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.

Hairy cell Leukemia in a Filipino male during the COVID-19 pandemic – report of a rare case

@#Hairy cell leukemia (HCL) is a rare, chronic, mature B-cell lymphoproliferative disorder accounting for 2% of all leukemias. In this paper, we would like to present our experience in the management of HCL in a financially limited setting where other diagnostic tests and chemotherapy are unavailable. The case report aims to emphasize the recognition of the distinctive morphology of hairy cells in the peripheral blood in the consideration of the initial diagnosis. A 60-year-old Filipino male was incidentally found to have anemia, thrombocytopenia and an absolute neutrophilic count below 1,000 in a pre-operative clearance for elective herniorrhaphy. Blood smear revealed atypical lymphocytes with hair like cytoplasmic projections. CT-scan of the abdomen showed splenomegaly and prominent paraaortic nodes. Flow cytometry of the bone marrow aspirate was consistent with an involvement of a Mature B cell neoplasm markers CD19, CD20, CD22 and surface immunoglobulin lambda and hairy cell leukemia markers CD11c, CD103 and CD25. He responded to six-weekly sessions of Cladribine with remission of the bone marrow and hematologic parameters. HCL is a rare type of a mature B cell neoplasm characterized by pancytopenia, splenomegaly, bone marrow fibrosis and the presence of atypical lymphoid cells with hairy projections in blood, bone marrow and spleen. Immunophenotyping express CD11c, CD103, CD123, and CD25. BRAF V600E mutation is the disease defining genetic event. Cladribine and Pentostatin are the first line of treatment. Cases of leukemia can be easily overlooked because of the mild derangement in the complete blood count. A meticulous differential review of the atypical lymphocyte, is the first step in the diagnosis of this rare disease.

Leucémie à tricholeucocytes, un cas chez un adulte de 25 ans au service d'hématologie clinique du CHU de Yopougon Abidjan (Côte D'ivoire)

La leucémie à tricholeucocytes est une hémopathie lymphoïde B rare. Le diagnostic repose sur l'identification morphologique des cellules tumorales sanguines et/ou médullaires puis la mise en evidence de certains marqueurs à l'immunophénotypage. Le diagnostic reste difficile en Afrique subsaharienne du fait du plateau technique limité. En Afrique noire, très peu d'études ont été réalisées. Nous rapportons un cas documenté de leucémie à tricholeucocytes chez un jeune homme de 25 ans dans notre service

Outcome of hairy cell leukemia patients treated with cladribine - a 10-year single-center experience in Pakistan

ABSTRACT Introduction and objective: Hairy cell leukemia is an uncommon, indolent B-cell lymphoproliferative disorder. Therapy with cladribine (2-chlorodeoxyadenosine) is able to induce complete remission (CR) in the majority of patients after a single course of treatment. We report the outcomes of patients treated at Aga Khan University Hospital, Karachi, Pakistan. Methods: This was a retrospective review. Medical records of patients were used to collect data. Results: A total of 21 patients with hairy cell leukemia were treated with cladribine. All patients achieved an initial CR. Four patients (19%) required hospitalization and therapy for neutropenic fever. Six patients (29%) relapsed at a median of 48 months. All 6 patients were treated for relapse, out of which 4 achieved CR, 1 had partial response and 1 had refractory disease. The overall survival rate was 90.5%, with a median follow-up of 35 months. Conclusion: A single course of cladribine is able to induce CR in a vast majority of patients. Unfortunately, relapse is not uncommon. Patients who relapse can be successfully retreated with cladribine. Cladribine has impressive efficacy and a favorable acute and long-term toxicity profile when administered to patients with HCL.

Efficacy of Annexin A1 Immunostaining in Bone Marrow for the Diagnosis of Hairy Cell Leukemia

Splenic B-cell lymphomas (SBCLs) show characteristically pronounced splenomegaly without significant lymphadenopathy. Distinguishing hairy cell leukemia (HCL) from other SBCLs (splenic marginal zone lymphoma [SMZL], variant HCL [v-HCL], and splenic diffuse red pulp small B-cell lymphoma [SDRPL]) is essential to determine suitable treatments and prognoses. With advances in diagnostic modalities and therapies, splenectomy is not commonly performed, and thus diagnosis of HCL must be based on the results obtained using blood and bone marrow samples. Annexin A1 is known as the most specific marker for HCL. There has yet been no report of the assessment of annexin A1 immunostaining from Korea. In this study we analyzed samples from 13 Korean patients with SBCLs (three HCL, three v-HCL, six SMZL, and one SDRPL) from May 2001 to December 2016. Immunohistochemical analyses for annexin A1 and CD20 were performed using bone marrow sections; molecular analyses for detection of the BRAF V600E mutation were also performed. All HCL patients showed positive results for annexin A1 immunostaining and the presence of the BRAF V600E mutation, and negative results for other SBCLs. Our results confirmed the high specificity of annexin A1 and the BRAF V600E mutation as HCL markers. Molecular analysis requires expensive equipment and substantial manpower. Annexin A1 is a better alternative as an HCL marker than the BRAF V600E mutation in terms of cost-effectiveness.

“Hairiness” is a Facsimile of Reorganized Cytoskeletons: A Cytopathic Effect of Coxiella burnetii

In 1993, I reported that Coxiella burnetii transforms human B cells into hairy cells (cbHCs), the first hairy cell reported outside of hairy cell leukemia (HCL). Over last few decades, advances in molecular biology have provided evidence supporting that C. burnetii induces hairiness and inhibits the apoptosis of host cells. The present review summarizes new information in support of cbHC. C. burnetii was shown to induce reorganization of the cytoskeleton and to inhibit apoptosis in host cells. Peritoneal B1a cells were found to be permissive for virulent C. burnetii Nine Mile phase I (NMI) strains in mice. C. burnetii severely impaired E-cad expression in circulating cells of Q fever patients. B-cell non-Hodgkin lymphoma was linked to C. burnetii. Mutation of BRAF V600E was pronounced in HCL, but “hairiness” was not linked to the mutation. Risk factors shared among coxiellosis and HCL in humans and animals were reported in patients with Q-fever. Accordingly, I propose that C. burnetii induces reorganization of the cytoskeleton and inhibits apoptosis as cytopathic effects that are not target cell specific. The observed hairiness in cbHC appears to be a fixed image of dynamic nature, and hairy cells in HCL are distinct among lymphoid cells in circulation. As the cytoskeleton plays key roles in maintaining cell structural integrity in health and disease, the pathophysiology of similar cytopathic effects should be addressed in other diseases, such as myopathies, B-cell dyscrasias, and autoimmune syndromes.

Simultaneous presentation of plasma cell myeloma and hairy cell leukemia

No abstract available.

Fludarabine and Rituximab in Relapsed or Refractory Hairy Cell Leukmia Variant: A Case Report and Review of Literature / 고신대학교의과대학학술지

Hairy cell leukemia (HCL) is a rare chronic B cell leukemia morphologically characterized by cells with an abundant cytoplasm and hair-like projections that can be found in the peripheral blood and bone marrow. The treatment for HCL is splenectomy or chemotherapy with the purine analogs pentostatin and cladribine. However, patients continue to relapse. Retreatment with the same or alternate purine analogs produces lower response rates and a shorter duration of response. Fludarabine is another purine analog widely used in treating indolent lymphoid cancers, often in combination with rituximab. Here, we report a case of HCL variant in a 60-year-old man who experienced multiple relapses after splenectomy and retreatment with cladribine. The patient was then treated with fludarabine and rituximab combination chemotherapy. After the treatment, he achieved complete remission that continued for 35 months.

Synchronous hairy cell leukemia and chronic lymphocytic leukemia: a case report with a brief review of literature

No abstract available.

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.

Hairy cell leukemia: a case report of atypical presentation without splenomegaly

No abstract available.

Asociación entre tumor de células germinales y malignidades hematológicas / Germ cell tumors associated with hematologic malignancies

Los tumores de células germinales representan el 2% de las malignidades humanas siendo más común en hombres entre los 15 y 35 años. Cerca de 2 a 5% ocurren extragonadales. Garnik informó la asociación entre malignidades hematológicas y TCG en 1983, desde entonces varios casos han sido reportados; la mayoría se presentan con TCG no seminomatosos y neoplasias hematológicas de índole megacariocítica. Tienen mal pronóstico y resistencia a los tratamientos, la mayoría mueren durante el manejo inicial al diagnóstico y no existen protocolos óptimos para su manejo. Reportamos un caso de leucemia de células peludas (LCP) tratada con rituximab con un TCG de tipo seminoma clásico manejado con protocolo (PEB) platino, etoposido y bleomicina, logrando una adecuada respuesta clínica...

Germ cell tumors account for 2% of malignancies in humans, predominantly affecting men aged 15 to 35 years. Almost 2 to 5% occur at extragonadal sites. Garnik reported the association between hematologic malignancies and GCTs in 1983. Several cases have been reported since then; most of them present as nonseminomatous GCTs associated with magakaryocytic hematologic malignancies. They are resistant to treatment and prognosis is poor, most patients die within the initial phase of treatment after diagnosis. Optimal management protocols are not available. We report one case of hairy cell leukemia (HCL) treated with rituximab, associated to a classic seminoma type GCT managed with a bleomycin, etoposide, platinum (BEP) combination regimen, achieving an adequate clinical response...

Complete recovery of pyoderma gangrenosum after successful treatment of underlying hairy cell leukemia with cladribine

No abstract available.

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

No abstract available.

Detection of BRAF V600E mutation in hairy cell leukemia by high- resolution melting analysis / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the feasibility and diagnostic implication of BRAF V600E mutation identified by high-resolution melting (HRM) assay in patients with hairy cell leukemia (HCL).</p><p><b>METHODS</b>The V600E mutation of BRAF exon 15 in four HCL patients were detected by HRM assay and patients' clinical data were retrospectively analyzed.</p><p><b>RESULTS</b>All four HCL patients were positive for the BRAF V600E mutation, which were identical to the results of DNA sequencing.</p><p><b>CONCLUSION</b>The HRM assay for BRAF V600E mutation provides a useful tool to aid the laboratory diagnosis of HCL with easy operability, accuracy, and low cost.</p>