Multidisciplinary diagnosis and treatment of mantle cell lymphoma Expert consensus • Asociación Colombiana de Hematología y Oncología (ACHO) / Diagnóstico y tratamiento multidisciplinario de linfoma de células del manto Consenso de expertos • Asociación Colombiana de Hematología y Oncología (ACHO)

Abstract Introduction: Among the sub-types of lymphoma, mantle cell lymphoma, or what was previously known as intermediate lymphocytic lymphoma, accounts for 3-10% of B-cell non-Hodgkin lymphomas. Treatment is directed according to the patient's classification, age, functional status and comorbidities, and is directly related to the ability to receive intensive treatment or transplantation. It is important to homogenize treatments to offer the best alternatives in the Colombian context, as there are different diagnostic and therapeutic options today, most of which are financed by the Colombian healthcare system. Objective: To structure a series of considerations for the diagnosis and treatment of MCL within the Colombian context. Methods: A formal, mixed (Delphi/nominal) expert consensus was developed. The options for each question were scored in two masked rounds and an open nominal session. The information was consolidated in Excel and analyzed using STATA 13. Results: 25 considerations were developed for the diagnosis and treatment of MCL. Twenty-two specialists participated: 16 hematologists and hematologist-oncologists, four hematopathologists, one radiation therapist and one nuclear medicine specialist from Bogotá, Medellín and Cali, with an average of 10.5 years' of practical experience and who were members of the Asociación Colombiana de Hematología y Oncología [Colombian Association of Hematology and Oncology]. Conclusions: The consensus established 26 considerations for the diagnosis and treatment of MCL, according to the Colombian context, aimed at healthcare professionals with a direct relationship with this disease. It is expected that clinical management will be homogenized by a consideration of this consensus and the referenced literature. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2606).

Resumen Introducción: Dentro de los subtipos de linfoma, el linfoma de células del manto o anteriormente denominado linfoma linfocítico intermedio corresponde a 3-10% de los linfoma no Hodgkin de células B. El tratamiento se enfoca según la clasificación del paciente, edad, estado funcional y comorbilidades, lo cual está directamente relacionado con la capacidad de recibir un tratamiento intensivo o trasplante. Es importante homogeneizar conductas con el fin de ofrecer las mejores alternativas bajo el contexto colombiano, pues actualmente existen diferentes opciones diagnósticas y terapéuticas, financiadas en su mayoría por el sistema de salud colombiano. Objetivo: Estructurar una serie de consideraciones para el diagnóstico y tratamiento para LCM, en el contexto colombiano. Métodos: Se llevó a cabo un consenso formal de expertos, tipo mixto (Delphi/ Nominal). Se calificaron las opciones de cada pregunta en dos rondas enmascaradas y una sesión abierta nominal. La información fue consolidada en Excel y analizada en STATA 13. Resultados: Se elaboraron 25 consideraciones para el diagnóstico y tratamiento de LCM. Participaron 22 médicos especialistas: 16 hematólogos y hemato-oncólogos, cuatro hemato-patólogos, un radioterapeuta y un especialista en medicina nuclear de Bogotá, Medellín y Cali, con experticia en la práctica de 10.5 años en promedio y quienes forman parte de la Asociación Colombiana de Hematología y Oncología. Conclusiones: El consenso definió 26 consideraciones para el diagnóstico y tratamiento de LCM, según el contexto colombiano, dirigidas a profesionales de la salud con relación directa a esta patología. Se espera homogeneizar las conductas clínicas teniendo en cuenta este consenso y la literatura referida. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2606).

Incidence and Prognostic Significance of High-Risk Cytogenetically Abnormalities in Multiple Myeloma Patients in Colombia.

INTRODUCTION: Multiple Myeloma (MM) is the second most common hematological cancer, several cytogenetics abnormalities such as t(4;14), del (17p), and t(14;16) were identified as a high-risk for survival, in Latin America, we have very little data on cytogenetic alterations in MM. This study describes the incidence of high-risk cytogenetically abnormalities in a Colombian population and prognostic significance. METHODS: In a retrospective cohort of new diagnostic Multiple Myeloma between 2016 and 2020, we identified a high-risk cytogenetically abnormalities t(4;14), t(14;16), and 17p deletions by FISH techniques and described incidence. We followed patients until progression or death and comparing progression free survival (PFS) and overall survival (OS), according with high- risk cytogenetically features. RESULTS: We included 135 newly diagnosed MM patients, the incidence of high-risk cytogenetically abnormalities were 30.3%, with 17.1% of 17p deletions, 14.1% of t(4;14) and 2.25% of t(14;16). According to the high risk cytogenetically abnormalities, the median PFS for the group of no abnormalities were 50.2 months 95% CI [25.2-62.4] and for the group of high-risk cytogenetic abnormalities 33.9 months 95% CI [23.6-NA] (P = .2). For OS the median were 76.9 months, 95% CI [67.5-NA] and 42.7 months 95% CI [33.3-NA], respectively (P = .009). CONCLUSION: High-risk cytogenetically abnormalities were independent risk factor for OS but not PFS in this cohort of patients, and the incidence of del (17p) was slightly higher than the literature reports.  MICROABSTRACT: Prognostic significance of high-risk cytogenetic abnormalities in Multiple Myeloma in Colombia is unknown. In a retrospective cohort study of 135 newly, diagnostic Multiple Myeloma we found incidence of high-risk cytogenetic abnormalities was 30.3%. The hazard ratio (HR) for disease progression or death compared high-risk cytogenetic group vs. control was 1.22, (95% CI, 0.73-2.05) (P = .2), and The HR for death for the group of high-risk cytogenetic abnormalities was 2.17, (95% CI, 1.19-3.97). In the group of high-risk cytogenetic abnormalities, if the patient received VRD as induction treatment the median PFS were 41.2 months 95% CI [13.3-NA] and 33.9 months 95% CI [24.9-NA] for patients with different induction treatment (P = .56).

Measurable Residual Disease Assessment and Allogeneic Transplantation as Consolidation Therapy in Adult Acute Lymphoblastic Leukemia in Colombia.

INTRODUCTION: Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. The objective of the study was to assess disease-free survival (DFS) and overall survival (OS) of patients with ALL according with MRD status at the end of induction therapy in a Colombian population. PATIENTS AND METHODS: We assessed a retrospective cohort to compare DFS and OS in adults with de novo ALL according to MRD status at the end of induction chemotherapy, and the type of postinduction consolidation strategy used. RESULTS: A total of 165 adults with ALL were included in the MRD part of the study, 73 patients in the MRD-negative group and 92 in the MRD-positive group. Median DFS for the MRD-positive group was 11 months (95% confidence interval, 11.7-22.2) and was not reached for the MRD-negative group (P < .001). At 3 years, DFS was 18% and 55%, respectively (P < .001). The median OS for MRD-positive patients was 16 months (95% confidence interval, 8.8-23.15) and was not reached in the MRD-negative group. At 3 years, OS was 26% and 51% for the former and latter group, respectively. Among subjects who did not receive a transplant, median DFS was 21 months for MRD-negative patients and 9 months for MRD-positive patients (P < .001). The median DFS was not reached in either group, whereas 3-year DFS was 64% for MRD-negative and 70% for MRD-positive patients who underwent transplantation in first remission (P = .861). CONCLUSION: MRD status at the end of induction is an independent prognostic factor for DFS and OS in adult ALL. Allogeneic transplantation in first remission could overcome the adverse prognostic impact of MRD.

[Disseminated juvenile paracoccidioidomycosis diagnosed in a girl in an urban area]. / Paracoccidioidomicosis juvenil diseminada diagnosticada en una niña en área urbana.

INTRODUCTION: Paracoccidioidomycosis is one of the most prevalent systemic fungal infections in Latin American countries. The incidence rate has been increasing and its detection has gotten increasingly common in travelers or immigrants from endemic areas. It is characterized by respiratory symptoms, lymphadenopathies and skin lesions, which gradually progress and subsequently lead to death in some untreated chronic disease cases. OBJECTIVE: To describe the clinical approach and diagnosis of an exotic tropical pathology in an urban area. CASE DESCRIPTION: Case description and extended literature review. We made a case report of urban paracoccidioidomycosis in a young patient, with a clinical syndrome of fever for a month, widespread nodal involvement, cutaneous manifestations and weight loss. During the physical examination, hepatosplenomegaly and a febrile episode were evidenced, whose diagnosis was difficult. Management started with itraconazole and trimethoprim sulfamethoxazole, with subsequent cessation of spiking fevers and significant improvement of the skin lesions. We performed a comprehensive literature review, with search criteria performed in PubMed and adapted for different databases. The review was conducted based on the studies found in Medline, LILACS, SciELO and Cochrane Library, from 1966 up to this moment. Studies were selected by the authors based on their relevance and scientific contribution to the discussion of this case. CONCLUSIONS: There are few cases of paracoccidiomycosis in the pediatric population despite the endemicity of this entity in Latin America. An increasing population influx from endemic areas makes suspecting of this disease a must.

Paracoccidioidomicosis juvenil diseminada diagnosticada en una niña en área urbana / Disseminated juvenile paracoccidioidomycosis diagnosed in a girl in an urban area

Introducción. La paracoccidioidomicosis es una de las infecciones micóticas sistémicas más prevalente en los países latinoamericanos. La tasa de incidencia ha ido en incremento y su detección es cada vez más común en viajeros o inmigrantes de las zonas endémicas. Se caracteriza por un cuadro de síntomas respiratorios, linfadenopatías y lesiones cutáneas que progresan paulatinamente, por lo que la enfermedad crónica no tratada puede llevar a la muerte. Objetivo. Describir el enfoque clínico y diagnóstico de una enfermedad tropical exótica en una zona urbana. Caso clínico. Se describe un caso de paracoccidioidomicosis juvenil en área urbana con un cuadro clínico de síndrome febril de un mes de evolución, compromiso ganglionar generalizado, manifestaciones cutáneas y pérdida de peso; el examen físico evidenció episodio febril y hepatoesplenomegalia, cuyo diagnóstico fue difícil. Se inició manejo con itraconazol y trimetoprim-sulfametozaxol con posterior cese de los picos febriles y mejoría significativa de las lesiones en la piel. Se hizo una revisión extensa de la literatura científica con los criterios de búsqueda de Pubmed adaptados para las diferentes bases de datos; la revisión se basó en los estudios hallados en Medline, LILACS, SciELO y Cochrane Library desde 1966 hasta la fecha. Los estudios fueron seleccionados por los autores con base en su relevancia y aporte científico a la discusión del caso en mención. Conclusiones. Son pocos los casos de paracoccidioidomicosis en la población pediátrica a pesar de ser endémica en América Latina. Las crecientes corrientes de urbanización de las zonas endémicas hacen que este cuadro deba sospecharse.

Introduction: Paracoccidioidomycosis is one of the most prevalent systemic fungal infections in Latin American countries. The incidence rate has been increasing and its detection has gotten increasingly common in travelers or immigrants from endemic areas. It is characterized by respiratory symptoms, lymphadenopathies and skin lesions, which gradually progress and subsequently lead to death in some untreated chronic disease cases. Objective: To describe the clinical approach and diagnosis of an exotic tropical pathology in an urban area. Case description: Case description and extended literature review. We made a case report of urban paracoccidioidomycosis in a young patient, with a clinical syndrome of fever for a month, widespread nodal involvement, cutaneous manifestations and weight loss. During the physical examination, hepatosplenomegaly and a febrile episode were evidenced, whose diagnosis was difficult. Management started with itraconazole and trimethoprim sulfamethoxazole, with subsequent cessation of spiking fevers and significant improvement of the skin lesions. We performed a comprehensive literature review, with search criteria performed in PubMed and adapted for different databases. The review was conducted based on the studies found in Medline, LILACS, SciELO and Cochrane Library, from 1966 up to this moment. Studies were selected by the authors based on their relevance and scientific contribution to the discussion of this case. Conclusions: There are few cases of paracoccidiomycosis in the pediatric population despite the endemicity of this entity in Latin America. An increasing population influx from endemic areas makes suspecting of this disease a must.

Linfoma de Burkitt primario de mama. Presentación de un caso / Burkitt Lymphoma Primary of the Breast. A Case Report

Se presenta el caso de una mujer en el último trimestre de embarazo con mastalgia y cambios inflamatorios en ambos senos, con aumento progresivo después del parto. Se le practicó biopsia por tru-cut que demostró linfoma de Burkitt en el estudio de patología. Los linfomas primarios de seno son raros, más frecuentes en mujeres que en hombres y entre la sexta y la séptima década de la vida. Sin embargo, algunos de ellos, como el linfoma de Burkitt, pueden ocurrir durante el embarazo o el posparto por estimulo hormonal. Debe sospecharse en mujeres en embarazo o puerperio con mastitis que no presenta mejoría con el tratamiento instaurado.

We report the case of a woman in her last trimester of pregnancy with bilateral breast pain and inflammatory changes that increased after delivery. Burkitt lymphoma was reported in the Pathology study of a trucut biopsy. Primary breast lymphomas are rare, being more frequent in women than in men during the sixth or seventh decade of life. However some of these lymphomas, like Burkitt lymphoma, can occur during pregnancy or puerperium due to hormonal stimulation. It should be suspected in pregnant women or in puerperium with mastitis that does not improve with the established treatment.

Leucemia/linfoma T del adulto en pacientes infectados con HTLV-1: reporte de dos casos de Colombia / Adult T-cell leukemia/lymphoma in HTLV-1 infected patients: report of two cases in Colombia

La leucemia/linfoma de células T del adulto ( Adult T-Cell Leukemia/Lymphoma , ATLL) es una neoplasia maligna de los linfocitos T CD4 maduros, que resulta de la infección con el virus T-linfotrópico humano de tipo 1 (HTLV-1), con varias manifestaciones sistémicas y cutáneas. Se presentan dos casos de leucemia/linfoma de células T del adulto en pacientes del suroccidente de Colombia, cuyos diagnósticos fueron confirmados por histología, inmunohistoquímica, citometría de flujo y pruebas ELISA y Western blot. También, se discute acerca del virus y cómo hacer el diagnóstico en países como el nuestro.

Adult T-cell leukemia/lymphoma (ATLL) is a malignant neoplasia of mature CD4+ T lymphocytes,resulting from infection with human T-lymphotropic virus type 1 (HTLV-1), with several systemic and cutaneous manifestations. We present two cases of adult T-cell leukemia/lymphoma, in patients from the Colombian Southwestern region, whose diagnoses were confirmed by histology, immunohistochemistry, flow cytometry, ELISA and Western blot tests. We also discuss about the virus and how to make this diagnosis in countries like Colombia.

[Adult T-cell leukemia/lymphoma in HTLV-1 infected patients: report of two cases in Colombia]. / Leucemia/linfoma T del adulto en pacientes infectados con HTLV-1: reporte de dos casos de Colombia.

Adult T-cell leukemia/lymphoma (ATLL) is a malignant neoplasia of mature CD4+ T lymphocytes,resulting from infection with human T-lymphotropic virus type 1 (HTLV-1), with several systemic and cutaneous manifestations. We present two cases of adult T-cell leukemia/lymphoma, in patients from the Colombian Southwestern region, whose diagnoses were confirmed by histology, immunohistochemistry, flow cytometry, ELISA and Western blot tests. We also discuss about the virus and how to make this diagnosis in countries like Colombia.