An elevated HScore is associated with poor clinical outcomes in COVID-19 / Un HScore elevado se asocia a mal pronóstico en pacientes con COVID-19

BACKGROUND: Patients with Coronavirus Disease 2019 (COVID-19) frequently experience a hyperinflammatory syndrome leading to unfavorable outcomes. This condition resembles Secondary Hemophagocytic Lymphohistiocytosis (sHLH) described in neoplastic, rheumatic and other infectious diseases. A scoring system (HScore) that evaluates underlying immunosuppression, temperature, organomegaly, cytopenias, ferritin, triglycerides, fibrinogen and AST was validated for sHLH, and recently proposed to evaluate hyperinflammation in COVID-19. AIM: To assess the presence of sHLH among patients with COVID-19 admitted for hospitalization and to evaluate Hscore as a prognostic tool for poor outcomes. MATERIAL AND METHODS: One hundred forty-three patients aged 21-100 years (64% males) admitted because of COVID-19 were enrolled in a prospective study. HScore was calculated within 72 hours admission. The incidence of sHLH during hospitalization was evaluated. Additionally, the relationship between a HScore ≥ 130 points and either the requirement of mechanical ventilation or 60-days mortality was explored. RESULTS: The median HScore was 96 (33-169). A SHLH was diagnosed in one patient (incidence 0.7%), whose HScore was 169. After adjusting for age, sex, comorbidities and obesity, HScore ≥ 130 was independently associated with the composite clinical outcome (Hazard rartio 2.13, p = 0.022). CONCLUSIONS: sHLH is not frequent among COVID-19 patients. HScore can be useful to predict the risk for poor outcomes.

ANTECEDENTES: Los pacientes con Enfermedad por Coronavirus 2019 (COVID-19), experimentan frecuentemente un síndrome hiperinflamatorio que lleva a resultados desfavorables. Esta situación se asemeja al Síndrome Hemofagocítico Secundario (sHLH) descrito en enfermedades neoplásicas, reumatológicas y por otros agentes infecciosos. Un sistema simple de puntaje (HScore) que evalúa inmunosupresión, temperatura organomegalia, citopenias, ferritina, triglicéridos, fibrinógeno y AST ha sido validado para el diagnóstico de sHLH y ha sido propuesto recientemente para evaluar la hiperinflamación en COVID-19. OBJETIVO: Medir la frecuencia de sHLH entre pacientes con COVID-19 hospitalizados, y evaluar a HScore como una herramienta pronóstica. MATERIAL Y MÉTODOS: Ciento cuarenta y tres pacientes de 21 a 100 años (64% hombres) fueron ingresados en este estudio de cohorte prospectivo, unicéntrico. Se calculó HScore dentro de las primeras 72 horas desde el ingreso, y se midió la incidencia de sHLH durante la hospitalización. Adicionalmente, se evaluó la relación entre HScore ≥ 130 puntos y un desenlace compuesto de ventilación mecánica o muerte a los 60 días. RESULTADOS: La mediana de HScore fue 96 (33-169) puntos. Un paciente fue diagnosticado con sHLH (incidencia 0,7%). Luego de ajustar por edad, sexo, comorbilidades y obesidad, un HScore ≥ 130 se asoció de manera independiente con el desenlace compuesto. CONCLUSIONES: El sHLH no es frecuente en los pacientes con COVID-19. El uso de HScore puede ser útil para predecir el riesgo de desenlaces clínicos desfavorables.

Sulfohemoglobinemia secundaria a zopiclona. Casos clínicos / Sulfhemoglobinemia secondary to the use of zopiclone. Report of two cases

Sulfhemoglobin (SulfHb) is formed by hemoglobin (Hb) oxidation by sulfur compounds. Sulfhemoglobinemia is mainly associated with drugs or intestinal bacterial overgrowth. Patients present with central cyanosis, an abnormal pulse oximetry and normal arterial oxygen partial pressure. These features are shared with methemoglobinemia (MetHb) whose diagnosis requires an arterial co-oximetry. Depending on the device used, SulfHb may produce interference with this technique. We report two females aged 31 and 43 years, consulting at the emergency room with cyanosis. Both had a history of acute and chronic, high dose zopiclone ingestion. Pulse oximetry showed desaturation but with normal arterial oxygen partial pressure. Cardiac and pulmonary diseases were ruled out. Co-oximetry in two different analyzers showed interference or normal MetHb percentages. No other complications ensued, and cyanosis decreased over days. Since MetHb was discarded among other causes of cyanosis in a compatible clinical context, the diagnosis of sulfhemoglobinemia was made. The confirmatory method is not available in Chile. The presence of SulfHb is difficult to diagnose, confirmatory tests are not readily available, and it frequently interferes with arterial co-oximetry. This is attributed to a similar absorbance peak of both pigments in arterial blood. Venous co-oximetry can be useful in this context. SulfHb is a self-limited condition in most cases, however it must be differentiated from methemoglobinemia to avoid inappropriate treatments like methylene blue.

Overall survival in Chilean patients with lymphoma and human immunodeficiency virus: A retrospective cohort study

ABSTRACT Introduction: People living with human immunodeficiency virus (PLWH) still face high morbidity and mortality resulting from lymphoma. Aim: To describe a population of PLWH and lymphoma in a Chilean public hospital and compare the overall survival (OS) with a previously reported cohort from the same institution. Methods: Retrospective single-center cohort study. All the patients diagnosed between 2010 and 2017 were included. Demographic and clinical variables were obtained from medical records. The overall survival (OS) was estimated in treated patients from diagnosis until death or October 2020. The OS was then compared with a cohort of patients diagnosed between 1992 and 2008. Main Results: Eighty-four patients were included. The most common histological types were Burkitt's lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), Hodgkin's lymphoma (HL) and plasmablastic lymphoma (PBL) at 31%, 27%, 21% and 14%, respectively. The three-year OS for the whole cohort of BL, DLBCL, HL and PBL was 58.9%, 65.2%, 47.4%, 76.4% and 50%, respectively. Compared to the cohort of 1992 to 2008, a global increase in the OS was found after excluding HL and adjusting for age and clinical stage (HR 0.38, p = 0.002). However, when the main types were analyzed individually, the increase in the OS was statistically significant only in DLBCL (HR 0.29, p = 0.007). Most patients with DLBCL received CHOP chemotherapy, as in the previous cohort. Conclusion: The OS has improved in this population, despite no major changes in chemotherapy regimens, mainly due to the universal access to antiretroviral therapy.

Polineuropatía por amiloidosis por transtiretina de inicio tardío. Caso clínico / Late-onset hereditary transthyretin amyloidosis with polyneuropathy. Report of one case

Hereditary transthyretin amyloidosis is a multisystemic autosomal dominant genetic disorder characterized by progressive distal sensory-motor polyneuropathy or restrictive cardiomyopathy, secondary to amyloid deposits. Its pathogenesis lies in the TTR gene mutation, and the Val50Met mutation is the most frequent. Patients have significant differences in the onset and severity of clinical presentation according to their country of origin. The diagnosis of this pathology is complex, even more in countries where it is not considered endemic. However, early suspicion and management are essential to improve survival and avoid unnecessary diagnostic and therapeutic strategies. We report a 69-year-old woman who presented a sensory-motor polyneuropathy, predominantly sensory, associated with distal neuropathic pain and bilateral vitritis. The history of her Italian father with polyneuropathy of unspecified etiology stood out. A vitreous biopsy identified amyloid substance deposits (congo red positive). These were also confirmed on a superficial peroneal nerve biopsy. During the etiological study of her polyneuropathy, an increased Kappa/Lambda index of 2.55 mg/L stood out. Therefore, light chain amyloidosis was suspected, and chemotherapy treatment was indicated without favorable response. After 10 years of progressive neurological and ophthalmological involvement, a genetic study confirmed the first case of late-onset hereditary transthyretin amyloidosis Val50Met with polyneuropathy in Chile.

Estudio de costo-efectividad de profilaxis con emicizumab versus agentes hemostáticos alternativos en pacientes con hemofilia A grave en Perú / Cost-effectiveness study of prophylaxis with emicizumab versus bypassing agents in patients with severe hemophilia A in Peru

Contexto La hemofilia es un trastorno hemorrágico de la coagulación que ocurre en uno de cada 5000 nacimientos masculinos. Los pacientes con hemofilia A grave no tratados tienen complicaciones hemorrágicas, incluyendo sangrados articulares y menor sobrevida. El emicizumab es un anticuerpo monoclonal aprobado por los Estados Unidos para la profilaxis rutinaria de pacientes pediátricos y adultos con hemofilia A grave con inhibidores del factor VIII de coagulación. Objetivos Realizar un estudio de costo-efectividad de la profilaxis con emicizumab para niños y adultos con hemofilia A grave, en comparación con el actual manejo de esos pacientes en el Ministerio de Salud y el Seguro Social de Salud de Perú. Metodología Se modeló la transición del paciente entre estados médicos con la metodología de Markov y se estimó a lo largo de su vida costos y efectos incrementales de emicizumab comparados con el actual manejo. Se estimó el impacto presupuestario de emicizumab proyectando costos netos anuales y su valor presente a cinco años. Resultados Emicizumab generaría ahorros en el Ministerio de Salud entre 14,6 y 16,0 por niño y 11,8 por adulto, en US$ millones actuales, y en el Seguro Social de Salud de 12,8 a 14,9 por niño y 40,1 por adulto. Además, se generan ganancias en efectividad, medidas en años de vida ajustados por calidad, de 0,36 por niño y 0,56 por adulto y de 0,25 por niño y 0,36 por adulto en esas respectivas instituciones. El impacto presupuestario sería un ahorro anual neto, en US$ millones, de 12,8 y 15,0 en esas entidades. Conclusión El actual manejo de la enfermedad es muy costoso y con resultados de salud inferiores a los posibles con emicizumab. Este fármaco produciría grandes ahorros y mejor salud. Ambas entidades debieran implementar protocolos para la profilaxis y tratamiento de la hemofilia y financiarla con presupuesto propio.

Settings Hemophilia is a coagulation disorder that occurs in one in 5000 male births. Patients with untreated severe hemophilia A have hemorrhagic complications, including joint bleeds and decreased survival. Emicizumab is a monoclonal antibody approved by the United States for routine prophylaxis of pediatric and adult patients with severe hemophilia A with factor VIII inhibitors. Objectives To perform a cost-effectiveness study of emicizumab prophylaxis for children and adults with severe hemophilia A compared with the current disease management in the Peruvian Ministry of Health and Social Security Health Insurance. Methods The patient transition between medical states was modeled with Markov methodology, and the lifetime costs and incremental effects of emicizumab compared to current management were estimated. The budgetary impact of emicizumab was estimated by projecting annual net costs and its five-year present value. Results In the Ministry of Health, emicizumab would generate savings between 14.6 and 16.0 per child and 11.8 per adult, in current US$ million. Social Security Health Insurance savings would be 12.8 to 14.9 per child and 40.1 per adult. In addition, this strategy would generate effectiveness gains, measured in quality-adjusted life-years, of 0.36 per child and 0.56 per adult and 0.25 per child, and 0.36 per adult in those respective institutions. The budgetary impact would be a net annual saving of 12.8 and 15.0 US$ million in those entities. Conclusions The current management of hemophilia A is very costly and has health outcomes inferior to those possible with emicizumab. This drug would produce significant savings and better patient health. The Ministry of Health and Social Health Insurance should implement hemophilia prophylaxis and treatment protocols and finance this drug.

Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile

Background: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). Aim: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. Material and Methods: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. Results: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. Conclusions: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL) para el manejo del linfoma en estado de pandemia SARS CoV-2 / COVID 19 / Latin American Study Group of Lymphoproliferatives (GELL) for the management of Lymphoma in a state of Pandemic SARS CoV-2 / COVID 19

Resumen En diciembre de 2019 se detectó por primera vez en China la existencia del SARS-CoV2, causante de la enfermedad COVID-19. El virus rápidamente se propagó por Europa y Asia, tardándose un par de meses antes de llegar a América Latina. Se ha demostrado que los pacientes que desarrollan una enfermedad severa y que tienen mayor riesgo de mortalidad por COVID-19 son aquellos con edades avanzadas y que presentan por lo menos una enfermedad crónica, incluyendo el cáncer. Debido a lo anterior, surgen muchas dudas en el grupo de profesionales encargados de brindar tratamiento a pacientes con cáncer durante la pandemia, pues se debe equilibrar el riesgo-beneficio de proveer tratamiento a pacientes que se encuentran de base con un riesgo incrementado para tener manifestaciones severas por COVID-19. En este consenso planteamos recomendaciones para los profesionales en hematología que brindan tratamiento a pacientes que padecen de algún tipo de linfoma, con el fin de aclarar el panorama clínico durante la pandemia.

Abstract The existence of SARS-CoV2, the cause of COVID 19 disease, was detected for the first time in China in December 2019. The virus quickly spread across Europe and Asia, taking a couple months to reach Latin America. It has been shown that elderly patients and those with chronic diseases, including cancer, have a higher risk of mortality from COVID-19. Consequently, many doubts arise in the group of health professionals responsible for treating patients with cancer during the pandemic, as they must balance the risk-benefit of delivering treatment to patients with an increased risk for severe manifestations resulting from COVID-19. In this consensus we propose recommendations for hematology professionals who provide treatment to patients suffering from some type of lymphoma, with the aim of clarifying the clinical picture during the pandemic.

Leucemia/linfoma T del adulto HTLV1, un desafío para el clínico / Leukemia / Lymphoma T Of The Adult HTLV1, A Challenge For The Clinic

La leucemia / linfoma de células T en adultos (LLTA) es una enfermedad agresiva de células T maduras activadas causada por el virus linfotrópico de células T humano tipo 1 (HTLV-1). ATL tiene un mal pronóstico debido a la quimiorresistencia intrínseca y la inmunosupresión severa. Las formas agresivas de LLTA, aguda y linfoma, se tratan con quimioterapia asociada con agentes antirretrovirales (AZT / IFN). Sin embargo, no han logrado un impacto en la supervivencia, que oscila entre 8 y 10 meses, respectivamente. Los pacientes con formas de LLTA crónicas y latentes tienen un mejor pronóstico, pero la supervivencia a largo plazo también es deficiente, tanto cuando estos pacientes se manejan con una política de espera vigilante o con quimioterapia. Aparentemente, las costuras AZT / IFN benefician a estos pacientes. Mientras tanto, la prevención de la diseminación del HTLV-1 es imprescindible en las políticas de salud pública, tanto por tamizaje del virus en bancos de sangre como a mujeres embarazadas para reducir / evitar la transmisión vertical del virus.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive disease of mature activated T cell caused by human T-cell lymphotropic virus type 1 (HTLV-1). ATL carries a bad prognosis due to intrinsic chemoresistance and severe immunosuppression. The aggressive ATL forms, acute and lymphoma, are treated with chemotherapy associated with antiretroviral agents (AZT/IFN) the acute form. However, they have failed to achieve an impact on survival, that ranges from 8-10 months, respectively. Patients with chronic and smoldering ATL forms, have a better prognosis, but long term survival is poor as well, when these patients are managed with a watchfulwaiting policy or with chemotherapy. Apparently, AZT/IFN seams to benefit these patients. Meanwhile, prevention of dissemination of HTLV-1, is a must in public health policies, performing screening in blood banks and a screening to pregnant women to reduce/avoid vertical transmission of the virus.

Mieloma múltiple en Chile: Respuesta a tratamiento en pacientes con mieloma múltiple elegibles para trasplante autólogo de progenitores hematopoyéticos / Response rates to first-line treatment in eligible patients to autologous stem transplantation in Chile

Background The treatment of choice of newly diagnosed multiple myeloma (NDMM) is an induction with proteasome inhibitors followed autologous stem cell transplantation (HSCT). Since 2013, the treatment of these patients in the public system is based on CTD (cyclophosphamide, thalidomide, and dexamethasone). Aim To evaluate the response rates achieved with CTD, and the results of HSCT in patients with NDMM in the public setting. Material and Methods Data from patients considered as candidates for HSCT from different centers of the National Adult Antineoplastic Drug Program (PANDA, for its acronym in Spanish), diagnosed between 2013 and 2017, was analyzed. The response to treatment of first and second lines of treatment was evaluated, in addition to the results of HSCT. An optimal Response was defined as the sum of strict complete remission, complete remission and very good partial response (sCR, CR and VGPR). Results One hundred and seventy-seven patients were analyzed, 54% women, and 53% with IgG multiple myeloma. Information about the international staging system was retrieved in 127 patients (71%). Seventeen percent were ISS I, 22% in ISS II and 32% ISS III. CTD was used as first treatment in 106 patients (60%), and cyclophosphamide, bortezomib and dexamethasone (CyBorD) in 13 (7%). As first line, CTD had an overall response of 50.9%, and CyBorD of 76.9%. Thirty patients were treated with bortezomib as second line treatment. Forty patients (22%) underwent HSCT. The 5-year Overall Survival (OS) in transplanted patients and non-transplanted patients was 100 and 62% respectively (p < 0.01). Conclusions The response rate achieved by CTD in these patients is suboptimal. The response to CyBorD was better.

Prognostic impact of renal failure recovery in patients with newly diagnosed multiple mieloma / Impacto pronóstico de remisión renal en pacientes con mieloma múltiple de reciente diagnóstico

ABSTRACT Background Renal failure (RF) is a common complication in patients with newly diagnosed multiple myeloma (NDMM). Aim To evaluate the frequency of RF in NDMM patients, and the prognostic impact of its reversibility. Material and Methods A retrospective study evaluating demographic and clinical characteristics of 154 consecutive patients with NDMM was carried out. Estimated glomerular filtration rate (eGFR) was calculated at the beginning and at the end of the induction therapy. In addition, we evaluated renal responses (RR) according to the International Myeloma Working Group (IMWG) criteria. The induction regimen was based on thalidomide in all cases. Results Fifty-three patients had RF (34.4%). Complete renal response (RR) was achieved in 51%. Three years overall survival in patients without RF, with RF and complete RR, and patients with RF and any other RR, was 66, 47 and 13%, respectively. Median survival was 53, 27 and 6 months, respectively (p < 0.01). In the multivariate analysis, RF and hypercalcemia were independent predictors of a worse outcome. Conclusions Achieving a complete RR in patients with NDMM, is associated with a better survival.

Antecedentes La falla renal (FR) es una complicación frecuente en pacientes con mieloma múltiple (MM). Objetivo Evaluar la frecuencia de FR en pacientes con reciente diagnóstico de MM y determinar la importancia pronóstica de su reversibilidad. Material y Métodos Se realizó un estudio retrospectivo de 154 pacientes consecutivos con MM. La función renal se evaluó mediante la tasa estimada de filtración glomerular al inicio y final de la terapia de inducción. Además, evaluamos las respuestas renales (RR) de acuerdo con los criterios del International Myeloma Working Group (IMWG). El régimen de inducción se basó en talidomida en todos los casos. Resultados Cincuenta y tres pacientes presentaron FR (34,4%) al diagnóstico. La RR completa se logró en 51%. La sobrevida global (SG) a 3 años en pacientes sin FR, con FR y RR completa, y pacientes con FR y cualquier otra RR, fue de 66, 47 y 13%, respectivamente. La SG media fue de 53, 27 y 6 meses (p < 0,01), respectivamente. En el análisis multivariado, la FR y la hipercalcemia fueron factores independientes de menor sobrevida. Conclusiones Lograr una RR completa en pacientes con MM recién diagnosticado se asocia con una mejor sobrevida.

AL amyloidosis in the Chilean public health system: a pending debt: multicenter study of the Chilean Monoclonal Gammopathies Cooperative Group / Amiloidosis AL en el sistema público de Chile: una deuda pendiente: estudio multicéntrico

ABSTRACT Background: Immunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed entity. Aim: To characterize patients with AL amyloidosis in Chilean public health centers. Material and Methods: We conducted a retrospective, multicenter study. Public centers of the Chilean Monoclonal Gammopathies Cooperative Group were asked to search for patients with AL amyloidosis in their databases. Epidemiological, clinical and laboratory characteristics were evaluated. Results: Forty-two patients aged 22 to 84 years were found. Twenty four percent had localized AL amyloidosis; 64% had a lambda light chain clone; 47% were associated with multiple myeloma and 9% with non-Hodgkin lymphoma. The most commonly involved organ was the kidney (76%). Serum free light chains were measured in 31% and an echocardiogram was performed in 74% of patients. Seventeen percent of patients received only palliative care, 17% were treated with bortezomib, 21% with thalidomide, and 40% with melphalan. No patient was transplanted. The mean overall survival (OS) of the group was 19 months. The 5-year OS was 28%. Conclusions: It is important to obtain these realistic, national data to initiate strategies to improve early diagnosis and proper management of this disease.

La amiloidosis AL es una entidad poco frecuente y subdiagnosticada. Mientras todo el mundo discute sobre las nuevas herramientas diagnósticas y terapéuticas, en Chile y en América Latina en general, estamos lejos de esa realidad. El objetivo del presente estudio fue caracterizar a los pacientes con amiloidosis AL en centros del sistema público de nuestro país. Se realizó un estudio retrospectivo, multicéntrico, descriptivo. Los centros públicos del grupo cooperativo hematológico chileno buscaron en sus bases de datos pacientes diagnosticados con amiloidosis AL. Se evaluaron las características epidemiológicas, clínicas y de laboratorio. La edad media fue de 65 años. A 24% de los pacientes se les diagnosticó amiloidosis AL localizada; 64% tuvo paraproteína con cadena ligera lambda; 47% se asoció con mieloma múltiple y 9% con linfoma no Hodgkin. El órgano afectado con mayor frecuencia fue el riñón (76%). Las cadenas ligeras libres de suero se realizaron en 31% y ecocardiograma en 74%. El 17% recibió solo cuidados paliativos, 17% recibió tratamiento con bortezomib, 21% con talidomida y 40% con melfalán. Ningún paciente fue trasplantado. La media de sobrevida global (SG) del grupo fue de 19 meses. La SG a 5 años fue de 28%. Es importante reportar estos resultados nacionales para iniciar estrategias que mejoren tanto el diagnóstico temprano como el tratamiento de esta patología. Por lo tanto, mejorar la sospecha diagnóstica es crucial.

Paraproteínas: claridad en la nebulosa / Paraproteins: a review

Hematological neoplasms are tumors of cells in different states of maturation and differentiation. Since monoclonal gammopathies (MG) refer to B mature lymphocyte neoplasms, lymphogenesis should be well known. We must keep in mind that the last stage of maturation of these lymphocytes is the plasma cell. This is how a MG could appear in the context of a plasma cell neoplasm, such as multiple myeloma or amyloidosis, but also in relation to a lymphoma. A monoclonal peak is produced by mature B lymphocytes or plasma cells that secrete a monoclonal protein (Immunoglobulin), and represents a MG. But it must be emphasized that, in the correct clinical context, a hypogammaglobulinemia can represent a MG as well. Another important point is the understanding and interpretation of requested tests, such as protein electrophoresis (PEP), immunofixation (IFx) or serum free light chains (sFLC). The current MG screening panel includes these three studies (PEF, IFx, sFLC), although a simpler panel measuring PEF and sFLC has also been proposed, but not yet formally validated. Therefore, screening done only with PEP is insufficient.

Anemia hemolítica autoinmune en Chile: un análisis retrospectivo de 43 pacientes / Autoimmune hemolytic anemia: review of 43 cases

Background: Autoimmune hemolytic anemia (AIHA) is an uncommon disease. In its presentation, it can be severe and even lethal. There is only one clinical report concerning this pathology in Chile. Objective: To describe the clinical characteristics and evolution of adult AIHA inpatients. Materials and Methods: Retrospective review of clinical records of adult AIHA inpatients between January 2010 and June 2018 was done. Demographic, clinical, laboratory and therapeutic information was analyzed. A descriptive, analytical and survival analysis was performed. Results: Forty-three adult patients diagnosed with AHIA were hospitalized in a period of 8 years. Median age was 63 years (range 22-86 years), mostly women (72%). Warm antibodies were detected in 36 cases (84%) and cold antibodies in seven. Seventy two percent of the patients had an underlying cause, and 58% were secondary to lymphoproliferative neoplasms. All patients except two, received steroids as initial treatment, with response in 37 (90%) of them. Three refractory patients received rituximab, with response in all of them, and relapse in one. Median follow-up was 38 months (range 2-98 months). Five year overall survival was 72%. Conclusion: AHIA in adults inpatients is a heterogeneous disease, mainly due to warm antibodies, and to secondary etiology.

Macroglobulinemia de Waldenström: experiencia de 15 años en el Hospital del Salvador, Santiago, Chile / Waldenström macroglobulinemia: experience in 31 patients

Background: Waldenström macroglobulinemia (WM) is an uncommon indolent B-cell lymphoma, due to the proliferation of lymphoplasmacytic cells, and secretion of a monoclonal IgM protein. Aim: To evaluate the clinical characteristics, management and results of treatment of patients with WM at a public hospital in Chile. Patients and Methods: Review of medical records of 31 patients aged 43 to 85 years (16 males) with WM diagnosed between 2002 and 2017. Clinical features and survival were recorded. Results: All patients had bone marrow compromise, and 31%, extranodal involvement. According to the International Prognostic Score System for WM (IPSSWM) 16, 58 and 26% were at low, intermediate and high risk, respectively. Twenty-five patients (81%) were treated, 32% with plasmapheresis and 36% with rituximab. Four cases (16%) achieved complete remission. Median follow up was 35 months (range 6-159). Estimated overall survival (OS) at 5 and 10 years was 74% and 53%, respectively. According to IPSSWM, the estimated five-year OS was 80, 92 and 39%, for low, intermediate and high-risk patients, respectively. Conclusions: OS was similar to that reported abroad, except for low risk patients, probably due to the low number of cases and short follow up. An improved survival should be expected with the routine use of immunochemotherapy.

Leucemia de células plasmáticas primaria: experiencia en un hospital público chileno / Primary plasma cell leukemia: report of five cases

Background: Primary plasma cell leukemia (pPCL) is uncommon, aggressive and has a different biology than multiple myeloma (MM). Aim: To report the features of patients with pPCL. Material and Methods: Review of databases of the Hematology Department and the Hematology laboratory. Results: Of 178 patients with monoclonal gammopathies, five (2.8%) patients aged 33 to 64 years (three females) had a pPCL. The mean hemoglobin was 7.3 g/dL, the mean white blood cell count was 52,500/mm3, with 58% plasma cells, and the mean platelet count was 83,600/mm3. The mean bone marrow infiltration was 89%, LDH was 2,003 IU/L, serum calcium was 13 mg/dL, and creatinine 1.5 mg/dL. Two patients had bone lesions. Three were IgG, one IgA lambda and one lambda light chain. CD20 was positive in one, CD56 was negative in all and CD117 was negative in 3 cases. By conventional cytogenetic analysis, two had a complex karyotype. By Fluorescence in situ Hybridization, one was positive for TP53 and another for t (11; 14). One patient did not receive any treatment, three patients received VTD PACE and one CTD. None underwent transplant. Three patients are alive. The mean survival was 14 months. Conclusions: These patients with pPCL were younger and had a more aggressive clinical outcome than in multiple myeloma.

Características citogenéticas y detección de anormalidades de alto riesgo en mieloma múltiple / High risk cytogenetic abnormalities in patients with multiple myeloma

Background: Cytogenetic abnormalities observed in the bone marrow of patients with multiple myeloma (MM) are an important prognostic factor for risk stratification. Aim: To investigate karyotype characteristics and frequency of the high-risk cytogenetic abnormalities t(4;14), t(14;16) and del(17p) in Chilean patients with MM. Material and Methods: We studied 30 patients with MM by conventional cytogenetics (CC) and fluorescent in situ hybridization of plasma cells selected using cytoplasmic immunoglobulin staining (cIg-FISH). Results: Overall, the two techniques in combination allowed us to identify clonal genetic abnormalities in 47% of patients. The t(4;14) abnormality was observed in 19% of patients, del(17p) was observed in 10% of patients, and t(14;16) was not detected. Conclusions: Our results showed frequencies of high-risk abnormalities similar to those reported abroad. Cytogenetic studies should be performed routinely for all MM patients at the moment of diagnosis.

Mieloma múltiple en Chile: pasado, presente y futuro del programa nacional de drogas antineoplásicas (PANDA). Revisión de 1.103 pacientes / Survival of 1, 103 Chilean patients with multiple myeloma receiving different therapeutic protocols from 2000 to 2016

Background: Multiple myeloma (MM) is one of the most common malignancies found in hematology. Aim: To describe the features of patients with MM and perform a survival analysis according to the different treatment protocols used between 2000 and 2016. Material and Methods: Analysis of the database of the Chilean national anti-neoplastic drug program. Information was obtained from 1,103 patients, with a median age of 64.5 years (range 27-95) and a male to female ratio of 1:1.2. Results: The mean overall survival (OS) of patients receiving or not receiving Thalidomide was 46 and 30 months, respectively (p < 0.01). The mean OS of patients treated before 2007 (treated with melphalan and prednisone) and between 2007 and 2012 (treated with thalidomide and dexamethasone) was 36 and 48 months respectively. In the group starting in 2013 (treated with cyclophosphamide, thalidomide and dexamethasone) the median survival had not been reached at 20 months of follow up (p = 0.01 for all comparisons). Autologous transplantation (AT) was carried out in only 18% of the eligible patients. The median OS of the patients who receive an AT had not been reached at 48 month compared with 36 month among those who did not received the procedure (p < 0.01). Conclusions: Even though overall survival has improved with time, new drugs must be introduced in our protocols to obtain similar results to those obtained worldwide.

Necrolisis epidérmica tóxica en el curso de un síndrome hemofagocítico secundario a linfoma de Hodgkin: caso clínico / Toxic epidermal necrolysis during a hemophagocytic syndrome secondary to Hodgkin lymphoma: report of one case

Toxic epidermal necrolysis (TEN) is a lethal entity, characterized by extensive epidermal necrosis and multiorgan failure. Hemophagocytic syndrome (HFS) is also a rare and lethal syndrome characterized by hyperinflammation that leads to the appearance of fever, pancytopenia, organomegaly and hemophagocytosis. The concomitance of these diseases is extremely uncommon. We report a 38 years old female, who during the course of a HFS secondary to Hodgkin Lymphoma (HL), presented a TEN secondary to antibiotics. She was admitted due to a consumptive syndrome, lymphadenopathy, visceromegaly and severe pancytopenia. Laboratory and bone marrow tests confirmed HFS. Due to constant fever, imipenem was indicated. On the third day she started with pain and skin rash. She evolved with positive Nikolsky sign. Cutaneous biopsy was concordant with extensive TEN, which was managed with intravenous immunoglobulin and dexamethasone. A complete response and normalization of the blood count were achieved. Finally, the lymph node biopsy showed HL of mixed cellularity type, which was managed with 8 cycles of ABVD chemotherapy, achieving complete remission.

Aplasia medular adquirida, experiencia en un hospital público de referencia / Acquired aplastic anemia: experience in a public hospital

Background: The first line treatment for patients < 40 years old with aplastic anemia (AA) is allogeneic HLA-identical sibling donor transplantation (SCT). Immunosuppressive therapy (IST) with a combination of Thymoglobuline (ATG) and cyclosporine is used for older patients or those without a donor. Five year overall survival (OS) for both therapies is > 70%. Aim: To report the experience with SCT and ATG for AA in a public hospital. Patients and Methods: AA was diagnosed in 42 patients between 1998 and 2016, according to Camitta criteria. Thirty eight (90%) received treatment, 7 (18%) under 40 years old received SCT, and 31 (82%) IST. The rest were not treated. OS was calculated from date of diagnosis until last control, death or loss from follow up. Results: Complete or partial hematologic response, was obtained in 71% and 58% of cases with SCT and IS, respectively. Five year OS was 71% and 55% with SCT and IST, respectively. No difference in response was observed between horse and rabbit ATG. Conclusions: SCT from an HLA-identical sibling donor had a high response rate and survival. IST instead, had a lower response and survival, due to an initial high mortality rate.