Successful Use of Extracorporeal Life Support and Continuous Renal Replacement Therapy in the Treatment of Cardiogenic Shock Induced by Tumor Lysis Syndrome in a Pediatric Patient With Lymphoma: A Case Report

The use of extracorporeal membrane oxygenation (ECMO) in the treatment of cardiopulmonary failure in children with malignant tumors is controversial. There are few reports on the use of ECMO in the treatment of children with tumor lysis syndrome. This article reports a case of a 9-year-old girl who presented with hyperkalemia and cardiogenic shock. The discovery of an abdominal mass with critical ultrasound provided key evidence for the initial diagnosis of tumor lysis syndrome. Cardiopulmonary resuscitation was performed for 1 h. Veno-arterial ECMO was installed at the bedside to provide cardiopulmonary support for the patient and was combined with continuous renal replacement therapy (CRRT) to improve her internal environment. The patient was ultimately diagnosed with mature B-cell lymphoma with tumor lysis syndrome. A severe electrolyte disorder led to cardiogenic shock. After the electrolyte imbalance was corrected, the patient's heart function gradually improved, ECMO was successfully weaned, and chemotherapy was continued with the support of CRRT. One month after ECMO weaning, the organ function of the patient had recovered and there were no serious complications. In this case report, we paid attention to the rapid diagnosis of the etiology behind a patient's shock with critical ultrasound as well as the initiation and management of extracorporeal cardiopulmonary resuscitation (ECPR), which provided us with valuable experience using VA-ECMO on critically ill children with tumors. It is also important evidence for the use of ECMO in the treatment of children with cardiopulmonary arrest secondary to malignancy.

Sézary syndrome preceded by mycosis fungoides and complicated by tumor lysis syndrome and macrophage activation syndrome

Sir, Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common malignancies of cutaneous T-cell lymphoma [1]. Herein, we report a case of SS complicated by tumor lysis syndrome and macrophage activation syndrome. A 54-year-old patient, followed since October 2017 for mycosis fungoides and undergoing various treatments (PUVA therapy, methotrexate, chlorambucil + prednisone), presented with an aggravation of lesions toward extensive and intensely pruritic. A clinical examination revealed dry erythroderma, scratch marks, wart plaques, an accentuation of frontal wrinkles and nasolabial folds (leonine facies), palmoplantar fissuring keratoderma, xanthopachyonychia of all nails, and a carapace-like appearance of the scalp (Figs. 1 – 3). Generalized lymphadenopathy, hepatomegaly, and a state of anasarca-type edema caused by hypoalbuminemia were also found. A skin biopsy revealed lymphoproliferation of CD4+ T-cells and an aberrant loss of pan-T antigens. The CD4-to-CD8 ratio was at 48.5% and Sézary cells were 6960 (absolute value). A lymph node biopsy showed a dense infiltration of Sézary cells. A PET scan revealed hypermetabolism in the entire skin and at the lymph node level. Tumor lysis syndrome was evident, with high levels of blood uric acid (at 182 mg/L), elevated LDH (at 924 U/L), and functional kidney failure. Macrophage activation syndrome was also present, with fever, anemia and thrombocytopenia, liver cytolysis, hypertriglyceridemia, and hyperferritinemia. The patient received an albumin infusion, oral corticosteroid therapy to treat the syndrome, and rasburicase for hyperuremia. Despite this, the patient died before multiagent chemotherapy could have been started. On rare occasions, SS may be preceded by a prior history of classic MF. The International Society for Cutaneous Lymphomas (ISCL) recommends that such cases be designated “SS preceded by MF” [2]. Traditionally, SS is defined as a leukemic form of CTCL associated with erythroderma. Sézary cells are a population of large lymphocytes in the peripheral blood, with grooved and lobulated nuclei, in the case of SS, numbering 1000 cells/mL or more [2]. The histopathologic findings in the skin often resemble those observed in MF, with less prominent epidermotropism. As in MF, immunohistochemical studies showing a CD4 predominance and loss of pan-T-cell markers may be helpful. Lymph node involvement is characterized by the complete effacement of the nodal architecture by the infiltrating Sézary cells (2). The poor prognostic factors in Sézary syndrome include an advanced stage of the disease, an older age at onset, and large cell transformation [3]. While high response rates may be achieved with systemic chemotherapy, they are frequently short-lived and associated with significant toxicities [2]. The management of SS is complicated and requires multidisciplinary collaboration between dermatologists, hematologists, biologists, and reanimators.

Kết quả điều trị u lympho tế bào B trưởng thành bằng phác đồ LMB 96 tại Bệnh viện Nhi Trung ương

TÓM TẮT Đặt vấn đề: U lympho tế bào B trưởng thành (B - NHL) là bệnh lý ác tính và tiến triển nhanh ở trẻ em. Kết quả điều trị đã được cải thiện đáng kể bằng phác đồ đa hóa chất liều cao. Nghiên cứu này nhằm đánh giá kết quả điều trị bệnh nhân B - NHL bằng phác đồ LMB 96 tại Bệnh viện Nhi Trung ương (BVNTƯ). Đối tượng và phương pháp nghiên cứu: Nghiên cứu mô tả cắt ngang các bệnh nhân dưới 16 tuổi được chẩn đoán B - NHL dưới 16 tuổi được điều trị tại BVNTƯ từ 01/01/2015 đến thời điểm kết thúc điều trị trước 30/06/2021, không bao gồm các bệnh nhân không theo dõi được. Kết quả: 84 bệnh nhân B - NHL được điều trị theo phác đồ LMB 96 trong thời gian 6 năm. 23 bệnh nhân tử vong (27,4%). Nguyên nhân tử vong chính là do nhiễm trùng nặng liên quan đến giảm bạch cầu hạt độ 4 (11,9%). Xác suất sống toàn bộ (OS) và xác suất sống không bệnh (EFS) 6 năm lần lượt là 69,6% và 63,9%. OS và EFS 6 năm của nhóm bệnh nhân giai đoạn 3 là 77,2% và 76,7%; giai đoạn 4 là 46,4% và 35,7%, thấp hơn giai đoạn 1 và 2 (p = 0). OS và EFS 6 năm của nhóm bệnh nhân có LDH ≥ 1000 UI/ml là 58,2% và 52,6%, thấp hơn nhóm có LDH < 1000 UI/ml (p ≤ 0,05). OS và EFS 6 năm của nhóm có thâm nhiễm tủy xương thấp hơn nhóm không thâm nhiễm tủy xương (p ≤ 0,05). Hội chứng ly giải u gặp ở 10,7% bệnh nhân trước điều trị và 11,9% bệnh nhân sau khi bắt đầu điều trị, xuất hiện chủ yếu trên bệnh nhân có LDH ≥ 1000 UI/ml, thể Burkitt, giai đoạn 3 và 4. Kết luận: Kết quả điều trị bệnh nhân B - NHL theo phác đồ LMB 96 tại BVNTƯ tương đương với các nước đang phát triển nhưng thấp hơn các nước phát triển. Các biện pháp điều trị hỗ trợ cần cải thiện hơn để nâng cao tỉ lệ sống cho bệnh nhân. ABSTRACT OUTCOME OF MATURE B CELL LYMPHOMA TREATED BY LMB 96 PROTOCOL IN VIETNAM NATIONAL CHILDREN’S HOSPITAL Mature B cell lymphoma (B - NHL) is a highly aggressive and fast - growing human disease in children. The outcome of childhood B - NHL treatment has improved steadily through the use of intensive multi -agent chemotherapy regimens. This study aims to reveal the outcome of treatment according to LMB 96 protocol in Vietnam National Children’s Hospital (VNCH). Objective and methods: A descriptive study was carried out in all B - NHL patients under 16 years old that start their treatment in VN CH since 01 January 2015 and end before 30 June 2021, excluding patients can’t follow up. Results: Eighty - four patients were diagnosed with B - NHL, who underwent chemotherapy by the LMB96 protocol and followed up in 6 years. Twenty - three patients (27.4%) died. The main cause of death was severe sepsis related to grade IV neutropenia in 11.9% of the patients. The 6 years OS and EFS were 69.6% and 63.9%, respectively, for the whole groups of patients. The 6 years OS and EFS were 77.2% and 76.7% at stage III; 46.4% and 35.7% at stage 4, lower than at stage Iand II (p = 0). The 6 years OS and EFS in the group with LDH ≥ 1000 UI/ml were 58.2% and 52.6%, worse than in the group with LDH < 1000 UI/ml (p ≤ 0,05). OS and EFS in the non - bone marrow involvement group were much lower than the bone marrow involvement patients (p ≤ 0,05). Tumor lysis syndrome was seen in 10.7% of the patients before starting chemotherapy and 11.9% of those after the beginning of treatment, mostly occurs in patients with LDH ≥ 1000 UI/ml, Burkitt lymphoma, stage 3 and 4. Conclusion: The outcome of treatment mature B cell lymphoma in VNCH according to LMB 96 protocol was similar to other results in developing countries but lower than those in developed countries.Supportive care needs to improve to increase the survival rate. Keywords: Mature B cell lymphoma, outcome, Vietnam National Children’s Hospital

Comprehensive Analysis of Bortezomib-Induced Adverse Events Using the Japanese Real-World Database

Background: Bortezomib is used as first-line therapy for multiple myeloma. Observational studies based on the FDA Adverse Event Reporting System (FAERS) database analysis and systematic reviews indicate that the incidence of peripheral neuropathy and tumor lysis syndrome (TLS) tends to be higher with bortezomib than that of other drugs. In a comprehensive analysis assessing drugs that cause peripheral neuropathy in Japanese patients, the incidence of bortezomib-induced adverse events (AEs) was reportedly high. However, a comprehensive assessment of bortezomib is lacking. Objectives: The purpose of this study was to determine the frequency of bortezomib AEs in Japanese patients and to determine the incidence, time to onset, and post hoc outcomes of unique AEs using the Japanese Adverse Drug Event Report (JADER) database. Method: To investigate the association between bortezomib and AEs, we analyzed the JADER database, which contains spontaneous AE reports submitted to the Pharmaceuticals and Medical Devices Agency from April 2004 to December 2020. Criteria indicating the presence of an AE signal were met when the following requirements were fulfilled: proportional reporting ratios (PRR) ≥ 2 and χ2 ≥ 4. Time to onset and post-event outcomes were analyzed for characteristic AEs. Results: Among 26 extracted AEs, 13 presented AE signals. The post-exposure outcomes of 12 AEs showed fatal outcomes at rates exceeding 10%, including cardiac failure (30%), lung disorder (24%), pneumonia (18%), and TLS (10%). Furthermore, a histogram of time to onset revealed that the 12 AEs were concentrated from the beginning to approximately one month after bortezomib administration. The median onset times for cardiac failure, lung disorder, pneumonia, and TLS were 28, 13, 42, and 5 days, respectively. Conclusions: Cardiac failure, lung disorder, pneumonia, and TLS had a higher rate of fatal clinical outcomes after onset than other AEs. These AEs exhibited a greater onset tendency in the early post-dose period. This study suggests that there is a need to monitor signs of cardiac failure, lung disorder, pneumonia, and TLS, potentially resulting in serious outcomes.

Frontline treatment in CLL: the case for time-limited treatment

Over the last decade, the advent of Bruton tyrosine kinase inhibitors (BTKi) has profoundly modified the therapeutic strategy in chronic lymphocytic leukemia (CLL), introducing the concept of treatment until progression. Initially, the bcl-2 inhibitor venetoclax (VEN) was used as a single agent and then was rapidly combined in VEN-based regimens associated with either anti-CD20 or with BTKi. These regimens yielded a high rate of complete remission, leading to their use as a fixed duration treatment. The decision between continuous treatment with BTKi and VEN-based combinations relies mostly on comorbidities, comedications, and patient/physician preferences. Notably, with BTKi, cardiovascular comorbidities, hypertension, and potential pharmacological interactions should be carefully evaluated. On the other hand, the risk of tumor lysis syndrome with VEN should be monitored at treatment initiation. TP53 alteration and IGHV mutational status should also be assessed, as they remain important for therapeutic decisions. Fit patients with a TP53 wild type and IGHV-mutated CLL may still benefit from fludarabine-cyclophosphamide-rituximab chemoimmunotherapy (CIT), as it may result in a very long remission duration. VEN-based treatments are well tolerated, and no additional toxicity has been observed when combined with anti-CD20 or BTKi. The 1-year fixed-duration association of VEN plus obinutuzumab was evaluated in frontline for older adult patients. Nonetheless, considering the favorable outcome, an extension of indication for fit younger patients is expected. The association of VEN and BTKi is promising, even if the follow-up is still short. It is currently being tested against CIT, BTKi continuous treatment, and VEN plus anti-CD20.

Venetoclax Shows Low Therapeutic Activity in BCL2-Positive Relapsed/Refractory Peripheral T-Cell Lymphoma: A Phase 2 Study of the Fondazione Italiana Linfomi

Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have a poor prognosis, with an expected survival of less than 1 year using standard salvage therapies. Recent advances in our understanding of the biology of PTCL have led to identifying B-Cell Lymphoma 2 (BCL2) protein as a potential therapeutic target. BLC2 inhibitor venetoclax was investigated in a prospective phase II trial in patients with BCL2-positive R/R PTCL after at least one previous standard line of treatment (NCT03552692). Venetoclax given alone at a dosage of 800 mg/day resulted in one complete response (CR) and two stable diseases (SDs) among 17 enrolled patients. The majority of patients (88.2%) interrupted the treatment due to disease progression. No relationship with BCL2 expression was documented. At a median follow-up of 8 months, two patients are currently still on treatment (one CR and one SD). No case of tumor lysis syndrome was registered. Therefore, venetoclax monotherapy shows activity in a minority of patients whose biological characteristics have not yet been identified.Clinical Trial Registrationwww.clinicaltrials.gov (NCT03552692, EudraCT number 2017-004630-29).