Spontaneous Tumor Lysis Syndrome Research Articles

A phase 3b study of venetoclax and azacitidine or decitabine in an outpatient setting in patients with acute myeloid leukemia.

Venetoclax, a highly selective BCL-2 inhibitor, combined with hypomethylating agents (HMAs) azacitidine or decitabine, is approved for the treatment of newly diagnosed acute myeloid leukemia (ND AML) in patients who are ineligible to receive intensive chemotherapy. Previous clinical studies initiated venetoclax plus HMA in an inpatient setting owing to concerns of tumor lysis syndrome (TLS). This study (NCT03941964) evaluated the efficacy and safety of venetoclax plus HMA in a United States community-based outpatient setting in patients with ND AML (N=60) who were treatment naïve for AML, ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at screening, and were deemed as appropriate candidates for outpatient initiation of venetoclax plus HMA by the investigator. Patients received venetoclax in combination with azacitidine (75mg/m2) or decitabine (20mg/m2) for up to 6 cycles during the study. With a median time on study of 18.3weeks, the best response rate of composite complete remission was 66.7%, and the overall post-baseline red blood cell (RBC) and platelet transfusion independence rate was 55.0%, consistent with results of studies in which treatment was initiated in an inpatient setting. Key adverse events included nausea, anemia, thrombocytopenia, neutropenia, and white blood cell count decrease of any grade (≥50% of patients). The observed safety profile was generally consistent with that of venetoclax plus HMA observed in inpatient AML studies. With close monitoring, 2 cases of TLS were identified, appropriately managed, and the patients were able to continue study treatment. CLINICAL TRIALS REGISTRATION: This study is registered at ClinicalTrials.gov. The registration identification number is NCT03941964.

27 Spontaneous tumor lysis syndrome with hypercalcemia in a patient with HIV associated Burkitt’s lymphoma

27 Spontaneous tumor lysis syndrome with hypercalcemia in a patient with HIV associated Burkitt’s lymphoma

104 Spontaneous Tumor Lysis Syndrome caused by a Neuroendocrine Carcinoma

104 Spontaneous Tumor Lysis Syndrome caused by a Neuroendocrine Carcinoma

Spontaneous tumor lysis syndrome (STLS) during biopsy for burkitt lymphoma: a case report

BackgroundTumor lysis syndrome (TLS) is a hematologic oncological emergency characterized by metabolic and electrolyte imbalances. On breakdown of tumor cells, enormous amounts of potassium, phosphate, and nucleic acids are released into systemic circulation. TLS mainly occurs during chemotherapy. However, there are rare incidences of spontaneous tumor lysis syndrome (STLS) prior to commencement of therapy.Case presentationIn the case being reported, the child had just undergone a biopsy. As the incision was being closed, there was a sudden onset of high fever, arrhythmia, severe hyperkalemia, hypocalcemia, and acidosis. Following timely symptomatic treatment and continuous renal replacement therapy(CRRT), the child’s laboratory results improved, and organ function was restored to normal. The final pathological diagnosis confirmed Burkitt lymphoma. The boy is currently on maintenance chemotherapy.ConclusionsTLS is a potentially life-threatening complication in hematologic oncology. Several important conclusions can be drawn from this case, reminding clinicians to: (1) be fully aware of the risk factors of TLS and evaluate the level of risk; (2) pay attention to the possibility of STLS during operation, if surgical procedures are necessary and operate with minimal trauma and in the shortest time possibly; (3) take preoperative prophylaxis actively for high-risk TLS patients, including aggressive fluid management and rational use of diuretics and uric-acid-lowering drugs. In addition, this case confirms the effectiveness of CRRT for severe STLS.

Spontaneous Tumor Lysis Syndrome Secondary to Iatrogenic Acute Kidney Injury: A Case Report

Spontaneous Tumor Lysis Syndrome Secondary to Iatrogenic Acute Kidney Injury: A Case Report

Leukostasis Twist in Mantle Cell Lymphoma: Systematic Review and Case Report

Introduction: Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma. Patients often present with lymphadenopathy, early satiety, and B-symptoms. Despite up to 92% of MCL patients having peripheral blood involvement by flow cytometry, presentation with leukemic involvement and hyperleukocytosis are uncommon. Hyperleukocytosis, marked by a white blood count (WBC) >100 x 10 9/L, often leads to symptomatic leukostasis due to tissue hypoxia, generally found in acute leukemias. We conducted a systematic review of leukostasis in MCL, and present a case we encountered in our clinical practice of a non-nodal MCL variant showing leukostasis, spontaneous tumour lysis syndrome (TLS), and severe anemia to identify treatment strategies and outcomes. Methods: We searched PubMed for peer-reviewed articles and abstracts on “mantle cell lymphoma,” “hyperleukocytosis,” and “leukostasis.” All articles and abstracts that discuss hyperleukocytosis leading to leukostasis in MCL were included. Results: The search yielded eight results. After exclusions, five case reports and abstracts were included. These studies featured different MCL variants, presenting WBCs ranging from 121 to 1227 x 10 9/L, and various leukostasis symptoms. Leukapheresis was used in all five published cases, leading to lower WBCs and symptom improvement. Results are summarized in Table 1. Our patient was found to have the small lymphocyte variant of MCL, with WBC of 543.3 x 10 9/L on presentation. Our facility does not have leukapheresis capability. As a result, our initial treatment consisted of only supportive care and escalating doses of corticosteroids, with close monitoring for TLS. To our knowledge, this report is the first demonstration that IV methylprednisolone, without leukapheresis, is effective for acute management of leukostasis. Our patient's WBC reduced from 543.3 x 10 9/L to 230 x 10 9/L, leading to improved neurological function and oxygenation. Steroids were particularly useful in our patient with secondary, MCL-related warm autoimmune hemolytic anemia. Conclusion: This review highlights the importance of recognizing non-specific leukostasis symptoms, even in patients with mature B-cell lymphoproliferative disorders. Leukapheresis is effective in treating leukostasis in MCL patients. In hospitals without leukapheresis, escalating doses of IV methylprednisolone can be considered as a safe and effective strategy.

Comparing Cairo Bishop and Howard Criteria for Identifying Clinically Meaningful Tumor Lysis Syndrome Among Acute Myeloid Leukemia Patients Treated with Venetoclax and Hypomethylating Agents: A Single Center Experience

Introduction Venetoclax (ven) in combination with hypomethylating agents (HMA) is the standard of care for the treatment of acute myeloid leukemia (AML) in patients (pts) who are ineligible for intensive chemotherapy. The most serious complication of ven is tumor lysis syndrome (TLS). The phase 1b trial of ven and HMA in AML pts included strict prophylactic measures to prevent TLS. Reported rates of TLS in real world cohorts vary widely and prophylactic measures are not standardized. Methods Here we describe TLS prophylaxis (ppx) and incidence in a cohort of 100 consecutive pts age ≥18 years at the University of Pennsylvania who received inpatient or outpatient ven and HMA for up front treatment of AML between 1/2017-8/2022. TLS ppx was at the discretion of the treating team. TLS was retrospectively defined by Cairo Bishop and Howard Criteria (table 1). Howard TLS (H-TLS) criteria differs from Cairo Bishop TLS (CB-TLS) in that it requires two lab abnormalities be present in the same 24-hour period, uses calcium corrected for albumin and does not include ≥25% changes from baseline lab values. Results 92 pts had a white blood cell count (WBC) <25,000 cells/μL on the first day of treatment (table 1). 34 pts developed laboratory (lab) CB-TLS; 8 of these pts met criteria for clinical CB-TLS due to acute kidney injury (AKI). 13 pts developed CB-TLS prior to starting ven. While the original phase 1b trial mandated frequent lab monitoring as well as starting allopurinol ≥72 hours prior to ven and suggested a target of 2L of intravenous (IV) fluid per day starting the night prior to ven, TLS ppx was variable in our pts. 56 pts received allopurinol ≥72 hours prior to starting ven, 21 received ≥2L of IV fluid per day starting at least the day prior to ven, and 56 had TLS labs measured every 8-12 hours during the first 3 days following ven initiation. CB-TLS was associated with a higher ECOG score and baseline lactate dehydrogenase as well as FLT3 and NPM1 mutations. The CB-TLS group had a higher mean WBC count but there was no difference in the proportion of pts with WBC counts ≥25,000 cells/μL. There was a trend towards increased CB-TLS in pts with WBC counts ≥15,000 cells/μL; this reached statistical significance when comparing the percent of pts with non-spontaneous CB-TLS with WBC count ≥15,000 cells/μL to the rest of the cohort (33% vs 13%, p=0.034). To characterize TLS severity, we categorized the pts with CB-TLS into three groups: insignificant TLS, significant TLS, and those whose lab abnormalities were explained by a different pathology. We defined significant TLS as pts who required hospitalization (if started treatment outpatient) or ICU transfer, received rasburicase, developed AKI, or had treatment held due to TLS. 17 pts had insignificant TLS, 14 had significant TLS, and 3 were ultimately felt not to have TLS (table 2). We also compared pts who developed CB-TLS with those who met criteria for H-TLS. Of the 34 pts who met lab CB-TLS criteria, only 6 also met Howard criteria. All 6 of these pts had significant TLS. Of the 8 pts with significant TLS who only met Cairo Bishop criteria, 6 developed spontaneous TLS >3 days prior to starting treatment with ven that would have met H-TLS criteria at onset. Their lab abnormalities were not as severe by ≤3 days prior to ven start when the formal time frame for defining TLS begins. Discussion Other studies have shown lab TLS rates of 0-40% in AML pts receiving ven with HMA, with the majority reporting rates <10%. Our data show a higher rate of lab CB-TLS than other published cohorts. However, our data also show that most pts do not develop significant TLS despite less aggressive ppx than was used in the original ven trial and suggest that less aggressive ppx is appropriate for most pts. There was a high rate of spontaneous TLS in our cohort. Debate exists over the most appropriate WBC threshold for ven initiation; our data suggest an association of WBC count <15,000 cells/μL with lower TLS risk. Of the pts who developed significant TLS, a majority had spontaneous TLS; only 5 pts had significant TLS occur after starting ven. We also found that the Howard criteria for TLS better identify pts who will have adverse outcomes from TLS and may be a more clinically meaningful set of criteria to use in future studies.

S2336 A Rare Case of Spontaneous Tumor Lysis Syndrome in a Patient With Colorectal Cancer

S2336 A Rare Case of Spontaneous Tumor Lysis Syndrome in a Patient With Colorectal Cancer

Tumor lysis syndrome in premature infant prompting early resection of a large sacrococcygeal teratoma: a case report

BackgroundSacrococcygeal teratomas (SCTs) are the most common congenital neoplasm and often require resection soon after birth. There are rare reports of cardiac arrest during surgery due to manipulation of the tumor triggering secondary necrosis and hyperkalemia.Case presentationThis case describes a very preterm infant with a SCT who develops spontaneous preoperative tumor lysis syndrome (TLS). The medical team utilized rasburicase and the patient underwent total gross resection at 40 h of life.ConclusionsWe emphasize the importance of the early recognition and management of tumor lysis syndrome in SCT with rasburicase, aggressive management of hyperkalemia and consideration of early resection of SCTs even in the case of a very premature infant.

Spontaneous tumour lysis syndrome, malignant hypertension and hypercalcemia of malignancy at presentation in an infant with hepatoblastoma

Spontaneous tumour lysis syndrome, malignant hypertension and hypercalcemia of malignancy at presentation in an infant with hepatoblastoma

Spontaneous tumour lysis syndrome, malignant hypertension and hypercalcemia of malignancy at presentation in an infant with hepatoblastoma

Spontaneous tumour lysis syndrome, malignant hypertension and hypercalcemia of malignancy at presentation in an infant with hepatoblastoma

A Case of Spontaneous Tumor Lysis After Pathologic Femur Fracture in Squamous Cell Lung Cancer.

Tumor lysis syndrome (TLS) occurs when large numbers of tumor cells lyse and release their contents, causing electrolyte derangements and renal injury. It is an uncommon complication of solid tumors and occurs most commonly after cytotoxic therapy rather than spontaneously. In this article, we describe a case of spontaneous TLS in a patient with squamous cell carcinoma of the lung. We also present a literature review of spontaneous TLS occurrence in solid tumors.

Spontaneous Tumor Lysis Syndrome in an Undiagnosed Solid Organ Malignancy: Adenocarcinoma of the Colon

Spontaneous Tumor Lysis Syndrome in an Undiagnosed Solid Organ Malignancy: Adenocarcinoma of the Colon

A Rare Case of Spontaneous Tumor Lysis Syndrome As a Consequence of Forgone Treatment in Multiple Myeloma

Being diagnosed with cancer comes with numerous challenges and tumor lysis syndrome (TLS) is just one of many complications a cancer patient may be faced with while undergoing treatment. This is considered an oncologic emergency that occurs when large amounts of tumor cells rapidly break down and release phosphate, potassium, lactate dehydrogenase, and nucleic acids into the bloodstream. The majority of cases are associated with treatment in acute lymphoblastic leukemia and high-grade lymphoma, although it can occur in other instances of cancer with a large tumor burden, high proliferative rate, and even rarer, may occur spontaneously in the absence of those features. A 55-year-old male with a past medical history of COPD, coronary artery disease status post CABG, heart failure with reduced ejection fraction, type 2 diabetes mellitus, hypothyroidism, and multiple myeloma was transferred to our facility for further workup of acute encephalopathy and severe hypercalcemia. He was initially taken to an outside hospital by family members after they noticed he became disoriented and lethargic over the course of a couple of days. His family also noticed he was gradually becoming weaker and experienced a 30-pound unintentional weight loss over the course of the month and a half following his discharge from the hospital after undergoing CABG. Labs were drawn upon admission and were significant for a critical calcium level of 16.4 mg/dL, PTH 6.7 pg/mL, creatinine 2.49 mg/dL, and ammonia 105.0 uMOL/L. Myeloma labs showed M spike of 4.7 g/dL, IgA of 6147 mg/dL with Kappa light chains of 1086 mg/L with a ratio of 221. When asked about his multiple myeloma diagnosis and treatment he was unable to provide much information, but our local oncology team was able to contact his home oncologist who informed us he had been diagnosed 2 years prior to this admission. He underwent a bone marrow transplant but chose to forgo any further treatment and was not following up regularly with his oncologist. The hypercalcemia was attributed to his malignancy and treated on arrival to the hospital with IV fluids, zoledronic acid, and calcitonin with a favorable response. He was continued on calcitonin until resolution of severe, symptomatic hypercalcemia. A uric acid level ordered the following morning came back at a critical value of 16.2 mg/dL. At that time, he was diagnosed with spontaneous tumor lysis syndrome and was immediately treated with 6 mg rasburicase followed by daily 300 mg allopurinol. Chemotherapy was initiated while inpatient and he received two rounds of bortezomib/cyclophosphamide therapy prior to discharge. He remained hospitalized for nine days with significant clinical improvement and on the day of discharge labs showed a calcium level of 6.6 mg/dL, improvement in renal function with creatinine down to 2.09 mg/dL, and uric acid level 4.5 mg/dL. He was set up with close outpatient follow-up with his home oncologist and plans to continue this chemotherapy regimen. Although not uncommon, in more recent years there has been a trend downward in the incidence of tumor lysis syndrome thanks in part to better prevention methods and early recognition. For multiple myeloma specifically, the risk of tumor lysis syndrome is actually less than one percent and the risk of spontaneous TLS is likely even rarer. The actual incidence of developing spontaneous TLS, in general, is difficult to predict and in multiple myeloma other than a few case reports, it has not been widely documented. The goal of sharing this case is to contribute to the information already known about this condition and hopefully encourage others to share similar cases to improve recognition for earlier treatment and lower morbidity and mortality associated with spontaneous TLS in the future.

Feasibility and Safety of Outpatient Hypomethylating Agent (HMA) + Venetoclax (Ven) Initiation +/- Ramp-up for Patients (pts) with Newly-Diagnosed Acute Myeloid Leukemia (AML)

Background: The feasibility/safety of outpatient (outpt) HMA + Ven administration and use of Ven ramp-up to target dose during cycle 1 (C1) for patients (pts) with newly-diagnosed AML is limited to small, single-center analyses of heterogeneous populations. Furthermore, appropriate pt selection for varying approaches is not well-described. Understanding these issues is crucial to efficient and cost-effective care delivery, especially considering the unique challenges older pts face. In this multi-center analysis, we examined the feasibility and safety of frontline HMA + Ven administration in the outpt setting as well as omission of Ven ramp-up during C1. Methods: We conducted a multi-center, retrospective study through the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND), a collaboration involving 10 academic institutions. A total of 272 pts with AML treated with frontline HMA + Ven were evaluated; pts presenting in spontaneous tumor lysis syndrome (TLS) or with incomplete data were excluded (n=24). We described the baseline characteristics of the overall study population. Continuous variables were summarized as a median with interquartile range (IQR), and categorical variables were reported as a frequency (percentage). Fisher's exact test was used for nominal data and Wilcoxon rank-sum testing was used for continuous variables Results: A total of 64 pts (23.5%) initiated HMA + Ven as outpts. Median age was 76 (IQR: 64-81.25) years, and the majority were male (n=35, 54.7%), white (n=54, 84.4%) and had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (n=42, 73.7%). Cardiac comorbidities, prior stroke and diabetes were noted in 32.8%, 12.5% and 10.9% of outpts, respectively. Median total white blood cell count (WBC), marrow and peripheral blasts at presentation were 2.18 (IQR: 1.08-6.75), 38% (IQR: 20-53.5%) and 14% (IQR: 2-35.3%), respectively. Pre-treatment WBC, serum creatinine, uric acid and LDH were noted to be 2.45 (IQR: 1.48-3.98), 0.90 (IQR: 0.77-1.32), 5.05 (IQR: 4.18-5.9) and 212 (IQR: 171-314), respectively. All outpts had a pre-treatment WBC <20, uric acid <10 and creatinine <2; 8 pts (12.5%) had an LDH >500. Baseline characteristics are summarized in Table 1. When compared with pts receiving C1 of HMA + Ven as an inpt (n=208), outpts were found to have a lower presenting WBC (p=0.002), trend towards lower pre-treatment WBC (p=0.08) and a lower LDH (p=0.0002); pre-treatment uric acid was higher among outpts (p=0.027)(Table 1). There were no differences in disease with mutations with an influence on proliferative AML. Most outpts received allopurinol TLS prophylaxis (ppx); inpts more frequently had rasburicase ppx (13.1% vs. 3.4%, p=0.052). Most outpts received azacitidine (n=36, 56.3%) vs decitabine (5-day schedule)(n=28, 43.7%) with a similar distribution among inpts (p=0.25). Approximately half of outpts (51.6%) received anti-fungal ppx and required Ven dose reduction during C1. TLS was not observed in any outpts, compared with 10% in inpatients (p=0.0053) including 8% by Cairo-Bishop criteria (p=0.025). There was no difference in the median number of days admitted during the entirety of C1 between inpts and outpts (8 vs 5, p=0.16); 11% of outpts were eventually admitted during C1. Although treatment-related mortality (TRM = up to 90 days from start of C1) was higher among inpts, this was not statistically significant (12.8% vs 1.6%, p=0.20)(Table 1). Among outpts, approximately 1/3 had no Ven ramp-up (n=20, 31.3%). When compared with outpts with Ven ramp-up (n=44, 68.7%), there were no differences observed in age, ECOG PS, comorbidities, molecular characteristics, presenting or pre-C1 WBC, marrow/blood blasts, serum creatinine, uric acid, LDH, TLS ppx patterns or Ven dose-reduction for antifungal ppx (Table 2). More outpts without Ven ramp-up received decitabine (75% vs 35.9%, p=0.006). Median number of days admitted was higher among outpts with Ven ramp-up (5 vs 0, p=0.039) with one TRM attributed to infection in this group (p=0.99) Conclusions: Our study demonstrates that many pts with newly-diagnosed AML can safely receive C1 of HMA + Ven as an outpt, particularly those with a pre-treatment WBC <20, uric acid <10 and creatinine <2. We observed no TLS among outpts, including those without Ven ramp-up, which may be safely omitted in select pts. Prospective studies are needed to confirm these findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

SYSTEMIC LUPUS ERYTHEMATOSUS MIMICKING A HEMATOLOGIC MALIGNANCY IN AN AFRICAN AMERICAN 12-YEAR-OLD MALE

<h3>Introduction</h3> A previously healthy 12-year-old African American male, who was found to have pancytopenia and electrolyte imbalance in the emergency department (ED), was subsequently diagnosed with systemic lupus erythematosus (SLE) complicated by lupus nephritis. <h3>Case Description</h3> A previously healthy 12-year-old boy presented to the ED with a 3-week history of worsening fatigue, headaches, and dizziness. He also had tactile fever and significant unintentional weight loss compared to one year prior. He had a benign physical examination and vital signs, except for pallor. There was no history of arthralgias, muco-cutaneous lesions, and neuro-psychiatric symptoms. Initial blood work revealed pancytopenia with low reticulocyte count requiring transfusion of platelets and red blood cells. Coombs test was negative, total bilirubin and LDH were normal, ruling out autoimmune hemolytic anemia. There was hyperuricemia, hyperkalemia, hypocalcemia, and hyperphosphatemia, elevated creatinine, proteinuria and hematuria suggesting kidney injury. Initially, a hematologic malignancy with spontaneous tumor lysis syndrome was suspected, and bone marrow biopsy was performed. Bone marrow was hypoplastic, flow cytometry ruled out malignancy. Immunological work-up confirmed the diagnosis of SLE with low C3 and C4 levels, and highly positive ANA, anti-dsDNA, anti-Smith, anti-SS-A, anti-SS-B. Anti-phospholipid antibodies were negative. The patient responded favorably to high-dose methylprednisolone followed by maintenance treatment with oral prednisone and mycophenolate mofetil. <h3>Discussion</h3> Aplastic anemia is a rare initial presentation of pediatric SLE, its exact pathogenic mechanism remains unknown. The diagnosis of SLE should be suspected in cases of aplastic anemia with no alternative explanation. Early diagnosis and treatment can prevent life-threatening complications.

MDS-065 Fatalities from Tumor Lysis Syndrome (TLS) After Anti-Hyperuricemic Monotherapy – Nationally Representative, Propensity Score Matched, Retrospective Study Comparison of Rasburicase and Allopurinol

This is the first US-representative, retrospective, real-world propensity score (PS) matching study comparing the occurrence of TLS-associated fatalities following allopurinol monotherapy versus rasburicase monotherapy. We have previously found rasburicase significantly and more rapidly reduces uric acid exposure (AUC) compared to allopurinol in patients with or at risk of TLS (Goldman/Cairo et al., Blood, 2001). To determine if a significant difference exists in the proportion of TLS-associated fatalities following treatment with allopurinol or rasburicase monotherapy for having or being at risk of TLS. 282 rasburicase and allopurinol patients were PS-matched for TLS risk using eleven predictive covariates. Patients were matched 1:1 using calipers of width equal to 0.2 of the standard deviation of the logit of the PS (d score). The overall PS logit was almost 0.6 before matching but near 0.0 afterward; covariates exhibited only a small imbalance (|d|<0 .25), indicating patients were well matched. Anonymized patient information from our 2021 physician-based, blinded, retrospective study, provided by 266 oncologists from US physician-owned practices, academic and non-academic hospitals, and outpatient clinics. Fielded June-September, the 2021 study included 715 randomized liquid-tumor patients treated in the past year for hyperuricemia (HU) risk and TLS potential. The 2022 PSM analysis included only those receiving rasburicase or allopurinol monotherapy and excluded patients with spontaneous TLS or TLS before HU treatment, leaving 533 potential subjects. 282 were matched on PS and eleven pre-HU treatment covariates: acute renal failure, age, anti-cancer regimen, creatinine, gender, lactate dehydrogenase, perceived risk, renal disease, tumor type, uric acid, and white blood count. Unmatched cases were discarded. Proportions of mortalities that physicians said were the direct result of TLS. The null hypothesis before matching was no significant difference between the groups. Analyzing all matched patients (n=141 in each group), regardless of TLS development following HU treatment, TLS-associated mortality was significantly less likely among rasburicase patients (2.1% vs. 7.1% [P-value 0.047]). Analyzing the subset who developed TLS after HU treatment, TLS-associated fatalities were even less likely among rasburicase patients, 3 of 36 rasburicase vs. 10 of 27 allopurinol patients [P-value 0.005]. Results indicate rasburicase compared to allopurinol significantly reduces TLS-associated fatalities.

Spontaneous tumor lysis syndrome in hyperaggressive mantle cell lymphoma.

An otherwise well 61-year-old male presented to his primary care practitioner with drenching sweats, weight loss, massive splenomegaly (30 cm as measured by computed tomography [CT], Figure 1A) and a lymphocytosis (white blood cell [WBC] at diagnosis 150 × 109/L). The peripheral smear was notable for the presence of pleomorphic abnormal lymphocytes, with clumped chromatin, high nuclear:cytoplasm ratio and irregular nuclei (Figure 1B). Peripheral blood flow cytometry revealed a kappa light chain restricted population of mature B-cells which co-expressed CD20 and CD5 (Figure 1C). CD23 and CD10 were negative. Fluorescent in situ hybridization revealed a CCND1/IGH rearrangement, consistent with a diagnosis of advanced stage mantle cell lymphoma (MCL). Approximately 3 weeks after diagnosis, he was admitted electively for chemotherapy. On admission to the unit he was well, with normal vital signs and a normal baseline tumor lysis profile (K, Phos, Ca, urate and creatinine all within institution limits). His WBC was noted to have increased modestly to 264 × 109/L. Unfortunately, over the course of the next 12 h, prior to the administration of any systemic anti–cancer therapy (including steroids), he developed spontaneous tumor lysis syndrome and died of catastrophic metabolic derangement, despite aggressive supportive care. He developed severe, refractory hyperkalemia (7.5 mmol/L), severe hyperphosphatemia (3.83 mmol/L) and profound metabolic acidosis (pH <6.9, HCO3– 3 mmol/L, lactate 17 mmol/L). His WBC had also climbed explosively to 695 × 109/L (Figure 1D), putting him at significant risk of leukostasis. I postulate that, via clonal evolution, his disease acquired a hyperproliferative phenotype, resulting in fulminant, spontaneous tumor lysis syndrome. There are limited reports of secondary translocations involving the MYC proto-oncogene in patients with MCL. This is associated with aggressive clinical course and short overall survival; however there are no reports of MCL behaving this aggressively in the literature. Practitioners should be aware of this rare but potentially devastating complication of MCL. James Wilson wrote the manuscript and took pictures. The author declares they have no conflicts of interest. The author received no specific funding for this work. No research on human was performed on this study. Data sharing not applicable—no new data generated.

Spontaneous tumor lysis syndrome in a patient with accelerated phase chronic myeloid leukemia treated successfully with rasburicase

Rationale: Tumor lysis syndrome (TLS) is an oncological emergency that occurs due to diffuse tumor cell destruction with the massive release of intracellular electrolytes. Spontaneous tumor lysis syndrome (STLS) is the development of TLS before the commencement of chemotherapy. To the best of our knowledge, there are no reported cases of STLS in the chronic or accelerated phase of chronic myeloid leukemia (CML). Patient concerns: A 37-year-old woman of Arabic descent with a history of CML presented with a 3-day history of nausea and abdominal pain. She had not started any new treatment for CML within the last 3 months of presentation. Diagnosis: The patient was diagnosed with hyperuricemia, hyperphosphatemia, hypocalcemia, and acute kidney injury. A peripheral blood smear confirmed the accelerated CML phase. Our patient met the criteria for clinical TLS, specifically, STLS. She was also diagnosed with autoimmune hemolytic anemia. Interventions: The patient was started on intravenous normal saline (200 mL/h) and rasburicase (6 mg/d). In addition, hydroxyurea was used as a cytoreductive agent. Outcomes: The creatinine level returned to normal within 48 hours of rasburicase initiation. Lessons: Any patient with hematological malignancy should be monitored for TLS even before the initiation of chemotherapy. The exact mechanism of spontaneous TLS remains unknown, and further studies are needed to explain the pathophysiology of this condition. Rapid initiation of rasburicase, in addition to vigorous hydration, is effective in the treatment of acute kidney injury associated with TLS.

Pediatric Multicentric Castleman Disease Presented with Spontaneous Tumor Lysis Syndrome and Acute Kidney Injury

Castleman disease (CD) is a rare lymphoproliferative disorder that is uncommon in the pediatric population. Tumor lysis syndrome (TLS) is a rare presentation in CD even after chemotherapy. There is only one case report for pediatric patients with CD where treatment was complicated by TLS. In this case, we report spontaneous TLS and acute kidney injury in a pediatric patient with idiopathic multicentric Castleman disease. Here, we present the case of a 14 year old male with no significant past medical history presented with TLS and AKI (Acute kidney injury). He was found to have idiopathic multicentric CD (iMCD) based on lymph node biopsy. The child was started on Siltuximab and high systemic steroid therapy with significant improvement. A short term continuous renal replacement therapy was required for fluid overload. The patient was discharged home within a month with normal renal function on maintenance therapy. Spontaneous TLS is a rare but significant complication that should be considered in adults and pediatric patients with MCD. Careful monitoring and immediate intervention with supportive care are essential even before the initiation of therapy.