilosas , Humanos , Cladribina/uso terapêutico , Leucemia de Células Pilosas/patologia , Medula Óssea/patologia , Estudos Retrospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia , Fatores Imunológicos/uso terapêutico , Antimetabólitos/uso terapêutico , Antineoplásicos/uso terapêuticoRESUMO
The variant form of hairy cell leukaemia (HCL-V) is a rare disease very different from hairy cell leukaemia (HCL), which is a very well-defined entity. The 5th WHO edition (Leukemia, 36, 2022 and 1720) classification (WHO-HAEM5) introduced splenic lymphomas/leukaemias including four different entities: (1) HCL, (2) splenic marginal zone lymphoma (SMZL) with circulating villous cells in the peripheral blood, (3) splenic lymphoma with prominent nucleolus (SLPN), which replaced HCL-V and CD5 negative B-prolymphocytic leukaemia (B-PLL), and (4) splenic diffuse red pulp lymphoma (SDRPL). All these entities have to be distinguished because of a different clinical course and the need for a different treatment. The diagnosis can be challenging because of complex cases and overlap and/or grey zones between all the entities and needs integrating clinical, histologic, immunophenotypic, cytogenetic and molecular data. We review the diagnostic criteria including clinical, immunophenotypic and molecular characteristics of patients with HCL-V and other HCL-like disorders including HCL, SDRPL, SMZL, B-PLL and the Japanese form of HCL. We also discuss the different criteria allowing us to separate these different entities and we will update the recent therapeutic options that have emerged, in particular the advances with chemoimmunotherapy and/or targeted therapies.
Assuntos
Leucemia de Células Pilosas , Leucemia Linfocítica Crônica de Células B , Linfoma , Humanos , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/patologia , Baço/patologiaRESUMO
Hairy cell leukemia (HCL) is a B-lymphoma induced by BRAF(V600E) mutation. However, introducing BRAF(V600E) in B-lymphocytes fails to induce hematological malignancy, suggesting that BRAF(V600E) needs concurrent mutations to drive HCL ontogeny. To resolve this issue, here we surveyed human HCL genomic sequencing data. Together with previous reports, we speculated that the tumor suppressor TP53, P27, or PTEN restrict the oncogenicity of BRAF(V600E) in B-lymphocytes, and therefore that their loss-of-function facilitates BRAF(V600E)-driven HCL ontogeny. Using genetically modified mouse models, we demonstrate that indeed BRAF(V600E)KI together with Trp53KO or pTENKO in B-lymphocytes induces chronic lymphoma with pathological features of human HCL. To further understand the cellular programs essential for HCL ontogeny, we profiled the gene expression of leukemic cells isolated from BRAF(V600E)KI and Trp53KO or pTENKO mice, and found that they had similar but different gene expression signatures that resemble that of M2 or M1 macrophages. In addition, we examined the expression signature of transcription factors/regulators required for germinal center reaction and memory B cell versus plasma cell differentiation in these leukemic cells and found that most transcription factors/regulators essential for these programs were severely inhibited, illustrating why hairy cells are arrested at a transitional stage between activated B cells and memory B cells. Together, our study has uncovered concurrent mutations required for HCL ontogeny, revealed the B cell origin of hairy cells and investigated the molecular basis underlying the unique pathological features of the disease, with important implications for HCL research and treatment.
Assuntos
Leucemia de Células Pilosas , Animais , Humanos , Camundongos , Linfócitos B/metabolismo , Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/metabolismo , Leucemia de Células Pilosas/patologia , Mutação , Proteínas Proto-Oncogênicas B-raf , Fatores de Transcrição/genéticaRESUMO
Hairy Cell Leukemia is an infrequent leukemia that can be recognized both microscopically and flow cytometrically once the patient develops symptoms. We present a case where early diagnosis was achieved using flow cytometry long before the patient became symptomatic. This was achieved by focusing on a small percentage (0.9%) of total leukocytes that exhibited a higher side scatter and brighter CD19/CD20 than the remaining lymphocytes. A bone marrow aspirate three weeks later confirmed the presence of malignant B-cells. Shortly after, the patient presented splenomegaly and complained of fatigue.
Assuntos
Leucemia de Células Pilosas , Humanos , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/patologia , Antígenos CD , Citometria de Fluxo , Imunofenotipagem , Antígenos CD19RESUMO
BACKGROUND AND OBJECTIVE: Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder for which diagnosis is typically straightforward, based on bone marrow morphology and flow cytometry (FC) or immunohistochemistry. Nevertheless, variants present atypical expressions of cell surface markers, as is the case of CD5, for which the differential diagnosis can be more difficult. The aim of the current paper was to describe diagnosis of HCL with atypical CD5 expression, with an emphasis on FC. METHODS: The detailed diagnostic methodology for HCL with atypical CD5 expression is presented, including differential diagnosis from other lymphoproliferative diseases with similar pathologic features, by FC analysis of the bone marrow aspirate. RESULTS: Diagnosis of HCL by means of FC started by gating all events based on side scatter (SSC) versus CD45 and B lymphocytes were selected from the lymphocytes gate as CD45/CD19 positive. The gated cells were positive for CD25, CD11c, CD20, and CD103, while CD10 proved to be dim to negative. Moreover, cells positive for CD3, CD4, and CD8, the three pan-T markers, as well as CD19, showed a bright expression of CD5. The atypical CD5 expression is usually correlated with a negative prognosis and thus chemotherapy with cladribine should be initiated. CONCLUSION: HCL is an indolent chronic lymphoproliferative disorder and diagnosis is usually straightforward. However, atypical expression of CD5 renders its differential diagnosis more difficult, but FC is a useful tool that allows an optimal classification of the disease and allows initiation of timely satisfactory therapy.
Assuntos
Leucemia de Células Pilosas , Transtornos Linfoproliferativos , Humanos , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/metabolismo , Leucemia de Células Pilosas/patologia , Citometria de Fluxo/métodos , Imunofenotipagem , Linfócitos B , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/metabolismoRESUMO
Multiple primary malignant tumors are characterized by independent occurrence and development of two or more malignant neoplasms in the same patient. We present an extremely rare case of synchronous double primary malignancies, hairy cell leukemia and hepatocellular carcinoma with lethal outcome. Diagnosis of hepatocellular carcinoma was difficult due to the presence of lymphoproliferative disease, which complicated the visualization of the process using ultrasonography. Carcinomatous emboli of hepatocellular carcinoma in small pulmonary arteries without the formation of metastatic foci have led to clinical manifestations typical of pulmonary embolism, pulmonary hypertension and severe respiratory failure. In lymphoproliferative diseases it is necessary to take into account the possibility of the development of another malignant neoplasm, which can be "buried" by tumor infiltration.
Assuntos
Carcinoma Hepatocelular , Leucemia de Células Pilosas , Neoplasias Hepáticas , Neoplasias Primárias Múltiplas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/patologia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologiaRESUMO
The detailed clinical course of coronavirus disease 2019 (COVID-19) in patients with hairy cell leukemia (HCL) is rarely reported. We report the first case of HCL diagnosed with prolonged pancytopenia after COVID-19 infection in Japan. We describe the case of a 56-year-old man who was diagnosed with COVID-19. Computed tomography revealed ground-glass opacities in the bilateral lung lobes as well as splenomegaly. Remdesivir and dexamethasone were administered for the treatment of COVID-19. Since the pancytopenia persisted, bone marrow examination was performed, and he was diagnosed with HCL. Although pancytopenia can occur with COVID-19 alone, clinicians should be alerted regarding the presence of hematologic malignancies in patients in whom pancytopenia persists after COVID-19 treatment or in those with splenomegaly. Further, the condition of all previously reported patients with COVID-19 associated with HCL was severe enough to require mechanical ventilation. This is the first case in which the disease was not severe. The interleukin-6 (IL-6) level was lower in this case than in previous cases, suggesting that racial differences in IL-6 production may have contributed to COVID-19 severity.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Coronavirus , Leucemia de Células Pilosas , Pancitopenia , COVID-19/complicações , Humanos , Interleucina-6 , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Pancitopenia/complicações , Esplenomegalia/complicações , Esplenomegalia/patologiaRESUMO
Hairy cell leukaemia (HCL) is a rare B cell malignancy with an indolent course leading to pancytopaenia due to bone marrow infiltration. It has been proposed that HCL patients are at risk of developing a secondary malignancy, with a marked likelihood of the development of other hematologic malignancies including Hodgkin lymphoma and high-grade non-Hodgkin lymphomas. Here, we present the case of two patients who developed diffuse large B cell lymphoma after a long course of hairy cell leukaemia. In the case of the female patient, we report on the occurrence of a third malignant disease, which is very uncommon. With our case descriptions we contribute to the very small number of similar cases reported.
Assuntos
Leucemia de Células Pilosas , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Linfócitos B/patologia , Medula Óssea/patologia , Feminino , Humanos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/patologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/patologiaRESUMO
Both characteristics and optimal treatment strategy for hairy cell leukemia-variant (HCL-v) remain elusive due to its rarity. We retrospectively analyzed the clinical features of HCL-v and the efficacy of first-line treatment options in a large Chinese cohort. In this study, we recruited 33 HCL-v patients (23 males and 10 females) with a median age of 59 years (range, 34-79 years). The chief complaints included abdominal mass and relative signs (67%) and abnormal complete blood count (27%). Immunophenotyping showed monoclonal B-cells positive for pan B-cell antigens and CD11c, weakly positive for CD103 and CD200, while negative for CD5, CD10, CD25, CD123, and annexin A1. No BRAF V600E mutation was detected, but TP53 abnormality was recurrent. Treatment choices included interferon-α (IFN-α) in 11 patients, chlorambucil (CLB) in 5 patients, single purine nucleoside analogs (PNA) in 3 patients, PNA plus rituximab (PNA + R) in 9 patients, and others in 3 patients. Four patients who received IFN-α or CLB treatment also underwent splenectomy. Patients who received PNA + R had a higher complete response rate (88% versus 5%, P < 0.001) and longer progression-free survival (PFS, 3-year PFS rate 42% [95% CI 1-84] vs. 16% [95% CI 3-40], P = 0.042) than those who received other regimens. Overall, HCL-v is an indolent lymphoma with unique characteristics. The PNA + R regimen is the preferred choice in the first-line treatment for HCL-v.
Assuntos
Leucemia de Células Pilosas , Adulto , Idoso , Clorambucila , Feminino , Humanos , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Nucleosídeos/uso terapêutico , Nucleosídeos de Purina , Estudos Retrospectivos , Rituximab/uso terapêuticoRESUMO
Hairy cell leukemia-Japanese variant (HCL-jv) shares some features with, but differs in other features from, HCL variant. Recently, it has been pointed out that HCL-jv and splenic diffuse red pulp small B-cell lymphoma (SDRPL) possibly constitute the same disease. We report a patient with HCL-jv, in which the neoplastic cells in the resected spleen were positive for CD11c, CD103, tartrate-resistant acid phosphatase (by immunohistochemistry), and weakly positive for cyclin D3. They were negative for CD25, CD123, annexin A1, and BRAF V600E-derived protein. Meta-analysis of HCL-jv cases in the literature showed considerable variation in the expression of HCL-related molecules. Although the clinical features and pattern of splenic involvement of HCL-jv are similar to those of SDRPL, some cytomorphological and phenotypical differences can be pointed out. To confirm whether the weak expression of cyclin D3 in our case suggests a spectrum from HCL-jv to SDRPL or one of the characteristics of HCL-jv, further studies on a large number of cases are necessary.
Assuntos
Leucemia de Células Pilosas , Linfoma de Células B , Ciclina D3/metabolismo , Humanos , Japão , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/metabolismo , Leucemia de Células Pilosas/patologia , Linfoma de Células B/diagnóstico , Linfoma de Células B/patologia , Baço/patologiaRESUMO
Hairy cell leukemia (HCL) is a rare hematologic disorder characterized by pancytopenia and splenomegaly for which a single course of cladribine is highly effective in inducing complete remissions. However, there is limited real-world data on outcomes and complications among geriatric patients with HCL treated with cladribine. We conducted a retrospective review of all patients 70 years or older within the Scripps Clinic HCL Database at the time of first treatment with cladribine. Of the 45 patients meeting inclusion criteria, 32 (71%) achieved CR and 4 (9%) achieved PR. Of the 9 remaining patients, 7 achieved normalization of peripheral blood counts after a single course of cladribine (complete hematologic response, CHR) and 2 had no response. The median duration of response for all responders was 119 months. Nine (20%) patients relapsed with a median time to first relapse of 28 months. Ten patients subsequently developed 12 primary malignancies with an excess frequency (observed-to-expected ratio) of 0.85 (95% confidence interval, 0.48-1.49). Median overall survival for the entire cohort was 166 months from time of HCL diagnosis and 119 months from time of first cladribine administration. Forty patient deaths were observed; the standardized mortality ratio (observed-to-expected ratio) was 1.42 (95% confidence interval, 1.03-1.96), representing a statistically significant increase in the risk of death (P = .03). This study supports the high rate of complete and durable responses following a single course of cladribine in geriatric patients.
Assuntos
Antineoplásicos , Leucemia de Células Pilosas , Idoso , Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Humanos , Leucemia de Células Pilosas/patologia , Indução de Remissão , Estudos RetrospectivosRESUMO
Hairy cell leukemia (HCL) responds very well to frontline chemotherapy with purine analogs (cladribine and pentostatine). However, approximately half of patients experience 1 or more relapses, which become progressively resistant to these myelotoxic and immunosuppressive agents. At progression, standard therapeutic options include a second course of purine analogs alone or in combination with rituximab and, upon second relapse, therapy with the anti-CD22 immunotoxin moxetumomab pasudotox. Furthermore, blockade of the mutant BRAF-V600E kinase (the pathogenetic hallmark of HCL) through orally available specific inhibitors (vemurafenib or dabrafenib) effaces the peculiar morphologic, phenotypic, and molecular identity of this disease and its typical antiapoptotic behavior and is emerging as an attractive chemotherapy-free strategy in various clinical scenarios. These include patients with, or at risk of, severe infections and, in a highly effective combination with rituximab, patients with relapsed or refractory HCL. Other treatments explored in clinical trials are BTK inhibition with ibrutinib and co-inhibition of BRAF (through dabrafenib or vemurafenib) and its downstream target MEK (through trametinib or cobimetinib). Here, we focus on our experience with BRAF inhibitors in clinical trials and as off-label use in routine practice by presenting 3 challenging clinical cases to illustrate their management in the context of all available treatment options.
Assuntos
Antineoplásicos , Leucemia de Células Pilosas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Recidiva , Rituximab/uso terapêutico , Vemurafenib/uso terapêuticoRESUMO
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.
Assuntos
Biomarcadores Tumorais/genética , Leucemia de Células Pilosas/patologia , Mutação , Recidiva Local de Neoplasia/patologia , Reação em Cadeia da Polimerase/métodos , Proteínas Proto-Oncogênicas B-raf/genética , Humanos , Leucemia de Células Pilosas/genética , Recidiva Local de Neoplasia/genética , PrognósticoRESUMO
Hairy cell leukaemia (HCL) is a rare CD20+ B cell malignancy characterised by rare "hairy" B cells and extensive bone marrow (BM) infiltration. Frontline treatment with the purine analogue cladribine (CDA) results in a highly variable response duration. We hypothesised that analysis of the BM tumour microenvironment would identify prognostic biomarkers of response to CDA. HCL BM immunology pre and post CDA treatment and healthy controls were analysed using Digital Spatial Profiling to assess the expression of 57 proteins using an immunology panel. A bioinformatics pipeline was developed to accommodate the more complex experimental design of a spatially resolved study. Treatment with CDA was associated with the reduction in expression of HCL tumour markers (CD20, CD11c) and increased expression of myeloid markers (CD14, CD68, CD66b, ARG1). Expression of HLA-DR, STING, CTLA4, VISTA, OX40L were dysregulated pre- and post-CDA. Duration of response to treatment was associated with greater reduction in tumour burden and infiltration by CD8 T cells into the BM post-CDA. This is the first study to provide a high multiplex analysis of HCL BM microenvironment demonstrating significant immune dysregulation and identify biomarkers of response to CDA. With validation in future studies, prospective application of these biomarkers could allow early identification and increased monitoring in patients at increased relapse risk post CDA.