ABSTRACT
Hyperleukocytosis in acute myeloid leukemia (AML) could cause life‐threatening complications, including leukostasis and tumor lysis syndrome (TLS). While leukocytapheresis and continuous renal replacement therapy (CRRT) are typically performed independently to maintain hemodynamic stability and manage anticoagulation, their simultaneous application is rarely reported. We report a case of a deteriorating patient with secondary AML treated with simultaneous leukocytapheresis and CRRT. For the CRRT circuit, two separate hemodialysis catheters were placed in the femoral vein (access) and internal jugular vein (return). The leukocytapheresis circuit was then connected to the CRRT return line. The procedure was completed without immediate bleeding or thrombotic complications. Reductions in white blood cell counts, ammonia, and lactic acid levels were observed, along with improved oxygenation. Simultaneous leukocytapheresis and CRRT can be a safe and effective modality for the urgent management of hyperleukocytosis and TLS in critically ill patients.
1. Introduction
Hyperleukocytosis in acute myeloid leukemia (AML) can lead to serious complications such as tumor lysis syndrome (TLS), disseminated intravascular coagulopathy (DIC), and leukostasis [1, 2]. Intervention treatments for these conditions include leukocytapheresis and continuous renal replacement therapy (CRRT) [3, 4, 5, 6]. Leukocytapheresis or CRRT are usually performed independently to ensure hemodynamic stabilization and optimize the amount of anticoagulant. Dual‐modality treatment using CRRT and therapeutic plasma exchange has previously been reported in several studies [7, 8]. However, leukocytapheresis combined with CRRT is rarely reported. Here, we report simultaneous CRRT and leukocytapheresis to treat a deteriorating patient with secondary AML evolved from chronic myelomonocytic leukemia (CMML). This case report was approved by the Institutional Review Board of Seoul St. Mary's Hospital, Korea (IRB No. KC25ZISI0614). Informed consent was waived as the study involved no more than minimal risk to the subject and the patient had passed away before the study's commencement.
2. Case Presentation
A 56‐year‐old male, who was previously diagnosed with CMML and undergoing routine follow‐up, was admitted to intensive care unit (ICU) via the emergency department for general weakness. Initial blood chemistry results were notable for marked elevations in serum creatinine (15.21 mg/dL), urea nitrogen (152.7 mg/dL), uric acid (37.8 mg/dL), potassium (5.9 mmol/L), phosphorus (10.5 mmol/L). The patient also exhibited a severely reduced estimated glomerular filteration rate (eGFR, 3 mL/min/1.73m2) and hypocalcemia (7.2 mmol/L). Total bilirubin was within reference range (0.67 mg/dL). Initial white blood cell (WBC) count, hemoglobin content, and platelet count was 119.07 × 109/L, 12.8 g/dL, and 71 × 109/L, respectively. Initial prothrombin time (PT), INR, activated partial thromboplastin time (aPTT) was 15.6 s, 1.41, and 37.4 s, respectively. Peripheral blood smear showed monocytosis (29%) with 1% blast. In addition, urine study demonstrated pyuria (WBC 10–19/high power field [HPF]), hematuria (RBC > 100/HPF), elevated urea nitrogen (924.1 mg/dL), uric acid (64.9 mg/dL), creatinine (74.24 mg/dL), and total protein (75.5 mg/dL) with protein‐creatinine ratio of 1.0170. The patient's urine output on the day of admission was 90 mL/day. Initial arterial blood gas analysis revealed a PaO2/FiO2 ratio of 109. Norepinephrine was titrated to 8 cc/h (mixed as 30 mg/500 mL in 5% dextrose water), maintaining a dose above the high‐dose threshold for the cardiovascular SOFA score. The patient's mental status was recorded as alert. The sequential organ failure assessment (SOFA) score was 12 at the time of admission. Abdomen and chest computed tomography demonstrated mild swelling of bilateral kidneys suggesting acute kidney injury (AKI) and bronchiolitis.
Under a presumed diagnosis of AKI caused by TLS due to CMML progression, CRRT was initiated from hospital day (HD) 1 to HD7 along with hydroxyurea from 2000 to 6000 mg/day according to WBC count and cytarabine 100 mg. Bronchiolitis was treated with antibiotics. The urine output trend showed a distinct transition from initial oligouria (90 mL/day) to a polyuric phase following the initiation of CRRT. From HD2, the urine output remained consistently high, ranging between 4000 and 7000 mL/day (Figure 1). Creatinine level steadily decreased and came within normal range (0.91 mg/dL) on HD12. On HD9, concurrent peripheral blood findings exhibited pancytopenia (WBC 2.8 × 109/L), hemoglobin 8.4 g/dL, and platelet 22 × 109/L with 11% monocytes without circulating blasts, which was consistent with the hypocellular bone marrow with 6% blasts identified on the bone marrow examination. WBC count continued to decline and reached a nadir of 0.85 × 109/L on HD12, and the patient was transferred to general ward on that day.
FIGURE 1.
Changes in SOFA scores, platelet, prothrombin time, WBC count, creatinine, urine output, bilirubin, PaO2/FiO2 ratio, ammonia, and lactic acid for the periprocedural period. CRRT, continuous renal replacement therapy; LP, leukocytapheresis; SOFA, sequential organ failure assessment; WBC, white blood cell.
However, WBC count and creatinine abruptly increased to 39.09 × 109/L and 1.12 mg/dL, respectively, on HD15. CRRT was reinitiated along with cytoreduction by hydroxyurea 2000 mg/day. Bronchiolitis progressed to bronchopneumonia on computed tomography, which was treated with anti‐microbials. As the clinical condition worsened, the patient was transferred back to ICU on HD18. WBC count escalated to 132.79 × 109/L on HD19. Creatinine level temporarily showed mild elevation (1.24 mg/dL, HD19), but returned to 0.97 mg/dL on HD20 and maintained level within normal range onwards due to ongoing CRRT support. The SOFA score surged from 11 (HD21) to 17 (HD22). On HD23, the patient manifested dyspnea due to suspected leukemic infiltration of the lung and persisting pneumonia. The patient's mental status deteriorated to a drowsy state, and mechanical ventilation was initiated. Urine output decreased from 2375 mL/day (HD22) to 1578 mL/day (HD23). Peripheral blood smear showed 61% leukemic cells (60% promonocytes, 1% blasts), and flow cytometry confirmed progression to AML with myelomonocytic differentiation (HD23). As leukocytosis above 100 × 109/L and the patient was unresponsive to chemotherapy, leukocytapheresis was performed on HD23.
For leukocytapheresis, Spectra Optia (Terumo BCT, Lakewood, CO, USA), with flow centrifugation device IDL set, was utilized via central venous access. The total processing blood volume was approximately 7000 mL, and the total depletion volume was approximately 750 mL. Packing factor was set to 4.5, and initial inlet velocity was set to 45 mL/min. Acid‐Citrate‐Dextrose Solution formula A (ACD‐A) was used as anticoagulant (AC) with AC to inlet ratio (AC:inlet) of 1:13. To avoid hypocalcemia, 1200 mg of 3% calcium gluconate added to 1000 mL normal saline was administered throughout the procedure.
On HD23, CRRT was discontinued during the first session of leukocytapheresis. After the first session, WBC count decreased from 280.32 × 109/L to 193.88 × 109/L. However, the patient showed severe lactic acidosis (13.72 mmol/L) and a sudden increase in ammonia level from 98mcg/dl to 254mcg/dl. Urea nitrogen increased to 24.6 mg/dL, while creatinine remained within normal range (0.89 mg/dL). CRRT discontinuation was unavailable due to the patient's condition, and leukocytapheresis was considered as a treatment option for the patient. After inter‐department consultations, simultaneous CRRT and leukocytapheresis was regarded as necessary to alleviate the leukemic burden and improve the patient's condition. On HD24, the second session of leukocytapheresis was combined with CRRT. CRRT (Prismaflex, Baxter, Deerfield, IL, USA) was performed in continuous venovenous hemodiafiltration (CVVHDF) mode with an ST150 filter set. The access and return line of leukocytapheresis was connected to the return line of CRRT (Figure 2). Leukocytapheresis flow rate was 45 mL/min, and CRRT flow rate was maintained at 150 mL/min. Extracorporeal volume (ECV) was 442 mL (189 mL, CRRT; 253 mL, Leukocytapheresis), which did not exceed 15% of the total blood volume. To optimize the dual procedure, the AC:inlet ratio was initially set at 1:13 and subsequently decreased to 1:15 once the interface was established.
FIGURE 2.
Dual‐modality circuit of leukocytapheresis and CRRT.
The patient's vital signs at each time point during the simultaneous procedure were as follows (blood pressure, heart rate, respiratory rate, body temperature): Initiation, 106/85 mmHg, 111 bpm, 24/min, and 36.1°C; Completion, 100/70 mmHg, 114 bpm, 26/min, and 36.2°C. Throughout the procedure, blood pressure, heart rate, and respiratory rate were maintained within the ranges of 91–106/58–85 mmHg, 111–115 bpm, and 24–28/min, respectively (Supporting Information Table S1). After the simultaneous therapy, WBC count decreased from 193.88 × 109/L to 79.26 × 109/L after the second session. The total reduction in WBC was 201.06 × 109/L (72%) after two consecutive sessions. On HD25, the WBC count further declined to 38.51 × 109/L. Ammonia level decreased from 254mcg/dL to 165mcg/dL, then returned to normal level in 2 days. Lactic acid decreased from 13.87 mmol/L to 4.60 mmol/L and steadily decreased afterwards. Further laboratory changes before and after simultaneous therapy are listed in Supporting Information Table S2. The patient's FiO2 decreased from 100% to 50% on the following day. Unfortunately, shortly after temporary improvement, the general condition of the patient once again deteriorated. The SOFA score remained constant at 17 from HD23 to HD 25, then steadily increased (Figure 1). Thrombocytopenia persisted, and total bilirubin surged to 10. In the total 59 mg/dL on HD27 and continued to rise (Figure 1). The patient expired on HD32; while multi‐organ failure was present, the terminal event was primarily driven by irreversible liver failure.
3. Discussion
The patient showed an increasing WBC count despite cytoreductive therapy, tumor lysis syndrome, and acute renal failure accompanied by lactic acidosis and increasing ammonia levels. The clinicians decided that leukocytapheresis‐CRRT dual‐application was needed for the patient's worsening condition. The patient was in a CRRT‐dependent state, and the stabilization of creatinine was a direct effect of the continuous dialysis. Given the rapid accumulation of lactic acid and ammonia, even a brief interruption of CRRT to perform leukocytapheresis would have posed a fatal risk.
Vascular access for CRRT was established using two separate sites: a hemodialysis catheter was inserted into the femoral vein for the access (arterial) line to blood outflow, while a second catheter was placed in the internal jugular vein for the return (venous) line. Vascular access was performed using sonography and challenges during line placement were not reported. We connected the access and return lines of leukocytapheresis to the return line of CRRT (Figure 2) to maintain blood flow and prevent hypotension.
Maintaining hemodynamic stability is a critical challenge during extracorporeal therapies, as intradialytic hypotension has been closely linked to increased mortality and adverse cardiovascular events [9]. Throughout the simultaneous procedure, the patient remained hemodynamically stable without any significant variations in vital signs or adverse events (Supporting Information Table S1). Although a transient decrease in blood pressure to 91/59 mmHg was observed at 12:00, it recovered spontaneously under close monitoring and stabilized around 100/70 mmHg, showing no further clinical deterioration throughout the procedure. In the present case, despite the complexity of simultaneous leukocytapheresis and CRRT, the patient's hemodynamic status remained stable without acute hypotensive episodes, which was essential for the successful completion of the simultaneous session.
Regarding procedure‐related complications, minor oozing at the catheter site and filter clotting occurred on the day prior to the simultaneous therapy. However, during the dual procedure itself, the circuit remained patent without any thrombotic events, bleeding, or filter clotting. While delayed filter clotting was noted on the subsequent day, no further bleeding or thrombotic complications were documented from 2 to 5 days post‐procedure (HD26 to HD29), demonstrating the short‐term safety of the simultaneous therapy. Frequent monitoring of coagulation profiles and platelet counts during this period showed no procedural exacerbation of the patient's baseline condition. Although the patient manifested worsening thrombocytopenia and the terminal decline in coagulation parameters, this was attributed to the irreversible progression of multiple organ failure.
The patient's urine output, which had dropped by 34% to 1548 mL prior to simultaneous therapy, remained constant during the dual procedure. This cessation of further decline, followed by a transient increase to 2160 mL post‐therapy, suggests that the simultaneous approach induced a brief clinical stasis in the patient's deteriorating course. This observation is further supported by the SOFA score, which remained unchanged at 17 until the following day. While this high score underscores the profound severity of the underlying secondary AML, the absence of an immediate post‐procedural increase suggests that the simultaneous leukocytapheresis and CRRT may have temporarily attenuated the rapid clinical deterioration by managing the acute metabolic and cellular burden. The subsequent rise in the SOFA score and the patient's death on HD32 were likely due to the inexorable progression of leukemia. These findings suggest that while simultaneous therapy may not reverse aggressive multi‐organ failure in AML, it can provide a temporary reduction in the acute physiological burden, potentially offering a window to stabilize the patient's condition for potential subsequent management.
4. Conclusion
The patient underwent simultaneous leukocytapheresis and CRRT without intra‐procedural complications. After the simultaneous therapy, the patient showed a significant decline in WBC count and a temporal improvement in metabolic parameters such as lactic acid and ammonia. Our case suggests that simultaneous leukocytapheresis and CRRT could be a safe and effective modality for patients with hyperleukocytosis and tumor lysis syndrome in the short‐term aspect.
Funding
The authors have nothing to report.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Table S1: Baseline vital signs and trends during simultaneous leukocytapheresis and CRRT.
Table S2: Details of simultaneous leukocytapheresis and CRRT.
Data Availability Statement
The data that supports the findings of this study are available in the Supporting Information of this article.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1: Baseline vital signs and trends during simultaneous leukocytapheresis and CRRT.
Table S2: Details of simultaneous leukocytapheresis and CRRT.
Data Availability Statement
The data that supports the findings of this study are available in the Supporting Information of this article.