Myelosuppression in a Metastatic Breast Cancer Patient with GSTP1 rs1695 Mutation Induced by Adriamycin and Cyclophosphamide

Myelosuppression in a Metastatic Breast Cancer Patient with GSTP1 rs1695 Mutation Induced by Adriamycin and Cyclophosphamide | 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 Case Report Myelosuppression in a Metastatic Breast Cancer Patient with GSTP1 rs1695 Mutation Induced by Adriamycin and Cyclophosphamide Dr Arun S, Dr Pramod Kumar, Dr Megha M, Dr Aswini Saravanan, Dr Rishi P Nair, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5513178/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Adriamycin and cyclophosphamide (AC) combination chemotherapy is one of the common regimens used for breast cancer and in metastatic breast cancer with oligo-metastasis. (1) AC combination chemotherapy regimen is associated with adverse drug reactions like myelosuppression, gastrointestinal toxicity, cardiotoxicity, peripheral neuropathy, and hand-foot syndrome. (2),(3),(4) It has been noticed from previous studies that the metabolism-related gene GSTP rs 1695 homozygous mutant allele has been associated with higher incidences of myelotoxicity and gastrointestinal toxicity post-combination chemotherapy regimens. (5) Case report: A 55-year-old female patient presented with the incidence of grade 3 febrile neutropenia and myelosuppression, 8 days following AC infusion. The patient also has symptoms of grade 2 peripheral neuropathy and diarrhea. She was treated as an inpatient from the local hospital with pegfilgrastim, packed RBC transfusion, and intravenous antibiotics for febrile neutropenia. She recovered completely with this treatment and was discharged without any sequelae or complications. She was then tested for the GSTP rs 1695 gene which revealed the homozygous mutant variant (GG allele). When reporting the causal association of the adverse drug reaction, it comes under the “ possible ” category of WHO causality assessment. Conclusion: Myelosuppression, Diarrhea, and other adverse events following AC combination chemotherapy can be related to the Genetic polymorphism in GSTP rs 1695 double mutant homozygous allele (GG ) and its altered drug metabolism effects. The Adverse drug reaction comes under the “ Possible” Category of WHO causality assessment. Clinical Pharmacology Oncology Adriamycin Myelosuppression Cyclophosphamide Hand-foot syndrome GSTP rs1695 Figures Figure 1 Figure 2 Figure 3 Introduction Adriamycin and cyclophosphamide-based chemotherapy is the most commonly selected chemotherapy regimen in the neoadjuvant and adjuvant setting for breast cancer patients. ( 1 ) It is often used for the treatment of oligometastatic breast cancer. The most common adverse events seen with this chemotherapy regimen are myelosuppression, hand-foot syndrome, gastrointestinal toxicity, cardiotoxicity, peripheral neuropathy, etc. ( 3 ), ( 4 ) It has been noticed from previous literature that the presence of the metabolism-related gene GSTP rs 1695 homozygous mutant SNP in patients is associated with higher incidences of myelotoxicity and gastrointestinal toxicity ( 5 ). GSTP rs 1695 is related to the variable incidence rate of myelotoxicity associated with different chemotherapy regimes in other cancer types like lung cancer and colorectal cancers ( 6 ), ( 7 ). In this patient, we report such an event of myelosuppression following the first dose of the Adriamycin and cyclophosphamide-based chemotherapy which occurred after 8 days post-chemotherapy infusion. Case report A 55-year-old female patient, diagnosed with metastatic breast cancer, after receiving the first cycle of AC chemotherapy regimen for oligometastatic breast cancer presented with the incidence of myelosuppression in the form of febrile neutropenia, anemia, and thrombocytopenia as well as hand-foot syndrome, peripheral neuropathy, oral mucositis, and diarrhoea. The patient received a dose of Adriamycin 110 mg and cyclophosphamide 1100 mg as per the standard treatment protocol. She also received Pegfilgrastim 6 mg on the next day after 24 hours of completion of the chemotherapy. After 8 days of receiving the chemotherapy, the patient complaints of fever, body pain, and severe fatigue on testing her WBC count was 1200/mm 3 , absolute neutrophil count – 209cells/mm 3 , hemoglobin- 6.8 gm/dl, and platelet count- 85000/mm 3 . (Table 1 )(Fig. 1 & 2 ) The patient was then admitted for inpatient treatment and transfusion with two units of packed cell RBC and 1 unit of Fresh blood transfusion along with Intravenous antibiotics and pegfilgrastim after initial blood cultures were sent. Table 1 Hematological parameters, liver function test, and kidney function test during chemotherapy Date/parameter Total WBC count (/dl) Absolute neutrophil count(/dl) Hemoglobin (gm/dl) Platelet count(*10 3 /dl) S.urea(mg/dl)/creatinine(mg/dl) S.bilirubin(total)/SGOT(IU/dl)/SGPT(IU/dl)/S.ALP(IU/dl) Prechemotherapy 1st cycle AC 5400 2160 8.6 140 34/1.2 0.2/42/55/102 Post chemotherapy(1st AC) 8th day 1200 210 6.8 85 Post chemotherapy 11th days 2500 1050 10 101 Prechemotherapy (2nd cycle AC) 13660 8390 13.2 412 38.7/1.03 0.41/52.07/35.3 Post chemotherapy (2nd cycle AC) 9th days 2200 1050 9.7 120 Prechemotherapy (3rd cycle AC) 10850 7820 11.2 328 29.7/1.09 0.68/48.9/35.9 Post chemotherapy (3rd AC 13th day) 2800 2430 8.2 61 28/1.35 0.9/15/23/95 After transfusion and treatment with antibiotics and pegfilgrastim, her total WBC count recovered to initially 2500/dl, hemoglobin − 10gm/dl, and platelet count- 101000/mm 3 .(Table 1 ) (Fig. 1 & 2 )And she recovered completely without any sequelae. However, the symptoms of diarrhoea recurred in the next cycle of chemotherapy with worsening of the hand-foot syndrome(Fig. 3 ) and peripheral neuropathy. Post-second cycle chemotherapy leukopenia was seen with a total leukocyte count of 2200/mm 3 without other features of myelosuppression or febrile neutropenia. The liver function and kidney functions of the patient were within normal limits. Post the third cycle of the AC patient’s blood counts revealed leukopenia (2800 cells/dl), anemia (Hb – 8.2 gm/dl ), and thrombocytopenia (61000 cells/dl).(Figs. 1 and 2 ) This patient has received 5 cycles of chemotherapy with paclitaxel and carboplatin for stage 4 metastatic breast cancer and showed a partial response to the treatment after which she was then treated with Adriamycin and cyclophosphamide-based combination chemotherapy on the lines of definite therapy for oligometastatic disease. On testing the Metabolism gene for the Adriamycin and cyclophosphamide GSTP rs 1695 it was noticed that the patient was a homozygous mutant SNP variant. On reviewing the previous studies and literature it was noticed that this type of variant is associated with more incidence of myelosuppression and gastrointestinal toxicity. ( 5 ) Discussion This patient has met with an episode of myelosuppression after 8 days of combination chemotherapy with Adriamycin and cyclophosphamide. The grade of anemia was grade 3 according to CTCAE criteria, neutropenia was grade 4, and thrombocytopenia was grade 1( 8 ). Usually, the count drop occurs post-chemotherapy on the 8th day to 11th day period reaches a nadir in 14–15 days, and then recovers by 20–21 days After assessing the patient for WHO causality for the adverse drug reaction, we have concluded that Adriamycin and cyclophosphamide chemotherapy are “ possible ” drugs behind the adverse drug event for the incidence of anemia, thrombocytopenia, and febrile neutropenia. The incidence of febrile neutropenia in this patient was grade 3 according to the CTCAE 5 grading system of the Adverse drug reaction. ( 8 ) From the previous studies, it has been noticed that there is an increased incidence of myelotoxicity and gastrointestinal toxicity post-cyclophosphamide-based chemotherapy regimens in GSTP rs 1695 double mutant homozygous allele(GG) variant patients. ( 5 ),( 7 ) The patient has presented with other adverse reactions like mucositis, diarrhoea, hand-foot syndrome, and peripheral neuropathy along with myelosuppression and febrile neutropenia. In the 2nd cycle of the Adriamycin and cyclophosphamide incidence of leukopenia was there with milder grade (grade 2), peripheral neuropathy and hand-foot syndrome persisted. Conclusion The above-mentioned patient is a homozygous mutant of GSTP rs 1695 Single nucleotide genetic polymorphism who presented with febrile neutropenia and myelosuppression and other adverse drug reactions like peripheral neuropathy, hand-foot syndrome, oral mucositis , diarrhea which comes under the “ Possible ” category of the WHO casualty assessment. Our case report reaffirms the finding that patients with the Single nucleotide genetic polymorphism GSTP rs 1695 (GG allele) have a higher incidence of myelosuppression and Gastrointestinal toxicities post-chemotherapy infusion which concurring with the previous studies. ( 5 ) Further studies can be conducted in the Western Indian population to confirm this initial evidence. STRENGTH AND LIMITATION OF THE STUDY: As the baseline WBC count and platelet count were normal in this patient before chemotherapy, this episode of febrile neutropenia can be attributed to the newly started Adriamycin and Cyclophosphamide-based chemotherapy regimen. None of the previous chemotherapy cycles in this patient were associated with febrile neutropenia and thrombocytopenia. No episode of diarrhea is noticed in the prior chemotherapy cycles. As this includes only one case report we need more prospective evidence before we infer the logical conclusion for relating the GSTP rs 1695 ( GG allele) SNP with the incidence of the myelosuppression. The background of 5 cycles of prior chemotherapy with Paclitaxel and Carboplatin combination chemotherapy regimens can also contribute to the cumulative toxicity on the bone marrow which might lead to anemia-like events. Abbreviations AC Adriamycin and cyclophosphamide combination chemotherapy GSTP glutathione S—transferases SNP Single nucleotide genetic polymorphism CTCAE Common Terminology Criteria for Adverse Events WHO World Health Organisation Declarations ETHICAL APPROVAL AND CONSENT TO PARTICIPATE: A waiver for ethics committee approval has been obtained from the institute due to the nature of the article being a case report. All the authors confirm that the patient consent form has been obtained from this patient. CONSENT FOR PUBLICATION: Written informed consent was obtained from the patients for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal AVAILABILITY OF DATA AND MATERIALS: Data sharing does not apply to this article as no datasets were generated or analyzed during the current study. All necessary information related to the case report has been provided in the article. Waiver from the Ethics Committee and the patient’s consent form will be provided upon reasonable request to the corresponding author COMPETING INTERESTS: The authors declare that they have no competing interests. FUNDING: The authors declare that there was no funding source for this work. AUTHORS' CONTRIBUTIONS: Case clinical scenarios and adverse drug events are monitored by initiating the conception of the case report. Case report written by AS, PK, MK, ASH, RP, SA Discussion and possible relations of the case scenario and adverse drug event inferred by AS, PK, ASH, RP, SS, SA. Consent was taken by AS. All authors read and approved the final manuscript. ACKNOWLEDGMENT: We extend our heartfelt appreciation to Dr.Anoop Pratheesh P , Surgeon in the Government Health Services, Kerala, Dr.G Krishna Kumar , Physician, and intensivist Dr.Govindans Hospital, Thiruvananthapuram, Dr.Mithu Banerjee Professor, and head Biochemistry department, and all the Consultants and Senior residents and Junior residents, especially Dr.Dipanshu of the Department of Medical Oncology, Radiation oncology Department, Dr.Amal Junior resident Biochemistry department, Sri Shailendra Vashistha, Laboratory technician Biochemistry Department, was involved in the treatment of Patient and For supporting the writing and suggestions for their invaluable suggestions and unwavering support, which have greatly enriched the quality and depth of our study. References Mai N, Myers S, Shen S, Downs-Canner S, Robson M, Norton L, et al. Dose-dense doxorubicin plus cyclophosphamide in a modified KEYNOTE522 regimen for triple-negative breast cancer. Npj Breast Cancer. 2024 Jun 4;10(1):1–7. Tadesse FA, Leminie AA. Effects of Adriamycin-Cytoxan chemotherapy on hematological and electrolyte parameters among breast cancer patients. Front Oncol. 2023 May 2;13:1103013. Gadisa DA, Assefa M, Wang SH, Yimer G. Toxicity profile of Doxorubicin-Cyclophosphamide and Doxorubicin-Cyclophosphamide followed by Paclitaxel regimen and its associated factors among women with breast cancer in Ethiopia: A prospective cohort study. J Oncol Pharm Pract Off Publ Int Soc Oncol Pharm Pract. 2020 Dec;26(8):1912–20. S A, Mohamedali SP, M A. Pattern of management of febrile neutropenia among breast cancer patients treated with different chemotherapeutic regimens. Int J Basic Clin Pharmacol. 2018 Aug 23;7(9):1829–36. Gong JY, Peng SY, Xing K, Fan L, Tan SL, Luo ZY, et al. Evaluating the role of GSTP1 genetic polymorphism (rs1695, 313A>G) as a predictor in cyclophosphamide-induced toxicities. Medicine (Baltimore). 2021 Mar 19;100(11):e24423. PharmGKB [Internet]. [cited 2024 Aug 5]. Very Important Pharmacogene: GSTP1. Available from: https://www.pharmgkb.org/vip/PA166169438 Lv F, Ma Y, Zhang Y, Li Z. Relationship between GSTP1 rs1695 gene polymorphism and myelosuppression induced by platinum-based drugs: a meta-analysis. Int J Biol Markers. 2018 Nov 1;33(4):364–71. Common Terminology Criteria for Adverse Events (CTCAE) | Protocol Development | CTEP [Internet]. 2022 [cited 2022 Aug 30]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-5513178","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":381873432,"identity":"62c7e3f0-db33-4761-9237-65663a30ab6f","order_by":0,"name":"Dr Arun S","email":"","orcid":"https://orcid.org/0000-0002-0871-6332","institution":"All India Institute of medical Sciences, Jodhpur","correspondingAuthor":false,"prefix":"Dr","firstName":"Arun","middleName":"","lastName":"S","suffix":""},{"id":381873433,"identity":"f6bd7e13-3518-4f91-9851-f303b48d3da3","order_by":1,"name":"Dr Pramod Kumar","email":"","orcid":"","institution":"All India 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09:08:11","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5513178/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5513178/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":70391661,"identity":"ddcd5b84-62da-459a-9d4e-e2fc5a3f476e","added_by":"auto","created_at":"2024-12-02 17:31:09","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":370482,"visible":true,"origin":"","legend":"\u003cp\u003eThe pattern of leukopenia and anemia pre and post-chemotherapy\u003c/p\u003e","description":"","filename":"FIG1.PATTERNOFLEUKOPENIAANEMIA.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5513178/v1/170794cad7e5d9e9c58997a7.jpg"},{"id":70391733,"identity":"df4be436-d41b-47c9-a6c6-965dc5011e66","added_by":"auto","created_at":"2024-12-02 17:31:21","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":169625,"visible":true,"origin":"","legend":"\u003cp\u003eThe pattern of thrombocytopenia pre and post-chemotherapy\u003c/p\u003e","description":"","filename":"FIG2.PATTERNOFTHROMBOCYTOPENIACASEREPORT.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5513178/v1/8c5568b4fabd7ddabab1f196.jpg"},{"id":70391713,"identity":"113269be-09ff-441a-ae49-227a8210d465","added_by":"auto","created_at":"2024-12-02 17:31:17","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":61786,"visible":true,"origin":"","legend":"\u003cp\u003eHand Foot syndrome\u003c/p\u003e","description":"","filename":"Figure3.Handfootsyndrome.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5513178/v1/5419773afa500891f48d82c2.jpg"},{"id":70391787,"identity":"6530efd2-f81f-4d37-a290-7b541f91f64d","added_by":"auto","created_at":"2024-12-02 17:31:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1139833,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5513178/v1/8ea48b7e-9de2-49ec-8816-62fe7ccecba2.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eMyelosuppression in a Metastatic Breast Cancer Patient with GSTP1 rs1695 Mutation Induced by Adriamycin and Cyclophosphamide\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction ","content":"\u003cp\u003eAdriamycin and cyclophosphamide-based chemotherapy is the most commonly selected chemotherapy regimen in the neoadjuvant and adjuvant setting for breast cancer patients. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) It is often used for the treatment of oligometastatic breast cancer. The most common adverse events seen with this chemotherapy regimen are myelosuppression, hand-foot syndrome, gastrointestinal toxicity, cardiotoxicity, peripheral neuropathy, etc. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) It has been noticed from previous literature that the presence of the metabolism-related gene GSTP rs 1695 homozygous mutant SNP in patients is associated with higher incidences of myelotoxicity and gastrointestinal toxicity (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). GSTP rs 1695 is related to the variable incidence rate of myelotoxicity associated with different chemotherapy regimes in other cancer types like lung cancer and colorectal cancers (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this patient, we report such an event of myelosuppression following the first dose of the Adriamycin and cyclophosphamide-based chemotherapy which occurred after 8 days post-chemotherapy infusion.\u003c/p\u003e"},{"header":"Case report ","content":"\u003cp\u003eA 55-year-old female patient, diagnosed with metastatic breast cancer, after receiving the first cycle of AC chemotherapy regimen for oligometastatic breast cancer presented with the incidence of myelosuppression in the form of febrile neutropenia, anemia, and thrombocytopenia as well as hand-foot syndrome, peripheral neuropathy, oral mucositis, and diarrhoea.\u003c/p\u003e \u003cp\u003eThe patient received a dose of Adriamycin 110 mg and cyclophosphamide 1100 mg as per the standard treatment protocol. She also received Pegfilgrastim 6 mg on the next day after 24 hours of completion of the chemotherapy. After 8 days of receiving the chemotherapy, the patient complaints of fever, body pain, and severe fatigue on testing her WBC count was 1200/mm\u003csup\u003e3\u003c/sup\u003e, absolute neutrophil count \u0026ndash; 209cells/mm\u003csup\u003e3\u003c/sup\u003e, hemoglobin- 6.8 gm/dl, and platelet count- 85000/mm\u003csup\u003e3\u003c/sup\u003e. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026amp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) The patient was then admitted for inpatient treatment and transfusion with two units of packed cell RBC and 1 unit of Fresh blood transfusion along with Intravenous antibiotics and pegfilgrastim after initial blood cultures were sent.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHematological parameters, liver function test, and kidney function test during chemotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDate/parameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal WBC count (/dl)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbsolute neutrophil count(/dl)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHemoglobin (gm/dl)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePlatelet count(*10\u003csup\u003e3\u003c/sup\u003e/dl)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eS.urea(mg/dl)/creatinine(mg/dl)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eS.bilirubin(total)/SGOT(IU/dl)/SGPT(IU/dl)/S.ALP(IU/dl)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrechemotherapy 1st cycle AC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5400\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2160\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34/1.2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2/42/55/102\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost chemotherapy(1st AC) 8th day\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1200\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e210\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePost chemotherapy 11th days\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e2500\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1050\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e101\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrechemotherapy (2nd cycle AC)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e13660\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e8390\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e13.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e412\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e38.7/1.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.41/52.07/35.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePost chemotherapy (2nd cycle AC) 9th days\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e2200\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1050\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e9.7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e120\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrechemotherapy (3rd cycle AC)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e10850\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e7820\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e11.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e328\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e29.7/1.09\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.68/48.9/35.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePost chemotherapy (3rd AC 13th day)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e2800\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e2430\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e8.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e61\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e28/1.35\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.9/15/23/95\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAfter transfusion and treatment with antibiotics and pegfilgrastim, her total WBC count recovered to initially 2500/dl, hemoglobin \u0026minus;\u0026thinsp;10gm/dl, and platelet count- 101000/mm\u003csup\u003e3\u003c/sup\u003e.(Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026amp; \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)And she recovered completely without any sequelae. However, the symptoms of diarrhoea recurred in the next cycle of chemotherapy with worsening of the hand-foot syndrome(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) and peripheral neuropathy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePost-second cycle chemotherapy leukopenia was seen with a total leukocyte count of 2200/mm\u003csup\u003e3\u003c/sup\u003e without other features of myelosuppression or febrile neutropenia. The liver function and kidney functions of the patient were within normal limits.\u003c/p\u003e \u003cp\u003ePost the third cycle of the AC patient\u0026rsquo;s blood counts revealed leukopenia (2800 cells/dl), anemia (Hb \u0026ndash; 8.2 gm/dl ), and thrombocytopenia (61000 cells/dl).(Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThis patient has received 5 cycles of chemotherapy with paclitaxel and carboplatin for stage 4 metastatic breast cancer and showed a partial response to the treatment after which she was then treated with Adriamycin and cyclophosphamide-based combination chemotherapy on the lines of definite therapy for oligometastatic disease.\u003c/p\u003e \u003cp\u003eOn testing the Metabolism gene for the Adriamycin and cyclophosphamide GSTP rs 1695 it was noticed that the patient was a homozygous mutant SNP variant. On reviewing the previous studies and literature it was noticed that this type of variant is associated with more incidence of myelosuppression and gastrointestinal toxicity. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e"},{"header":"Discussion ","content":"\u003cp\u003eThis patient has met with an episode of myelosuppression after 8 days of combination chemotherapy with Adriamycin and cyclophosphamide. The grade of anemia was grade 3 according to CTCAE criteria, neutropenia was grade 4, and thrombocytopenia was grade 1(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Usually, the count drop occurs post-chemotherapy on the 8th day to 11th day period reaches a nadir in 14\u0026ndash;15 days, and then recovers by 20\u0026ndash;21 days\u003c/p\u003e \u003cp\u003eAfter assessing the patient for WHO causality for the adverse drug reaction, we have concluded that Adriamycin and cyclophosphamide chemotherapy are \u0026ldquo;\u003cb\u003epossible\u003c/b\u003e\u0026rdquo; drugs behind the adverse drug event for the incidence of anemia, thrombocytopenia, and febrile neutropenia. The incidence of febrile neutropenia in this patient was grade 3 according to the CTCAE 5 grading system of the Adverse drug reaction. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eFrom the previous studies, it has been noticed that there is an increased incidence of myelotoxicity and gastrointestinal toxicity post-cyclophosphamide-based chemotherapy regimens in GSTP rs 1695 double mutant homozygous allele(GG) variant patients. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e),(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe patient has presented with other adverse reactions like mucositis, diarrhoea, hand-foot syndrome, and peripheral neuropathy along with myelosuppression and febrile neutropenia.\u003c/p\u003e \u003cp\u003eIn the 2nd cycle of the Adriamycin and cyclophosphamide incidence of leukopenia was there with milder grade (grade 2), peripheral neuropathy and hand-foot syndrome persisted.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe above-mentioned patient is a homozygous mutant of GSTP rs 1695 Single nucleotide genetic polymorphism who presented with \u003cb\u003efebrile neutropenia and myelosuppression\u003c/b\u003e and other adverse drug reactions like \u003cb\u003eperipheral neuropathy, hand-foot syndrome, oral mucositis\u003c/b\u003e, diarrhea which comes under the \u0026ldquo;\u003cb\u003ePossible\u003c/b\u003e\u0026rdquo; category of the WHO casualty assessment. Our case report reaffirms the finding that patients with the Single nucleotide genetic polymorphism \u003cb\u003eGSTP rs 1695 (GG allele)\u003c/b\u003e have a higher incidence of myelosuppression and Gastrointestinal toxicities post-chemotherapy infusion which concurring with the previous studies. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) Further studies can be conducted in the Western Indian population to confirm this initial evidence.\u003c/p\u003e\n\u003ch3\u003eSTRENGTH AND LIMITATION OF THE STUDY:\u003c/h3\u003e\n\u003cp\u003eAs the baseline WBC count and platelet count were normal in this patient before chemotherapy, this episode of febrile neutropenia can be attributed to the newly started Adriamycin and Cyclophosphamide-based chemotherapy regimen. None of the previous chemotherapy cycles in this patient were associated with febrile neutropenia and thrombocytopenia. No episode of diarrhea is noticed in the prior chemotherapy cycles.\u003c/p\u003e \u003cp\u003eAs this includes only one case report we need more prospective evidence before we infer the logical conclusion for relating the GSTP rs 1695 ( GG allele) SNP with the incidence of the myelosuppression. The background of 5 cycles of prior chemotherapy with Paclitaxel and Carboplatin combination chemotherapy regimens can also contribute to the cumulative toxicity on the bone marrow which might lead to anemia-like events.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eAC\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdriamycin and cyclophosphamide combination chemotherapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGSTP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eglutathione S\u0026mdash;transferases\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSNP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSingle nucleotide genetic polymorphism\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCTCAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCommon Terminology Criteria for Adverse Events\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organisation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eETHICAL APPROVAL AND CONSENT TO PARTICIPATE:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA waiver for ethics committee approval has been obtained from the institute due to the nature of the article being a case report. All the authors confirm that the patient consent form has been obtained from this patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT FOR PUBLICATION:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patients for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAVAILABILITY OF DATA AND MATERIALS:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sharing does not apply to this article as no datasets were generated or analyzed during the current study. All necessary information related to the case report has been provided in the article. Waiver from the Ethics Committee and the patient’s consent form will be provided upon reasonable request to the corresponding author\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOMPETING INTERESTS:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING:\u0026nbsp;\u003c/strong\u003eThe authors declare that there was no funding source for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHORS' CONTRIBUTIONS:\u0026nbsp;\u003c/strong\u003eCase clinical scenarios and adverse drug events are monitored by initiating the conception of the case report. Case report written by AS, PK, MK, ASH, RP, SA Discussion and possible relations of the case scenario and adverse drug event inferred by AS, PK, ASH, RP, SS, SA. Consent was taken by AS. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENT:\u0026nbsp;\u003c/strong\u003eWe extend our heartfelt appreciation to \u003cstrong\u003eDr.Anoop Pratheesh P\u003c/strong\u003e, Surgeon in the Government Health Services, Kerala, \u003cstrong\u003eDr.G Krishna Kumar\u003c/strong\u003e, Physician, and intensivist Dr.Govindans Hospital, Thiruvananthapuram, \u003cstrong\u003eDr.Mithu Banerjee\u003c/strong\u003e Professor, and head Biochemistry department, and all the Consultants and Senior residents and Junior residents, especially \u003cstrong\u003eDr.Dipanshu\u003c/strong\u003e of the Department of \u0026nbsp;Medical Oncology, Radiation oncology Department, \u003cstrong\u003eDr.Amal\u0026nbsp;\u003c/strong\u003eJunior resident Biochemistry department, \u003cstrong\u003eSri Shailendra Vashistha,\u0026nbsp;\u003c/strong\u003eLaboratory technician Biochemistry Department, was involved in the treatment of Patient and \u0026nbsp; For supporting the writing and suggestions for their invaluable suggestions and unwavering support, which have greatly enriched the quality and depth of our study.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMai N, Myers S, Shen S, Downs-Canner S, Robson M, Norton L, et al. Dose-dense doxorubicin plus cyclophosphamide in a modified KEYNOTE522 regimen for triple-negative breast cancer. Npj Breast Cancer. 2024 Jun 4;10(1):1\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eTadesse FA, Leminie AA. Effects of Adriamycin-Cytoxan chemotherapy on hematological and electrolyte parameters among breast cancer patients. Front Oncol. 2023 May 2;13:1103013. \u003c/li\u003e\n\u003cli\u003eGadisa DA, Assefa M, Wang SH, Yimer G. Toxicity profile of Doxorubicin-Cyclophosphamide and Doxorubicin-Cyclophosphamide followed by Paclitaxel regimen and its associated factors among women with breast cancer in Ethiopia: A prospective cohort study. J Oncol Pharm Pract Off Publ Int Soc Oncol Pharm Pract. 2020 Dec;26(8):1912\u0026ndash;20. \u003c/li\u003e\n\u003cli\u003eS A, Mohamedali SP, M A. Pattern of management of febrile neutropenia among breast cancer patients treated with different chemotherapeutic regimens. Int J Basic Clin Pharmacol. 2018 Aug 23;7(9):1829\u0026ndash;36. \u003c/li\u003e\n\u003cli\u003eGong JY, Peng SY, Xing K, Fan L, Tan SL, Luo ZY, et al. Evaluating the role of GSTP1 genetic polymorphism (rs1695, 313A\u0026gt;G) as a predictor in cyclophosphamide-induced toxicities. Medicine (Baltimore). 2021 Mar 19;100(11):e24423. \u003c/li\u003e\n\u003cli\u003ePharmGKB [Internet]. [cited 2024 Aug 5]. Very Important Pharmacogene: GSTP1. Available from: https://www.pharmgkb.org/vip/PA166169438\u003c/li\u003e\n\u003cli\u003eLv F, Ma Y, Zhang Y, Li Z. Relationship between GSTP1 rs1695 gene polymorphism and myelosuppression induced by platinum-based drugs: a meta-analysis. Int J Biol Markers. 2018 Nov 1;33(4):364\u0026ndash;71. \u003c/li\u003e\n\u003cli\u003eCommon Terminology Criteria for Adverse Events (CTCAE) | Protocol Development | CTEP [Internet]. 2022 [cited 2022 Aug 30]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"All India Institute of Medical Sciences Jodhpur","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Adriamycin, Myelosuppression, Cyclophosphamide, Hand-foot syndrome, GSTP rs1695","lastPublishedDoi":"10.21203/rs.3.rs-5513178/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5513178/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003e Adriamycin and cyclophosphamide (AC) combination chemotherapy is one of the common regimens used for breast cancer and in metastatic breast cancer with oligo-metastasis. (1) AC combination chemotherapy regimen is associated with adverse drug reactions like myelosuppression, gastrointestinal toxicity, cardiotoxicity, peripheral neuropathy, and hand-foot syndrome. (2),(3),(4) It has been noticed from previous studies that the metabolism-related gene GSTP rs 1695 homozygous mutant allele has been associated with higher incidences of myelotoxicity and gastrointestinal toxicity post-combination chemotherapy regimens. (5)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase report:\u003c/strong\u003e A 55-year-old female patient presented with the incidence of grade 3 febrile neutropenia and myelosuppression, 8 days following AC infusion. The patient also has symptoms of grade 2 peripheral neuropathy and diarrhea. She was treated as an inpatient from the local hospital with pegfilgrastim, packed RBC transfusion, and intravenous antibiotics for febrile neutropenia. She recovered completely with this treatment and was discharged without any sequelae or complications. She was then tested for the \u003cstrong\u003eGSTP rs 1695 gene \u003c/strong\u003ewhich revealed the \u003cstrong\u003ehomozygous mutant variant (GG allele).\u003c/strong\u003eWhen reporting the causal association of the adverse drug reaction, it comes under the “\u003cstrong\u003epossible\u003c/strong\u003e” category of WHO causality assessment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Myelosuppression, Diarrhea, and other adverse events following AC combination chemotherapy can be related to the Genetic polymorphism in \u003cstrong\u003eGSTP rs 1695 double mutant homozygous allele (GG\u003c/strong\u003e ) and its altered drug metabolism effects. The Adverse drug reaction comes under the “\u003cstrong\u003ePossible”\u003c/strong\u003eCategory of WHO causality assessment.\u003c/p\u003e","manuscriptTitle":"Myelosuppression in a Metastatic Breast Cancer Patient with GSTP1 rs1695 Mutation Induced by Adriamycin and Cyclophosphamide","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-02 17:30:30","doi":"10.21203/rs.3.rs-5513178/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1ab529c8-75b8-4a54-88ab-f26cab741184","owner":[],"postedDate":"December 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":40671224,"name":"Clinical Pharmacology"},{"id":40671225,"name":"Oncology"}],"tags":[],"updatedAt":"2024-12-02T17:30:30+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-02 17:30:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5513178","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5513178","identity":"rs-5513178","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}