Tumor Lysis Syndrome Research Articles

Clinical Relevance of Intensive Laboratory Monitoring With Standard Venetoclax Ramp-Up for Chronic Lymphocytic Leukemia: A Real-World Experience

PURPOSE Venetoclax is the standard of care for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) but requires intensive monitoring for optimal safety. Clinical relevance of intensive monitoring in practice is unknown, especially for patients with low or intermediate risk for tumor lysis syndrome (TLS). PATIENTS AND METHODS A retrospective review was conducted to determine clinical significance of monitoring for TLS during standard ramp-up for patients with CLL/SLL. Patients receiving abbreviated ramp-up, clinical trials, or concurrent Bruton tyrosine kinase inhibitors were excluded. The primary end point was TLS incidence, with secondary end points describing associated clinical interventions. RESULTS Fifty-five patients met study criteria. The majority of patients received venetoclax as first-line therapy (58%), with anti-CD20 antibody therapy (82%), and were at low risk of TLS (75%). No clinical TLS events occurred, whereas laboratory TLS occurred in only 1.8% of patients. No patients required antihyperuricemic therapy, and few interventions for hyperphosphatemia or hypocalcemia (3.6% of patients) were required. Additional intravenous fluids were uncommonly required (1.8% of patients), and no unplanned hospitalizations were required. CONCLUSION These findings support efforts to reduce intensive monitoring requirements during venetoclax ramp-up for patients with CLL, potentially increasing accessibility of venetoclax.

Evaluation of the Impact of Monitoring for Tumor Lysis During Venetoclax Ramp-Up in Chronic Lymphocytic Leukemia in Routine Clinical Practice

PURPOSE Venetoclax has made a significant impact in the treatment of chronic lymphocytic leukemia (CLL) due to its ability to induce deep and durable remissions with a finite duration of oral therapy. However, it can lead to tumor lysis syndrome (TLS) which is mitigated with dose escalation strategies. Patients who initiate venetoclax need to follow rigorous, and potentially burdensome, TLS monitoring during dose ramp-up. The frequency with which this rigorous monitoring leads to therapeutic interventions in clinical practice has not been well described. We conducted a study to assess the incidence of TLS and interventions needed after initiation of venetoclax in patients with CLL. METHODS Adult patients with CLL who started treatment with venetoclax between July 2017 and March 2021 at Levine Cancer Institute were included in this study. Adherence to the venetoclax package insert (PI) for tumor lysis monitoring, incidence of laboratory as well as clinical TLS, and interventions resulting from the monitoring of TLS were collected. RESULTS We report outcomes on 73 consecutive patients with CLL who initiated venetoclax. The majority of patients had low (49%) or medium (44%) tumor burden. During venetoclax ramp-up, 66% of patients adhered strictly to TLS monitoring as per the venetoclax PI. One patient developed laboratory TLS, and no patients developed clinical TLS. Six patients received unplanned interventions to treat TLS; all had medium or high tumor burden. There were no unplanned interventions in patients with low tumor burden. CONCLUSION In patients with low and medium tumor burden CLL who start venetoclax, the incidence of TLS is very low, and interventions are uncommonly needed.

Acute Kidney Injury Following CAR-T Cell Therapy: A Nephrologist Perspective

Abstract Chimeric antigen receptor T-cell (CAR-T cell) therapy, an emerging personalized immunotherapy for various hematologic malignancies, autoimmune diseases, and other conditions, involves the modification of patients’ T cells to express a chimeric antigen receptor which recognizes tumor or autoimmune cell antigens. Thereby CAR-T cells destroy cancerous and other target cells selectively. Despite remarkable clinical improvements in patients, multiple adverse effects have been associated with CAR-T cell therapy. Among the most recognized adverse effects are cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and tumor lysis syndrome. Even though less recognized, the incidence of acute kidney injury (AKI) ranges from 5% to 33%. The wide range of reported AKI incidence rates might depend on patient population characteristics and comorbidities and specific CAR-T cell therapy features. Even though the exact pathophysiology remains unknown, several key mechanisms including cytokine release syndrome, tumor lysis syndrome, and other factors such as direct renal toxicity of CAR-T cell therapy, conditioning regimens or other medications (e.g. antibiotics), and infectious complications (e.g. sepsis) have been proposed. Risk factors for CAR-T-related AKI include lower baseline glomerular filtration rate, higher rates of allopurinol or rasburicase use, intravenous contrast material exposure, elevated baseline lactate dehydrogenase, and grade 3 or higher cytokine release syndrome. Future prospective studies with larger patient populations are needed to gain more insight regarding the pathophysiology of CAR-T-related AKI, and, more importantly, to be able to prevent as well as to develop novel and more efficient treatment modalities. In this narrative review, we discuss the underlying pathophysiology, risk factors, potential interventions, and future directions related to AKI following CAR-T cell therapy.

Venetoclax plus low intensity chemotherapy for adults with acute lymphoblastic leukemia.

In acute lymphoblastic leukemia (ALL), the BCL2 inhibitor venetoclax may enhance the efficacy of chemotherapy allowing dose reductions that reduce toxicity. We designed a phase 1b study of venetoclax plus attenuated chemotherapy to determine the recommended phase 2 dose (RP2D) of venetoclax. The study enrolled 19 patients with ALL either newly diagnosed (≥60 years, n=11 [B-cell, n=8; T-cell, n=3]) or R/R (≥18 years, n=8 [B-cell, n=3; T-cell, n=5]). Venetoclax was given for 21 days with each cycle of mini-hyper-CVD (cyclophosphamide, vincristine, dexamethasone alternating with methotrexate and cytarabine). There were no dose limiting toxicities at dose level (DL) 1 (n=3, 400 mg/day) or DL2 (n=6, 600 mg/day); DL2 was the RP2D and explored further (n=10). The most common non-hematologic adverse events were grade 3+ infections. There were no deaths within 60 days and no patients discontinued therapy for toxicity. There was no tumor lysis syndrome, hepatotoxicity, or prolonged cytopenias. Among patients with newly diagnosed ALL, 10/11 (90.9%) achieved a measurable residual disease-negative (<0.01% sensitivity) complete remission (CR) including 6 patients with hypodiploid TP53 mutated ALL. All patients in CR bridged to hematopoietic stem cell transplant (n=9) or completed protocol (n=1). With a median follow-up of 60.0 months, median disease-free survival (DFS) for patients with newly diagnosed ALL was 54.6 months (95% CI: 35.5 months - NA) with a 2-year DFS rate of 90% (95% CI, 71% - 100%). Among patients with R/R ALL, 3/8 (37.5%) achieved CR. In summary, for patients with newly diagnosed ALL, venetoclax plus mini-HCVD is well-tolerated with promising efficacy. NCT03319901.

Risky Remedy: Rasburicase-Induced Methemoglobinemia in Tumor Lysis Syndrome Complicated by G6PD Deficiency

Risky Remedy: Rasburicase-Induced Methemoglobinemia in Tumor Lysis Syndrome Complicated by G6PD Deficiency

Tumor Lysis Syndrome Following PSMA Radioligand Therapy.

Tumor lysis syndrome (TLS) is a rare complication following treatment in prostate cancer patients. We present a 65-year-old man with history of castration-resistant prostate cancer who developed TLS following 2 sessions of 177Lu-PSMA therapy. The patient presented with bulky axillary and mediastinal lymphadenopathies, an unusual site for prostate cancer metastasis. Although his PSA levels declined following treatment, he reported excessive weakness leading to immobility. Laboratory correlation showed markedly increased lactate dehydrogenase, from 413 to 543,000 U/L, suggesting the occurrence of TLS. Although being considered a relatively safe treatment, 177Lu-PSMA can sometime lead to life-threatening events, which is reviewed here.

Spontaneous Tumor Lysis Syndrome in the Setting of Pancreatic Adenocarcinoma

Spontaneous Tumor Lysis Syndrome in the Setting of Pancreatic Adenocarcinoma

Pediatric cancer mortality: Analyzing early deaths and fatalities in a resource-limited tertiary care context.

Children with suspected cancer may succumb to their bad condition shortly after admission, even before a definitive diagnosis can be reached. We aimed to address the issue of delayed presentation and early deaths among children suspected of having cancer. We analyzed also the types and causes of mortalities across different tumor types. A retrospective review of reports from newly admitted patients between 2006 and 2010 at the pediatric oncology department of the South Egypt Cancer Institute (SECI) was done. Parameters included age, gender, diagnosis, symptoms, the interval between initial symptoms and the first visit to SECI, the duration from admission to death, and the cause of death. Among the 502 patients with confirmed malignancies, 238 (47.4%) succumbed. Causes of death were predominantly treatment-related mortalities (TRM) (66%). Mortalities within hematological malignancies were mainly TRM (81%), whereas solid tumors were primarily disease-related (70%), p <0.0001. The leading causes of TRM was infection (60%). About 5% of patients experienced early death within 48 hours after presenting to SECI. The mean duration from initial symptoms to the first SECI visit was 67 days, and the period from admission to death averaged 27 hours. Common initial symptoms included abdominal swelling (29.6%), or fever (26%). The leading causes of death were respiratory failure (29.6%), tumor lysis syndrome (22%), or septicemia (22%). Delayed presentation leading to early deaths poses a significant obstacle to the successful treatment of childhood cancers. Early diagnosis and improved supportive care are essential to enhancing the overall survival, particularly in patients with hematologigical malignancies.

Mining and analysis of adverse event signals of vandetanib based on the FAERS database.

By analyzing the signal mining of vandetanib AEs, it provides a reference for the rational clinical use of the drug. This study provides signal detection and analysis of AEs associated with vandetanib using the FAERS from Q2 2011 to Q1 2023. Disproportionality analyses were conducted using the ROR and the MHRA method, with AEs categorized and described based on SOC and PT from the MedDRA. A total of 1,721 AEs reports identified vandetanib as the primary suspect. The analyses yielded 187 AEs signals across 20 SOCs categories, with 47 signals not previously reported in the vandetanib labeling. Additionally, the study analyzes factors influencing AEs. The results are as follows: There are significant differences in Investigations based on gender and nationality (p < 0.05); skin and subcutaneous tissue disorders and gastrointestinal disorders exhibit differences based on gender, age, and nationality (p < 0.05). Common AEs signals identified align with those documented in the drug labeling. However, AEs such as tumor lysis syndrome, skin discoloration, and pigmentary disorders, which are not listed in the labeling, warrant special attention. It is essential that abnormalities in patients' skin and laboratory indicators are closely monitored and addressed promptly to safeguard medication safety.

Opportunities and Challenges of Application of Cytosorb Therapy in Sepsis Management

Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. In 2017, an estimated 48·9 million incident cases of sepsis were recorded worldwide, and 11·0 million sepsis-related deaths were reported, representing 19·7% of all global deaths.1 Though overall data related to sepsis is poor but it is also a major health care challenge for resource limited countries. Severe sepsis is a significant &amp; common health problem in ICU patients of Bangladesh2. A continuum of severity from sepsis to septic shock and multi-organ dysfunction syndrome (MODS) exists. MODS is a clinical syndrome characterized by the development of progressive and potentially reversible physiologic dysfunction in 2 or more organs or organ systems that is induced by a variety of acute insults, including sepsis. Sepsis leads to malignant intravascular inflammation, coagulopathy, circulatory derangement, tissue hypoxia, cytotoxicity and apoptosis. As a result, dysfunction of vital organ systems occur. Host response and other factors influenc outcome. Patients with sepsis must be treated with-timely, appropriate antibiotics, intravenousfluids, vasopressor and inotropic support &amp; oxygen therapy.3 Other additional treatments including extracorporeal blood purification techniques (BPT). These techniques include hemofiltration, hemoperfusion, intermittent or continuous high-volume hemofiltration (HVHF), plasmapheresis or adsorption.4 The rationale behind such an approach is to achieve “immune homeostasis” which theoretically reduces the potential damage caused by dysregulation of the host response to infection. Given the pivotal role of cytokine production in sepsis, it follows that removal of these substances, through such BPT, may attenuate the response particularly in the early phase of sepsis.5 Indications include 1) Rhabdomyolysis resulting from Reperfusion syndrome, Trauma, Malignant Hyperthermia. 2) External injuries including Sepsis/Septic shock, Hemorrhagic shock, Trauma, Ruptured aortic aneurysm, Post-Cardiac Arrest Syndrome, Cardio-pulmonary resuscitation, Extensive surgery, Organ transplantation, Cardiosurgical intervention, Severe skin and soft tissue damage, Burns, Necrotizing fasciitis, Post-Cardiotomy Syndrome, Acute Respiratory Distress Syndrome. 3) Diseases: Pancreatitis, Liver insufficiency, Renal insufficiency, Stroke, Myocardial infarction, Cardiogenic shock/Heart failure, Tumor Lysis Syndrome, Hemophagocytosis Syndrome. Liver failure/Hyperbilirubinemia bridging to transplant or to recovery, Life-threatening bleeding under Direct Oral Anticoagulants (DOAC)6. Bangladesh Crit Care J September 2024; 12 (2): 79-80

Buffy coat removal to mitigate reporting false normal G6PD phenotype results in patients undergoing rasburicase therapy for tumor lysis syndrome

Abstract Glucose-6-phosphate dehydrogenase (G6PD) is the primary source of NADPH in red blood cells (RBCs). NADPH reduces reactive oxygen species (ROS) thereby protecting RBCs from oxidative stress-mediated hemolytic anemia (HA). Individuals with partial or full G6PD deficiency are therefore susceptible to acute HA provoked by medications that generate high ROS loads in vivo, e.g., rasburicase. Rasburicase is an enzyme-based therapeutic used to degrade uric acid (UA) in patients with tumor lysis syndrome (TLS); however, catalysis of UA generates H2O2, a potent ROS, which poses a risk of HA in individuals who are deficient in G6PD activity. Screening G6PD activity prior to rasburicase administration is clinically indicated in ethnic groups with high rates of G6PD deficiency, although reports of HA in rasburicase-treated patients have been reported across low prevalence ethnic groups as well. TLS occurs most commonly during the treatment of highly proliferative neoplasms, such as leukemia and lymphoma. Since WBCs contain significant G6PD activity, an elevated WBC count in these patients can cause the false assurance of low HA risk due to a falsely normal G6PD activity. We sought to establish and evaluate a novel method to mitigate WBC contamination of G6PD measurements in patients undergoing rasburicase therapy. In this study, we first developed and validated an innovative method (“piercing method”) to minimize the interference of WBCs in G6PD measurements. The piercing method demonstrated acceptable accuracy (slope: 1.008; bias: -6.22%) and precision (1.4% CV between 9.9 to 20.7 U/g Hb) and was effective at eliminating a broad range of WBC types and concentrations from whole blood samples (N = 85, tested range = 0.31 – 413.05 K/μL, 93% reduction in WBCs). We compared G6PD activity in rasburicase-treated patients (N = 39) with varying WBC counts before and after buffy coat removal using the piercing method. Average percent change in G6PD activity (post-pierce – pre-pierce) between patients with and without elevated WBCs was substantial (45% versus 12%). In comparing G6PD activity in patients before and after the initiation of rasburicase therapy, there is no evidence that in vivo-generated ROS from rasburicase affect G6PD measurement in vitro in an assay that relies on monitoring absorbance of NADPH (22.2 U/g Hb versus 22.9 U/g Hb, p=0.721). Results demonstrate how WBCs increase risk for false elevation in G6PD activity in patients being considered for rasburicase therapy. At greatest risk are patients with partial G6PD deficiency, e.g., heterozygous females, where G6PD from WBCs could mask deficiency. Literature describing testing of G6PD in specimens with elevated WBCs is lacking. This study shows that the piercing method provides accurate G6PD results in samples with elevated WBCs from patients at risk of TLS, who might develop HA after starting rasburicase therapy.

Clinical Rarity Unveiled: Adenocarcinoma with Enteroblastic Differentiation at the Gastroesophageal Junction in a Young Patient - A Diagnostic Challenge Shaping Therapeutic Paradigms

Abstract Introduction/Objective This report details a case of a young patient diagnosed with an adenocarcinoma with enteroblastic differentiation at the gastroesophageal junction (GEJ), characterized by Alpha-Fetoprotein (AFP) production. This manifestation previously rarely documented in young patients (25-44 years old), underscores the critical role of precise pathology diagnosis in guiding effective patient management. Methods/Case Report The patient’s clinical presentation included chest pain, abdominal pain, and weight loss, prompting imaging studies revealing liver masses, lesions in the lung and adrenal gland, and retroperitoneal adenopathy with unremarkable testicular findings. Rapidly progressing dysphagia led to a liver biopsy and esophagogastroduodenoscopy (EGD), where a fungating mass extending from the distal esophagus into the stomach was biopsied. A subsequent serologic test unveiled an elevated serum AFP level (approximally 31, 000 ng/ml). Results (if a Case Study enter NA) Histological examination revealed similarities between the liver and distal esophageal tumors, characterized by moderately differentiated carcinoma with solid and glandular growth patterns. The tumor cells, resembling fetal gut epithelium, exhibited positive immunostaining for SALL4, AFP, CK8-18, CK19, and CDX2. A diagnosis of adenocarcinoma with enteroblastic differentiation at the GEJ was determined, correlating with clinical and radiological assessments. Despite initiating one cycle of gastrointestinal related chemotherapy, the patient succumbed to tumor lysis syndrome within a month of diagnosis. Conclusion This case highlights the critical need for a comprehensive differential diagnosis when encountering young patients with AFP-producing malignancies. Although metastatic non-seminomatous germ cell cancer is a primary consideration, upper gastrointestinal adenocarcinoma with unique characteristics, as demonstrated in this case, requires distinct therapeutic approaches, emphasizing the importance of accurate and timely diagnosis.

Extracorporeal pediatric renal replacement therapy: diversifying application beyond kidney failure.

The utilization of extracorporeal renal replacement therapy (RRT), including continuous renal replacement therapy (CRRT) and hemodialysis (HD), beyond the treatment of volume overload and acute kidney injury (AKI) has witnessed a significant shift, demonstrating the potential to improve patient outcomes for a range of diseases. This comprehensive review explores the non-kidney applications for RRT platforms in critically ill children, focusing on diverse clinical scenarios such as sepsis, inborn errors of metabolism, liver failure, drug overdose, tumor lysis syndrome, and rhabdomyolysis. In the context of sepsis and septic shock, RRT not only facilitates fluid, electrolyte, and acid/base homeostasis, but may offer benefits in cytokine regulation, endotoxin clearance, and immunomodulation which may improve multi-organ dysfunction as well as hemodynamic challenges posed by this life-threatening condition. RRT modalities also have an important role in caring for children with inborn errors of metabolism, liver failure, and tumor lysis syndrome as they can control metabolic derangements with the efficient clearance of endogenous toxins in affected children. In cases of drug overdose, RRT is a crucial tool for rapid extracorporeal clearance of exogenous toxins, mitigating potential organ damage. The intricate interplay between liver failure and kidney function is examined, elucidating the role of RRT and plasma exchange in maintaining fluid and electrolyte balance when hepatic dysfunction complicates the clinical picture. Furthermore, RRT and HD are explored in the context of rhabdomyolysis, highlighting their utility in addressing AKI secondary to traumatic events and crush syndrome.

8690 Severe Hypocalcemia Following Treatment with Venetoclax for AML

Abstract Disclosure: K. Ruddiman: None. C. Price: None. Background: Venetoclax is a chemotherapeutic agent which has known side effects of tumor lysis syndrome, but few reports of isolated hypocalcemia. Clinical case: A 73 year old male with medical history pertinent for myeloproliferative and myelodysplastic disease was admitted for evaluation of failure to thrive. Workup revealed progression to acute myeloid leukemia. Following treatment with decitabine 34mg/day for 5 doses and initiation of venetoclax 100mg daily, he developed progressive, severe, symptomatic hypocalcemia with positive Trousseau and Chvostek sign. The patient was normocalcemic prior to admission with serum calcium ranging between 8.6-9.7mg/dL. Corrected calcium at admission was 8.8mg/dL. Serum calcium decreased steadily following venetoclax, requiring repletion with 3 doses of calcium chloride and gluconate 1gm IV and initiation of oral calcium carbonate 1900mg TID. At its nadir, corrected calcium was 6.1mg/dL on day 19 of treatment with venetoclax despite oral and IV repletion. Further workup showed undetectable 25 hydroxy vitamin D, PTH 62pg/mL, normal range uric acid, low phosphorus (lowest 2.2mg/dL), mild hypokalemia (lowest 3.2mg/dL), and mild hypomagnesemia of 1.8mg/dL. GFR was &amp;gt;90mL/min. Hypocalcemia improved after 3 infusions of calcium gluconate 10gm IV in 1 L normal saline to 7.2mg/dL. Oral repletion with calcium carbonate was transitioned to calcium citrate due to concomitant PPI use. PO calcium citrate titrated to 2850 mg TID to target corrected calcium 7.5 - 8.5 and limit further need for diuresis following calcium gluconate infusions. Ergocalciferol 50,000 IU was given thrice weekly in addition to daily cholecalciferol 5,000 IU with improvement in 25 hydroxy vitamin D to 17ng/mL. This patient was suspected to have multifactorial etiology for hypocalcemia, secondary to undetectable 25 hydroxy vitamin D as well as diuresis with furosemide during the admission, but the most strongly attributed factor was initiation of venetoclax prior to development of progressive hypocalcemia. FDA prescribing information reports hypocalcemia as a side effect of venetoclax when used in treatment for CML, but in phase 2 and 3 studies of venetoclax used alone and in combination with low dose cytarabine to treat AML, no significant episodes of hypocalcemia were reported. Tumor lysis syndrome (TLS) is a known adverse effect of venetoclax in which hypocalcemia is an expected feature, however, this patient did not have laboratory to support this diagnosis. His other electrolyte deficiencies were mild and transient. Conclusion: While electrolyte abnormalities associated with TLS are an expected side effect of venetoclax, isolated severe hypocalcemia is a rarely reported side effect. Calcium should be closely monitored during treatment. Presentation: 6/1/2024

A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children

Objective: To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis. Methods: Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups. Results: Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old (OR=0.54,95%CI 0.30-0.93), tumor lysis syndrome before chemotherapy (OR=0.48,95%CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy (OR=0.55,95%CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions: The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Effectiveness of fractionated rituximab in preventing tumor lysis syndrome in aggressive B-cell lymphoma: Insights from real-life clinical practice.

Tumor lysis syndrome (TLS) is a potentially life-threatening condition resulting from the rapid destruction of malignant cells, leading to electrolyte imbalances and severe complications, such as acute kidney injury, arrhythmias, and seizures. TLS can be managed through hyperhydration, urate-lowering treatments, and a steroid prophase strategy. This study aims to explore the impact of fractionated rituximab, an anti-CD20 antibody, on the occurrence and severity of TLS during the initial cycle in patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). Data was retrospectively collected from 94 of 186 patients. Among the 94 patients included in the analysis, the median age was 70. Histologies were diffuse large B-cell lymphoma (75%), Burkitt lymphoma (13%) and high-grade B-cell lymphoma (8%). The majority were at an advanced stage (93%) with a high IPI score (75%). Most patients received anthracycline-containing regimens (72%) and prophylactic allopurinol (83%) and/or rasburicase (26%). Steroid prophase was administered to 82% of patients. The study identified one clinical TLS case and six laboratory TLS cases. Significant TLS factors included BL histology, elevated baseline LDH (⟩500 U/l), and rasburicase usage. Infusion reactions were rare (3%). Median progression-free survival was 2.6 years, and 2-year overall survival was 33%, irrespective of TLS occurrence. In this real-life study, clinical TLS occurrence was low (1%). TLS appeared more frequent in BL but did not impact overall survival. Fractionated initial rituximab dosing in addition to preventive strategies is a feasible approach in preventing clinical TLS, warranting further prospective investigation.

Subphenotypes of Tumor Lysis Syndrome with AKI

Subphenotypes of Tumor Lysis Syndrome with AKI

Ifosfamide-Induced Encephalopathy in Relapsed Lymphoma: Report of Two Cases

Objective: Ifosfamide is a chemotherapeutic drug available for various malignancy, including lymphoma. Ifosfamide has adverse effects including myelosuppression, nephrotoxicity, hemorrhagic cystitis, and neurotoxicity. Encephalopathy is a severe manifestation of neurotoxicity due to ifosfamide, with an incidence of 10-40%. This study aimed to report two cases of ifosfamide-induced encephalopathy. Case: This case studies reported two relapsed lymphoma patients with almost similar characteristics who received ifosfamide chemotherapy. The first case of 48-year-old woman with relapsed High-Grade B-cell lymphoma stage IIIBE while the second case of 38-year-old woman with relapsed non-hodgkin lymphoma.Results: The first case showed a good outcome with improvement in consciousness 48 hours after stopping ifosfamide and thiamine, while the second case experienced tumor lysis syndrome, leading to the death of the patient.Conclusion: Mechanism of ifosfamide-induced encephalopathy remains unclear, with the hypothesis from the neurotoxic effects of the resultant metabolite chloracetyldehide. Radiology examination of the brain and electroencephalography is required to rule out other differential diagnoses. Early recognition of adverse effects, followed by immediate discontinuation of ifosfamide, administration of therapy, such as methylene blue and/or thiamine, and supportive treatment usually produced good outcomes.

Leukapheresis in Pediatric Acute Leukemia with Hyperleukocytosis: A Single Center Experience

Background: Hyperleukocytosis (HL) in pediatric acute leukemia is associated with increased morbidity and mortality. The indications for leukapheresis (LPH) in these patients remain unclear, and the use of LPH remains controversial. Objectives: This study aimed to review the clinical characteristics and outcomes of newly diagnosed leukemia patients with HL, comparing those who received LPH and those who did not. Methods: We analyzed clinical data from patients enrolled in frontline protocols for acute leukemia between 2017 and 2022. We documented adverse events within the first 30 days in patients with a white blood cell (WBC) count ≥ 100,000 cells/mm³ and reviewed their management. Treatment strategies included hyperhydration, administration of allopurinol or rasburicase, early induction chemotherapy (CT), and LPH. Results: Of 404 pediatric patients with newly diagnosed acute leukemia, 41 (10.1%) presented with HL (median WBC count: 136,000 cells/mm³; range HL: 101,000 - 844,000 cells/mm³). Leukapheresis was used in 9 of the 41 (13%) patients with HL. The median WBC count in patients who received LPH was 520,000 cells/mm³ compared to 158,800 cells/mm³ in those who did not (P = 0.01). Pulmonary leukostasis occurred in 2 patients, one of whom underwent LPH. No early deaths related to cerebral leukostasis, coagulopathy, or pulmonary leukostasis were observed in any patient within the first 30 days. The LPH procedure was well tolerated, with no reported complications. The time from presentation to the initiation of CT was similar between patients who received LPH and those who did not, with a mean of 17 hours versus 18 hours, respectively (P &gt; 0.05). Tumor lysis syndrome (clinical or laboratory) was observed in 2 patients (23%) with LPH and 2 patients (6.25%) without LPH. Conclusions: The early morbidity and mortality often associated with HL in children with newly diagnosed acute leukemia can be avoided through conservative management, potentially reducing the need for LPH. However, LPH is a safe and well-tolerated procedure at our institution. It may be considered for patients with leukostasis when early induction CT is not feasible.

Development and validation of a predictive model for tumor lysis syndrome in childhood acute lymphoblastic leukemia

BackgroundTumor lysis syndrome (TLS) frequently manifests shortly after induction chemotherapy for acute lymphoblastic leukemia (ALL), with the potential for swift progression. This study endeavored to develop a nomogram to predict the risk of TLS, utilizing clinical indicators present at the time of ALL diagnosis. MethodsWe retrospectively gathered data from 2243 patients with ALL, spanning December 2008 to December 2021, utilizing the clinical research big data platform of the National Center for Clinical Research on Children's Health and Diseases. The Least Absolute Shrinkage and Selection Operator (LASSO) method was employed to filter variables and identify predictors, followed by the application of multivariate logistic regression to construct the nomogram. ResultsThe LASSO regression identified six critical variables among ALL patients, upon which a nomogram was subsequently constructed. Multifactorial logistic regression revealed that an elevated white blood cell count (WBC), serum phosphorus <2.1 mmol/L, potassium <3.5 mmol/L, aspartate transaminase (AST) ≥50 U/L, uric acid (UA) ≥476μmol/L, and the presence of acute kidney injury (AKI) at the time of initial diagnosis were significant risk factors for the development of TLS in ALL patients (P<0.05). The predictive model achieved an area under the receiver operating characteristic curve (AUC) of 0.824 [95 % CI (0.783, 0.865)], with an internal validation AUC of 0.859 [95 % CI (0.806, 0.912)]. The Hosmer-Lemeshow goodness-of-fit test confirmed the model’s robustness (P=0.687 for the training cohort; P=0.888 for the validation cohort). Decision curve analysis (DCA) indicated that the predictive model provided substantial clinical benefit across threshold probabilities ranging from 10 % to 70 %. ConclusionsA nomogram incorporating six predictive variables holds significant potential for accurately forecasting TLS in pediatric patients with ALL.