Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report
Chronic Lymphocytic Leukemia (CLL) is a B cell lymphoproliferative malignancy in which lymphomatous transformation to Richter's Syndrome (RS) occurs in 5-15% of patients. It is associated with Diffuse Large B Cell Lymphoma (DLBCL) in 80% of cases, while transformation to Hod...
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Universidad Nacional Cba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2019
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/25557 |
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I10-R10-article-25557 |
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Universidad Nacional de Córdoba |
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I-10 |
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Revistas de la UNC |
| language |
Español |
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Artículo revista |
| topic |
CLL progression diffuse lymphoma hodgkin lymphoma Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report transformación linfoma difuso linfoma hodkin LCC |
| spellingShingle |
CLL progression diffuse lymphoma hodgkin lymphoma Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report transformación linfoma difuso linfoma hodkin LCC Heller , VB Sastre , D Acosta , M Slavutsky , I Dionisio de Cabalier , ME Negri , I Rodríguez , MC Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report |
| topic_facet |
CLL progression diffuse lymphoma hodgkin lymphoma Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report transformación linfoma difuso linfoma hodkin LCC |
| author |
Heller , VB Sastre , D Acosta , M Slavutsky , I Dionisio de Cabalier , ME Negri , I Rodríguez , MC |
| author_facet |
Heller , VB Sastre , D Acosta , M Slavutsky , I Dionisio de Cabalier , ME Negri , I Rodríguez , MC |
| author_sort |
Heller , VB |
| title |
Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report |
| title_short |
Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report |
| title_full |
Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report |
| title_fullStr |
Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report |
| title_full_unstemmed |
Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report |
| title_sort |
progression of chronic lymphocytic leukemia into hodgkin lymphoma during ibrutinib treatment. case report |
| description |
Chronic Lymphocytic Leukemia (CLL) is a B cell lymphoproliferative malignancy in which lymphomatous transformation to Richter's Syndrome (RS) occurs in 5-15% of patients. It is associated with Diffuse Large B Cell Lymphoma (DLBCL) in 80% of cases, while transformation to Hodgkin Lymphoma (HL) has been reported in extremely rare cases with an estimated prevalence of 0.4%. Mutations in P53 and NOTCH1 genes are the most common aberrations observed in the progression to RS, and the cells may be clonally related or unrelated to the underlying clone. Bruton’s tyrosine Kinase (BtK) inhibitors, such as Ibrutinib (Ibru), has been approved for treatment of patients with 17p deletion, P53 mutations or relapsed / refractory CLL . However, it has been recently shown that BtK inhibitors can induce genomic instability in B cells, so in the context of the use of this new therapy, new emerging cases are of relevance. In this work we aimed to report the clinical picture, pathology and genetics of a HL CLL transformation after Ibru treatment .
Clinical case report: a 58-year-old man was diagnosed with LLC, by flow cytometry in April 2008 (Rai Stage II). Among prognostic biomarkers, IgHV was unmutated, ZAP70: 58% (+) and CD38: 80% (+). The patient was treated with Rituximab / Fludarabine / Cyclophosphamide and then as second line of treatment, he received Bendamustine. He was followed up until June 2016, when he arrived at Hospital because of progressive disease. At that moment, the FISH analysis showed genetic alterations like: deletion 13q (34.5%), deletion 11q monoallelic: 3.1%, biallelic: 65.6%, normal TP53. The patient received Ibru 420 mg / day. After 35 days of therapy, the blood count showed a notable lymphocytosis (WBC: 413 x 109 / l, 90.5% Lymphocytes, absolute count: 176 x 109 / l), without clinical symptoms, marked decrease size in adenomegaly, and hepatosplenomegaly. Eighteen months later, the patient presented progressive constitutional symptoms, with enlarging of supraclavicular lymphadenopathy, liver and spleen and pleural effusion. Supraclavicular lymph node biopsy sugested small cell lymphocytic lymphoma with high grade transformation. Inmunohistochemistry confirmed the presence of Hodgkin Reed Sternberg cells (CD30+, CD15+) on a background of CLL cells.
We reported a rare case of CLL with HL transformation during treatment with Ibrutinib. Considering the increase in ITKB indications for this pathology, it is important to examine carefully the new cases that arise in order to identify particular characteristics that suggest the causal mechanism. |
| publisher |
Universidad Nacional Cba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2019 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/25557 |
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I10-R10-article-255572019-11-11T21:18:27Z Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report Progresión de la Leucemia linfática crónica a Linfoma de Hodgkin luego del tratamiento con Ibrutinib. Presentación de un caso Heller , VB Sastre , D Acosta , M Slavutsky , I Dionisio de Cabalier , ME Negri , I Rodríguez , MC CLL progression diffuse lymphoma hodgkin lymphoma Progression of Chronic Lymphocytic Leukemia into Hodgkin Lymphoma during Ibrutinib treatment. Case Report transformación linfoma difuso linfoma hodkin LCC Chronic Lymphocytic Leukemia (CLL) is a B cell lymphoproliferative malignancy in which lymphomatous transformation to Richter's Syndrome (RS) occurs in 5-15% of patients. It is associated with Diffuse Large B Cell Lymphoma (DLBCL) in 80% of cases, while transformation to Hodgkin Lymphoma (HL) has been reported in extremely rare cases with an estimated prevalence of 0.4%. Mutations in P53 and NOTCH1 genes are the most common aberrations observed in the progression to RS, and the cells may be clonally related or unrelated to the underlying clone. Bruton’s tyrosine Kinase (BtK) inhibitors, such as Ibrutinib (Ibru), has been approved for treatment of patients with 17p deletion, P53 mutations or relapsed / refractory CLL . However, it has been recently shown that BtK inhibitors can induce genomic instability in B cells, so in the context of the use of this new therapy, new emerging cases are of relevance. In this work we aimed to report the clinical picture, pathology and genetics of a HL CLL transformation after Ibru treatment . Clinical case report: a 58-year-old man was diagnosed with LLC, by flow cytometry in April 2008 (Rai Stage II). Among prognostic biomarkers, IgHV was unmutated, ZAP70: 58% (+) and CD38: 80% (+). The patient was treated with Rituximab / Fludarabine / Cyclophosphamide and then as second line of treatment, he received Bendamustine. He was followed up until June 2016, when he arrived at Hospital because of progressive disease. At that moment, the FISH analysis showed genetic alterations like: deletion 13q (34.5%), deletion 11q monoallelic: 3.1%, biallelic: 65.6%, normal TP53. The patient received Ibru 420 mg / day. After 35 days of therapy, the blood count showed a notable lymphocytosis (WBC: 413 x 109 / l, 90.5% Lymphocytes, absolute count: 176 x 109 / l), without clinical symptoms, marked decrease size in adenomegaly, and hepatosplenomegaly. Eighteen months later, the patient presented progressive constitutional symptoms, with enlarging of supraclavicular lymphadenopathy, liver and spleen and pleural effusion. Supraclavicular lymph node biopsy sugested small cell lymphocytic lymphoma with high grade transformation. Inmunohistochemistry confirmed the presence of Hodgkin Reed Sternberg cells (CD30+, CD15+) on a background of CLL cells. We reported a rare case of CLL with HL transformation during treatment with Ibrutinib. Considering the increase in ITKB indications for this pathology, it is important to examine carefully the new cases that arise in order to identify particular characteristics that suggest the causal mechanism. La Leucemia Linfática Crónica (LLC) es un Sindrome Linfoproliferativo B, en el cual la transformación linfomatosa a Sindrome de Richter (SR) ocurre en 5-15% de los pacientes. Se asocia a Linfoma Difuso de Grandes Células B (LDGCB) en el 80% de los casos, mientras que la transformación a Linfoma Hodgkin (LH) es extremadamente rara con prevalencia estimada de 0,4%. Las mutaciones en genes P53 y NOTCH1 son las mas frecuentemente observadas en la progresión , y las células pueden estar o no clonalmente relacionadas con el clon pre existente. Los inhibidores de la Tirosin Kinasa de Bruton (ITKB) como Ibrutinib, se utilizan en el tratamiento de LLC recaída/ refractaria, o no tratados que presenten o no, deleción 17p o mutaciones en P53. Recientemente se ha demostrado que los ITKB inducen inestabilidad genómica en las células B, por lo cuál en el contexto del uso de esta nueva terapia, los nuevos casos emergentes son de relevancia. El objetivo del trabajo fue reportar la transformación de LLC a LH luego del tratamiento con BITK CASO CLÍNICO: Paciente sexo masculino, 58 años de edad. Diagnóstico: LLC por citometría de flujo en Abril 2008, Estadio II de Rai, factores pronósticos realizados al inicio: IgVH No mutada, ZAP70 58% (+), CD38 80%(+). Tratamiento inicial: Rituximab/ Fludarabina/ Ciclofosfamida. Segunda línea: Bendamustina. Junio 2016, progresión de enfermedad. Alteraciones genéticas por FISH: deleción 13q (34,5%), deleción 11q monoalélica 3.1%, bialélica 65.6%, P53 normal. Tratamiento: Ibrunib 420 mg/día. A 35 días del inicio, pico de linfocitosis en SP (GB: 413x109/l, Li:90.5%, recuento absoluto: 176 x109/l), sin síntomas, marcada disminución de adenomegalias, y de hepatoesplenomegalia. A 18 meses de tratamiento, síntomas B, voluminosa adenopatía supraclavicular derecha, derrame pleural, aumento del volumen de hígado y bazo. Biopsia ganglionar: Hallazgos vinculables a Linfoma Linfocítico de células pequeñas con transformación a Linfoma de alto grado. Inmunohistoquímica: se observan células de Reed Sternberg CD15+, CD30+ compatible con LH. Paciente fallece por fallo multisistémico. Reportamos un caso poco frecuente de LLC con transformación a LH durante el tratamiento con Ibrutinib. Considerando el incremento en las indicaciones de ITKB para esta patología, se considera importante examinar cuidadosamente los nuevos casos que se presenten, a fines de identificar características particulares que sugieran el mecanismo causal. Universidad Nacional Cba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2019-10-02 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion application/pdf https://revistas.unc.edu.ar/index.php/med/article/view/25557 Revista de la Facultad de Ciencias Médicas de Córdoba.; 2019: Suplemento JIC XX Revista de la Facultad de Ciencias Médicas de Córdoba; 2019: Suplemento JIC XX Revista da Faculdade de Ciências Médicas de Córdoba; 2019: Suplemento JIC XX 1853-0605 0014-6722 spa https://revistas.unc.edu.ar/index.php/med/article/view/25557/27350 Derechos de autor 2019 Universidad Nacional de Córdoba |