Clinical and molecular characteristics and prognosis of classical hairy cell leukemia and hairy cell leukemia variant / 中华内科杂志

Objective: To evaluate the clinical characteristics, treatment response, and outcomes in patients with classical hairy cell leukemia (cHCL) and HCL variant (HCL-V). Methods: This is a retrospective case series study. Between January 2011 and December 2021, clinical data of 30 patients newly with diagnosed HCL at Peking Union Medical College Hospital were analyzed. The main outcome measures include clinical characteristics, treatment efficacy and survival. The Kaplan-Meier method was used for survival analysis. Results: Twenty-one cases of cHCL and 9 cases of HCL-v were included. The median age at diagnosis was 55.5 (range, 30-86) years, with the ratio of male to female 2.75∶1. The main clinical manifestations included fatigue in 11 cases (36.7%), abdominal distension in 7 cases (23.3%), and infection in 4 cases, while 8 cases were asymptomatic. Splenomegaly was reported in 24 cases (80.0%), including 7 (23.3%) with megalosplenia. The white blood cell count, lymphocyte count, and the proportion of peripheral hairy cells in HCL-v group were significantly higher than those in cHCL group, whereas the development of anemia, thrombocytopenia, and monocytopenia in cHCL group was more remarkable than that in HCL-v group (all P<0.05). The BRAF-V600E gene mutation was detected only in cHCL patients (11/14 vs. 0/9, P<0.001). In terms of immunophenotype, the expression of CD25, CD103, CD123 and CD200 in cHCL group (20/20, 20/20, 4/7, 7/17) were all stronger than those in HCL-v group (3/9, 7/9, 0/4, 2/8). Twenty-two patients were treated, of which 13 cases (12 cases of cHCL and 1 case of HCL-v) with cladribine, and 9 cases (4 cHCL and 5 HCL-v) with interferon. Complete remission rate and overall response rate were comparable between cladribine and interferon treatment groups (both P<0.05). The median follow-up time was 31 (range, 1-125) months, and the median overall survival (OS) of the entire group was 125 months. The 5-year OS rate in HCL-v patients represented a trend of inferior (50.0% vs. 95.0%, P=0.207). Conclusions: The clinical features of HCL are unspecific, which includes fatigue, splenomegaly and recurrent infection. The clinical features, immunophenotype, treatment response and prognosis of HCL-v are different from those of cHCL. BRAF-V600E gene mutation is suggested as a key marker for differential diagnosis. Cladribine is recommended as front-line regimen of cHCL patients with satisfactory efficacy and prognosis. Conversely, response and clinical outcome in HCL-v patients still need to be improved.

An extremely rare case of concurrent BRAF V600E mutation driven hairy cell leukemia and melanoma: case report and review of literature

BRAF protein is a serine/threonine kinase with 766 amino acids. Approximately 15% of human cancers harbor BRAF mutations as well as other BRAF anomalies (amplifications, fusions). Somatic mutations mainly occur in the catalytic kinase domain (CR3), and the predominant mutation is p.V600E which is the substitution of glutamic acid (E) for valine (V) as result of a mutation at codon 600 of the kinase domain. To our knowledge, the vast majority of the cancers have non-germline BRAF mutations. Here we describe a case of a 60-year-old female with a history of hairy cell leukemia (HCL) who presented with aphasia and forgetfulness. A follow-up Brain CT scan showed three distinct brain lesions which were found to be diagnostic of melanoma (confirmed by immunohistochemistry) with no evidence of a concurrent brain involvement by a B-cell neoplasm. Molecular studies confirmed the same BRAF p.V600E mutation in both malignancies (hairy cell leukemia and melanoma). Thereafter the patient was started on BRAF inhibitor treatment and is now symptom-free after one year of follow up. Having two concurrent malignancies with a shared BRAF mutation is extremely rare and makes this an excellent example of a genomic marker-driven treatment in two histologically and immunophenotypically distinct tumors.

Eficacia y seguridad de cladribina en el tratamiento de pacientes con diagnóstico de tricoleucemia / Efficacy and safety of cladribine in the treatment of patients diagnosed with tricholeukemia

INTRODUCCIÓN: Antecedentes: En el present dictamen preliminar expone la evaluación de tecnología de la eficacia y seguridad del uso de cladribina en el tratamiento de pacientes adultos con diagnostico de leucemia de células vellosas o tricoleucemia. Así, los médicos hematólogos. Aspectos Generaels: La leucemia de células vellosas o tricoleucemia es una neoplasia de los linfocitos B pequeños que se caracteriza por la presencia de "células peludas" o células con núcleos ovales indentados y citoplasma abundante con proyecciones citoplasmáticas "pelulas", obervables en el 90% de los pacientes que se padecen. Los marcadores más comunes expresados por las células peludas son el CD19, CD20 y CD22, con una notable co-expressión de CD103, CD25, CD11c. Tecnologia Sanitaria de Interés: Cladribina es un agente antineoplásico sintético que se encuentra disponbile en viales para infusión endovenosa continua. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de cladribina en el tratamiento de pacientes con tricoleucemia en las bases de datos de Medline, Embase, Scopus, Web of Science, Cinahl, Cochrane y Tripdatabase. RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de la evidencia que sustente el uso de cladribina en el tratamiento de la tricoleucemia según la pregunta PICO establecida. CONCLUSIONES: Rituximab ha sido empleado en EsSalud como primera linea de tratamiento frente a la falta de acceso a cladribina. Sin embargo, ciertos pacientes presentan respuesta inadecuada o intolerancia a rituximab y requieren otras alternativas de tratamiento. Adicionalmente, se ha solicitado el uso de cladribina como terapia de primera línea en pacientes con tricoleucemia dado que en la actualidad se emplea un medicamento que no se encuentra indicado como primera líena para lla condición. En base a esta solicitud se llevó a cabo una rewvisión de la literatura sobre la eficacia y seguridad de cladribina en la poblaciones de pacientes previamente tratados y no-tratados. El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI aprueba el uso de cladribina como alternativa de tratamiento en pacientes con tricoleucemia previamente tratados o como primera línea de tratamiento. El perído de vigencia del presente dictamen preliminar es de dos años y la continuación de dicha aprobación estará sujeta a los resultados obtenidos de los pacientes que se beneficien con dicho tratamiento y a nueva evidencia que pueda surgir en el tiempo.

BRAF V600E and MAP2K1 Mutations in Hairy Cell Leukemia and Splenic Marginal Zone Lymphoma Cases

No abstract available.

Clinico-pathological presentation and therapeutic options for hairy cell leukemia

To look at clinical and hematological presentation as well as treatment outcome of patients with diagnosis of Hairy Cell Leukemia [HCL] in our population. All patients diagnosed with HCL by morphological and immunohistochemical methods presenting to Medical Oncology Ward at Hayatabad Medical Complex, Peshawar since August 2008 were included in the study. Out of 7 patients diagnosed with HCL, 6 were male and 1 was female [M:F ratio 6:1]. Median age at diagnosis was 44 years. Fever, pallor, palpitations and fatigue were the commonest presenting complaints. Spleenomegaly was noted in all patients [100%]. Pancytopenia was noted in all patients at presentation. Five patients were treated with Interferon while 2 were treated with Cladribine. At 18 months of follow-up, one out five patients treated with IFN had relapse while both the patients treated with Cladribine were in complete remission. Our study showed that HCL patients present at a younger age in our region but further studies with larger sample size are required to confirm this. All patients showed a complete response to Interferon and Cladribine with all patients alive at 18 months of follow-up.

2-CdA in the treatment of hairy cell leukaemia.

INTRODUCTION: Hairy cell leukaemia (HCL) is a rare lymphoproliferative disorder. Treatment options available are splenectomy, interferon, DCF and 2-CdA. 2-CdA is considered to have curative potential as proved by the other studies. METHODS: We gave 2-CdA in a dose of 0.09/kg/day as a continuous infusion in sixteen patients of hairy cell leukaemia. RESULTS: Three patients developed neutropenia post transfusion. At the end of three months all patients were in remission. Two patients relapsed at the median follow-up of 15 months. CONCLUSION: 2-CdA in HCL can achieve complete remission, prolonged survival and care as well.

Interferón alfa intermitente en el tratamiento de la leucemia de células peludas / Intermittent alpha interferon in hairy cell leukemia

Objetivo. Evaluar si el interferón alfa utilizado en ciclos cortos e intermitentes es útil en el tratamiento a largo plazo de la leucemia de células peludas (LCP). Métodos. Nueve pacientes con leucemia de células peludas recibieron 3 megaunidades de IFN tres veces por semana por 12 semanas. Posteriormente recibieron tratamiento nuevamente de 8 semanas, al reactivarse la leucemia o después de 10 meses en observación cada año. Resultados. Todos tuvieron remisión hematológica antes de las 12 semanas de tratamiento. Unicamente tres pacientes recibieron tratamiento nuevamente antes de 10 meses por recaída. Todos están vivos y sin complicaciones con una mediana de seguimiento de 62 meses. Conclusiones. Los ciclos cortos de IFN intermitente fueron un tratamiento eficaz en la leucemia de células peludas. Esta opción terapéutica tiene un costo más bajo y fue efectiva y comparable a otras formas de terapia con IFN en el tratamiento y mantenimieto de pacientes con este tipo de leucemia

Tratamento da leucemia de células cabeludas com interferon alfa / Treatment of hairy cell leukemia with alpha interferon

O presente trabalho descreve cinco casos de pacientes portadores de leucemia de células cabeludas (LCC) ou tricoleucemia, que foram tratados com interferon alfa, um modificador da resposta biológica com grande atividade nesta doença crônica linfoproliferativa. Novos conceitos considerando seu uso como terapêutica de primeira linha säo discutidos, bem como aspectos marcantes de sua etiopatogenia, diagnóstico clínico-laboratorial e histopatológico.

Tricoleucemia: tratamento com alfa-interferon; relato de dois casos

Säo relatados dois casos de tricoleucemia, tratados com sucesso com interferon alfa recombinante. Um paciente havia sido esplenectomizado, com melhora transitória das citopenias, e o outro recebeu interferon como primeira forma de tratamento. Ambos desenvolveram infecçöes graves no curso de suas enfermedades e obtiveram remissäo completa, sete e oito meses após o início do interferon, respectivamente. A tentativa da retirada da droga em um paciente resultou em recaída três meses após, com pronta recuperaçäo com a sua reinstituiçäo. É feita uma revisäo do uso de interferon na tricoleucemia e os critérios de remissäo e retirada da medicaçäo säo comentadas