Early T-cell precursor acute lymphoblastic leukemia: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To improve the understanding of the diagnosis and treatment of early T-cell precursor acute lymphoblastic leukemia (ETP-ALL).Methods:The clinical data of a patient with ETP-ALL who was misdiagnosed as peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) admitted to the Second Hospital of Lanzhou University in October 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient who presented "inguinal lymphadenopathy" as the first symptom underwent lymph node biopsy and pathological examination at local hospital, and he was diagnosed as PTCL-NOS according to the consultation of another 2 hospitals. After 2 courses of chemotherapy (CHOPE regimen, GLD regimen, unknown specific medication and dosage), the therapeutic efficacy was poor. For further diagnosis and treatment, this patient came to Lanzhou University Second Hospital. Flow cytometry found blast cells in the bone marrow, and then other related examinations were completed, he was finally diagnosed as ETP-ALL. The chemotherapy regimens of Hyper-CVAD and EA were alternatively used, progressive disease (PD) occurred after 3 courses of treatment, and chidamide was added in the 4th and 5th courses of treatment, the disease still progressed, and the patient died after follow-up. The disease course of the patient was about 12 months.Conclusions:ETP-ALL has unique immunophenotypic characteristics. ETP-ALL patients have a low remission rate after conventional induction therapy, high recurrence rate and poor prognosis. Currently, there is no effective standard treatment regimen, and allogeneic hematopoietic stem cell transplantation or timely addition of new drugs may improve the prognosis.

Decitabine combined with chemotherapy in treatment of relapsed T lymphoblastic lymphoma/leukemia with TP53 mutation after allogeneic hematopoietic stem cell transplantation: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To observe the efficacy and safety of decitabine combined with chemotherapy in treatment of relapsed/refractory T lymphoblastic lymphoma/leukemia (T-LBL/ALL) with TP53 mutation.Methods:The clinical data of a T-LBL/ALL patient with TP53 mutation who had recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) treated with decitabine combined with chemotherapy in the First Affiliated Hospital of Soochow University in June 2018 were retrospectively analyzed and the relevant literature was reviewed.Results:The patient, a 42-year-old male, diagnosed as T-LBL/ALL with TP53 mutation by comprehensive examination underwent sibling-matched donor allo-HSCT after a second complete remission. The patient relapsed 8 months later and was treated with decitabine combined with CLAG regimen to achieve complete remission again. And then, he had leukemia-free survival until now through maintenance treatment with decitabine.Conclusion:Decitabine combined with chemotherapy may be a safe and effective treatment option for relapsed T-LBL/ALL patients with TP53 mutation after allo-HSCT.

Raoultella ornithinolytica urinary tract infection in a pediatric patient with T-cell precursor acute lymphoblastic leukemia / Infección de vías urinarias por Raoultella ornithinolytica en un paciente pediátrico con leucemia linfoblástica aguda de células T

Abstract Background: Currently, Raoultella ornithinolytica is considered an emerging pathogen of community- and hospital-acquired infection, particularly in patients with immunodeficiencies, malignancies, anatomical abnormalities, or after invasive procedures. Pediatric infections with R. ornithinolytica are exceedingly rare, with only six previously reported cases, of which only two were reported as a urinary tract infection. Case report: Here, we describe a polymicrobial urinary tract infection (R. ornithinolytica and Enterococcus faecalis) in a pediatric patient with T-cell precursor acute lymphoblastic leukemia, which was successfully treated with ampicillin-sulbactam. Conclusions: To the extent of our knowledge, we report the seventh case in a pediatric patient and only the third case of a urinary tract infection in this age group caused by R. ornithinolytica.

Resumen Introducción: Actualmente Raoultella ornithinolytica es considerado un patógeno emergente involucrado en infecciones adquiridas en la comunidad y en el hospital, en particular en pacientes con algún tipo de inmunodeficiencia, malignidad, alteraciones anatómicas o sometidos a procedimientos invasivos. Las infecciones pediátricas causadas por R. ornithinolytica son sumamente raras, con solo seis casos publicados, de los cuales nada más dos se presentaron como infección de vías urinarias. Caso clínico: Se describe una infección de vías urinarias polimicrobiana (R. ornithinolytica y Enterococcus faecalis) en un paciente pediátrico con leucemia linfoblástica aguda de células T, que fue tratado satisfactoriamente con ampicilina-sulbactam. Conclusiones: Con base en lo que se sabe hasta el momento, se reporta el séptimo caso en un paciente pediátrico y el tercer caso de infección de vías urinarias causada por R. ornithinolytica en este grupo de edad.

Progress of the mechanism of Wnt signaling pathway in T-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

T-cell acute lymphoblastic leukemia (T-ALL) is derived from the malignant transformation and clonal proliferation of precursor T cells. T-ALL is usually associated with the genetic mutations and/or chromosomal translocation, thus causing the change of survival, proliferation and progenitor cell differentiation of T cells in T-cell development. Studies have shown that Wnt signaling pathway plays a key role in the regulation of hematopoietic stem cell and normal T-cell development, and it is also abnormally altered in T-ALL. This article reviews the research progress of the mechanism of Wnt signaling pathway in T-ALL development.

Outcome and Prognostic Factors in Pediatric Precursor T-Cell Acute Lymphoblastic Leukemia: A Single-Center Experience / 임상소아혈액종양

BACKGROUND: Precursor T-cell acute lymphoblastic leukemia (T-ALL) has worse prognosis than B-cell ALL. We aimed to evaluate prognostic variables in pediatric T-ALL. METHODS: Medical records of 36 T-ALL patients (27 males and 9 females; median age at diagnosis, 10.6 years) diagnosed and treated at Asan Medical Center from 2001 to 2017 were reviewed. Six patients (16.7%) had early T-cell precursor ALL (ETP-ALL). Most patients received the Children's Cancer Group-1882 (CCG1882) or Korean multicenter high risk ALL (ALL0601) protocols and prophylactic cranial irradiation. Clinical features at presentation, response to therapy, and treatment outcomes were analyzed. RESULTS: The six patients with ETP-ALL and 17 of 30 with non-ETP-ALL received CCG1882 or ALL0601 chemotherapy. Three patients, including two with ETP-ALL, did not achieve complete remission after induction. Rapid early response during induction was achieved by 26 patients. Five year overall survival (OS) and event free survival (EFS) rates were 71.4% and 70.2%, respectively. ETP-ALL and slow early response during induction were significant adverse prognostic factors, while hyperleukocytosis at diagnosis was not. CCG1882/ALL0601 chemotherapy resulted in superior survival (OS: 78.9%, EFS: 73.3%) compared with CCG1901 chemotherapy (OS: 64.3%, EFS: 64.3%), and patients undergoing prophylactic cranial irradiation had superior EFS to non-radiated patients. CONCLUSION: A high risk ALL protocol with intensified post-remission therapy, including prophylactic cranial irradiation, conferred T-ALL survival outcomes comparable with those of Western studies. Further treatment intensification should be considered for patients with ETP-ALL and slow induction responders. Additionally, CNS-directed treatment intensification, without prophylactic cranial irradiation, is needed.

Hipercalcemia grave como forma de apresentação de leucemia linfoblástica aguda em crianças / Severe hypercalcemia as a form of acute lymphoblastic leukemia presentation in children

RESUMO A hipercalcemia é um distúrbio metabólico raro em pediatria, potencialmente fatal, apresentando um vasto diagnóstico diferencial, incluindo neoplasias. Relatamos aqui o caso de uma criança de 3 anos, previamente saudável, admitida no serviço de urgência por fadiga, hiporreatividade, febre e claudicação da marcha com 5 dias de evolução, de agravamento progressivo. À observação, apresentava-se inconsciente (escore de coma Glasgow: 8). Laboratorialmente, apresentava hipercalcemia grave (cálcio total 21,39mg/dL, ionizado 2,93mmol/L) e anemia microcítica. Iniciou hiper-hidratação e foi transferido para a unidade de cuidados intensivos pediátricos. Instituiu-se hemodiafiltração venovenosa contínua com soluto livre de cálcio, ocorrendo a progressiva normalização da calcemia, com melhoria do estado de consciência. Administrou-se zolendronato. Excluíram-se causas metabólicas, infecciosas e intoxicação. O mielograma permitiu o diagnóstico de leucemia linfoblástica aguda. A hipercalcemia associada à malignidade em pediatria é rara, ocorrendo como forma de apresentação da neoplasia ou na recorrência desta. Em situações com risco de vida iminente, deve se considerar hemodiafiltração venovenosa contínua.

ABSTRACT Hypercalcemia is a rare metabolic disorder in children and is potentially fatal. It has a wide differential diagnosis, including cancer. Here, we report the case of a previously healthy 3-year-old who was admitted to the emergency room with fatigue, hyporeactivity, fever and limping gait that had evolved over 5 days and that was progressively worsening. On examination the patient was unconscious (Glasgow coma score: 8). Laboratory tests indicated severe hypercalcemia (total calcium 21.39mg/dL, ionized calcium 2.93mmol/L) and microcytic anemia. Hyperhydration was initiated, and the child was transferred to the pediatric intensive care unit. Continuous venovenous hemodiafiltration with calcium-free solution was instituted, which brought progressive normalization of serum calcium and an improved state of consciousness. Zoledronate was administered, and metabolic and infectious causes and poisoning were excluded. The bone marrow smear revealed a diagnosis of acute lymphoblastic leukemia. Hypercalcemia associated with malignancy in children is rare and occurs as a form of cancer presentation or recurrence. Continuous venovenous hemodiafiltration should be considered in situations where there is imminent risk to life.

Outcome of children and adolescents with lymphoblastic lymphoma / Evolução de crianças e adolescentes com linfoma linfoblástico

Summary Introduction: lymphoblastic lymphoma (LBL) is the second most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course of children and adolescents with LBL treated at a tertiary center. Methods: this is a retrospective cohort study of 27 patients aged 16 years or younger with LBL admitted between January 1981 and December 2013. Patients were treated according to the therapy protocol used for acute lymphoblastic leucemia. Diagnosis was based on biopsy of tumor and/or cytological examination of pleural effusions. The overall survival was analyzed using the Kaplan-Meier method. Results: the median age at diagnosis was 11.6 years (interquartile range, 4.6- 13.8). LBL had T-cell origin in 16 patients (59%). The most common primary manifestation in T-cell LBL was mediastinal involvement, in 9 patients (56%). Intra-abdominal tumor was the major site of involvement in patients with precursor B-LBL. Most patients had advanced disease (18 patients – 67%) at diagnosis. Twenty-four patients (89%) achieved complete clinical remission. After a median follow-up of 43 months (interquartile range, 6.4-95), 22 patients (81%) were alive in first complete remission. Five children (18.5%) died, three of them soon after admission and two after relapsing. The probability of survival at five years for 20 patients with de novo LBL was 78% (SD 9.4). Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy.

Resumo Objetivos: linfoma linfoblástico (LL) é o segundo subtipo mais comum de linfoma não Hodgkin em crianças. O objetivo deste estudo foi caracterizar a evolução clínica de crianças e adolescentes com LL em um centro terciário. Métodos: estudo de coorte retrospectivo de 27 pacientes com idade de até 16 anos com LL admitidos entre janeiro de 1981 e dezembro de 2013. Os pacientes foram tratados de acordo com o protocolo de tratamento para leucemia linfoblástica aguda (LLA). O diagnóstico foi baseado em biópsia do tumor e/ou no exame citológico de derrame pleural. A sobrevida global foi analisada pelo método de Kaplan-Meier. Resultados: a média de idade ao diagnóstico foi de 11,6 anos (variação interquartil, 4,6-13,8). Linfoma linfoblástico de células T foi identificado em 16 pacientes (59%) e a manifestação primária mais comum foi o acometimento mediastinal (56%). Tumor intra-abdominal foi a manifestação clínica principal nos pacientes com LL de células pré- -B. A maioria dos pacientes apresentava doença avançada (18 pacientes, 67%) ao diagnóstico. Vinte e quatro pacientes (89%) alcançaram remissão clínica completa. Após um período de acompanhamento médio de 43 meses (intervalo interquartil, 6,4-95), 22 pacientes (81%) continuam vivos em primeira remissão clínica completa. Cinco crianças (18,5%) morreram, três delas logo após a admissão e duas após recidiva. A probabilidade de sobrevida em cinco anos para 20 pacientes com LL de novo foi de 78% (DP 9,4). Conclusão: os resultados confirmam o prognóstico favorável de crianças com LL tratadas com regime de quimioterapia intensiva derivado da terapia de LLA.

Long-Term Survival after T-cell Lymphoblastic Lymphoma Treated with One Cycle of Hyper-CVAD Regimen / Journal of the Korean Cancer Association, 대한암학회지

T-lymphoblastic lymphoma (T-LBL) is a rare form of aggressive non-Hodgkin's lymphoma. The standard approach for management of T-LBL involves intensive multiagent chemotherapy regimens for induction and consolidation phases with central nervous system prophylaxis and a maintenance phase lasting 12-18 months. We report on a case of long-term survival after one cycle of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) and high-dose methotrexate. A 30-year-old woman diagnosed with T-LBL with a large mediastinal mass underwent one cycle of hyper-CVAD. Four days after the start of treatment, the mediastinal mass was markedly reduced. Treatment continued with one cycle of consolidation chemotherapy, comprising high-dose methotrexate and high-dose cytarabine. The patient then refused all further chemotherapeutic treatment. Seven years have passed without relapse.

Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus) with unusual manifestations and without detectable autoantibodies.

We describe a patient with paraneoplastic autoimmune multiorgan syndrome (PAMS) secondary to a lymphoblastic T‑ cell lymphoma who presented with a lichenoid dermatitis and vitiligo, later developing bronchiolitis obliterans and autoimmune hepatitis. Notably, he had no detectable autoantibodies. The development of vitiligo and autoimmune hepatic involvement probably indicate a role for cytotoxic T‑ cell lymphocytes in the pathogenesis of this syndrome.

Clinical study on treatment of adult T lymphoblastic lymphoma with Hyper-CVAD regime / 白血病·淋巴瘤

Objective To improve the recognition of treatment of adult T lymphoblastic lymphoma (TLL) with Hyper-CVAD regime.Methods The turnovers of 7 cases treated with Hyper-CVAD regime were summarized.Results Among the 7 cases,1 case died after the first unfinished chemotherapy,1 case gained complete remission before autologous stem cell transplantation but relapsed after transplantation,3 cases gained complete remission until now,2 cases without transplantation relapsed and then gave up following treatments after treating with ICE regime or the virgin regime,but the therapeutic effects were poor.Conclusions Adult TLL should get early chemotherapy treatments,and some special characteristics should be noted,the treatment does not relate to the stage,the chemotherapy treatment should be carried out regularly and enough,radiation of mediastinum mass can be applied after 4 cycles of Hyper-CVAD regime,choose suitable transplantation method.

The value of core needle biopsy in differential diagnosis of mediastinal T lymphoblastic lymphoma and type B1 thymoma / 解放军医学杂志

Objective To analyze the clinical and pathological characteristics of T lymphoblastic lymphoma (T-LBL) and type B1 thymoma in the mediastinum, and to improve the accuracy of differential diagnosis between two diseases. Methods Pathology of consecutive 34 cases of T-LBL and 10 cases of type B1 thymoma were reviewed in this study. All the initial diagnosis was made with core needle biopsy specimens of mediastinal masses and confirmed by subsequent chemotherapy and/or excision biopsy specimens. The clinical and pathological features of T-LBL and type B1 thymoma were compared by reviewing clinical records and analysis of HE and immunohistochemical staining sections. The chi-square test was used for statistic analysis. Results The mean age of the patients with type B1 thymoma was 43 years, and the ratio of male to female was 2:3, while the patients with T-LBL were much younger (with mean age of 25, 73% of them younger than 30 years old) and the male to female ratio was 3.3:1. All the T-LBL cases presented symptoms including chest tightness, shortness of breath and cough. Three patients of thymoma complained of chest tightness and shortness of breath, and 2 cases presented symptoms of myasthenia gravis. Imaging examination showed solitary mass in anterior mediastinum in patients of both groups, 88% of the T-LBL patients had mass>10cm, while accounting for 50% in B1 thymoma patients. Concurrent pleural effusion was only observed in the T-LBL patients. Histopathologically, T-LBL and thymoma showed significant differences, including the infiltration of tumor cells in fibrous tissue (65% in T-LBL vs 0% in thymoma), invasion of peripheral fat tissue (59% vs 20%), invasion of skeletal muscle (41% vs 0%), tumor necrosis (21% vs 0%), and remaining of thymus lobular structure was found in only 3% of T-LBL. Intact cytokeratin network was shown in B1 thymoma (100%) by immunohistochemical staining. Conclusions Patients' gender, age, clinical features and imaging features, especially pathological characteristics were remarkable different between T-LBL and type B1 thymoma. Combining clinical manifestations and pathological changes will help to improve the accuracy of core needle biopsy in differential diagnosis of T-LBL and thymoma.