Effect of pre-emptive rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder in pediatric kidney transplant recipients: A case series from the pediatric nephrology research consortium.

BACKGROUND: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia. METHODS: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab. RESULTS: Twenty-six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1-10.3). EBV DNA load monitoring by qPCR was performed at 1-3 month intervals. EBV DNAemia onset occurred at a median of 73 days post-transplant (IQR 52-307), followed by DNAemia peak at a median of 268 days (IQR 112-536). Rituximab was administered at a median of 9 days post peak (IQR 0-118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375-439) weekly for 1-4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow-up (median 2094 days post-transplant [IQR 1538-3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons. CONCLUSIONS: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short-term reduction in DNA load; however, recurrent DNAemia is common.

Ibrutinib as part of risk-stratified treatment for posttransplant lymphoproliferative disorder: the phase 2 TIDaL trial.

ABSTRACT: Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, and patients with low-risk disease after initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD. Eligible patients were adults with newly diagnosed CD20+ B-cell PTLD after solid organ transplant and performance status 0 to 2. Initial treatment comprised 49 days of ibrutinib 560 mg once daily, with 4 doses of weekly rituximab. Treatment response on interim scan and baseline International Prognostic Index were used to allocate patients to either a low-risk arm (who continued ibrutinib, alongside 4 further doses of 3-weekly rituximab) or high-risk (escalation to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] immunochemotherapy, with ibrutinib continuing in patients aged <65 years). The primary outcome was complete response on interim scan, achieved by 11 of 38 patients (29%; 95% confidence interval [CI], 15-46). This did not reach the prespecified threshold for clinically significant activity. Secondary outcomes included allocation to the low-risk arm (41% of patients), 2-year progression-free survival (58%; 95% CI, 44-76), and 2-year overall survival (76%; 95% CI, 63-91). Adverse events were mostly hematological, gastrointestinal, and infective. Although TIDaL does not support adding ibrutinib into first-line treatment of PTLD, increasing the proportion of patients who can be treated without cytotoxic chemotherapy remains an important aim of future research. This trial was registered at www.clinicaltrials.gov as #ISRCTN32667607.

Iatrogenic immunodeficiency-associated lymphoproliferative disorder presenting as small bowel perforation.

A woman in her late 50s on mycophenolate for limited systemic sclerosis presented with abdominal pain. Vital signs and investigative evaluations were normal. Cross-sectional imaging identified gastric and small bowel wall thickening, free fluid, and pneumoperitoneum. In the operating room, a small bowel perforation was found and resected. Postoperatively, immunosuppression was held and she completed a course of amoxicillin/clavulanate. She discharged home and re-presented on postoperative day 8 with seizures and was found to have a frontal brain mass which was biopsied. Pathology from both the resected bowel and brain biopsy demonstrated Epstein-Barr virus-positive B-cell lymphoproliferative disorder with polymorphic B-cell features. The patient's immunosuppression was discontinued, and she was enrolled in a clinical trial for chemotherapy. Lymphoproliferative disorder can present years after immunosuppression initiation with either spontaneous perforation or solid tumour. Pathological assessment determines treatment options. Heightened concern for atypical clinical presentations in immunosuppressed patients is always warranted.

Gastric Burkitt's monomorphic post-transplant lymphoproliferative disorder after kidney transplantation: A case report.

We report on a 53-year-old Japanese man diagnosed with gastric Burkitt's monomorphic post-transplant lymphoproliferative disorder (B-PTLD) after endoscopy for gastric discomfort 28 months after the patient underwent renal transplantation in Ethiopia. Serum Epstein-Barr virus (EBV) tests were negative before transplantation, but the tumor cells collected from a gastric biopsy showed positive EBV-encoded small RNAs (EBER) at B-PTLD onset. Intensive treatment started with R(rituximab)-CHOP therapy and continued with DA-EPOCH-R therapy has been effective, and relapse has not yet occurred. Burkitt lymphoma has a poor prognosis, but B-PTLD may be effectively treated with high-dose chemotherapy. This is a rare case of gastric B-PTLD in a Japanese patient.

Regression of Necrotic Lesions after Methotrexate Withdrawal in Patients with Methotrexate-Associated Lymphoproliferative Disorders: A Retrospective CT Study.

This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD.

Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial.

BACKGROUND: Survival in Epstein-Barr virus (EBV)-positive post-transplant lymphoproliferative disease following haematopoietic stem-cell transplant (HSCT) or solid organ transplant (SOT) is poor after failure of initial therapy, indicating an urgent need for therapies for this ultra-rare disease. With recent EU marketing authorisation, tabelecleucel is the first off-the-shelf, allogeneic, EBV-specific T-cell immunotherapy to receive approval for treatment of relapsed or refractory EBV-positive post-transplant lymphoproliferative disease. We aimed to determine the clinical benefit of tabelecleucel in patients with relapsed or refractory EBV-positive post-transplant lymphoproliferative disease following HSCT or SOT. METHODS: In this global, multicentre, open-label, phase 3 trial, eligible patients (of any age) had biopsy-proven EBV-positive post-transplant lymphoproliferative disease, disease that was relapsed or refractory to rituximab after HSCT and rituximab with or without chemotherapy after SOT, and partially HLA-matched and appropriately HLA-restricted tabelecleucel available. Patients received tabelecleucel administered intravenously at 2 × 106 cells per kg on days 1, 8, and 15 in 35-day cycles and are assessed for up to 5 years for survival post-treatment initiation. The primary endpoint was objective response rate. All patients who received at least one dose of tabelecleucel were included in safety and efficacy analyses. This trial is registered with ClinicalTrials.gov, NCT03394365, and is ongoing. FINDINGS: From June 27, 2018, to Nov 5, 2021, 63 patients were enrolled, of whom 43 (24 [56%] male and 19 [44%] female) were included, 14 had prior HSCT, 29 had SOT. Seven (50%, 95% CI 23-77) of 14 participants in the HSCT group and 15 (52%, 33-71) of 29 participants in the SOT group had an objective response, with a median follow-up of 14·1 months (IQR 5·7-23·9) and 6·0 months (1·8-18·4), respectively. The most common grade 3 or 4 treatment-emergent adverse events were disease progression (in four [29%] of 14 in HSCT and eight [28%] of 29 in SOT) and decreased neutrophil count (in four [29%] of 14 in HSCT and four [14%] of 29 in SOT). Treatment-emergent serious adverse events were reported in 23 (53%) of 43 patients and fatal treatment-emergent adverse events in five (12%); no fatal treatment-emergent adverse event was treatment-related. There were no reports of tumour flare reaction, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, transmission of infectious diseases, marrow rejection, or infusion reactions. No events of graft-versus-host disease or SOT rejection were reported as related to tabelecleucel. INTERPRETATION: Tabelecleucel provides clinical benefit in patients with relapsed or refractory EBV-positive post-transplant lymphoproliferative disease, for whom there are no other approved therapies, without evidence of safety concerns seen with other adoptive T-cell therapies. These data represent a potentially transformative and accessible treatment advance for patients with relapsed or refractory disease with few treatment options. FUNDING: Atara Biotherapeutics.

Lymphoproliferative disorder progressing after partial remission following immunosuppressive drugs withdrawal in a patient with rheumatoid arthritis.

Lymphoproliferative disorders (LPDs) are serious complications that arise in patients with rheumatoid arthritis (RA) receiving immunosuppressive drugs (ISDs). Here, we reported a 73-year-old woman diagnosed with RA at 60 years of age and treated with methotrexate, bucillamine, prednisolone, and infliximab. She was referred to our hospital, Osaka Metropolitan University Hospital, with general malaise, pancytopenia, a right adrenal mass, and enlarged periaortic lymph nodes. Epstein-Barr virus was detected in serum. We suspected LPD development and performed a bone marrow biopsy, on which no malignant cells could be detected. Upon ISDs withdrawal, her symptoms and blood counts improved, and the right adrenal mass and enlarged lymph nodes regressed. The patient was followed up for clinical LPD. However, 7 months after the initial visit to our hospital, she developed fever and pancytopenia. A repeat bone marrow biopsy confirmed the diagnosis of Epstein-Barr virus-positive diffuse large B-cell lymphoma complicated by haemophagocytic syndrome. After pulse steroid therapy, the patient received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, which resulted in a complete response. In conclusion, when LPDs develop in patients with RA during ISD treatment, LPDs can progress and complicate haemophagocytic syndrome after partial remission following ISDs withdrawal. Therefore, we should carefully follow up RA patients with LPDs, and aim to achieve an early diagnosis of LPD and promptly initiate chemotherapy.

Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children's Oncology Group study.

ABSTRACT: Posttransplant lymphoproliferative disease (PTLD) in pediatric solid organ transplant (SOT) recipients is characterized by uncontrolled proliferation of Epstein-Barr virus-infected (EBV+) B cells due to decreased immune function. This study evaluated the feasibility, safety, clinical and immunobiological outcomes in pediatric SOT recipients with PTLD treated with rituximab and third-party latent membrane protein-specific T cells (LMP-TCs). Newly diagnosed (ND) patients without complete response to rituximab and all patients with relapsed/refractory (R/R) disease received LMP-TCs. Suitable LMP-TC products were available for all eligible subjects. Thirteen of 15 patients who received LMP-TCs were treated within the prescribed 14-day time frame. LMP-TC therapy was generally well tolerated. Notable adverse events included 3 episodes of rejection in cardiac transplant recipients during LMP-TC therapy attributed to subtherapeutic immunosuppression and 1 episode of grade 3 cytokine release syndrome. Clinical outcomes were associated with disease severity. Overall response rate (ORR) after LMP-TC cycle 1 was 70% (7/10) for the ND cohort and 20% (1/5) for the R/R cohort. For all cohorts combined, the best ORR for LMP-TC cycles 1 and 2 was 53% and the 2-year overall survival was 70.7%. vßT-cell receptor sequencing showed persistence of adoptively transferred third-party LMP-TCs for up to 8 months in the ND cohort. This study establishes the feasibility of administering novel T-cell therapies in a cooperative group clinical trial and demonstrates the potential for positive outcomes without chemotherapy for ND patients with PTLD. This trial was registered at www.clinicaltrials.gov as #NCT02900976 and at the Children's Oncology Group as ANHL1522.

CAD204520 Targets NOTCH1 PEST Domain Mutations in Lymphoproliferative Disorders.

NOTCH1 PEST domain mutations are often seen in hematopoietic malignancies, including T-cell acute lymphoblastic leukemia (T-ALL), chronic lymphocytic leukemia (CLL), splenic marginal zone lymphoma (SMZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL). These mutations play a key role in the development and progression of lymphoproliferative tumors by increasing the Notch signaling and, consequently, promoting cell proliferation, survival, migration, and suppressing apoptosis. There is currently no specific treatment available for cancers caused by NOTCH1 PEST domain mutations. However, several NOTCH1 inhibitors are in development. Among these, inhibition of the Sarco-endoplasmic Ca2+-ATPase (SERCA) showed a greater effect in NOTCH1-mutated tumors compared to the wild-type ones. One example is CAD204520, a benzimidazole derivative active in T-ALL cells harboring NOTCH1 mutations. In this study, we preclinically assessed the effect of CAD204520 in CLL and MCL models and showed that NOTCH1 PEST domain mutations sensitize cells to the anti-leukemic activity mediated by CAD204520. Additionally, we tested the potential of CAD204520 in combination with the current first-line treatment of CLL, venetoclax, and ibrutinib. CAD204520 enhanced the synergistic effect of this treatment regimen only in samples harboring the NOTCH1 PEST domain mutations, thus supporting a role for Notch inhibition in these tumors. In summary, our work provides strong support for the development of CAD204520 as a novel therapeutic approach also in chronic lymphoproliferative disorders carrying NOTCH1 PEST domain mutations, emerging as a promising molecule for combination treatment in this aggressive subset of patients.

HIV-associated CD8+ T-cell Skin Infiltrative Disease and EBV-associated Polymorphic B-cell Lymphoproliferative Disorder in an AIDS Patient Who Improved Dramatically with Antiretroviral Therapy Alone.

Human immunodeficiency virus (HIV)-associated CD8+ T-cell skin infiltrative disease with severe erythroderma has rarely been reported. While HIV-positive patients are prone to develop lymphoma, which is often associated with Epstein-Barr virus, polymorphic lymphoproliferative disorder is rare, accounting for <5% of cases. We herein report a 41-year-old HIV-positive man who presented with a fever, erythroderma, and lymphadenopathy and was diagnosed with the coexistence of both diseases. His condition improved significantly with continued antiretroviral therapy. This case suggests that HIV-induced immunodeficiency is central to the pathogenesis of both entities and that improvement of the immunodeficient state is an effective treatment.

Treatment of Monomorphic Posttransplant Lymphoproliferative Disorder in Pediatric Solid Organ Transplant: A Multicenter Review.

Posttransplant lymphoproliferative disorder (PTLD) is the most common posttransplant malignancy in children. We reviewed data from 3 Canadian pediatric centers to determine patient characteristics, treatment approaches, and outcomes for children with monomorphic PTLD. There were 55 eligible children diagnosed between January 2001 to December 2021. Forty-eight patients (87.2%) had B-cell PTLD: Burkitt lymphoma (n = 25; 45.4%) and diffuse large B-cell lymphoma (n = 23; 41.2%), the remainder had natural killer (NK)/T-cell lymphoma (n = 5; 9.1%), Hodgkin lymphoma (n = 1;1.8%), or other (n = 1;1.8%). Thirty-nine (82.1%) patients with B-cell PTLD were treated with rituximab and chemotherapy with or without a reduction in immunosuppression (reduced immune suppression). The chemotherapy used was primarily one of 2 regimens: Mature Lymphoma B-96 protocol in 22 patients (56.4%) and low-dose cyclophosphamide with prednisone in 14 patients (35%). Most patients with T/NK-cell lymphoma were treated with reduced immune suppression + chemotherapy (n = 4; 80%). For all patients with monomorphic PTLD, the projected 3-year event-free survival/3-year overall survival was 62% and 77%, respectively. Of the patients, 100% with T/NK-cell PTLD 100% progressed or relapsed and, subsequently, died of disease. For patients with B-cell PTLD, there was no significant difference in outcome between the two main chemotherapy regimens employed.

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.