RESUMO
La infiltración cutánea por células leucémicas conocida como leucemia cutis es una presentación infrecuente de esta patología y constituye un desafío diagnóstico. Los diagnósticos como infecciones, otras patologías neoplásicas con afectación cutánea y los trastornos histiocíticos, entre otros, constituyen los principales diagnósticos diferenciales, ya que configuran un escenario pronóstico y terapéutico diferente. Se presentan dos pacientes que fueron diagnosticados inicialmente como leucemia cutis, cuyo diagnóstico final fue de patologías no malignas.
The infiltration of leukemia cells into the skin, known as leukemia cutis, is a rare presentation of this disease and accounts for a diagnostic challenge. The main differential diagnoses include infections, other neoplastic diseases with skin involvement and histiocytic disorders, among others, as they entail different prognostic and therapeutic approaches. Here we describe two patients who were initially diagnosed with leukemia cutis, whose final diagnosis was of non-malignant diseases.
Assuntos
Humanos , Masculino , Lactente , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Leucemia/diagnóstico , Pele , Diagnóstico DiferencialRESUMO
The outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer pediatric patients was initially uncertain. The objective of this study was to describe the characteristics and outcome of cancer patients and hematopoietic stem cell transplant recipients from 0 to 19 years with detectable SARS-CoV-2 from April 23, 2020, to April 30, 2022, treated in a tertiary-level hospital in Argentina. A total of 348 cases were registered in 339 patients. The median age was 89.5 (3 to 224) months. The sex was predominantly male: 193 (55.5%). The most common malignant disease was leukemia (42.8%). One hundred four cases (29.9%) had comorbidities. Of the 346 cases with an available blood count, 17.6% had a lymphocyte count <300/mm 3 . Fever was the most common symptom. In most cases (93.1%) presented asymptomatic or mild disease. Twenty-one cases (6%) presented severe or critical status. Eleven of 24 admissions to the intensive care unit were due to COVID-19 (coronavirus disease 2019). Eight patients (2.3%) died. Two deaths were attributable to SARS-CoV-2 (0.6%). Being older, having fever, lymphopenia at diagnosis, and having received hematopoietic stem cell transplant were associated with a more severe disease. Around 90% of the children continued their cancer treatment without any change.
Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Humanos , Masculino , Criança , Idoso de 80 Anos ou mais , Feminino , COVID-19/epidemiologia , SARS-CoV-2 , Centros de Atenção Terciária , Argentina/epidemiologia , Neoplasias/epidemiologia , Neoplasias/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
PURPOSE: The International Berlin-Frankfurt-Münster (BFM) study group conducted a study on pediatric acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD) was assessed using flow cytometry (FCM), and the impact of early intensification and methotrexate (MTX) dose on survival was evaluated. PATIENTS AND METHODS: We included 6,187 patients younger than 19 years. MRD by FCM refined the risk group definition previously used in the ALL intercontinental-BFM 2002 study on the basis of age, WBC count, unfavorable genetic aberrations, and treatment response measured morphologically. Patients at intermediate risk (IR) and high risk (HR) were randomly assigned to protocol augmented protocol I phase B (IB) versus IB regimen. MTX doses of 2 versus 5 g/m2 every 2 weeks, four times, were evaluated in precursor B-cell-ALL (pcB-ALL) IR. RESULTS: The 5-year event-free survival (EFS ± SE) and overall survival (OS ± SE) rates were 75.2% ± 0.6% and 82.6% ± 0.5%, respectively. Their values in risk groups were standard risk (n = 624), 90.7% ± 1.4% and 94.7% ± 1.1%; IR (n = 4,111), 77.9% ± 0.7% and 85.7% ± 0.6%; and HR (n = 1,452), 60.8% ± 1.5% and 68.4% ± 1.4%, respectively. MRD by FCM was available in 82.6% of cases. The 5-year EFS rates in patients randomly assigned to protocol IB (n = 1,669) and augmented IB (n = 1,620) were 73.6% ± 1.2% and 72.8% ± 1.2%, respectively (P = .55), while those in patients receiving MTX doses of 2 g/m2 (n = 1,056) and MTX 5 g/m2 (n = 1,027) were 78.8% ± 1.4% and 78.9% ± 1.4%, respectively (P = .84). CONCLUSION: The MRDs were successfully assessed using FCM. An MTX dose of 2 g/m2 was effective in preventing relapse in non-HR pcB-ALL. Augmented IB showed no advantages over the standard IB.[Media: see text].
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Lactente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Metotrexato/uso terapêutico , Fatores de Risco , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Intervalo Livre de Doença , Resultado do TratamentoRESUMO
The infiltration of leukemia cells into the skin, known as leukemia cutis, is a rare presentation of this disease and accounts for a diagnostic challenge. The main differential diagnoses include infections, other neoplastic diseases with skin involvement and histiocytic disorders, among others, as they entail different prognostic and therapeutic approaches. Here we describe two patients who were initially diagnosed with leukemia cutis, whose final diagnosis was of non-malignant diseases.
La infiltración cutánea por células leucémicas conocida como leucemia cutis es una presentación infrecuente de esta patología y constituye un desafío diagnóstico. Los diagnósticos como infecciones, otras patologías neoplásicas con afectación cutánea y los trastornos histiocíticos, entre otros, constituyen los principales diagnósticos diferenciales, ya que configuran un escenario pronóstico y terapéutico diferente. Se presentan dos pacientes que fueron diagnosticados inicialmente como leucemia cutis, cuyo diagnóstico final fue de patologías no malignas.
Assuntos
Leucemia , Neoplasias Cutâneas , Humanos , Leucemia/diagnóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Pele , Diagnóstico DiferencialRESUMO
Children with Down syndrome (DS) are at an increased risk of developing clonal myeloproliferative disorders. The balance between treatment intensity and treatment-related toxicity has not yet been defined. We analyzed this population to identify risk factors and optimal treatment. This single-center retrospective study included 78 DS patients <16 years-old with Transient Abnormal Myelopoiesis (TAM, n = 25), Acute Myeloblastic Leukemia (DS-AML, n = 41) of which 35 had classical Myeloid Leukemia associated with DS (ML-DS) with megakaryoblastic immunophenotype (AMKL) and 6 sporadic DS-AML (non-AMKL). Patients with DS-AML were treated according to four BFM-based protocols. Classical ML-DS vs. non-DS-AMKL were compared and the outcome of ML-DS was analyzed according to treatment intensity. Only four patients with TAM required cytoreduction with a 5-year Event-Free Survival probability (EFSp) of 74.4 (±9.1)%. DS-AML treatment-related deaths were due to infections, with a 5-year EFSp of 60.6 (±8.2)%. Megakaryoblastic immunophenotype was the strongest good-prognostic factor in univariate and multivariate analysis (p = 0.000). When compared ML-DS with non-DS-AMKL, a better outcome was associated with a lower relapse rate (p = 0.0002). Analysis of administered treatment was done on 32/33 ML-DS patients who achieved CR according to receiving or not high-dose ARA-C block (HDARA-C), and no difference in 5-year EFSp was observed (p = 0.172). TAM rarely required treatment and when severe manifestations occurred, early intervention was effective. DS-AML good outcome was associated with AMKL with a low relapse-rate. Even if treatment-related mortality is still high, our data do not support the omission of HDARA-C in ML-DS since we observed a trend to detect a higher relapse rate in the arm without HDARA-C.
RESUMO
Acute leukemias are the most common neoplasm in pediatric patients. Currently, 80% of children with diagnosis of acute lymphoblastic leukemia (ALL) are cured with conventional chemotherapy, but 20% of them will have a recurrence of the disease. Measurable Residual Disease (MRD) has been described as an important prognostic factor that allows evaluating the response of patients to treatment. One of the most sensitive techniques to study MRD is the quantification of immunoglobulins (Ig) and T-lymphocyte receptors (TCR) genes rearrangements. The aims of this study were to describe the detected Ig/TCR rearrangements, to evaluate the prognostic impact of MRD in our population of children with ALL and to compare the MRD values by Ig/TCR with those obtained by multiparametric flow cytometry (MFC). A total of 455 patients were studied. In 96% of the cases, it was possible to characterize at least one Ig/TCR rearrangement. The total number of Ig/TCR rearrangements detected was 1550. MRD was successfully applied in 89% of the cases. The combined positive MRD values at day 33 and 78 of treatment allow the identification of high-risk patients in cases previously stratified by MRD using flow cytometry at day 15. The comparison between MRD determination by Ig/TCR rearrangements and FC showed excellent correlation. The present work constitutes a study of MRD by Ig/TCR carried out in a very significant number of patients consecutively diagnosed, treated within a homogeneous protocol and with excellent clinical follow-up.
Las leucemias agudas constituyen la neoplasia más frecuente en pacientes pediátricos. Actualmente, el 80% de los niños con leucemia linfoblástica aguda (LLA) logran curarse con quimioterapia convencional pero el 20% de los mismos presentarán una reaparición de la enfermedad. La enfermedad residual medible (ERM) ha sido descripta como un importante factor pronóstico, que permite evaluar la respuesta de los pacientes al tratamiento. Una de las técnicas más sensibles par a estudiar ERM es la cuantificación de reordenamientos génicos de inmunoglobulinas (Ig) y receptores de linfocitos-T (TCR). Los objetivos del presente trabajo fueron describir los reordenamientos detectados de Ig/TCR, evaluar el efecto de la ERM en la supervivencia de niños con LLA y comparar la ERM por Ig/TCR con la cuantificada mediante citometría de flujo multiparamétrica (CFM). Del total de 455 pacientes estudiados, en el 96% fue posible caracterizar al menos un reordenamiento de Ig/TCR. El total de reordenamientos clonales detectados fue de 1550. La ERM pudo ser estudiada en forma exitosa en el 89% de los casos. El valor de ERM positiva combinada al día 33 y 78 de tratamiento, permitió identificar pacientes de alto riesgo, entre los previamente estratificados por la ERM mediante CFM al día 15. La comparación entre la determinación de ERM mediante reordenamientos Ig/TCR y CFM mostró una excelente correlación. El presente trabajo constituye un estudio de ERM mediante Ig/TCR realizado en un número muy significativo de pacientes diagnosticados en forma consecutiva, tratados en el marco de un protocolo homogéneo y con excelente seguimiento clínico.
Assuntos
Rearranjo Gênico do Linfócito T , Imunoglobulinas , Criança , Humanos , Neoplasia Residual/genética , Reação em Cadeia da Polimerase , Receptores de Antígenos de Linfócitos T/genética , Linfócitos TRESUMO
Resumen Las leucemias agudas constituyen la neoplasia más frecuente en pacientes pediátricos. Actualmente, el 80% de los niños con leucemia linfoblástica aguda (LLA) logran curarse con quimioterapia con vencional pero el 20% de los mismos presentarán una reaparición de la enfermedad. La enfermedad residual medible (ERM) ha sido descripta como un importante factor pronóstico, que permite evaluar la respuesta de los pacientes al tratamiento. Una de las técnicas más sensibles par a estudiar ERM es la cuantificación de reordena mientos génicos de inmunoglobulinas (Ig) y receptores de linfocitos-T (TCR). Los objetivos del presente trabajo fueron describir los reordenamientos detectados de Ig/TCR, evaluar el efecto de la ERM en la supervivencia de niños con LLA y comparar la ERM por Ig/TCR con la cuantificada mediante citometría de flujo multiparamétrica (CFM). Del total de 455 pacientes estudiados, en el 96% fue posible caracterizar al menos un reordenamiento de Ig/TCR. El total de reordenamientos clonales detectados fue de 1550. La ERM pudo ser estudiada en forma exitosa en el 89% de los casos. El valor de ERM positiva combinada al día 33 y 78 de tratamiento, permitió identificar pacientes de alto riesgo, entre los previamente estratificados por la ERM mediante CFM al día 15. La comparación entre la determinación de ERM mediante reordenamientos Ig/TCR y CFM mostró una excelente correlación. El presente trabajo constituye un estudio de ERM mediante Ig/TCR realizado en un número muy significativo de pacientes diagnosticados en forma consecutiva, tratados en el marco de un protocolo homogéneo y con excelente seguimiento clínico.
Abstract Acute leukemias are the most common neoplasm in pediatric patients. Currently, 80% of children with diagnosis of acute lymphoblastic leukemia (ALL) are cured with conventional chemotherapy, but 20% of them will have a recurrence of the disease. Measurable Residual Disease (MRD) has been described as an important prognostic factor that allows evaluating the response of patients to treatment. One of the most sensitive techniques to study MRD is the quantification of immunoglobulins (Ig) and T-lymphocyte receptors (TCR) genes rearrangements. The aims of this study were to describe the detected Ig/TCR rearrangements, to evaluate the prognostic impact of MRD in our population of children with ALL and to compare the MRD values by Ig/TCR with those obtained by multiparametric flow cytometry (MFC). A total of 455 patients were studied. In 96% of the cases, it was possible to characterize at least one Ig/TCR rearrangement. The total number of Ig/TCR rear rangements detected was 1550. MRD was successfully applied in 89% of the cases. The combined positive MRD values at day 33 and 78 of treatment allow the identification of high-risk patients in cases previously stratified by MRD using flow cytometry at day 15. The comparison between MRD determination by Ig/TCR rearrangements and FC showed excellent correlation. The present work constitutes a study of MRD by Ig/TCR carried out in a very significant number of patients consecutively diagnosed, treated within a homogeneous protocol and with excellent clinical follow-up.
Assuntos
Humanos , Criança , Imunoglobulinas , Rearranjo Gênico do Linfócito T , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T , Reação em Cadeia da Polimerase , Neoplasia Residual/genéticaRESUMO
BACKGROUND: Infant acute lymphoblastic leukemia (ALL) is an infrequent disease characterized by clinical and biological features related to poor prognosis. Adapted therapies were designed without a clear consensus regarding the best treatment options. We aimed to compare the outcome between infant ALL cases receiving Interfant versus BFM-based protocols. PROCEDURE: This is a retrospective observational study. From April 1990 to June 2018, infant ALL cases were enrolled in one of the five consecutive treatment protocols. Clinical, demographic, and biological features and outcome were evaluated. A comparative analysis was performed between Interfant protocols and BFM-based protocols. RESULTS: During the studied period, 1913 ALL patients were admitted and 116 (6%) were infants. Treatment administered was: ALL-BFM'90 (n = 16), 1-ALL96-BFM/HPG (n = 7), Interfant-99 (n = 39), Interfant-06 (n = 35), and ALLIC-BFM'2009 (n = 19). The 5-year event-free survival probability (EFSp) was 31.9(standard error [SE] 4.6)% for the entire population, with a significant difference among risk groups according to Interfant-06 criteria (P = .0029). KMT2A-rearrangement status was the strongest prognostic factor (P = .048), independently of the protocol strategy. The median time for relapse was 24.1 months for patients with minimal residual disease (MRD)-negative versus 11.5 months for those with MRD-positive (P = .0386). EFSp and cumulative relapse risk probability (CRRp) were similar. Interfant protocols showed comparable induction (8.1% vs 7.1%, P = .852) and complete remission mortality (21.6% vs 28.6%, P = .438), failing to reduce the relapse rate (48.5% vs 30.7%, P = .149). CONCLUSIONS: Interfant protocols and BFM-based protocols presented comparable results. The risk group stratification proposed by Interfant-06 was validated by our results, and MRD seems useful to identify patients with an increased risk of early relapse.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/classificação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
La leucemia aguda es la enfermedad oncológica más frecuente en la infancia. La leucemia linfoblástica aguda representa el 75% y la mieloblástica aguda el 25% de ellas. La eritroleucemia es una entidad infrecuente, representando menos del 5% de las leucemias mieloblásticas agudas. Su definición ha variado a lo largo del tiempo. La OMS en 2017 define el subtipo de eritroleucemia cuando el porcentaje de eritroblastos representa el 80% de la celularidad total de la médula ósea. El presente trabajo, de tipo analítico, retrospectivo, tuvo como finalidad revisar los hallazgos de morfología, citometría de flujo, citogenética, respuesta al tratamiento y evolución de los casos previamente definidos como eritroleucemia, en nuestro centro, en los últimos 25 años y reclasificar aquellos que no cumplían con los nuevos criterios de la OMS 2017. Entre enero de 1990 y diciembre de 2015, se diagnosticaron 576 casos de leucemia mieloblástica aguda siendo 11 (1.9%) de ellos clasificados como eritroleucemia. Resultaron evaluables 10 casos. La distribución por sexo fue 1:1 y la edad mediana fue 5 (rango: 0.9-14) años. Seis pacientes presentaban antecedentes de síndrome mielodisplásico. Según los nuevos criterios, ninguno de los casos analizados puede ser actualmente definido como eritroleucemia. De acuerdo a la recategorización, fueron definidos como leucemias de subtipos de mal pronóstico, como leucemia aguda indiferenciada, sin diferenciación y megacarioblástica. Solo dos pacientes se encuentran libres de enfermedad, probablemente debido a estos subtipos desfavorables, sumado al antecedente frecuente de mielodisplasia.
Acute leukemia is the most frequent malignant disease in childhood. Acute lymphoblastic leukemia represents 75% and acute myeloblastic leukemia 25% of them. Erythroleukemia is a rare entity, corresponding to less than 5% of acute myeloblastic leukemia. Its definition has changed over the time. WHO in 2017 defines erythroleukemia when the percentage of erythroblasts represent 80% of the total cellularity of the bone marrow aspirate. This analytical and retrospective study was performed with the aim of reviewing morphology, flow cytometry and cytogenetic features, response to treatment and outcome of cases previously defined as erythroleukemia in our center during the last 25 years and, in addition to reclassify those cases which do not meet the new WHO 2017 criteria. From January 1990 to December 2015, 576 patients were diagnosed as acute myeloblastic leukemia and 11 (1.9%) of them were classified as erythroleukemia. Ten cases were evaluable. Sex distribution was 1:1 and the median age at diagnosis was 5 (range: 0.9-14) years. Six of them had presented with previous myelodysplastic syndrome. None of the analyzed cases can be currently defined as erythroleukemia, according to the new criteria. When reclassified, the cases were defined as leukemias of subsets with poor prognosis such as acute undifferentiated leukemia, without differentiation and megakaryoblastic leukemia. Only 2 patients remain leukemia-free and this could be explained both by the unfavorable prognosis of these leukemia subtypes, and the antecedent of myelodysplastic syndrome in most of the cases.
Assuntos
Humanos , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Organização Mundial da Saúde , Leucemia Eritroblástica Aguda/classificação , Leucemia Eritroblástica Aguda/diagnóstico , Argentina , Leucemia Eritroblástica Aguda/terapia , Estudos Retrospectivos , Resultado do Tratamento , Guias de Prática Clínica como Assunto , Progressão da Doença , Análise Citogenética/métodos , Citometria de Fluxo/métodosRESUMO
Acute leukemia is the most frequent malignant disease in childhood. Acute lymphoblastic leukemia represents 75% and acute myeloblastic leukemia 25% of them. Erythroleukemia is a rare entity, corresponding to less than 5% of acute myeloblastic leukemia. Its definition has changed over the time. WHO in 2017 defines erythroleukemia when the percentage of erythroblasts represent 80% of the total cellularity of the bone marrow aspirate. This analytical and retrospective study was performed with the aim of reviewing morphology, flow cytometry and cytogenetic features, response to treatment and outcome of cases previously defined as erythroleukemia in our center during the last 25 years and, in addition to reclassify those cases which do not meet the new WHO 2017 criteria. From January 1990 to December 2015, 576 patients were diagnosed as acute myeloblastic leukemia and 11 (1.9%) of them were classified as erythroleukemia. Ten cases were evaluable. Sex distribution was 1:1 and the median age at diagnosis was 5 (range: 0.9-14) years. Six of them had presented with previous myelodysplastic syndrome. None of the analyzed cases can be currently defined as erythroleukemia, according to the new criteria. When reclassified, the cases were defined as leukemias of subsets with poor prognosis such as acute undifferentiated leukemia, without differentiation and megakaryoblastic leukemia. Only 2 patients remain leukemia-free and this could be explained both by the unfavorable prognosis of these leukemia subtypes, and the antecedent of myelodysplastic syndrome in most of the cases.