Clinical significance of Epstein-Barr Virus detection in the cerebrospinal fluid of patients who underwent hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the detection rate, clinical significance, and prognosis of Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of patients following allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis was performed on 1100 patients who underwent the CSF virus test after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital between January 2017 and June 2022. Among them, 19 patients were screened positive for EBV in their CSF, and their clinical characteristics, treatment, and prognosis were analyzed. Results: Among 19 patients with EBV-positive cerebrospinal fluid, 12 were male and 7 were female, with 5 patients aged <18 years and 12 aged ≥18 years, with a median age of 27 (5-58) years old. There were 7 cases of acute myeloid leukemia, 8 of acute lymphocytic leukemia, 2 of aplastic anemia, 1 of Hodgkin's lymphoma, and 1 of hemophagocytic syndrome. All 19 patients underwent haploid hematopoietic stem cell transplantation, including 1 secondary transplant. Nineteen patients had neurological symptoms (headache, dizziness, convulsions, or seizures), of which 13 had fever. Ten cases showed no abnormalities in cranial imaging examination. Among the 19 patients, 6 were diagnosed with EB virus-related central nervous system diseases, with a median diagnosis time of 50 (22-363) days after transplantation. In 9 (47.3%) patients, EBV was detected in their peripheral blood, and they were treated with intravenous infusion of rituximab (including two patients who underwent lumbar puncture and intrathecal injection of rituximab). After treatment, EBV was not detected in seven patients. Among the 19 patients, 2 died from EBV infection and 2 from other causes. Conclusion: In patients who exhibited central nervous system symptoms after allogeneic hematopoietic stem cell transplantation, EBV should be screened as a potential pathogen. EBV detected in the CSF may indicate an infection; however, it does not confirm the diagnosis.

High-dose methylprednisolone with Rituximab and fresh frozen plasma in the treatment of six patients with B-cell lymphoproliferative disorders harboring TP53 abnormalities / 中华血液学杂志

Objective: To investigate whether high-dose methylprednisolone with Rituximab and fresh frozen plasma (HDMP+RTX+FFP) is an effective therapy for patients with B-cell chronic lymphoproliferative disorders (B-CLPD) with TP53 abnormalities. Methods: Six B-CLPD patients with TP53 abnormalities from May 2008 to May 2012 were prospectively enrolled in the study. The patients were treated with HDMP+RTX+FFP for up to 6 cycles. Results: Of the six B-CLPD patients, there were 4 cases of chronic B-cell lymphoproliferative disorders-unclassified (B-CLPD-U) , 1 B-cell prolymphocytic leukemia (B-PLL) and 1 mantle cell lymphoma (MCL) . After a median 3 courses of treatment, 4 patients achieved complete remission (CR) including 3 with undetectable minimal residual disease (MRD(-)) . One patient was evaluated as stable disease (SD) and another one patient was in disease progression (PD) . After a median follow-up of 30 (4-56) months, 2 non-responders progressed quickly and died. All of CR patients survived and no one succumbed to disease progression at the last follow-up. The hematopoietic function was significantly improved after the treatment whereas there was also significant decrease in serum IgA, IgG and IgM levels. All patients showed well tolerance to this regimen. The incidence of myelosuppression was low and adverse events (AE) were mainly neutropenia which did not exceed grade 3 and infection. All AE were controllable. Conclusion: HDMP+RTX+FFP is an effective and relatively tolerable therapy for patients with B-CLPD accompanying with TP53 abnormalities.

Biological therapy and development of neoplastic disease in patients with juvenile rheumatic disease: a systematic review / Uso de imunobiológicos e desenvolvimento de doenças neoplásicas em pacientes com doenças reumáticas juvenis: revisão sistemática

Abstract Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents.

Resumo As doenças reumáticas juvenis afetam o sistema musculoesquelético e se iniciam antes dos 18 anos. Apresentam etiologia variada, identificável ou desconhecida, porém as de natureza inflamatória autoimune têm sido associadas ao maior risco de desenvolvimento de neoplasias, independentemente do tratamento. Este artigo propõe avaliar, por meio de revisão sistemática da literatura de acordo com os critérios de qualidade Prisma (Preferred Reporting Items for Systematic Reviews and Meta- Analyses), o risco de câncer em pacientes com doenças reumáticas juvenis e sua associação com imunobiológicos. Os critérios descritos pela iniciativa Strengthening the Reporting of Observational Studies in Epidemiology foram usados para avaliar a qualidade metodológica individual dos artigos selecionados no presente estudo. Foram analisadas nove publicações, de 251 incialmente selecionadas. Houve aumento no risco de câncer na população com doença reumática juvenil comparada com a população em geral. A maioria dos cânceres especificados foi de natureza linfoproliferativa. Sete estudos não especificaram a terapêutica ou não definiram associação entre ela e o risco de câncer. Apenas um estudo sugeriu essa associação e observou maior risco em pacientes diagnosticados nos últimos 20 anos, período de advento de novas terapias. Um estudo constatou maior risco em uma população não tratada com imunobiológicos, sugeriu tratar-se da evolução natural da doença, e não do efeito adverso da terapêutica. Os estudos demonstram aumento no risco de malignidade associada a doenças reumáticas juvenis que pode estar relacionada à atividade da doença, e não especificamente ao tratamento com imunobiológicos.

Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor / Tratamiento de la enfermedad linfoproliferativa post-trasplante renal con Rituximab y conversión a inhibidor m-TOR

Abstract Background: Post-transplantation lymphoproliferative disorders are serious complications of organ transplantation which treatment is not yet standardized. Objective: To describe the clinical response, overall and graft survival of patients in our center with this complication after kidney transplantation, which received rituximab as part of their treatment as well as conversion to m-TOR. Methods: Retrospective study, which included patients, diagnosed with post-transplant lymphoproliferative disorders after kidney transplantation from January 2011 to July 2014. Results: Eight cases were found with a wide spectrum of clinical presentations. Most had monomorphic histology, 85% were associated with Epstein-Barr virus, 25% of patients had tumor involvement of the renal graft, and 12.5% ​​had primary central nervous system lymphoma. All patients were managed with reduction of immunosuppression, conversion to m-TOR (except one who lost the graft at diagnosis) and rituximab-based therapy. The overall response rate was 87.5% (62.5% complete response, 25% partial response). Survival was 87.5% with a median follow-up of 34 months. An additional patient lost the graft, with chronic nephropathy already known. All the remaining patients had stable renal function. Conclusions: There are no standardized treatment regimens for lymphoproliferative disorders after kidney transplantation, but these patients can be managed successfully with reduction of immunosuppression, conversion to m-TOR and rituximab-based schemes.

Resumen Antecedente: La enfermedad linfoproliferativa post-trasplante es una complicación grave del trasplante de órganos cuyo tratamiento aún no se encuentra estandarizado. Objetivo: Describir la respuesta clínica, supervivencia global y del injerto en pacientes con esta complicación post trasplante renal en nuestro centro y que recibieron rituximab como parte de su tratamiento y la conversión a m-TOR. Métodos: Estudio retrospectivo que incluyó pacientes con diagnóstico de enfermedad linfoproliferativa postrasplante renal entre enero de 2011 y julio de 2014. Resultados: Se encontraron ocho casos, con presentaciones clínicas variables. La mayoría correspondieron a histología monomórfica, en 85% se asoció con virus de Epstein-Barr, 25% de los pacientes tenían compromiso tumoral del injerto renal y 12.5% linfoma primario de sistema nervioso central. Todos los pacientes se manejaron con reducción de inmunosupresión, conversión a m-TOR (excepto uno que perdió el injerto al diagnóstico) y tratamiento basado en rituximab. La tasa de respuesta global fue del 87.5% (62.5% respuesta completa, 25% respuesta parcial). La supervivencia fue del 87.5% con una mediana de seguimiento de 34 meses. Un paciente adicional perdió el injerto renal, con nefropatía crónica ya conocida. Los pacientes restantes con función renal estable. Conclusiones: No existen esquemas estandarizados de tratamiento para la enfermedad linfoproliferativa post-trasplante renal, pero estos pacientes pueden ser manejados de forma exitosa con reducción de la inmunosupresión, conversión a m-TOR y esquemas basados en rituximab.

What is the Incidence of Kidney Stones after Chemotherapy in Patients with Lymphoproliferative or Myeloproliferative Disorders?

Introduction This study describes the incidence and risk factors of de novo nephrolithiasis among patients with lymphoproliferative or myeloproliferative diseases who have undergone chemotherapy. Materials and Methods From 2001 to 2011, patients with lymphoproliferative or myeloproliferative disorders treated with chemotherapy were retrospectively identified. The incidence of image proven nephrolithiasis after chemotherapy was determined. Demographic and clinical variables were recorded. Patients with a history of nephrolithiasis prior to chemotherapy were excluded. The primary outcome was incidence of nephrolithiasis, and secondary outcomes were risk factors predictive of de novo stone. Comparative statistics were used to compare demographic and disease specific variables for patients who developed de novo stones versus those who did not. Results A total of 1,316 patients were identified and the incidence of de novo nephrolithiasis was 5.5% (72/1316; symptomatic stones 1.8% 24/1316). Among patients with nephrolithiasis, 72.2% had lymphoproliferative disorders, 27.8% had myeloproliferative disorders, and 25% utilized allopurinol. The median urinary pH was 5.5, and the mean serum uric acid, calcium, potassium and phosphorus levels were 7.5, 9.6, 4.3, and 3.8 mg/dL, respectively. In univariate analysis, mean uric acid (p=0.013), calcium (p<0.001)), and potassium (p=0.039) levels were higher in stone formers. Diabetes mellitus (p<0.001), hypertension (p=0.003), and hyperlipidemia (p<0.001) were more common in stone formers. In multivariate analysis, diabetes mellitus, hyperuricemia, and hypercalcemia predicted stone. Conclusions We report the incidence of de novo nephrolithiasis in patients who have undergone chemotherapy. Diabetes mellitus, hyperuricemia, and hypercalcemia are patient-specific risk factors that increase the odds of developing an upper tract stone following chemotherapy. .

Anticuerpo monoclonal humanizado itolizumab (anti-cd6) en síndromes linfoproliferativos cd 6+. Experiencia preliminar / Itolizumab humanized monoclonal antibody (anti-cd6) in patients with cd6+ lymphoproliferative disorders. Preliminary experience

Introducción: la molécula CD6 es una glicoproteína de membrana considerada un antígeno de diferenciación leucocitario. El anticuerpo monoclonal humanizado itolizumab (anti-CD6) reconoce la molécula CD6 humana en las células mononucleares periféricas malignas de pacientes con leucemia linfocítica crónica- B y en los linfocitos de lesiones cutáneas de pacientes con linfoma T cutáneo. Objetivo: exponer los resultados preliminares de tres pacientes con leucemia linfocítica crónica-B tratados con el itolizumab, con dosis de 0.8 mg/kg/dosis semanal por 12 semanas. Métodos: la evaluación de la toxicidad asociada a la administración del itolizumab se realizó según Common Terminology Criteria for Adverse Events, versión 3.0, y la evaluación del beneficio clínico se definió según los criterios de respuesta, previamente establecidos por el National Cancer Institute Work Group, en remisión completa, remisión parcial, enfermedad estable, progresión y recaída. La evaluación de la respuesta se realizó después de haber recibido 6 administraciones del itolizumab (semana 7), después de haber recibido las 12 administraciones del itolizumab (semana 13), 6 semanas después de la última dosis (semana 18) y 12 semanas después de la última dosis (semana 24). Los datos de cada paciente se recogieron en las historias clínicas. Resultados: se evaluó la seguridad de la administración del producto en pacientes con síndromes linfoproliferativos CD6+ y se obtuvieron evidencias preliminares del efecto terapéutico de dicho fármaco. Conclusiones: en el 100 por ciento de los pacientes incluidos se reportó la aparición de fiebre y escalofríos relacionados con la primera infusión. No se observaron efectos adversos serios. Todos los pacientes evaluados tuvieron al menos alguna mejoría clínica o hematológica...

CD6 molecule is a membrane glycoprotein considered a leukocyte differentiation antigen. Itolizumab, humanized monoclonal antibody (anti-CD6) recognizes the human CD6 molecule in malignant peripheral mononuclear cells of patients with B-cell chronic lymphocytic leukemia and in lymphocytes of cutaneous lesions in patients with cutaneous T- cell lymphoma. We describe preliminary results of 3 patients with B-cell chronic lymphocytic leukemia treated with itolizumab at a weekly dose of 0.8mg/kg/dose for 12 weeks. Product administration safety was evaluated in patients with CD6+ lymphoproliferative disorders and preliminary evidence of therapeutic effect of the drug was obtained. In 100 percent of the patients the onset of fever and chills associated to the first infusion were reported. No serious adverse effects were observed. All patients evaluated had at least some clinical or hematological improvement...

Desordem linfoproliferativa pós-transplante em paciente pediátrico / Post-transplantation lymphoproliferative disorder in pediatric patient / Post-transplantation lymphoproliferative disorder in pediatric patient

Terapias de imunossupressão, a que pacientes transplantados devem ser submetidos, os expõe a um alto risco de desenvolver desordens linfoproliferativas pós-transplante (PTLD). Descrevemos o caso de uma criança submetida a transplante cardíaco aos sete meses de idade e que acabou desenvolvendo PTLD, aos nove anos, diagnosticada por meio de retirada de nódulo pulmonar.

Immunosuppressive therapy for transplanted patients exposes them to a high risk of developing posttransplantation lymphoproliferative disorders (PTLD). We report the case of a child undergoing heart transplantation at seven months of age who developed PTLD at nine years of age, diagnosed by resection of a pulmonary nodule.

Acute abdomen in patients receiving chemotherapy.

OBJECTIVE: To assess the incidence of acute abdomen in patients receiving chemotherapy and to evaluate the factors affecting the clinical decision-making. MATERIAL AND METHODS: Retrospective analysis of surgical oncology references for the patients developing acute abdomen while receiving chemotherapy was carried out. A surgical oncologist reviewed each referral and a full work-up was carried out. Surgical interventions were carried out as and when deemed necessary. Response to treatment, whether surgical or conservative, was used as main outcome variable. RESULTS: Mean age of the patients was 37 years (7-58 years). Half of the patients were receiving chemotherapy for lymphoproliferative disorders, 13 for haematological malignancies and 3 for ovarian cancer. Clinical diagnosis was of acute appendicitis in 13, paralytic ileus in 9, typhilitis in 3 and intestinal perforation in 2, acute intestinal obstruction in 3, and obstructed hernia and intussception in one each. Six patients underwent surgery. Two patients expired postoperatively of progressive septicaemia and multi-system organ failure. CONCLUSION: Evaluation of cancer patients on chemotherapy is difficult. Tenderness, presence of peritoneal signs and absence of exaggerated bowel sounds are most important clinical signs, however they may be blunted by progressive neutropenia or corticosteroid administration. Decision to operate, should be made with extreme caution as mortality and morbidity after surgery is high.