Novel CD19-KIRS2/Dap12-BB CAR-T Treatment for 3 Patients with Relapsed and Refractory B-Cell Tumors / 中国实验血液学杂志

OBJECTIVE@#To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM).@*METHODS@#Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed.@*RESULTS@#After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively.@*CONCLUSION@#The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.

Clinical study of mature B-cell lymphoma in 11 children with chromosome 11 long-arm abnormalities / 中华血液学杂志

Objective: To explore the clinical, pathological, diagnostic, treatment, and prognostic features of children with mature B-cell lymphoma (MBCL) . Methods: This retrospective study included pediatric patients with MBCL with chromosome 11 long-arm abnormalities who were diagnosed and treated at our hospital from December 2018 to February 2023. Results: Among the 11 pediatric patients with MBCL, nine were male and two were female, with a median age of 9 (2-13) years and a median disease course of 1.8 (0.5-24) months. The clinical manifestations were cervical lymph node enlargement in four patients, nasal congestion and snoring in four patients, abdominal pain in two patients, and difficulty breathing in one patient. There were seven cases of Burkitt's lymphoma, two of follicular lymphoma, and two of advanced B-cell lymphoma according to the pathological morphology examination. No patients had central nervous system or bone marrow involvement, and no extensive metastasis was observed on B-ultrasound or positron emission tomography-computed tomography (PET/CT). One patient had a huge tumor lesion. The Revised International Pediatric Non-Hodgkin Lymphoma Staging System classified four patients as stage Ⅱ, five as stage Ⅲ, and two as stage Ⅳ. 11q probe detection showed five cases of 11q gain, three of 11q loss, and three of both gain and loss. FISH showed positive MYC expression in three patients, including eight with advanced B-cell lymphoma with 11q abnormalities and three with Burkitt's lymphoma with 11q abnormalities. According to the 2019 edition of the National Health Commission's diagnostic and treatment guidelines for invasive MBCL in children, one patient was classified as Group A, two as Group B, and eight as Group C. Early evaluation of the efficacy showed complete remission. After mid-term evaluation, the intensity of chemotherapy was reduced in Group B and Group C. Among two cases of chemotherapy, the remaining nine cases had a median follow-up of 32 (6-45) months, and none had event-related survival. Conclusion: The incidence of MBCL with 11q abnormalities in children is low, clinical symptoms are mild, and progression is slow. The absence of MYC, BCL2, BCL6 rearrangements, C-MYC negative and 11q abnormalities on FISH is an important diagnostic indicator, and reducing the intensity of chemotherapy can improve prognosis.

Long-term follow-up of humanized and murine CD19 CAR-T-cell therapy for B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P=0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P=0.027). Bridging transplantation was an independent factor in prolonging OS (χ(2)=8.017, P=0.005) and PFS (χ(2)=6.584, P=0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.

Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

Clinical Significance of Minimal Residual Disease in Pediatric Patients with TCF3/PBX1+ B-cell Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the consistency of flow cytometry (FCM) method and polymerase chain reaction (PCR) technique in the detection of minimal residual disease (MRD) at different treatment stages in pediatric patients with TCF3/PBX1+ B-cell acute lymphoblastic leukemia (B-ALL) and the correlations between the detection results and prognosis.@*METHODS@#The clinical data of 64 newly diagnosed pediatric patients with TCF3/PBX1+ B-ALL admitted to the Department of Pediatrics of Peking University People's Hospital from January 2005 to December 2017 were retrospectively analyzed. FCM and PCR methods were used to monitor the MRD level in bone marrow samples from 64 children during the same period of treatment on d33 and d90 respectively, and the detection results were analyzed.@*RESULTS@#There were 37 males and 27 females in the 64 patients, with a median age of 8 years(range 0.8 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 98.4% (62/63), with overall CR rate of 100%. 12 patients experienced recurrence, with a median recurrence time of 16.9 (5.3-46.3) months. The median follow-up time of the 64 patients was 77.2 (1.0-184.8) months , and the 5-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±4.7% and 75.0%±5.4%, respectively. On d90, the concordance rate of the MRD results from the two methods was 98.4%, and the related kappa value was 0.792 (P < 0.001), which were significantly higher than those on d33. After induction chemotherapy (d33), the 5-year EFS rate of MRD-FCM- group (79.3%±5.3%) was significantly better than that of MRD-FCM+ group (40.0%±21.9%) (P =0.028), there were no significant differences in the 5-year OS rate and EFS rate between MRD-PCR+ group and MRD-PCR- group, and the 5-year EFS rate of MRD-FCM-/PCR- group (85.4%±5.5%) was significantly better than that of MRD-FCM+/PCR+ group (40.0 %±21.9%) (P =0.026).@*CONCLUSION@#In children with TCF3/PBX1+ B-ALL, the MRD results detected by FCM and PCR methods show good consistency, especially in consolidation therapy period (d90). The MRD level at the end of induction therapy (d33) is an important factor affecting the long-term prognosis, especially the MRD results detected by FCM method, which is significantly associated with prognosis.

Genetic analysis of two cases with MYC "negative" Burkitt lymphoma / 中华医学遗传学杂志

OBJECTIVE@#To carry out combined genetic analysis on two patients suspected for Burkitt lymphoma to facilitate their diagnosis and treatment.@*METHODS@#G banded karyotyping and interphase and metaphase fluorescence in situ hybridization (FISH) were used to detect the specific sites of chromosomes by using separate and fusion probes.@*RESULTS@#The separate probe showed no presence of MYC gene abnormality, while fusion probe confirmed the IGH::MYC translocation in the samples. Combined with the clinical features and pathological characteristics, the two patients were finally diagnosed with Burkitt lymphoma, which was confirmed by targeted capture next generation sequencing.@*CONCLUSION@#The separate probe for the MYC gene has some shortcomings and should be used together with dual fusion probe to improve the accuracy of diagnosis.

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.

Linfoma de Burkitt como diagnóstico diferencial de infecção odontogênica / Burkitt's Lymphoma as a differential diagnosis of dental infection / El Linfoma de Burkitt como diagnóstico diferencial de infección dental

Introdução: O linfoma de Burkitt é um linfoma altamente agressivo do tipo não-hodgkin originado a partir de mutação nos linfócitos B. Clinicamente demonstra características de malignidade como evolução rápida, destruição das corticais ósseas e mobilidade dentária, além de aumento de volume facial adjacente aos ossos maxilares. Esse tumor é de difícil diagnóstico devido às características clínicas inespecíficas, o que pode muitas vezes levar a um diagnóstico e tratamento tardio, piorando o prognóstico e a taxa de sobrevida do paciente. Relato de Caso: O caso clínico se trata de uma paciente, sexo feminino, 21 anos de idade, com história de aumento de volume em hemiface esquerda de evolução repentina, associada a dor, febre e relato de exodontia recente. A história clínica e os achados clínicos inespecíficos simularam uma infecção odontogênica, a qual atrasou o diagnóstico e o tratamento correto. Após exames imaginológicos específicos, exploração cirúrgica e exame histopatológico foi possível chegar a um diagnóstico definitivo de linfoma de Burkitt e manejo adequado dessa patologia. Conclusão: É de extrema importância o papel do cirurgião-dentista na detecção precoce dessa patologia com envolvimento dos maxilares, uma vez que a remissão e/ou a cura depende da extensão da doença, do seu comportamento biológico e do momento do diagnóstico... (AU)

Introduction: Burkitt's lymphoma is a highly aggressive non-Hodgkin type lymphoma originated from a mutation in B lymphocytes. It clinically demonstrates malignant characteristics such as rapid evolution, destruction of bone corticals and tooth mobility, in addition to increased facial volume adjacent to the maxillary bones. This tumor is difficult to diagnose due to its nonspecific clinical characteristics, which can often lead to a late diagnosis and treatment, worsening the patient's prognosis and survival rate. Case Report: The clinical case is a female patient, 21 years old, with a history of swelling in the left hemiface of sudden evolution, associated with pain, fever and a report of recent extraction. Clinical history and nonspecific clinical findings simulated an odontogenic infection, which delayed diagnosis and correct treatment. After specific imaging exams, surgical exploration and histopathological examination, it was possible to reach a definitive diagnosis of Burkitt's lymphoma and adequate management of this pathology. Conclusion: The role of dentists in the early detection of this pathology with involvement of the jaws is extremely important, since remission and/or cure depends on the extent of the disease, its biological behavior and the time of diagnosis... (AU)

Introducción: El linfoma de Burkitt es un linfoma de tipo no Hodgkin altamente agresivo originado por una mutación en los linfocitos B. Clínicamente demuestra características malignas como rápida evolución, destrucción de corticales óseas y movilidad dentaria, además de aumento de volumen facial adyacente a los huesos maxilares. Este tumor es de difícil diagnóstico debido a sus características clínicas inespecíficas, lo que muchas veces puede llevar a un diagnóstico y tratamiento tardíos, empeorando el pronóstico y la supervivencia del paciente. Caso Clínico: El caso clínico es una paciente femenina, de 21 años de edad, con antecedente de tumefacción en hemifacial izquierdo de evolución súbita, asociada a dolor, fiebre y reporte de extracción reciente. La historia clínica y los hallazgos clínicos inespecíficos simularon una infección odontogénica, lo que retrasó el diagnóstico y el tratamiento correcto. Luego de exámenes imagenológicos específicos, exploración quirúrgica y examen histopatológico, se logró llegar a un diagnóstico definitivo de linfoma de Burkitt y manejo adecuado de esta patología. Conclusión: El papel de los odontólogos en la detección temprana de esta patología con compromiso de los maxilares es de suma importancia, ya que la remisión y/o curación depende de la extensión de la enfermedad, su comportamiento biológico y el momento del diagnóstico... (AU)

Analysis of serum immunoglobulin level in children with Burkitt lymphoma / 中华儿科杂志

Objective: To summarize changes of serum immunoglobulin levels before and after chemotherapy in children with Burkitt lymphoma (BL), so as to investigate the effects of chemotherapy and rituximab on serum immunoglobulin levels in children with BL. Methods: Clinical data of 223 children with newly diagnosed Burkitt lymphoma at Beijing Children's Hospital from January 2009 to April 2017 were analyzed retrospectively. They were treated according to the modified LMB 89 regimen and some of them received combined rituximab therapy during the chemotherapy. The serum immunoglobulin (IgA, IgM, IgG) before chemotherapy, at the time of discontinuing chemotherapy, as well as 6, 12, 24, 36 months after chemotherapy were collected. Changes of serum IgA, IgM and IgG with time among different treatment groups were compared using repeated measures ANOVA. Results: According to risk group, 223 children were devided into group B（n=53）and group C（n=170）. Before chemotherapy, 109 cases (48.9%) were combined with hypogammaglobulinemia. The serum IgA, IgM, and IgG levels of all the patients were (0.9±0.7), 1.2 (0.5, 1.3) and (7.2±2.9) g/L before chemotherapy, (0.5±0.4), 0.2 (0.1, 0.3) and (6.3±2.3) g/L at the time of discontinuing chemotherapy (t=13.63, Z=-11.99, t=4.57, all P<0.05). There were statistical difference in IgA, IgM levels of group B and IgA, IgM, IgG levels of group C before chemotherapy and at the time of discontinuing chemotherapy (t=8.86, Z=-6.28, t=11.19, Z=-10.15, t=4.50, all P<0.05). The differences of serum IgA and IgG levels at the time after chemotherapy among patients treated with chemotherapy alone and those treated with chemotherapy combined rituximab in group B and C were significant (F=5.38, P=0.002 and F=4.22, P=0.007). Conclusions: Approximately half of children with BL have already existed hypogammaglobulinemia at initial diagnosis prior to the start of treatment. The modified LMB 89 regimen have significant effect on humoral immunity of children with BL. In the process of immune reconstruction after chemotherapy, rituximab has more significant effect on serum IgA and IgG levels in BL patients.

Prognostic significance of IKZF1 gene deletions in patients with B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: This study aimed to investigate the prognostic significance of IKZF1 gene deletion in patients with acute B lymphoblastic leukemia (B-ALL) . Methods: The clinical data of 142 patients with B-ALL diagnosed in Nanfang Hospital between March 2016 and September 2019 were analyzed. Results: IKZF1 deletion was found in 36.0% of the 142 patients with B-ALL, whereas exon 4-7 deletion was found in 44.0% . White blood cell counts were higher in patients with the IKZF1 deletion (52.0% and 28.3% , P=0.005) ; these patients also experienced worse effects of mid-term induction therapy (40.0% and 70.7% , P<0.001) and had a higher proportion of Philadelphia chromosome-positive (52.0% and 21.7% , respectively, P<0.001) . Univariate analysis revealed that the 3-year overall survival rate (OS) and event-free survival rate (EFS) in the IKZF1 deletion group were significantly lower than the IKZF1 wild-type group [ (37.1±7.3) % vs (54.7±5.4) % , (51.8±7.9) % vs (73.9±4.7) % ; P=0.025, 0.013, respectively]. Multivariable analysis showed that harboring IKZF1 deletion was an adverse factor of EFS and OS (HR=1.744, 2.036; P=0.022, 0.020, respectively) . Furthermore, the IKZF1 deletion/chemotherapy group had significantly lower 3-year OS, EFS, and disease-free survival rates than other subgroups. In the IKZF1 deletion cohort, allo-hematopoietic stem cell transplantation (HSCT) significantly improved OS and EFS compared to non-allo-HSCT[ (67.9±10.4) % vs (31.9±11.0) % , (46.6±10.5) % vs (26.7±9.7) % ; P=0.005, 0.026, respectively]. Conclusion: Pediatric-inspired chemotherapy was unable to completely reverse the negative effect of IKZF1 deletion on prognosis. Pediatric-inspired regimen therapy combined with allo-HSCT, in contrast, significantly improved the overall prognosis of IKZF1 deletion B-ALL.

Prognostic Value of Average Daily Platelet Increase in Childhood B-cell Acute Lymphoblastic Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To evaluate the prognosis value of average daily platelet amount increase in children with B-cell acute lymphoblastic leukemia(B-ALL) treated by CCCG-ALL-2015 regimen.@*METHODS@#106 children with primary B-ALL were retrospective analyzed, standardized MRD test protocol was used to detect the MRD level (19 d and 46 d) after chemotherapy. The platelet count was measured by Sysmex XE-2100. Kaplan-Meier survival curve statistics was used to analyze the event free survival(EFS) rate of the children.@*RESULTS@#The trend of negative correlation existed between PPC and TPR (rs=-0.519, P=0.021). The 3-year EFS rate of the patients in Ap>5.4×109/L group was 95.7%, which was significantly higher than those in Ap≤5.4×109/L group(79.5%) (χ2=5.236, P=0.035); multivariate analysis showed that Ap≤5.4×109/L was the independent prognostic factor affecting survival of the patients (RR=3.978; 95%CI: 1.336-11.523, P=0.041). With both MRD and Ap≤5.4×109/L as candidate variables, Ap≤5.4×109/L lost its independent prognostic value (RR=1.225; 95%CI: 0.892-13.696, P=0.089), the correlation between d 19/d 46 MRD levels and Ap>5.4×109/L (χ2=4.318, P=0.038) could explain the phenomenon.@*CONCLUSION@#Ap can reflect the effect of B-ALL chemotherapy and can be used to monitor the curative effect and prognosis of B-ALL children.

Clinical features and prognosis of children with Burkitt's lymphoma: an analysis of 62 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features and chemotherapy response of Burkitt's lymphoma (BL) in children and the influence of rituximab on the prognosis of children with BL.@*METHODS@#A retrospective analysis was performed for the medical data of 62 children with BL, including clinical features, therapeutic efficacy, and prognostic factors. The Cox regression model was used to identify the factors associated with poor prognosis in children with BL. According to whether rituximab was used, the children with advanced (stage III/IV) BL were divided into two groups: chemotherapy plus rituximab and chemotherapy alone. The prognosis was compared between the two groups.@*RESULTS@#For these 62 children, the median age of onset was 5 years (range 1-14 years), and there were 58 boys (94%) and 4 girls (6%). The primary site was abdominal cavity in 41 children (66%), and head and neck in 16 children (26%). There were 1 child with stage I BL (2%), 8 with stage II BL (13%), 33 with stage III BL (53%), and 20 with stage IV BL (32%). The median follow-up time was 29 months, with progression/recurrence observed in 15 children (24%), and the 3-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±5.2% and 77.3%±5.8%, respectively. For the children with stage III/IV BL, there was a significant difference in the 3-year the OS rate between the chemotherapy plus rituximab group (16 children) and the chemotherapy alone group (30 children) (93.3%±6.4% vs 65.6%±9.9%, P=0.042), while there was no significant difference in the 3-year EFS rate between the two groups (86.2%±9.1% vs 61.8%±10.1%, P>0.05). The Cox regression analysis showed that central nervous system involvement, lactate dehydrogenase >1 000 U/L, and early incomplete remission were the factors associated with poor prognosis (P<0.05).@*CONCLUSIONS@#Chemotherapy combined with rituximab can improve the prognosis of children with stage III/IV BL. Central nervous system involvement, elevated lactate dehydrogenase level, and early incomplete remission may indicate a poor prognosis in children with BL.

Linfoma de Burkitt Primário de Mama: Relato de Caso / Primary Breast Burkitt Lymphoma: Case Report / Linfoma de Burkitt Primario de Mama: Relato de Caso

Introdução: O linfoma primário de mama (LPM) representa cerca de 0,5% das neoplasias mamárias, sendo considerado um tipo raro de tumor. Alguns dos tipos de LPM, por sua vez, possuem ligação intensa com o período gravídico e pós-parto em virtude do estímulo hormonal. O objetivo deste estudo é relatar um caso de LPM com apresentação rara de linfoma de Burkitt, considerando propostas terapêuticas eficazes para o seguimento. Relato do caso: Paciente do sexo feminino, 23 anos, portadora de tumoração periareolar em mama direita com aspecto de casca de laranja e crescimento rápido há um mês, queixas flogísticas no local da lesão, bom estado geral e sem outros sintomas associados. O quadro relatado iniciou-se sete meses após a expulsão fetal com feto morto. A paciente foi submetida à biópsia da lesão e encaminhada para seguimento ambulatorial sem sucesso, necessitando de retorno ao ambiente hospitalar por piora das condições clínicas e extensão da tumoração. Houve diagnóstico de linfoma de Burkitt, com tratamento multidisciplinar, sendo submetida a protocolo CODOX-M de quimioterapia, com óbito após 22 dias de acompanhamento hospitalar. Conclusão: Este relato demonstra uma situação rara em uma paciente jovem, ressaltando a importância de investigar as alterações mamárias, de maneira eficaz, para um diagnóstico precoce correto e um tratamento adequado, em todas as faixas etárias

Introduction: Primary breast lymphoma (PML) represents about 0.5% of breast cancers, being considered a rare type of tumor. Some of the types of PML, in turn, have an intense connection with the pregnancy and postpartum period due to hormonal stimulation. The aim of this study is to report a case of PML with a rare presentation of Burkitt's lymphoma, considering effective therapeutic proposals for follow-up. Case report: A 23-year-old female patient with a peri-areolar tumor in the right breast with orange peel aspect and rapid growth for one month, phlogistic complaints at the lesion site, good general condition and no other associated symptoms. The reported condition started seven months after fetal expulsion with a dead fetus. The patient underwent lesion biopsy and was referred to an outpatient follow-up with unsuccessful outcome, requiring return to the hospital due to worsening of clinical conditions and extension of the tumor. There was a diagnosis of Burkitt's lymphoma, with multidisciplinary treatment. She underwent the CODOX-M chemotherapy protocol, and died after 22 days of hospital follow-up. Conclusion: This report demonstrates a rare situation in a young patient, emphasizing the importance of effective investigation of breast changes so that correct early diagnosis and appropriate treatment can be made for all age groups

Introducción: El linfoma primario de mama (LMP) representa aproximadamente el 0,5% de los cánceres de mama, siendo considerado un tipo de tumor poco común. Algunos de los tipos de LPM, a su vez, tienen una conexión intensa con el embarazo y el posparto debido a la estimulación hormonal. El objetivo de este estudio es reportar un caso de LMP con rara presentación de linfoma de Burkitt, considerando propuestas terapéuticas efectivas para el seguimiento. Relato del caso: Paciente, 23 años, con un tumor periareolar en la mama derecha con aspecto de piel de naranja y rápido crecimiento durante un mes, quejas flogísticas en el sitio de la lesión, buen estado general y ningún otro. síntomas asociados. La condición reportada comenzó siete meses después de la expulsión fetal con un feto muerto. El paciente fue sometido a biopsia de la lesión y fue derivado sin éxito a seguimiento ambulatorio, requiriendo el retorno al entorno hospitalario por empeoramiento de la clínica y extensión del tumor. Hubo un diagnóstico de linfoma de Burkitt, con tratamiento multidisciplinario. Se sometió al protocolo de quimioterapia CODOX-M y murió a los 22 días de seguimiento hospitalario. Conclusión: Este informe demuestra una situación poco común en una paciente joven, enfatizando la importancia de investigar de manera efectiva los cambios en los senos para un diagnóstico temprano correcto y un tratamiento adecuado en todos los grupos de edad

Linfoma de Burkitt como complicación de la agammaglobulinemia de Bruton / Burkitt's lymphoma as a complication of Bruton's Agammaglobulinemia

Introducción: La agammaglobulinemia de Bruton es una inmunodeficiencia primaria (IDP) originada por una mutación del gen que codifica la tirosina kinasa de Bruton (BTK). Se sospecha principalmente en varones con infecciones frecuentes de las vías respiratorias y tiene entre otras complicaciones, los tumores, fundamentalmente linfoproliferativos. Se reportan agammaglobulinemias autosómicas recesivas con similares características clínicas en ambos sexos. Objetivo: Presentar el primer caso pediátrico reportado en Cuba, con diagnóstico de linfoma de Burkitt asociado a esta inmunodeficiencia primaria y que además utilizó tratamiento combinado sustitutivo de inmunoglobulinas y antitumoral. Presentación del caso: Paciente masculino, que a los 2 años se le realizó diagnóstico de enfermedad de Bruton. Con el tratamiento de reemplazo con inmunoglobulina endovenosa (Intacglobín) se mantuvo tres años sin infecciones graves. A los 5 años de edad presentó linfoma de Burkitt, tratado con poliquimioterapia, según el esquema AEIOP al que se asoció rituximab. Aunque no se dispone de la detección por biología molecular de la mutación del gen BTK, la disminución por debajo del 2 por ciento de las células B CD19+ y los valores ausentes de IgG, IgA e IgM permitieron el diagnóstico. Conclusión: Coexistieron con resultados clínicos satisfactorios el tratamiento antitumoral y la terapia de reemplazo con inmunoglobulina endovenosa. El paciente se mantiene con buen estado general(AU)

Introduction: Bruton's Agammaglobulinemia is a primary immunodeficiency (PID) caused by a mutation in the gene that encodes Bruton's tyrosine kinase (BTK). It is suspected mainly in men with frequent respiratory tract infections and has, among other complications, tumors, mainly lymphoproliferative. Autosomal recessive agammaglobulinemias with similar clinical characteristics have been reported in both sexes. Objective: To present the first pediatric case reported in Cuba, with a diagnosis of Burkitt's lymphoma associated with PID and that also used combined immunoglobulin replacement and antitumor therapy. Case report: 2-year-old male diagnosed with Bruton's disease. With the replacement treatment with intravenous immunoglobulin (Intacglobin), he maintained three years without serious infections. At 5 years of age, he presented Burkitt's lymphoma, treated with polychemotherapy according to the AEIOP scheme, associating Rituximab. Although do not have molecular biology detection of the BTK gene mutation, the decrease of CD19 + B cells to below 2 percent and the absent values of IgG, IgA and IgM allowed the diagnosis. Conclusion: Antitumor treatment and intravenous immunoglobulin replacement therapy coexisted with satisfactory clinical results. The patient remains in good general condition(AU)

Linfoma de Burkitt esporádico en cavidad bucal: caso clínico / Sporadic Burkitt´s lymphoma in the oral cavity: a clinical case report

Objetivo: Presentar un caso clínico de Linfoma de Burkitt esporádico en cavidad bucal como manifestación inicial en un paciente adulto joven, tratado en el Hospital Interzonal General de Agudos "General José de San Martín" de La Plata. Caso clínico: Un paciente masculino de 20 años de edad se presenta con una lesión tumoral localizada en sector posterior de reborde mandibular, pérdida espontánea de piezas dentarias y parestesia del nervio dentario inferior. Acompañado de un aumento de volumen testicular, compromiso intestinal y poliadenopatías. El cuadro morfológico y de inmuno-marcación confirma un Linfoma de Células B "agresivo". El paciente fue tratado con esquema intensivo de 6 bloques de quimioterapia y terapia intratecal. No se observaron señales de recurrencia durante el período de seguimiento de 12 meses. Las manifestaciones bucales iniciales del Linfoma de Burkitt deben considerarse en el diagnóstico diferencial de las enfermedades bucales benignas. Debido a su naturaleza agresiva, el reconocimiento temprano y rápido de este linfoma es esencial para la administración oportuna de la terapia adecuada y mejora el pronóstico del paciente (AU)

Aim: To present a case of sporadic Burkitt's lymphoma with oral initial manifestatios in a young adult patient, who received treatment at the Hospital Interzonal General de Agudos "General José de San Martín", La Plata. Clinical case: A 20-year-old male patient presents with a tumor lesion located in the posterior area of the mandibular ridge, spontaneous loss of teeth and paresthesia of the inferior dental nerve, increase in testicular volume, intestinal compromise and polyadenopathy. The morphological and immunostaining conditions confirm an "aggressive" B-Cell Lymphoma. The patient received an intensive scheme of 6 blocks of chemotherapy and intrathecal therapy. No signs of recurrence were observed during the 12-month follow-up period. Oral manifestations of Burkitt´s lymphoma in the initial stages should be considered in the differential diagnosis of benign oral diseases. Due to its aggressive nature, early and rapid recognition of these this lymphoma is essential for the timely administration of adequate therapy and for a patient's better prognosis (AU)

Linfoma de amígdala: reporte de un caso pediátrico / Palatine tonsil lymphoma: a pediatric case report

El linfoma es la neoplasia maligna de cabeza y cuello más común en la población pediátrica. Las anifestaciones clínicas de linfoma en amígdala palatina son generalmente asimetría amigdalina, alteración en la apariencia de la mucosa y adenopatías cervicales. Ante una hipertrofia amigdalina unilateral, se debe diferenciar de cuadros infecciosos, procesos crónicos, otros tumores o simplemente una hiperplasia amigdalina benigna. El seguimiento estricto de la asimetría amigdalina es un pilar importante a la hora del diagnóstico de los pacientes con linfoma amigdalino, debido a que un tratamiento temprano es fundamental para el pronóstico. Se presenta una niña de 14 años con hipertrofia amigdalina unilateral y odinofagia, de aproximadamente 21 días de evolución sin respuesta al tratamiento antibiótico, con diagnóstico de linfoma de Burkitt. Presenta remisión completa de la enfermedad al año del diagnóstico.

Lymphoma is the most common childhood malignancy in the head and neck. The most common clinical manifestations of lymphoma in palatine tonsil are the tonsils asymmetry, alteration in the appearance of the mucous and cervical lymphadenopathy. The unilateral tonsillar hypertrophy must be differentiated with infectious processes, with chronic processes, other tumors or benign tonsillar hyperplasia. The monitoring of tonsillar hypertrophy is strict, because early diagnosis and treatment are of great importance in the prognosis of tonsillar lymphoma patients. A 14 year-old girl presents unilateral tonsillar enlargement and odynophagia. After 21 days of antibiotic treatment, she has not clinical improvement. The diagnosis is Burkitt's lymphoma. One year after diagnosis, she presents complete remission of the disease.

Linfoma de Burkitt primario de mama durante el embarazo / Primary Burkitt's Lymphoma of the Breast During Pregnancy

El linfoma de Burkitt es una neoplasia altamente agresiva y es un tipo raro de linfoma no Hodgkin localizado. Aunque los niños son los más frecuentemente afectados, en adultos ocurren principalmente durante el embarazo o el puerperio. La mama rara vez constituye la localización primaria del linfoma no Hodgkin. Se presenta un caso de linfoma de Burkitt primario de mama durante el embarazo. Paciente de 37 años con embarazo de 24 semanas quien presentó aumento de volumen difuso de mama derecha. La mama estaba aumentada de tamaño, dolorosa y homogénea con tumoración elástica y firme. La ecografía demostró inflamación difusa con tumoración heterogénea e hipoecoica con contornos ligeramente irregulares, marcadores tumorales estaban normales las pruebas serológicas fueron negativas. La biopsia de la lesión mostró tejido mamario reemplazado por células linfoideas de tamaño mediano con citoplasma basófilo y múltiples vacuolas. Estudios inmunohistoquímicos fueron positivos para el antígeno leucocitario común, CD10, CD20, CD43, Bcl-6. El análisis cromosómico reveló que más del 90 % de las células neoplásicas exhibieron translocación t llevando al diagnóstico final de linfoma de Burkitt de mama. Luego de evaluar las posibilidades terapéuticas y del consentimiento de la paciente se inició tratamiento citostático sistémico. Los linfomas primarios de mama son extremadamente raros. El linfoma de Burkitt primario de la mama es mucho menos común que los otros linfomas. Los métodos de clasificación, detección y tratamiento de esta afección siguen siendo objeto de debates e investigaciones(AU)

The Burkitt's lymphoma is a highly aggressive neoplasm and is a rare type of localized non-Hodgkin lymphoma. Although children are the most frequently affected, in adults they occur mainly during the pregnancy or the puerperium. The breast rarely constitutes the primary location for non-Hodgkin lymphoma. The study of a case of primary Burkitt lymphoma of the breast during pregnancy is presented. This is a 37 year old patient with a 24 week pregnancy who presented a diffuse increase in the volume of the right breast. The breast was enlarged, painful and homogeneous with a firm, elastic mass. The ultrasonography showed diffuse inflammation with a heterogeneous and hypoechoic tumor with slightly irregular contours. The tumor marker values were normal and the serological tests were negative. The biopsy of the lesion showed breast tissue replaced by medium-sized lymphoid cells with basophilic cytoplasm and multiple vacuoles. Immunohistochemically studies were positive for the common leukocyte antigen, CD10, CD20, CD43, Bcl-6. The chromosomal analysis revealed that more than 90 % of neoplastic cells exhibited t translocation leading to the final diagnosis of Burkitt lymphoma of the breast. After evaluating the therapeutic possibilities and the patient's consent, systemic cytostatic treatment was started. Primary breast lymphomas are extremely rare. The primary Burkitt lymphoma of the breast is much less common than other lymphomas. The methods of classification, detection, and the treatment of this condition continue to be the subject of debate and research(AU)