Case report: a critically ill patient with aggressive NK-cell leukemia receiving emergency chemotherapy in the ICU

Case report: a critically ill patient with aggressive NK-cell leukemia receiving emergency chemotherapy in the ICU | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Case report: a critically ill patient with aggressive NK-cell leukemia receiving emergency chemotherapy in the ICU Yuqing Zeng, Yuanyuan Yang, Jian Huang, Haitao Liu, Xiuwen Lan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6129223/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Jun, 2025 Read the published version in Virology Journal → Version 1 posted 8 You are reading this latest preprint version Abstract Aggressive NK-cell leukemia (ANKL) is a scarce mature NK-cell neoplasm frequently associated with Epstein-Barr virus (EBV) infection. We report the case of a 47-year-old male patient who was admitted to the hospital due to recurrent fever, jaundice, and dyspnea, and was diagnosed with ANKL accompanied by multi-organ failure. Upon transfer to the intensive care unit (ICU), he received emergency chemotherapy consisting of etoposide, pegaspargase, and gemcitabine, in conjunction with organ support therapies including DPMAS, LPE, and CVVHD. Subsequently, the patient's condition stabilized, and he was discharged. However, following the second cycle of chemotherapy, he was readmitted due to altered mental status. Due to financial constraints, the family decided not to pursue further treatment, leading to the patient's eventual demise. Overall, this case highlights the critical importance of multidisciplinary collaboration for managing critically ill ANKL patients. Careful evaluation of the risks associated with chemotherapy, combined with timely administration of emergency chemotherapy in the ICU and comprehensive multi-organ support, can potentially offer a survival opportunity. Aggressive NK-cell Leukemia (ANKL) Lymphoma/Leukemia Emergency Chemotherapy ICU Figures Figure 1 Figure 2 Introduction Aggressive Natural Killer Cell Leukemia (ANKL) is a rare and highly aggressive neoplastic disorder of mature NK cells, with rapid progression and a poor prognosis [ 1 ] . Over the past few years, advancements in medical research have enhanced our understanding and expanded therapeutic options for ANKL. Previous literature has predominantly concentrated on the management of ANKL patients in hematology departments. This report details a case of critically ill ANKL managed with artificial liver support and emergency chemotherapy in the Intensive Care Unit (ICU). This approach underscores the potential advantages for ANKL patients with multi-organ dysfunction, providing new perspectives into the comprehensive management of such cases. Case Presentation A 47-year-old male patient was admitted to our hospital on July 4, 2024. He had been experiencing recurrent fever (Max Temp ≥ 38.5°C) and jaundice for over half a month, followed by tonsillar enlargement and chest tightness. His dyspnea worsened three days prior to admission. Over the past two months, he had experienced a weight loss of 5 kg. Previously, he had visited another hospital where leukocytosis (with a WBC count of 36.3×10⁹/L) was detected, and a bone marrow biopsy indicated lymphoma. Further tests at our hospital, including examinations of the bone marrow structure and cell flow analysis (Fig. 1 ), confirmed the diagnosis of aggressive NK cell lymphoma/leukemia (stage IV). Upon admission, the patient's condition deteriorated rapidly, manifesting multiple organ failures (respiratory, hepatic, renal, and cardiac systems) and the onset of hemophagocytic lymphohistiocytosis (HLH), as defined by the HLH-2004 diagnostic criteria [ 2 ] . Given the severity of his condition, he was transferred to the ICU. He received dual plasma molecular adsorption system (DPMAS) combined with low-volume plasma exchange (LPE), continuous renal replacement therapy (CRRT), mechanical ventilation, and symptomatic treatment. Concurrently, he underwent chemotherapy with a regimen of etoposide, pegaspargase, and gemcitabine. Despite the challenges, the treatment process was relatively smooth. Following three sessions of artificial liver support and six days of continuous renal replacement therapy (DPMAS + LPE + CVVHD), the patient exhibited significant improvements in white blood cell count, as well as hepatic and renal function markers (Fig. 2 ). Additionally, respiratory and circulatory functions were stabilized. He was ultimately discharged from the hospital. During the chemotherapy intermission, the patient's symptoms improved, and his routine blood tests and biochemical indicators remained stable. He was readmitted on July 29, 2024, for the initiation of a second cycle of chemotherapy using the L-GEMOX regimen, which comprises pegaspargase, gemcitabine, and oxaliplatin. On August 23, 2024, the patient was readmitted owing to altered mental status. After three days of symptomatic treatment, his family opted to discontinue chemotherapy and organ support because of financial constraints. Regrettably, the patient passed away on August 27, 2024. Upon admission to our hospital, laboratory tests disclosed the following results: The glucose (Glu) was 1.7 mmol/L, the triglyceride (TG) was 3.93 mmol/L, the fibrinogen (Fbg) was 1.25 g/L, the lactate (Lac) was > 15 mmol/L, the procalcitonin (PCT) was 4.26 ng/mL, the interleukin-6 (IL-6) was 20.55 pg/mL, the interleukin-10 (IL-10) was 14.20 pg/mL, the ferritin (FERR) was 1,969.00 ng/mL, the soluble CD25 (sCD25) was 87,104 pg/mL, the natural killer (NK) lymphocyte subset (CD3⁻CD16⁺CD56⁺) was 97.12%, and the NK cell activity was 17.16%. The copy number of Epstein-Barr virus (EBV) DNA was measured at 1.04×10 5 IU/mL. For detailed results, see Table 1 . Table 1 Laboratory Test Results Upon Admission MV : mechanical ventilation; DPMAS : dual plasma molecular adsorption system; LPE : Low-volume plasma exchange; CVVHD : continuous venous-venous hemodialysis. Discussion ANKL was initially described in the 1980s. In 2016, the World Health Organization classified it as a subtype of mature NK cell neoplasms, which also includes extranodal NK-/T-cell lymphoma, nasal type (ENKTL-N), and chronic lymphoproliferative disorder of NK cells (NK-CLPD) [ 3 ] . ANKL has a higher prevalence in Asia, predominantly affecting young to middle-aged adults (aged 30–40 years), and is strongly associated with EBV infection [ 4 , 5 ] . It typically manifests as a systemic disease involving multiple organ systems, characterized by fever, weight loss, hepatosplenomegaly, pancytopenia, and abnormal liver function. The clinical course is frequently fulminant, rapidly progressing to disseminated intravascular coagulation (DIC) and HLH, resulting in multi-organ failure [ 6 ] . The prognosis is extremely poor, with most patients succumbing within days to weeks after onset, and a median survival time of only 2 months [ 7 , 8 ] . Currently, there is no standardized treatment protocol for ANKL. Studies have demonstrated that NK tumor cells can express P-glycoprotein, which expels anthracycline drugs from the cells, thereby reducing intracellular drug concentrations and leading to drug resistance [ 9 ] . As a result, traditional CHOP and CHOP-like regimens demonstrate limited efficacy in the treatment of ANKL [ 10 ] . In contrast, L-asparaginase (L-ASP) is not influenced by P-glycoprotein and has the ability to induce apoptosis in NK cell tumors. Therefore, treatment regimens that incorporate L-ASP may enhance patient outcomes [ 11 ] . The currently used regimens are as follows [ 12 , 13 ] : SMILE regimen : Dexamethasone, Methotrexate, Ifosfamide, L-Asparaginase, and Etoposide. VIDL regimen : Etoposide, Ifosfamide, Dexamethasone, and L-Asparaginase. AspMetDex regimen : L-Asparaginase, Methotrexate, and Dexamethasone. Pegaspargase in conjunction with GDP regimen : Gemcitabine, Cisplatin, and Dexamethasone. Pegaspargase in conjunction with GEMOX regimen : Gemcitabine and Oxaliplatin. For patients diagnosed with HLH, the HLH-1994 protocol may be employed as an initial therapeutic approach prior to chemotherapy [ 14 ] . Furthermore, the combination of L-ASP and Hematopoietic Stem Cell Transplantation (HSCT) represents a promising curative strategy for these patients [ 15 , 16 ] . In the case of this critically ill patient, upon transfer to the ICU, we initiated artificial liver support therapy to detoxify the body, stabilize the internal environment, and preserve organ function. Meanwhile, in collaboration with hematologists, we have developed an emergency chemotherapy regimen for ANKL complicated by HLH. The patient exhibited promising therapeutic responses after completing two cycles of chemotherapy. Unfortunately, during the final hospitalization triggered by altered mental status, the family declined further active medical interventions, and as a result, lumbar puncture and head imaging were not conducted. This precluded us from effectively distinguishing between neuroinflammation associated with HLH and leukemic infiltration. Additionally, hepatic encephalopathy and sepsis-associated encephalopathy remain plausible contributors to the neurological symptoms and cannot be conclusively ruled out. Research demonstrates that emergency chemotherapy in the ICU is primarily indicated for patients diagnosed with acute leukemia or aggressive lymphoma, who may present with critical conditions such as leukostasis, DIC, HLH, and tumor lysis syndrome [ 17 – 19 ] . Historically, emergency chemotherapy in critically ill patients has been regarded as ineffective and associated with prolonged ICU stays and increased mortality rates. However, contemporary evidence suggests that elevated mortality rates are primarily observed in patients with solid tumors, whereas emergency chemotherapy does not significantly influence mortality in patients with hematologic malignancies [ 20 ] . Indeed, long-term outcomes for the latter group are promising, with a reported 12-month survival rate of 30%, and 70% achieving complete remission [ 19 , 21 ] . It is undeniable that emergency chemotherapy possesses both beneficial and adverse effects. On the one hand, it can mitigate life-threatening complications associated with cancer and thereby reduce mortality. On the other hand, side effects such as bone marrow suppression and pulmonary toxicity may exacerbate organ dysfunction and contribute to increased mortality [ 20 ] . Nevertheless, for critically ill patients, emergency chemotherapy serves as a potentially life-saving last-resort intervention, providing a glimmer of hope to both patients and their families. Therefore, providing cancer treatment in the ICU is not only feasible but may be essential for patients experiencing severe exacerbation of hematologic disorders ICU physicians play a pivotal role in identifying patients who stand to benefit from emergency chemotherapy. Through close collaboration with a multidisciplinary expert team, individualized treatment plans have been developed for these patients. This approach may serve as a vital bridge, facilitating their progression toward recovery. Abbreviations ANKL Aggressive natural killer cell leukemia ICU Intensive care unit HLH Hemophagocytic lymphohistiocytosis DPMAS Dual plasma molecular adsorption system CRRT Continuous renal replacement therapy LPE Low-volume plasma exchange Glu Glucose TG Triglyceride Fbg Fibrinogen Lac Lactate PCT Procalcitonin IL-6 Interleukin-6 IL-10 Interleukin-10 FERR Ferritin sCD25 Soluble CD25 EBV Epstein-Barr virus MV Mechanical ventilation ENKTL-N Extranodal NK-/T-cell lymphoma, nasal type NK-CLPD Chronic lymphoproliferative disorder of NK cells DIC Disseminated intravascular coagulation L-ASP L-asparaginase HSCT Hematopoietic Stem Cell Transplantation Declarations Ethics approval and consent to participate The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Clinical Research Ethics Committee of The Affiliated Tumor Hospital of Harbin Medical University (Harbin, People’s Republic of China). All methods were performed according to the relevant guidelines and regulations. Consent for publication Informed consent for this was obtained from the patient’s legal guardian(s). Competing interests The authors declare that they have no competing interests. Funding This study was supported in part by grants from the Hai Yan Scientific Research Fund of Harbin Medical University Cancer Hospital (JJMS 2023-10). Author Contribution Y.Z. and Y.Y. were responsible for collecting the clinical information and drafting the manuscript. J.H. and H.L. provided support in the analysis and interpretation of the data. X.L. and L.Q. reviewed and edited the manuscript. All authors read and approved the final manuscript. Acknowledgements Not applicable. Availability of data and materials All data analysed during this study are included in this published article. References Sumbly V, Vest M, Landry I: Aggressive Natural Killer Cell Leukemia: A Brief Overview of Its Genomic Landscape, Histological Features, and Current Management. Cureus 2022, 14(2):e22537. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J et al : HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007, 48(2):124-131. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD et al : The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016, 127(20):2375-2390. Kwong YL, Anderson BO, Advani R, Kim WS, Levine AM, Lim ST: Management of T-cell and natural-killer-cell neoplasms in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol 2009, 10(11):1093-1101. Lima M: Aggressive mature natural killer cell neoplasms: from epidemiology to diagnosis. Orphanet J Rare Dis 2013, 8:95. Hoffmann JC, Maeda LS, Ohgami RS: Indolent and Aggressive Mature T-Cell and Natural Killer–Cell Lymphomas - ScienceDirect. Atlas of Diagnostic Hematology 2021:251-273. Suzuki R, Suzumiya J, Yamaguchi M, Nakamura S, Kameoka J, Kojima H, Abe M, Kinoshita T, Yoshino T, Iwatsuki K et al : Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type. Ann Oncol 2010, 21(5):1032-1040. Tang YT, Wang D, Luo H, Xiao M, Zhou HS, Liu D, Ling SP, Wang N, Hu XL, Luo Y et al : Aggressive NK-cell leukemia: clinical subtypes, molecular features, and treatment outcomes. Blood Cancer J 2017, 7(12):660. Egashira M, Kawamata N, Sugimoto K, Kaneko T, Oshimi K: P-glycoprotein expression on normal and abnormally expanded natural killer cells and inhibition of P-glycoprotein function by cyclosporin A and its analogue, PSC833. Blood 1999, 93(2):599-606. Tse E, Kwong YL: The diagnosis and management of NK/T-cell lymphomas. J Hematol Oncol 2017, 10(1):85. Ando M, Sugimoto K, Kitoh T, Sasaki M, Mukai K, Ando J, Egashira M, Schuster SM, Oshimi K: Selective apoptosis of natural killer-cell tumours by l-asparaginase. Br J Haematol 2005, 130(6):860-868. Zhang Y, Lee D, Gesiotto Q, Sokol L: Aggressive natural killer cell leukemia: diagnosis, treatment recommendations, and emerging therapies. Expert Rev Hematol 2021, 14(8):731-740. Ishida F: Aggressive NK-Cell Leukemia. Front Pediatr 2018, 6:292. Wu J, Lu AD, Zhang LP, Zuo YX, Jia YP: [Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia]. Zhonghua Xue Ye Xue Za Zhi 2019, 40(1):52-57. Ishida F, Ko YH, Kim WS, Suzumiya J, Isobe Y, Oshimi K, Nakamura S, Suzuki R: Aggressive natural killer cell leukemia: therapeutic potential of L-asparaginase and allogeneic hematopoietic stem cell transplantation. Cancer Sci 2012, 103(6):1079-1083. Jung KS, Cho SH, Kim SJ, Ko YH, Kang ES, Kim WS: L-asparaginase-based regimens followed by allogeneic hematopoietic stem cell transplantation improve outcomes in aggressive natural killer cell leukemia. J Hematol Oncol 2016, 9:41. Pastores SM, Goldman DA, Shaz DJ, Kostelecky N, Daley RJ, Peterson TJ, Tan KS, Halpern NA: Characteristics and outcomes of patients with hematologic malignancies receiving chemotherapy in the intensive care unit. Cancer 2018, 124(14):3025-3036. Moors I, Pène F, Lengline É, Benoit D: Urgent chemotherapy in hematological patients in the ICU. Curr Opin Crit Care 2015, 21(6):559-568. Lafarge A, Chean D, Whiting L, Clere-Jehl R: Management of hematological patients requiring emergency chemotherapy in the intensive care unit. Intensive Care Med 2024, 50(6):849-860. de Oliveira MCF, Ferreira JC, Nassar Junior AP, Dettino ALA, Caruso P: Impact of Urgent Chemotherapy in Critically Ill Patients. J Intensive Care Med 2020, 35(4):347-353. Wohlfarth P, Staudinger T, Sperr WR, Bojic A, Robak O, Hermann A, Laczika K, Carlström A, Riss K, Rabitsch W et al : Prognostic factors, long-term survival, and outcome of cancer patients receiving chemotherapy in the intensive care unit. Ann Hematol 2014, 93(10):1629-1636. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Jun, 2025 Read the published version in Virology Journal → Version 1 posted Editorial decision: Revision requested 07 May, 2025 Reviews received at journal 07 May, 2025 Reviewers agreed at journal 27 Apr, 2025 Reviewers agreed at journal 27 Apr, 2025 Reviewers agreed at journal 25 Apr, 2025 Reviewers invited by journal 22 Apr, 2025 Submission checks completed at journal 21 Apr, 2025 First submitted to journal 20 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6129223","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":446538957,"identity":"17c4abb5-ab30-4b54-9515-cc1ac0c1fd5d","order_by":0,"name":"Yuqing Zeng","email":"","orcid":"","institution":"Harbin Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuqing","middleName":"","lastName":"Zeng","suffix":""},{"id":446538958,"identity":"5407f447-cac6-4bf5-bf09-11f86b0a48db","order_by":1,"name":"Yuanyuan Yang","email":"","orcid":"","institution":"Harbin Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuanyuan","middleName":"","lastName":"Yang","suffix":""},{"id":446538959,"identity":"dc6e25ee-c643-4149-a9ce-448e1f89faca","order_by":2,"name":"Jian Huang","email":"","orcid":"","institution":"Harbin Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Huang","suffix":""},{"id":446538960,"identity":"b0038db7-2309-4c75-a3fc-6703c022d01c","order_by":3,"name":"Haitao Liu","email":"","orcid":"","institution":"Harbin Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Haitao","middleName":"","lastName":"Liu","suffix":""},{"id":446538961,"identity":"4f016546-85c5-4100-9f9e-31e4a8426d1f","order_by":4,"name":"Xiuwen Lan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYBACfmbGxsc/ftgkMEiA+cyEtUi2NzcbM/akkaDFoOd4mzQD22FStEgkNhsX8JzPM5/dnSbBUGGd2MB+9gBeLeYSiY2PZ1jcLpa5c3abBMOZ9MQGnrwEvFosZyQ2G/Dw3E6cIZG7TYKx7XBigwSPAX6H3Uhsk+BhOwfV8o8YLWcOtknzsB2AamkgQotke2Oz4cye5MQZMmc3WyQcSzdu48nBr4Wfmf3hgw8/7BJnSPduvPGhxlq2n/0Mfi2oIAGI2UhQPwpGwSgYBaMABwAAF2dIXJqK5vMAAAAASUVORK5CYII=","orcid":"","institution":"Harbin Medical University Cancer Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xiuwen","middleName":"","lastName":"Lan","suffix":""},{"id":446538962,"identity":"59a9efdc-f3ec-4239-9e03-3ce7290d46f5","order_by":5,"name":"Lina Quan","email":"","orcid":"","institution":"Harbin Medical University Cancer Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lina","middleName":"","lastName":"Quan","suffix":""}],"badges":[],"createdAt":"2025-02-28 14:08:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6129223/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6129223/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12985-025-02798-4","type":"published","date":"2025-06-12T15:57:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82050869,"identity":"d026632f-fcea-4c3e-8cd4-2ce6bf449253","added_by":"auto","created_at":"2025-05-06 09:58:56","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1594466,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMorphology and Flow Cytometry Analysis of Patient's Bone Marrow Cells\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA. Morphological Report of Bone Marrow Cells (Wright-Giemsa stain, 100×) \u003c/strong\u003eThe bone marrow exhibits markedly active proliferation, with abnormal lymphocytes constituting 41% of nucleated cells. These cells show mild variability in size, characterized by coarse and dense chromatin. Nucleoli are evident in some cells, while most nuclei display irregular shapes with twisting and folding. The cytoplasm is scant and slightly basophilic, with occasional cells showing a few purple-red granules. A minority of cells contain cytoplasmic vacuoles. \u003cstrong\u003e\u0026nbsp;B. Cytochemical Staining Report (Periodic Acid-Schiff stain, 100×) \u003c/strong\u003eAbnormal lymphocytes have a 4% positivity rate, with a coarse granular staining pattern. \u003cstrong\u003e\u0026nbsp;C. Flow Cytometry Results \u003c/strong\u003e75.3% of nucleated cells express CD5dim, CD2, CD56, CD38dim, Ki-67 (73.3%), and HLA-DR. A subset of these cells also expresses cCD3, which indicates phenotypically abnormal NK cells.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6129223/v1/8db1ae83605fc6f0355e0c57.png"},{"id":82050870,"identity":"4b2e70a4-d88e-4c10-88f0-81c34b7b2d5e","added_by":"auto","created_at":"2025-05-06 09:58:56","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":958976,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSkin Manifestations and Imaging Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA and B.\u003c/strong\u003e Skin Involvement Before and After Treatment \u0026nbsp;\u0026nbsp;\u003cstrong\u003eC and D.\u003c/strong\u003e Doppler Ultrasound Findings of the Spleen Before and After Treatment\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6129223/v1/c060ee7481c91be768627fec.png"},{"id":84726734,"identity":"ad9796cf-7d15-4741-a0a0-8026aec38347","added_by":"auto","created_at":"2025-06-16 16:07:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3675059,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6129223/v1/bdd93fd3-749b-498c-b01d-fe92d0004b73.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Case report: a critically ill patient with aggressive NK-cell leukemia receiving emergency chemotherapy in the ICU","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAggressive Natural Killer Cell Leukemia (ANKL) is a rare and highly aggressive neoplastic disorder of mature NK cells, with rapid progression and a poor prognosis\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Over the past few years, advancements in medical research have enhanced our understanding and expanded therapeutic options for ANKL. Previous literature has predominantly concentrated on the management of ANKL patients in hematology departments. This report details a case of critically ill ANKL managed with artificial liver support and emergency chemotherapy in the Intensive Care Unit (ICU). This approach underscores the potential advantages for ANKL patients with multi-organ dysfunction, providing new perspectives into the comprehensive management of such cases.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 47-year-old male patient was admitted to our hospital on July 4, 2024. He had been experiencing recurrent fever (Max Temp\u0026thinsp;\u0026ge;\u0026thinsp;38.5\u0026deg;C) and jaundice for over half a month, followed by tonsillar enlargement and chest tightness. His dyspnea worsened three days prior to admission. Over the past two months, he had experienced a weight loss of 5 kg. Previously, he had visited another hospital where leukocytosis (with a WBC count of 36.3\u0026times;10⁹/L) was detected, and a bone marrow biopsy indicated lymphoma. Further tests at our hospital, including examinations of the bone marrow structure and cell flow analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), confirmed the diagnosis of aggressive NK cell lymphoma/leukemia (stage IV). Upon admission, the patient's condition deteriorated rapidly, manifesting multiple organ failures (respiratory, hepatic, renal, and cardiac systems) and the onset of hemophagocytic lymphohistiocytosis (HLH), as defined by the HLH-2004 diagnostic criteria\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Given the severity of his condition, he was transferred to the ICU. He received dual plasma molecular adsorption system (DPMAS) combined with low-volume plasma exchange (LPE), continuous renal replacement therapy (CRRT), mechanical ventilation, and symptomatic treatment. Concurrently, he underwent chemotherapy with a regimen of etoposide, pegaspargase, and gemcitabine. Despite the challenges, the treatment process was relatively smooth. Following three sessions of artificial liver support and six days of continuous renal replacement therapy (DPMAS\u0026thinsp;+\u0026thinsp;LPE\u0026thinsp;+\u0026thinsp;CVVHD), the patient exhibited significant improvements in white blood cell count, as well as hepatic and renal function markers (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Additionally, respiratory and circulatory functions were stabilized. He was ultimately discharged from the hospital. During the chemotherapy intermission, the patient's symptoms improved, and his routine blood tests and biochemical indicators remained stable. He was readmitted on July 29, 2024, for the initiation of a second cycle of chemotherapy using the L-GEMOX regimen, which comprises pegaspargase, gemcitabine, and oxaliplatin. On August 23, 2024, the patient was readmitted owing to altered mental status. After three days of symptomatic treatment, his family opted to discontinue chemotherapy and organ support because of financial constraints. Regrettably, the patient passed away on August 27, 2024.\u003c/p\u003e \u003cp\u003eUpon admission to our hospital, laboratory tests disclosed the following results: The glucose (Glu) was 1.7 mmol/L, the triglyceride (TG) was 3.93 mmol/L, the fibrinogen (Fbg) was 1.25 g/L, the lactate (Lac) was \u0026gt;\u0026thinsp;15 mmol/L, the procalcitonin (PCT) was 4.26 ng/mL, the interleukin-6 (IL-6) was 20.55 pg/mL, the interleukin-10 (IL-10) was 14.20 pg/mL, the ferritin (FERR) was 1,969.00 ng/mL, the soluble CD25 (sCD25) was 87,104 pg/mL, the natural killer (NK) lymphocyte subset (CD3⁻CD16⁺CD56⁺) was 97.12%, and the NK cell activity was 17.16%. The copy number of Epstein-Barr virus (EBV) DNA was measured at 1.04\u0026times;10\u003csup\u003e5\u003c/sup\u003e IU/mL. For detailed results, see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp; Laboratory Test Results Upon Admission\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cimg 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\" width=\"694\" height=\"440\"\u003e\u003c/strong\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cstrong\u003eMV\u003c/strong\u003e:\u0026nbsp;mechanical ventilation;\u0026nbsp;\u003cstrong\u003eDPMAS\u003c/strong\u003e: dual plasma molecular adsorption system;\u0026nbsp;\u003cstrong\u003eLPE\u003c/strong\u003e:\u0026nbsp;Low-volume plasma exchange;\u0026nbsp;\u003cstrong\u003eCVVHD\u003c/strong\u003e:\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003econtinuous venous-venous hemodialysis.\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eANKL was initially described in the 1980s. In 2016, the World Health Organization classified it as a subtype of mature NK cell neoplasms, which also includes extranodal NK-/T-cell lymphoma, nasal type (ENKTL-N), and chronic lymphoproliferative disorder of NK cells (NK-CLPD)\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. ANKL has a higher prevalence in Asia, predominantly affecting young to middle-aged adults (aged 30\u0026ndash;40 years), and is strongly associated with EBV infection\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. It typically manifests as a systemic disease involving multiple organ systems, characterized by fever, weight loss, hepatosplenomegaly, pancytopenia, and abnormal liver function. The clinical course is frequently fulminant, rapidly progressing to disseminated intravascular coagulation (DIC) and HLH, resulting in multi-organ failure\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. The prognosis is extremely poor, with most patients succumbing within days to weeks after onset, and a median survival time of only 2 months\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCurrently, there is no standardized treatment protocol for ANKL. Studies have demonstrated that NK tumor cells can express P-glycoprotein, which expels anthracycline drugs from the cells, thereby reducing intracellular drug concentrations and leading to drug resistance\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. As a result, traditional CHOP and CHOP-like regimens demonstrate limited efficacy in the treatment of ANKL\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. In contrast, L-asparaginase (L-ASP) is not influenced by P-glycoprotein and has the ability to induce apoptosis in NK cell tumors. Therefore, treatment regimens that incorporate L-ASP may enhance patient outcomes\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe currently used regimens are as follows \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eSMILE regimen\u003c/b\u003e: Dexamethasone, Methotrexate, Ifosfamide, L-Asparaginase, and Etoposide.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eVIDL regimen\u003c/b\u003e: Etoposide, Ifosfamide, Dexamethasone, and L-Asparaginase.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eAspMetDex regimen\u003c/b\u003e: L-Asparaginase, Methotrexate, and Dexamethasone.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePegaspargase in conjunction with GDP regimen\u003c/b\u003e: Gemcitabine, Cisplatin, and Dexamethasone.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePegaspargase in conjunction with GEMOX regimen\u003c/b\u003e: Gemcitabine and Oxaliplatin.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eFor patients diagnosed with HLH, the HLH-1994 protocol may be employed as an initial therapeutic approach prior to chemotherapy\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Furthermore, the combination of L-ASP and Hematopoietic Stem Cell Transplantation (HSCT) represents a promising curative strategy for these patients\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the case of this critically ill patient, upon transfer to the ICU, we initiated artificial liver support therapy to detoxify the body, stabilize the internal environment, and preserve organ function. Meanwhile, in collaboration with hematologists, we have developed an emergency chemotherapy regimen for ANKL complicated by HLH. The patient exhibited promising therapeutic responses after completing two cycles of chemotherapy. Unfortunately, during the final hospitalization triggered by altered mental status, the family declined further active medical interventions, and as a result, lumbar puncture and head imaging were not conducted. This precluded us from effectively distinguishing between neuroinflammation associated with HLH and leukemic infiltration. Additionally, hepatic encephalopathy and sepsis-associated encephalopathy remain plausible contributors to the neurological symptoms and cannot be conclusively ruled out.\u003c/p\u003e \u003cp\u003eResearch demonstrates that emergency chemotherapy in the ICU is primarily indicated for patients diagnosed with acute leukemia or aggressive lymphoma, who may present with critical conditions such as leukostasis, DIC, HLH, and tumor lysis syndrome\u003csup\u003e[\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Historically, emergency chemotherapy in critically ill patients has been regarded as ineffective and associated with prolonged ICU stays and increased mortality rates. However, contemporary evidence suggests that elevated mortality rates are primarily observed in patients with solid tumors, whereas emergency chemotherapy does not significantly influence mortality in patients with hematologic malignancies\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Indeed, long-term outcomes for the latter group are promising, with a reported 12-month survival rate of 30%, and 70% achieving complete remission\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt is undeniable that emergency chemotherapy possesses both beneficial and adverse effects. On the one hand, it can mitigate life-threatening complications associated with cancer and thereby reduce mortality. On the other hand, side effects such as bone marrow suppression and pulmonary toxicity may exacerbate organ dysfunction and contribute to increased mortality\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Nevertheless, for critically ill patients, emergency chemotherapy serves as a potentially life-saving last-resort intervention, providing a glimmer of hope to both patients and their families. Therefore, providing cancer treatment in the ICU is not only feasible but may be essential for patients experiencing severe exacerbation of hematologic disorders ICU physicians play a pivotal role in identifying patients who stand to benefit from emergency chemotherapy. Through close collaboration with a multidisciplinary expert team, individualized treatment plans have been developed for these patients. This approach may serve as a vital bridge, facilitating their progression toward recovery.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eANKL\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAggressive natural killer cell leukemia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eICU\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eHLH\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHemophagocytic lymphohistiocytosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDPMAS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDual plasma molecular adsorption system\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCRRT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eContinuous renal replacement therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eLPE\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLow-volume plasma exchange\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGlu\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlucose\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTG\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTriglyceride\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eFbg\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFibrinogen\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eLac\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLactate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePCT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProcalcitonin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIL-6\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterleukin-6\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIL-10\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterleukin-10\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eFERR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFerritin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003esCD25\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSoluble CD25\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eEBV\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEpstein-Barr virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMV\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMechanical ventilation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eENKTL-N\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eExtranodal NK-/T-cell lymphoma, nasal type\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNK-CLPD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChronic lymphoproliferative disorder of NK cells\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDIC\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDisseminated intravascular coagulation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eL-ASP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eL-asparaginase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eHSCT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHematopoietic Stem Cell Transplantation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThe study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Clinical Research Ethics Committee of The Affiliated Tumor Hospital of Harbin Medical University (Harbin, People\u0026rsquo;s Republic of China). All methods were performed according to the relevant guidelines and regulations.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eInformed consent for this was obtained from the patient\u0026rsquo;s legal guardian(s).\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was supported in part by grants from the Hai Yan Scientific Research Fund of Harbin Medical University Cancer Hospital (JJMS 2023-10).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eY.Z. and Y.Y. were responsible for collecting the clinical information and drafting the manuscript. J.H. and H.L. provided support in the analysis and interpretation of the data. X.L. and L.Q. reviewed and edited the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eAll data analysed during this study are included in this published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSumbly V, Vest M, Landry I: Aggressive Natural Killer Cell Leukemia: A Brief Overview of Its Genomic Landscape, Histological Features, and Current Management. \u003cem\u003eCureus \u003c/em\u003e2022, 14(2):e22537.\u003c/li\u003e\n\u003cli\u003eHenter JI, Horne A, Aric\u0026oacute; M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J\u003cem\u003e et al\u003c/em\u003e: HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. \u003cem\u003ePediatr Blood Cancer \u003c/em\u003e2007, 48(2):124-131.\u003c/li\u003e\n\u003cli\u003eSwerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD\u003cem\u003e et al\u003c/em\u003e: The 2016 revision of the World Health Organization classification of lymphoid neoplasms. \u003cem\u003eBlood \u003c/em\u003e2016, 127(20):2375-2390.\u003c/li\u003e\n\u003cli\u003eKwong YL, Anderson BO, Advani R, Kim WS, Levine AM, Lim ST: Management of T-cell and natural-killer-cell neoplasms in Asia: consensus statement from the Asian Oncology Summit 2009. \u003cem\u003eLancet Oncol \u003c/em\u003e2009, 10(11):1093-1101.\u003c/li\u003e\n\u003cli\u003eLima M: Aggressive mature natural killer cell neoplasms: from epidemiology to diagnosis. \u003cem\u003eOrphanet J Rare Dis \u003c/em\u003e2013, 8:95.\u003c/li\u003e\n\u003cli\u003eHoffmann JC, Maeda LS, Ohgami RS: Indolent and Aggressive Mature T-Cell and Natural Killer\u0026ndash;Cell Lymphomas - ScienceDirect. \u003cem\u003eAtlas of Diagnostic Hematology \u003c/em\u003e2021:251-273.\u003c/li\u003e\n\u003cli\u003eSuzuki R, Suzumiya J, Yamaguchi M, Nakamura S, Kameoka J, Kojima H, Abe M, Kinoshita T, Yoshino T, Iwatsuki K\u003cem\u003e et al\u003c/em\u003e: Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type. \u003cem\u003eAnn Oncol \u003c/em\u003e2010, 21(5):1032-1040.\u003c/li\u003e\n\u003cli\u003eTang YT, Wang D, Luo H, Xiao M, Zhou HS, Liu D, Ling SP, Wang N, Hu XL, Luo Y\u003cem\u003e et al\u003c/em\u003e: Aggressive NK-cell leukemia: clinical subtypes, molecular features, and treatment outcomes. \u003cem\u003eBlood Cancer J \u003c/em\u003e2017, 7(12):660.\u003c/li\u003e\n\u003cli\u003eEgashira M, Kawamata N, Sugimoto K, Kaneko T, Oshimi K: P-glycoprotein expression on normal and abnormally expanded natural killer cells and inhibition of P-glycoprotein function by cyclosporin A and its analogue, PSC833. \u003cem\u003eBlood \u003c/em\u003e1999, 93(2):599-606.\u003c/li\u003e\n\u003cli\u003eTse E, Kwong YL: The diagnosis and management of NK/T-cell lymphomas. \u003cem\u003eJ Hematol Oncol \u003c/em\u003e2017, 10(1):85.\u003c/li\u003e\n\u003cli\u003eAndo M, Sugimoto K, Kitoh T, Sasaki M, Mukai K, Ando J, Egashira M, Schuster SM, Oshimi K: Selective apoptosis of natural killer-cell tumours by l-asparaginase. \u003cem\u003eBr J Haematol \u003c/em\u003e2005, 130(6):860-868.\u003c/li\u003e\n\u003cli\u003eZhang Y, Lee D, Gesiotto Q, Sokol L: Aggressive natural killer cell leukemia: diagnosis, treatment recommendations, and emerging therapies. \u003cem\u003eExpert Rev Hematol \u003c/em\u003e2021, 14(8):731-740.\u003c/li\u003e\n\u003cli\u003eIshida F: Aggressive NK-Cell Leukemia. \u003cem\u003eFront Pediatr \u003c/em\u003e2018, 6:292.\u003c/li\u003e\n\u003cli\u003eWu J, Lu AD, Zhang LP, Zuo YX, Jia YP: [Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia]. \u003cem\u003eZhonghua Xue Ye Xue Za Zhi \u003c/em\u003e2019, 40(1):52-57.\u003c/li\u003e\n\u003cli\u003eIshida F, Ko YH, Kim WS, Suzumiya J, Isobe Y, Oshimi K, Nakamura S, Suzuki R: Aggressive natural killer cell leukemia: therapeutic potential of L-asparaginase and allogeneic hematopoietic stem cell transplantation. \u003cem\u003eCancer Sci \u003c/em\u003e2012, 103(6):1079-1083.\u003c/li\u003e\n\u003cli\u003eJung KS, Cho SH, Kim SJ, Ko YH, Kang ES, Kim WS: L-asparaginase-based regimens followed by allogeneic hematopoietic stem cell transplantation improve outcomes in aggressive natural killer cell leukemia. \u003cem\u003eJ Hematol Oncol \u003c/em\u003e2016, 9:41.\u003c/li\u003e\n\u003cli\u003ePastores SM, Goldman DA, Shaz DJ, Kostelecky N, Daley RJ, Peterson TJ, Tan KS, Halpern NA: Characteristics and outcomes of patients with hematologic malignancies receiving chemotherapy in the intensive care unit. \u003cem\u003eCancer \u003c/em\u003e2018, 124(14):3025-3036.\u003c/li\u003e\n\u003cli\u003eMoors I, P\u0026egrave;ne F, Lengline \u0026Eacute;, Benoit D: Urgent chemotherapy in hematological patients in the ICU. \u003cem\u003eCurr Opin Crit Care \u003c/em\u003e2015, 21(6):559-568.\u003c/li\u003e\n\u003cli\u003eLafarge A, Chean D, Whiting L, Clere-Jehl R: Management of hematological patients requiring emergency chemotherapy in the intensive care unit. \u003cem\u003eIntensive Care Med \u003c/em\u003e2024, 50(6):849-860.\u003c/li\u003e\n\u003cli\u003ede Oliveira MCF, Ferreira JC, Nassar Junior AP, Dettino ALA, Caruso P: Impact of Urgent Chemotherapy in Critically Ill Patients. \u003cem\u003eJ Intensive Care Med \u003c/em\u003e2020, 35(4):347-353.\u003c/li\u003e\n\u003cli\u003eWohlfarth P, Staudinger T, Sperr WR, Bojic A, Robak O, Hermann A, Laczika K, Carlstr\u0026ouml;m A, Riss K, Rabitsch W\u003cem\u003e et al\u003c/em\u003e: Prognostic factors, long-term survival, and outcome of cancer patients receiving chemotherapy in the intensive care unit. \u003cem\u003eAnn Hematol \u003c/em\u003e2014, 93(10):1629-1636.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"virology-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"virj","sideBox":"Learn more about [Virology Journal](http://virologyj.biomedcentral.com/)","snPcode":"12985","submissionUrl":"https://submission.nature.com/new-submission/12985/3","title":"Virology Journal","twitterHandle":"@VirologyJ","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Aggressive NK-cell Leukemia (ANKL), Lymphoma/Leukemia, Emergency Chemotherapy, ICU","lastPublishedDoi":"10.21203/rs.3.rs-6129223/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6129223/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAggressive NK-cell leukemia (ANKL) is a scarce mature NK-cell neoplasm frequently associated with Epstein-Barr virus (EBV) infection. We report the case of a 47-year-old male patient who was admitted to the hospital due to recurrent fever, jaundice, and dyspnea, and was diagnosed with ANKL accompanied by multi-organ failure. Upon transfer to the intensive care unit (ICU), he received emergency chemotherapy consisting of etoposide, pegaspargase, and gemcitabine, in conjunction with organ support therapies including DPMAS, LPE, and CVVHD. Subsequently, the patient's condition stabilized, and he was discharged. However, following the second cycle of chemotherapy, he was readmitted due to altered mental status. Due to financial constraints, the family decided not to pursue further treatment, leading to the patient's eventual demise. Overall, this case highlights the critical importance of multidisciplinary collaboration for managing critically ill ANKL patients. Careful evaluation of the risks associated with chemotherapy, combined with timely administration of emergency chemotherapy in the ICU and comprehensive multi-organ support, can potentially offer a survival opportunity.\u003c/p\u003e","manuscriptTitle":"Case report: a critically ill patient with aggressive NK-cell leukemia receiving emergency chemotherapy in the ICU","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-06 09:58:51","doi":"10.21203/rs.3.rs-6129223/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-07T18:02:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-07T16:57:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"14431480391574412865645167384790241758","date":"2025-04-28T02:00:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"43005873822518853992653287310369234407","date":"2025-04-27T10:22:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"231363342929972127532170347718142055440","date":"2025-04-25T04:05:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-22T08:09:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-21T13:00:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Virology Journal","date":"2025-04-20T14:50:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"virology-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"virj","sideBox":"Learn more about [Virology Journal](http://virologyj.biomedcentral.com/)","snPcode":"12985","submissionUrl":"https://submission.nature.com/new-submission/12985/3","title":"Virology Journal","twitterHandle":"@VirologyJ","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3b766f56-4dce-42cd-a1ac-41342492c849","owner":[],"postedDate":"May 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-16T16:04:55+00:00","versionOfRecord":{"articleIdentity":"rs-6129223","link":"https://doi.org/10.1186/s12985-025-02798-4","journal":{"identity":"virology-journal","isVorOnly":false,"title":"Virology Journal"},"publishedOn":"2025-06-12 15:57:59","publishedOnDateReadable":"June 12th, 2025"},"versionCreatedAt":"2025-05-06 09:58:51","video":"","vorDoi":"10.1186/s12985-025-02798-4","vorDoiUrl":"https://doi.org/10.1186/s12985-025-02798-4","workflowStages":[]},"version":"v1","identity":"rs-6129223","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6129223","identity":"rs-6129223","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}