RESUMO
OBJECTIVE: In this study, we retrospectively analyzed the clinical outcome, treatment responses, infectious complications, and survival rates of 71 hairy cell leukemia (HCL) cases. MATERIALS AND METHODS: Sixty-seven patients received a first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA) was administered in 31 cases, 19 patients received interferon-alpha (INF-α), splenectomy was performed in 16 cases, and rituximab was used in one. RESULTS: Although the highest overall response rate (ORR) was observed in patients receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-α, and splenectomy subgroups. Relapse rates were significantly lower in patients who received first-line 2-CdA. The progression-free survival (PFS) rate with 2-CdA was significantly higher than in patients with INF-α and splenectomy, but we found similar overall survival rates with all three upfront treatment modalities. Infections including tuberculosis were a major problem. CONCLUSION: Although purine analogues have improved the ORRs and PFS, there is still much progress to make with regard to overall survival and relapsed/refractory disease in patients with HCL.
Assuntos
Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia de Células Pilosas/terapia , Esplenectomia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esplenectomia/métodos , Resultado do TratamentoAssuntos
Úlcera da Perna/cirurgia , Leucemia de Células Pilosas/cirurgia , Esplenectomia , Síndrome de Sweet/cirurgia , Humanos , Úlcera da Perna/tratamento farmacológico , Úlcera da Perna/patologia , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Síndrome de Sweet/tratamento farmacológico , Síndrome de Sweet/patologiaRESUMO
Telomeres, which protect the ends of chromosomes, are shortened in several hematologic malignancies, often with adverse prognostic implications, but their effect on prognosis of classic and variant hairy cell leukemia (HCL and HCLv) has not been reported. HCL/HCLv genomic DNA from 46 patients was studied by PCR to determine the ratio of telomere to single copy gene number (T/S). T/S was unrelated to diagnosis of HCL or HCLv (p=0.27), but shorter T/S was associated with unmutated immunoglobulin rearrangements (p=0.033) and age above the median at diagnosis (p=0.017). Low T/S was associated with shorter overall survival from diagnosis (OS), particularly T/S <0.655 (p=0.0064, adjusted p=0.019). Shorter OS was also associated with presence of unmutated (p<0.0001) or IGHV4-34+ (p<0.0001) rearrangements, or increasing age (p=0.0002). Multivariable analysis with Cox modeling showed that short T/S along with either unmutated or IGHV4-34+ rearrangements remained associated with reduced OS (p=0.0071, p=0.0024, respectively) after age adjustment. While T/S is relatively long in HCL and the disease usually indolent with excellent survival, shortened telomeres in HCL/HCLv are associated with decreased survival. Shortened T/S could represent a risk factor needing further investigation/intervention to determine if non-chemotherapy treatment options, in addition to or instead of chemotherapy, might be particularly useful.
Assuntos
Leucemia de Células Pilosas/genética , Encurtamento do Telômero , Telômero/ultraestrutura , Fatores Etários , Antimetabólitos Antineoplásicos/uso terapêutico , Terapia Combinada , DNA de Neoplasias/genética , Resistencia a Medicamentos Antineoplásicos , Feminino , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Imunofenotipagem , Estimativa de Kaplan-Meier , Leucemia de Células Pilosas/classificação , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/mortalidade , Leucemia de Células Pilosas/cirurgia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Esplenectomia , Homeostase do TelômeroRESUMO
Since its discovery in 1923 and further characterization in 1958, hairy cell leukemia (HCL) has undergone enormous advances in the understanding of the biology and treatment of the disease. Initially a uniformly fatal disease, new therapies in rapid succession transformed HCL into a chronic disease with a normal life expectancy in many cases. More recently, the identification of BRAFV600E mutations in the majority of patients with classic HCL have enabled targeted therapies as a therapeutic option. Additional discoveries into the biology of the disease have identified new subtypes of HCL. Modern approaches to the evaluation and treatment of HCL include detailed molecular analysis which informs therapeutic options, which may consist of traditional therapies such as purine nucleoside analogs, or targeted therapies with antibodies, BTK inhibitors, or BRAF inhibitors, or combination therapy. Because HCL is a rare disease, continued progress depends on patients being enrolled on clinical trials whenever possible.
Assuntos
Antineoplásicos/uso terapêutico , Linfócitos B/efeitos dos fármacos , Indóis/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/história , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Sulfonamidas/uso terapêutico , Linfócitos B/patologia , Cladribina/uso terapêutico , Gerenciamento Clínico , História do Século XX , História do Século XXI , Humanos , Imunotoxinas/uso terapêutico , Leucemia de Células Pilosas/mortalidade , Leucemia de Células Pilosas/cirurgia , Mutação , Pentostatina/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/imunologia , Indução de Remissão , Rituximab/uso terapêutico , Esplenectomia , Análise de Sobrevida , VemurafenibRESUMO
Significant advances in the diagnosis and treatment of hairy cell leukemia (HCL) have recently been made. Improved distinction of HCL from its mimics though clinical presentations, morphologic and immunophenotypic features, and more recently molecular biology, has highlighted marked differences in treatment response and overall prognosis between these disorders. As our understanding of the unique pathobiology of HCL has grown, exciting new avenues of treatment as well as insight into immune function have been obtained. This review provides an overview of the clinical features and diagnostic attributes of HCL, with contrast to other mature B cell lymphoproliferative disorders with overlapping features.
Assuntos
Leucemia de Células Pilosas/diagnóstico , Leucemia Prolinfocítica Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Macroglobulinemia de Waldenstrom/diagnóstico , Antineoplásicos/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/patologia , Diagnóstico Diferencial , Fadiga/diagnóstico , Fadiga/patologia , Feminino , Humanos , Indóis/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/patologia , Leucemia de Células Pilosas/cirurgia , Leucemia Prolinfocítica Tipo Células B/tratamento farmacológico , Leucemia Prolinfocítica Tipo Células B/patologia , Leucemia Prolinfocítica Tipo Células B/cirurgia , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Mutação , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Fatores Sexuais , Esplenectomia , Esplenomegalia/diagnóstico , Esplenomegalia/patologia , Esplenomegalia/cirurgia , Sulfonamidas/uso terapêutico , Vemurafenib , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/patologia , Macroglobulinemia de Waldenstrom/cirurgiaRESUMO
This brief review highlights the sequence of therapeutic milestones and advances in our understanding of the biology of hairy cell leukemia (HCL) with a focus on recent molecular findings and how these may be applied to improve disease outcomes in the future. Targeted therapy is discussed in the context of the recently identified BRAF mutation and other genetic findings.
Assuntos
Antineoplásicos/uso terapêutico , Linfócitos B/efeitos dos fármacos , Indóis/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/história , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Sulfonamidas/uso terapêutico , Linfócitos B/patologia , Cladribina/uso terapêutico , Gerenciamento Clínico , História do Século XX , História do Século XXI , Humanos , Imunotoxinas/uso terapêutico , Leucemia de Células Pilosas/mortalidade , Leucemia de Células Pilosas/cirurgia , Mutação , Pentostatina/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/imunologia , Indução de Remissão , Rituximab/uso terapêutico , Esplenectomia , Análise de Sobrevida , VemurafenibAssuntos
Antineoplásicos/uso terapêutico , Imidazóis/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Oximas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Terapia de Salvação , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Cladribina/efeitos adversos , Cladribina/uso terapêutico , Terapia Combinada , Ensaios de Uso Compassivo , Resistencia a Medicamentos Antineoplásicos , Humanos , Leucemia de Células Pilosas/sangue , Leucemia de Células Pilosas/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Neutropenia/induzido quimicamente , Neutropenia/complicações , Mutação Puntual , Proteínas Proto-Oncogênicas B-raf/genética , Aspergilose Pulmonar/etiologia , Indução de Remissão , Rituximab , EsplenectomiaRESUMO
Abstract Purine analogs are highly effective in hairy cell leukemia (HCL) with response rates of 85%, but with many late relapses. We have retrospectively reviewed the clinical data from 107 patients treated with pentostatin (n = 27) or cladribine (n = 80), to investigate the long-term efficacy and to identify factors associated with the treatment-free interval (TFI). Complete remission and minimal residual disease (MRD) rates were similar in both groups. Median TFI was shorter (95 vs. 144 months) in the pentostatin group, although the difference was not significant (p = 0.476). MRD+ patients had shorter TFI than MRD- patients (97 months vs. not reached, p < 0.049). A hemoglobin level < 10 g/dL predicted for a shorter TFI only in the pentostatin group. Quality of response and number of hairy cells in the bone marrow are independent risk factors of treatment failure. The relationship between MRD+ and shorter TFI makes it of special interest to explore consolidation therapy with monoclonal antibodies to achieve durable responses.
Assuntos
Cladribina/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Pentostatina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cladribina/administração & dosagem , Feminino , Humanos , Interferon-alfa/administração & dosagem , Leucemia de Células Pilosas/mortalidade , Leucemia de Células Pilosas/cirurgia , Masculino , Pessoa de Meia-Idade , Pentostatina/administração & dosagem , Rituximab , Esplenectomia , Resultado do TratamentoRESUMO
The paper describes a case of a patient with refractory hairy cell leukemia. In spite of the absence of CD25 expression, the disease was classified as a classical form according to the WHO classification (2008), as also confirmed by the detection of BRAFV600E mutation. The disease was characterized by resistance to all lines of therapy (interferon-a, splenectomy, cladribin). Clinical and hematological remission was achieved within 2 months of administration of the BRAF kinase inhibitor vemurafenib.
Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Indóis/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Sulfonamidas/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/cirurgia , Masculino , Pessoa de Meia-Idade , Esplenectomia , Esplenomegalia/complicações , Esplenomegalia/cirurgia , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do Tratamento , VemurafenibRESUMO
Hairy cell leukemia is a mature B-cell non-Hogkin lymphoma characterized by unique clinical, morphological and immunhistochemical features. Patients with hairy cell leukemia usually present with splenomegaly, progressive pancytopenia and a relative indolent clinical course. The diagnosis does not always indicate immediate treatment, as treatment depends on the clinical stage of the leukemia. Asymptomatic disease without progression requires a watchful waiting policy, while other categories usually need treatment. The treatment of choice is purine nucleoside analogues (pentostatin, cladribine) which can achieve complete remission even for decades. Interferon and monoclonal CD20 antibodies can also significantly prolong event-free survival. Unfortunately, only the latter two therapies are easily available in Hungary. Splenectomy, which was suggested as first line treatment before the era of purine nucleoside analogues, is only recommended as a last resort. Although hairy cell leukemia is a well-defined lymphoproliferative disease, sometimes it is difficult to differentiate it from other similar entities such as hairy cell leukema variant, splenic marginal zone lymphoma, small lymphocytic lymphoma etc. Making the correct diagnosis is of utmost importance because of the great difference in treatment modalities. Recently, a somatic mutation was found in all analysed hairy cell leukemia samples, but not in other splenic B-cell lymphomas. This article reviews the significance of this observation and presents the different types of methods for the detection of this mutation.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/terapia , Mutação , Nucleosídeos de Purina/uso terapêutico , Esplenectomia , Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/imunologia , Cladribina/uso terapêutico , Diagnóstico Diferencial , Intervalo Livre de Doença , Humanos , Hungria , Interferons/uso terapêutico , Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/cirurgia , Estadiamento de Neoplasias , Pancitopenia/etiologia , Pentostatina/uso terapêutico , Indução de Remissão , Esplenomegalia/etiologia , Esplenomegalia/cirurgia , Conduta ExpectanteAssuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/cirurgia , Esplenectomia , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Leucemia de Células Pilosas/diagnóstico , Rituximab , Resultado do TratamentoRESUMO
The reported case of Hairy cell leukemia (HCL) refers to a 47-year-old man with pancytopenia, splenomegaly, a month and a half history of dyspnea on mild effort and in common daily activities and a purplish-brown cutaneous node on the back of the left hand at the time of hospital admission. Bone marrow aspiration showed an infiltration by a lymphoproliferative malignancy and the following cytochemical studies on bone marrow sample led to diagnosis of HCL. The biopsy of the skin lesion revealed a infiltrate of medium and large-size cells in the dermis with the the same cytologic features of leukemic blasts appearing in the bone marrow, upon which the diagnosis of Leukemia cutis was established. The differential diagnosis of leukemia includes other neoplastic hematopoietic disorders, such as lymphoma, myelodysplastic syndromes, multiple myeloma, aplastic anemia, severe megaloblastic anemia, severe lymphocytosis, severe monocytosis, and bone marrow failure. In our case, the skin lesion was surgically removed and then left to heal by secondary intention due to the presence of bacterial infection by Staphylococcus aureus and Streptococcus pyogenes. The wound was finally medicated to total healing with Promogran®, an advanced dressings which consists of a sterile, freeze-dried matrix composed of collagen and oxidised regenerated cellulose. The importance of our case lies in the fact that cases with association of HCL with leukemia cutis are very rare, and furthermore that after the excision of the skin lesion of the left hand, the surgeons heal to let the wound close by secondary intention.
Assuntos
Mãos/patologia , Leucemia de Células Pilosas/patologia , Infiltração Leucêmica/diagnóstico , Pele/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Curativos Hidrocoloides , Biópsia , Medula Óssea/patologia , Doenças da Medula Óssea/diagnóstico , Infecções Relacionadas a Cateter/complicações , Procedimentos Cirúrgicos Dermatológicos , Diagnóstico Diferencial , Mãos/cirurgia , Neoplasias Hematológicas/diagnóstico , Humanos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/cirurgia , Infiltração Leucêmica/patologia , Infiltração Leucêmica/cirurgia , Masculino , Pessoa de Meia-Idade , Infecções Cutâneas Estafilocócicas/complicações , Infecções Estreptocócicas/complicações , Streptococcus pyogenes , CicatrizaçãoAssuntos
Anticorpos Monoclonais Murinos/farmacologia , Antineoplásicos/uso terapêutico , Flavonoides/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Pentostatina/farmacologia , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Flavonoides/administração & dosagem , Flavonoides/efeitos adversos , Humanos , Hiperpotassemia/induzido quimicamente , Interferons/administração & dosagem , Leucemia de Células Pilosas/cirurgia , Masculino , Pentostatina/uso terapêutico , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Indução de Remissão , Rituximab , EsplenectomiaAssuntos
Perfilação da Expressão Gênica , Leucemia de Células Pilosas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aberrações Cromossômicas , Terapia Combinada , DNA de Neoplasias/genética , Feminino , Dosagem de Genes , Genes Neoplásicos , Genes Supressores de Tumor , Humanos , Leucemia de Células Pilosas/classificação , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/cirurgia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , EsplenectomiaAssuntos
Doença de Hodgkin/patologia , Leucemia de Células Pilosas/patologia , Neoplasias Primárias Múltiplas/patologia , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Humanos , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/cirurgia , Masculino , Mitoxantrona/administração & dosagem , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/cirurgia , Rituximab , Esplenectomia , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Vimblastina/uso terapêuticoRESUMO
Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder, but is gratifying to treat for both physicians and patients. During the 50 years since its initial description as a clinical entity, hematologists have been fascinated by the bizarre appearance of the malignant cell with its hair-like projections. Therapeutic strategies have evolved from splenectomy to interfere to the purine analogues which have become the treatments of-choice and are very effective. Immunoconjugate Therapy with BL22 (anti-CD22 [corrected] antibody linked to truncated to Pseudomonas exotoxin) represents the newest milestone in the development of effective treatment for hairy cell leukemia.
Assuntos
Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/cirurgia , Oncologia/história , Oncologia/tendências , Terapia Combinada , História do Século XX , História do Século XXI , Humanos , Imunoconjugados/uso terapêutico , Oncologia/métodos , Purinas/antagonistas & inibidores , Purinas/uso terapêutico , Esplenectomia , Resultado do TratamentoAssuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Imunoterapia , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/imunologia , Adulto , Anticorpos Monoclonais Murinos , Humanos , Leucemia de Células Pilosas/patologia , Leucemia de Células Pilosas/cirurgia , Masculino , Indução de Remissão , Rituximab , Transplante Homólogo/imunologiaRESUMO
OBJECTIVE: To investigate the clinicopathologic features, diagnosis, differential diagnosis and the prognosis of hairy cell leukemia (HCL). METHODS: Fifteen splenectomy specimens of HCL patients were investigated retrospectively using HE and immunohistochemistry in correlation with the follow-up information. RESULTS: (1) The male to female ratio was 2.75:1, age ranged from 36 to 68 years with a median of 47 years. The most consistent clinical feature at presentation was marked splenomegaly (100%). Other symptoms included anemia (80.0%), thrombocytopenia (60.0%), leucocytosis (53.3%), pancytopenia (20.0%) and the absence of B-symptom. (2) The proportion of hairy cells was (14.6 +/- 7.2)% in periphery blood and (47.3 +/- 23.8)% in bone marrow. The positive rate of TRAP assay was 62.5% in bone marrow; 85.7% for TPA test and the detection rate for RLC was 25% by transmission electric microscopy. The frequency of bone marrow involvement was 100%. (3) The average weight of 15 spleens was (3012 +/- 1974) g. The size of 6 spleens ranged from 16 cm x 10 cm x 5 cm to 32 cm x 20 cm x 14 cm. The white pulp of spleen showed a characteristic atrophy feature or even absent due to leukemic infiltration, predominantly involving the red pulp with some sinusoidal pattern. "Blood pool" change was an infrequent feature (3/15 cases). The nuclei of leukemic cells were round (13 cases) or bean-shaped (2 cases), nucleoli inconspicuous or disappeared. The abundant cytoplasm and prominent cell border resulted in a "fried egg" appearance. By immunohistochemistry, leukemic cells were positive for CD45RA, CD20, PAX-5, CD25, CD11c, Annexin A1 and cyclinD1, but negative for CD3 and CD43. (4) 13 cases (86.7%) have been followed-up and all are alive. Among them, 9 cases are living well more than 5 years and 7 more than 10 years. CONCLUSIONS: Splenomegaly is frequently the first manifestation of patients with HCL and occurred predominantly in the middle to elderly adults. Definite diagnosis of HCL requires a combined histological and immunohistochemical assessment of the splenectomy specimen, bone marrow biopsy and aspirate.