Neonatal Leukemia: A Case report of a rare disease with an atypical presentation

Neonatal Leukemia: A Case report of a rare disease with an atypical presentation | 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 Neonatal Leukemia: A Case report of a rare disease with an atypical presentation Alazar Wogayehu Gebrehana, Wondwosen Mengist Dereje, Nestanet Gete Kasawudeg, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4852511/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 Background Even though Leukemia is one of the commonest causes of childhood cancer its occurrence in the newborn period is very uncommon, specially when presenting with non-specific symptoms. Case Presentation A 10 days old female Ethiopian infant was referred from a tertiary hospital to the Neonatal intensive care unit of Gondar university comprehensive specialized hospital after they found a markedly elevated leukocyte count while working her up for early onset neonatal sepsis as she was experiencing persistent vomiting since the first day of delivery. Physical examination was only notable for palpable spleen 3cm below the left costal margin. Further evaluation with peripheral morphology and bone marrow aspiration revealed numerous blast cells and a diagnosis of acute lymphoblastic leukemia. Conclusion Neonatal leukemia, a rare disease in newborns, may present with unusual symptoms. It should be considered among the differential diagnosis when accompanied by the presence of abnormalities in blood counts and other suggestive features. Neonatal leukemia Congenital leukemia Leukemia Acute lymphoblastic leukemia Figures Figure 1 Background Leukemia presenting in the first 4 weeks of life is termed as neonatal or congenital leukemia. This type of leukemia is rare with estimated incidence ranging from 1 to 5 per million live births(1). Reports have shown that acute myeloid leukemia (AML) is more common than acute lymphoblastic leukemia(ALL) in neonatal leukemia(2,3). The most common clinical signs are hepatomegaly, splenomegaly and skin lesions(leukemic cutis). The most consistent hematologic abnormality is hyperleucocytosis(4) which is usually associated with anemia and thrombocytopenia. Aside from trisomy 21, the most frequently occurring chromosomal aberration in both neonatal AML and ALL is a translocation involving the KMT2A gene formerly known as mixed lineage leukaemia (MLL) gene, located on chromosomal band 11q23. The prognosis for NL is typically poor and it is usually associated with treatment- related mortality. Additionally, there is a high rate of relapse in NL compared to leukemia in older children(2). Case Presentation A 10 days old female Ethiopian neonate was referred from a tertiary hospital to Gondar university comprehensive specialized hospital, Neonatal intensive care unit after she was found to have markedly elevated leukocyte count while working her up for early onset neonatal sepsis. She was experiencing non bilious vomiting of ingested matter occurring two to three times per day since the first day of life. Other than the vomiting the neonate had no failure to suck, fast breathing, fever, change in mentation or abdominal distention. She also has no sunkening of eyes, decreased urine output or weight loss. She was born to a 27 years old para I mother at gestational age of 40 weeks +2 days . The mother had regular ANC visits during her pregnancy and she has had all cares and services . the mother has no history of radiation exposure or any chemotherapy drug intake. There was no family history of malignancy. The pregnancy was uneventful. The labor started spontaneously lasting 12 hours and the mode of delivery was spontaneous vaginal delivery and birth weight was 2600gram . Initially the mother took her to a nearby health center at the 3 rd day of life, where she was reassured it was a physiologic regurgitation. Over the following days, the vomiting did not subside and the mother took her to a tertiary hospital at the 10 th day of birth where a complete blood count was done as part of evaluation foe neonatal sepsis. The WBC was markedly elevated(248,000/mm 3 ) which prompted the team for a peripheral morphology examination which revealed numerous atypical lymphocytes and blast cells. Finally she was referred to our center for further evaluation of possible leukemia. At admission at our hospital the neonate was alert and her vitals were within normal range. She had no dysmorphic features. The only notable finding on physical examination was a palpable spleen 3 centimeters below the left costal margin. CBC results showed WBC (273*10 3 /mm 3 ), Hemoglobin(14.3g/dl), Hematocrit (42 %) and Platelet count (56*10 3/ mm 3 ). Her uric acid, Lactate dehydrogenase, serum electrolytes and serum Creatinine levels were within normal range. Bone marrow aspiration revealed ALL(Figure 1). Because of in-availability other standard diagnostic testing like flow cytometry for immunophenotyping, karyotype, fluorescence in situ hybridizationation were not done.The patient was started on antibiotics and IV hydration. After discussion with the parents about the treatment options available and their possible benefits and toxicities, the parents decided not to start chemotherapy and the patient was discharged as she had no complications needing supportive care. Contact with the parents was maintained via telephone and the newborn developed fast breathing and became pale and was taken to a local health center and later died at the age of 55 days at the health center. Discussion and Conclusions Neonatal leukemia accounts for less than 1% of all childhood leukemia(5). NL is the third-most prevalent malignancy in infants after teratoma and neuroblastoma(6). AML is more common than ALL in NL and out of the reported ALL cases, nearly all are of B- lineage with fewer than 5% T- lineage(7). Based on cytogenetic and molecular characteristics a high proportion of NL patients have a KMT2A/11q23.3 rearrangement which is found in 70-80% of patients with ALL and in 50% of those with AML(8,9). Trisomy 21 is also associated with a preleukemic disorder which usually resolves spontaneously known as TAM(transient abnormal myelopoiesis ). Although infrequent, TAM may later develop into AML. The most common clinical manifestations in NL include hepatomegaly, splenomegaly and leukemic cutis. Lymphadenopathy is less common in NL compared to leukemias in older children. CNS infiltration occurs in approximately 50% of cases and usually presents with bulging fontanelle, reduced level of consciousness and papilledema(10).Cutaneous involvements are specially seen in neonatal AML and can occur without peripheral blood and bone marrow involvement.(11,12). Criteria used for the diagnosis of NL include(13): Diagnosis within 28 d of birth; specific number or proportion(usually 20%) of primitive or immature cells in the bone marrow aspirate, and significantly high peripheral blood leukocyte counts (> 25 × 109/L); spread of primitive cells to areas beyond the blood and bone marrow; and no evidence of other disorder that might cause infiltration of non-hematopoietic tissues. The differential diagnosis of NL include leukemoid reactions secondary to infections, Severe hemolytic disease of the newborn, particularly Rh incompatibility, TAM associated with down syndrome and advanced stages of neuroblastoma among others. The newborn’s unique susceptibility to complications and toxicities has proven to be a challenge in treatment of NL. Even though chemotherapy for neonatal leukemia(NL) can be curative(14,15), its usually have a poorer prognosis compared to leukemia in older children. Studies has shown that Prognosis for ALL is worse than that of AML(16). The 4 year event-free survival (EFS) in Interfant-99,the largest trial of infant ALL to date, was 47%(17). Different clinical trials use a hybrid chemotherapy which combines the standard ALL regimen mixed with some elements of AML treatments. Certain characteristics in NL have been identified as high risk which pertain poorer prognosis. These include presence of KMT2A rearrangement, younger infants and those with higher WBC count.(18). Interestingly in some patients with NL spontaneous remission has occurred(19). Its unclear which patients are likely to have a spontaneous remission and can avoid chemotherapy but a case series has shown 7 neonatal cases all with t(8;16) have shown spontaneous remission(20). out of the 7 some eventually relapsed. In conclusion, Our case shows that NL may present with unusual symptoms and a high index suspicion is important to reveal the diagnosis, specially when accompanied by abnormalities in blood counts. Abbreviations AML Acute myeloid leukemia ALL Acute Lymphoblastic leukemia NL Neonatal Leukemia ANC Antenatal care WBC White blood counts CBC Complete blood counts TAM Transient abnormal myelopoiesis Declarations Acknowledgments The authors gratefully acknowledge that all team members dedicate their best efforts to care for our patient. We would also like to thank the parents of our patient for maintaining continuous contact with us via telephone despite facing difficulties related to their infant’s illness. Author contributions AWG was a major contributor in conceptualizing and writing this manuscript and was also involved in diagnosis of the patient and counseling of parents. WMD and NGK were involved with the diagnosis of the patient and also maintaining contact with the parents after discharge. BA, GM and EA were involved with preparing and reviewing the Bone marrow aspiration and peripheral smears of the patient. Funding This research received no funding or grant support. Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Ethics approval and consent to participate This study was conducted in accordance with the fundamental principles of the Declaration of Helsinki. Consent for publication Written informed consent was obtained from the patient’s mother for publication of this case report and any accompanying images. A copy of the written consent is available for review by the corresponding author. Competing interests The authors declare that they have no competing interests. References Bader JL, Miller RW. US cancer incidence and mortality in the first year of life. Am J Dis Child. 1979;133:157–9. Bresters D, Reus AC, Veerman AJ, van Wering ER, den Berg A, Kaspers GJ. Congenital leukaemia: the Dutch experience and review of the literature. Br J Haematol. 2002;117:513–24. Isaacs H Jr. Fetal and neonatal leukemia. J Pediatr Hematol Oncol. 2003;25:348–61. Heikinheimo M, Pakkala S, Juvonen E, Saarinen UM. Immuno- and cytochemical characterization of congenital leukemia: a case report. Med Pediatr Oncol. 1994;22:279–82. Tsujimoto H, Kounami S, Mitani Y, Watanabe T, Takifuji K. Neonatal Acute Megakaryoblastic Leukemia Presenting with Leukemia Cutis and Multiple Intracranial Lesions Successfully Treated with Unrelated Cord Blood Transplantation. Case Rep Hematol. 2015;2015:610581. Orbach D, Sarnacki S, Brisse HJ, Gauthier-Villars M, Jarreau PH, Tsatsaris V, Baruchel A, Zerah M, Seigneur E, Peuchmaur M, Doz F. Neonatal cancer. Lancet Oncol. 2013;14:e609–20. Brown PA. Neonatal Leukemia. Clin Perinatol. 2021;48(1):15–33. 10.1016/j.clp.2020.11.002 . Pieters R, De Lorenzo P, Ancliffe P, et al. Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant–06 protocol: results from an international phase III randomized study. J Clin Oncol. 2019;37(25):2246–56. Harrison CJ, Hills RK, Moorman AV, et al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol. 2010;28(16):2674–81. Roberts I, Fordham NJ, Rao A, Bain BJ. Neonatal leukaemia. Br J Haematol. 2018;182(2):170–84. 10.1111/bjh.15246 . Zhang IH, Zane LT, Braun BS, Maize J, Zoger S, Loh ML. Congenital leukemia cutis with subsequent development of leukemia. J Am Acad Dermatol. 2006;54(Suppl):S22–7. Lee EG, Kim TH, Yoon MS, Lee HJ. Congenital leukemia cutis preceding acute myeloid leukemia with t(9;11)(p22;q23), MLL-MLLT3. J Dermatol. 2013;40:570–1. Green K, Tandon S, Ahmed M, Toscano W, O'Connor D, Ancliff P, Vora A, Bartram J, Samarasinghe S, Ghorashian S, Pavasovic V, Rao A. Congenital acute myeloid leukemia: challenges and lessons. A 15-year experience from the UK. Leuk Lymphoma. 2021;62:688–95. Van der Linden MH, Valsecchi MG, De Lorenzo P, M€oricke A, Janka G, Leblanc TM, Felice M, Biondi A, Campbell M, Hann I, Rubnitz JE, Stary J, Szczepanski T, Vora A, Ferster A, Hovi L, Silverman LB, Pieters R. Outcome of congenital acute lymphoblastic leukemia treated on the Interfant–999 protocol. Blood. 2009;114:3764–8. Creutzig U, Zimmermann M, Bourquin J-P, Dworzak MN, Kremens B, Lehmbecher T, von Neuhoff C, Sander A, von Stackelberg A, Schmid I, Stary J, Steinbach D, Vormoor J, Reinhardt D. Favorable outcome in infants with AML after intensive first- and second-line treatment: an AML-BFM study group report. Leukemia. 2012a;26:654–61. Bresters D, Reus ACW, Veeman AJP, et al. Congenital leukaemia: The Dutch experience and review of the literature. Br J Haematol. 2002;117:513–24. Pieters R, De Lorenzo P, Ancliffe P, et al. Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant–06 protocol: results from an international phase III randomized study. J Clin Oncol. 2019;37(25):2246–56. Sande JE, Arceci RJ, Lampkin BC. Congenital and neonatal leukemia. Sem Perinatol. 1999;23:274–85. Rossoff J, Akpan I, Platanias LC. Spontaneous remission in congenital leukemia. Leuk Lymphoma. 2018;59:2271–2. Coenen EA, Zwaan CM, Reinhardt D, Harrison CJ, Haas OA, de Haas V, Mihal V, De Moerloose B, Jeison M, Rubnitz JE, Tomizawa D, Johnston D, Alonzo TA, Hasle H, Auvrignon A, Dworzak M, Pession A, van der Velden VH, Swansbury J, Wong KF, Terui K, Savasan S, Winstanley M, Vaitkeviciene G, Zimmermann M, Pieters R, van den Heuvel-Eibrink MM. Pediatric acute myeloid leukemia with t(8;16)(p11; p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Munster AML-study group. Blood. 2013;122:2704–271. Additional Declarations No competing interests reported. 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-4852511","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":342984927,"identity":"39381b25-095d-4b80-a334-b17af64949fc","order_by":0,"name":"Alazar Wogayehu Gebrehana","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIiWNgGAWjYDACdjijAUgYWBChhRnG4DkA0iJBihaJBDBJWAd/M/PjDz/3HJaTj3x+dcOPAgkG/vbuBLxaJA6zGRj2PDtsbHg7p+xmD9BhEmfObsBvzWEGgwSeA7cTN87OSbvBA9RiIJGLX4v8YfYPB/+AtMw8k3bzDzFaDA7zGDaDbJkvwX7sNlG2GB7mKWaWOfDf2IAnh+22jIEED0G/yB1v3/zxzYE0Ofn2489uvvljI8ff3kvA+3AXHuAxANE8xCkHAfkG9gfEqx4Fo2AUjIIRBQC890m0zLhcFAAAAABJRU5ErkJggg==","orcid":"","institution":"University of Gondar","correspondingAuthor":true,"prefix":"","firstName":"Alazar","middleName":"Wogayehu","lastName":"Gebrehana","suffix":""},{"id":342984928,"identity":"7f2894b4-27ae-423c-9d0c-942ebb246a96","order_by":1,"name":"Wondwosen Mengist Dereje","email":"","orcid":"","institution":"University of Gondar","correspondingAuthor":false,"prefix":"","firstName":"Wondwosen","middleName":"Mengist","lastName":"Dereje","suffix":""},{"id":342984929,"identity":"287f5dde-7b19-4afd-a6ce-111e05814221","order_by":2,"name":"Nestanet Gete Kasawudeg","email":"","orcid":"","institution":"University of Gondar","correspondingAuthor":false,"prefix":"","firstName":"Nestanet","middleName":"Gete","lastName":"Kasawudeg","suffix":""},{"id":342984930,"identity":"379728a4-8f01-4fe4-bc61-63a6f4ed405f","order_by":3,"name":"Bewketu Abebe","email":"","orcid":"","institution":"University of Gondar","correspondingAuthor":false,"prefix":"","firstName":"Bewketu","middleName":"","lastName":"Abebe","suffix":""},{"id":342984931,"identity":"848f099e-9ebf-4549-b8ee-a2db088a4949","order_by":4,"name":"Gebremariam maru","email":"","orcid":"","institution":"University of Gondar","correspondingAuthor":false,"prefix":"","firstName":"Gebremariam","middleName":"","lastName":"maru","suffix":""},{"id":342984932,"identity":"b64145dd-b89b-4ff0-9d39-cbd1abb37e89","order_by":5,"name":"Ephrem Awoke","email":"","orcid":"","institution":"University of Gondar","correspondingAuthor":false,"prefix":"","firstName":"Ephrem","middleName":"","lastName":"Awoke","suffix":""}],"badges":[],"createdAt":"2024-08-03 09:23:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4852511/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4852511/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63127065,"identity":"8c4d1f53-a7d0-418d-b985-7e506e3fdbd6","added_by":"auto","created_at":"2024-08-23 12:27:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":591772,"visible":true,"origin":"","legend":"\u003cp\u003eBone Marrow is bussy with proliferation of small to intermediate sized lymphoid cells having scant to moderate amount of deep blue finely vaculoated cytoplasm, round to indentented to irregular nuclei some with multiple conspicuous to prominent nuclei and numerous smudged cells. No auer rods seen.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4852511/v1/55a35f42163d966d20d4c49e.png"},{"id":63127938,"identity":"eab6ac6e-112e-4644-8e72-2be4267c057f","added_by":"auto","created_at":"2024-08-23 12:35:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1023146,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4852511/v1/4314e7f7-eb25-423c-b69c-ec89085fa4ca.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neonatal Leukemia: A Case report of a rare disease with an atypical presentation","fulltext":[{"header":"Background","content":"\u003cp\u003eLeukemia presenting in the first 4 weeks of \u0026nbsp;life is termed as neonatal or congenital leukemia. This type of leukemia is rare with estimated incidence ranging from 1 to 5 per million live births(1). \u0026nbsp;Reports have shown that acute myeloid leukemia (AML) \u0026nbsp;is more common than acute lymphoblastic leukemia(ALL) in neonatal leukemia(2,3).\u003c/p\u003e\n\u003cp\u003eThe most common clinical signs are hepatomegaly, splenomegaly and skin lesions(leukemic cutis). The most consistent hematologic abnormality is hyperleucocytosis(4) which is usually associated with anemia and thrombocytopenia.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAside from trisomy 21, the most frequently occurring chromosomal aberration in both neonatal AML and ALL is a translocation involving the KMT2A gene formerly known as \u0026nbsp;mixed lineage leukaemia (MLL) gene, located on chromosomal band 11q23.\u003c/p\u003e\n\u003cp\u003eThe prognosis for NL is typically poor and it is usually associated with treatment- related mortality. Additionally, there is a high rate of relapse in NL compared to leukemia in older children(2).\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 10 days old female Ethiopian \u0026nbsp;neonate was \u0026nbsp; referred from a tertiary hospital to Gondar university comprehensive specialized hospital, Neonatal intensive care unit after she was found to have markedly elevated leukocyte count while working her up for early onset neonatal sepsis. She was experiencing non bilious vomiting of ingested matter occurring two to three times per day \u0026nbsp;since the first day of life. Other than the vomiting the neonate had no failure to suck, fast breathing, fever, change in mentation or abdominal distention. She also has no sunkening of eyes, decreased urine output or weight loss.\u003c/p\u003e\n\u003cp\u003eShe was born to a 27 years old para I mother at gestational age of 40 weeks +2 days . The mother had regular ANC visits during her pregnancy and she has had all cares and services . the mother has no history of radiation exposure or any chemotherapy drug intake. There was no family history of malignancy. The pregnancy was uneventful. The labor started spontaneously lasting 12 hours and the mode of delivery was spontaneous vaginal delivery and birth weight was 2600gram .\u003c/p\u003e\n\u003cp\u003eInitially the mother took her to a nearby health center at the 3\u003csup\u003erd\u003c/sup\u003e day of \u0026nbsp; life, where she was reassured it was a physiologic regurgitation. Over the following days, the vomiting did not subside and the mother took her to a tertiary hospital at the 10\u003csup\u003eth\u003c/sup\u003e day of birth where a complete blood count was done as part of evaluation foe neonatal sepsis. The WBC was markedly elevated(248,000/mm\u003csup\u003e3\u0026nbsp;\u003c/sup\u003e) which prompted the team for a peripheral morphology examination which revealed numerous atypical lymphocytes and blast cells. Finally she was referred \u0026nbsp;to our center for further evaluation of \u0026nbsp;possible leukemia.\u003c/p\u003e\n\u003cp\u003eAt admission at our hospital the neonate was alert and her vitals were within normal range. She had no dysmorphic features. The only notable finding on physical examination was a palpable spleen 3 centimeters below the left costal margin.\u003c/p\u003e\n\u003cp\u003eCBC results showed\u0026nbsp;WBC (273*10\u003csup\u003e3\u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e\u0026nbsp; ), Hemoglobin(14.3g/dl), Hematocrit (42 %) and Platelet count (56*10\u003csup\u003e3/\u003c/sup\u003emm\u003csup\u003e3\u003c/sup\u003e). Her uric acid, Lactate dehydrogenase, serum electrolytes \u0026nbsp;and \u0026nbsp; serum Creatinine levels were within normal range. Bone marrow aspiration \u0026nbsp;revealed \u0026nbsp;ALL(Figure 1).\u003c/p\u003e\n\u003cp\u003eBecause of in-availability other standard diagnostic testing like flow cytometry for immunophenotyping, karyotype, fluorescence in situ hybridizationation were not done.The patient was started on antibiotics and IV hydration. After discussion with the parents about the treatment options available and their possible benefits and toxicities, the parents decided \u0026nbsp;not to start chemotherapy and the patient was discharged as she had no complications needing supportive care.\u003c/p\u003e\n\u003cp\u003eContact with the parents was maintained via telephone and the newborn developed fast breathing and became pale and was taken to a \u0026nbsp;local health center and \u0026nbsp;later died at the age of 55 days at the health center.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eNeonatal leukemia accounts for less than 1% of all childhood leukemia(5). NL is the third-most prevalent malignancy in infants after teratoma and neuroblastoma(6).\u003c/p\u003e\n\u003cp\u003eAML is more common than ALL in NL and out of the reported ALL cases, nearly all are of B- lineage with fewer than 5% T- lineage(7). Based on cytogenetic and molecular characteristics a high proportion of NL patients have a KMT2A/11q23.3 rearrangement which is found in 70-80% of patients with ALL and in 50% of those with AML(8,9). Trisomy 21 is also associated with a preleukemic disorder which usually resolves spontaneously known as \u0026nbsp; TAM(transient abnormal myelopoiesis ). Although infrequent, TAM may later develop into AML.\u003c/p\u003e\n\u003cp\u003eThe most common clinical manifestations in NL include hepatomegaly, splenomegaly and leukemic cutis. Lymphadenopathy is less common in NL compared to leukemias in older children. CNS infiltration occurs in approximately 50% of cases and usually presents with bulging fontanelle, reduced level of consciousness and papilledema(10).Cutaneous involvements are specially seen in neonatal AML and can occur without peripheral blood and bone marrow involvement.(11,12).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCriteria used for the diagnosis of NL include(13): \u0026nbsp; Diagnosis within 28 d of birth; specific number or proportion(usually 20%) of primitive or immature cells in the bone marrow aspirate, and significantly high peripheral blood leukocyte counts (\u0026gt; 25 \u0026times; 109/L); spread of primitive cells to areas beyond the blood and bone marrow; and \u0026nbsp;no evidence of other disorder that might cause infiltration of non-hematopoietic tissues.\u003c/p\u003e\n\u003cp\u003eThe differential diagnosis \u0026nbsp;of NL include leukemoid reactions secondary to infections, Severe hemolytic disease of the newborn, particularly Rh incompatibility, TAM associated with down syndrome and advanced stages of neuroblastoma among others.\u003c/p\u003e\n\u003cp\u003eThe newborn\u0026rsquo;s unique susceptibility to complications and toxicities has proven to be a challenge in treatment of NL. Even though chemotherapy for neonatal leukemia(NL) can be curative(14,15), its usually have a poorer prognosis compared to leukemia in older children. Studies has shown that \u0026nbsp;Prognosis for ALL is worse than that of AML(16). The 4 year event-free survival (EFS) in Interfant-99,the largest trial of infant ALL to date, was 47%(17). Different clinical trials use a hybrid chemotherapy which combines the standard ALL regimen mixed with some elements of AML treatments.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCertain characteristics in NL have been identified as high risk which pertain poorer prognosis. These include presence of KMT2A rearrangement, younger infants and those with \u0026nbsp;higher WBC count.(18).\u003c/p\u003e\n\u003cp\u003eInterestingly in some patients with NL spontaneous remission has occurred(19). Its unclear which patients are likely to have a spontaneous remission and can avoid chemotherapy but a case series has shown 7 neonatal cases all with t(8;16) have shown spontaneous remission(20). out of the 7 some eventually relapsed.\u003c/p\u003e\n\u003cp\u003eIn conclusion, Our case shows that NL may present with unusual symptoms and a high index suspicion is important to reveal the diagnosis, specially when accompanied by abnormalities in blood counts.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAML\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcute myeloid leukemia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcute Lymphoblastic leukemia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeonatal Leukemia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAntenatal care\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWhite blood counts\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComplete blood counts\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTAM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTransient abnormal myelopoiesis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge that all team members dedicate their best efforts to care for our patient. We would also like to thank the parents of our patient for maintaining continuous contact with us via telephone despite facing difficulties related to their infant\u0026rsquo;s illness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAWG was a major contributor in conceptualizing and writing this manuscript and was also involved in diagnosis of the patient and counseling of parents. WMD and NGK were involved with the diagnosis of the patient and also maintaining contact with the parents after discharge. BA, GM and EA were involved with preparing and reviewing the Bone marrow aspiration and peripheral smears of the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no funding or grant support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analyzed during the current \u0026nbsp;study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the fundamental principles of the Declaration of Helsinki.\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 patient\u0026rsquo;s mother for publication of this case report and any accompanying images. A copy of the written consent is available for review by the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBader JL, Miller RW. US cancer incidence and mortality in the first year of life. Am J Dis Child. 1979;133:157\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBresters D, Reus AC, Veerman AJ, van Wering ER, den Berg A, Kaspers GJ. Congenital leukaemia: the Dutch experience and review of the literature. Br J Haematol. 2002;117:513\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIsaacs H Jr. Fetal and neonatal leukemia. 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Leukemia. 2012a;26:654\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBresters D, Reus ACW, Veeman AJP, et al. Congenital leukaemia: The Dutch experience and review of the literature. Br J Haematol. 2002;117:513\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePieters R, De Lorenzo P, Ancliffe P, et al. Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant\u0026ndash;06 protocol: results from an international phase III randomized study. J Clin Oncol. 2019;37(25):2246\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSande JE, Arceci RJ, Lampkin BC. Congenital and neonatal leukemia. Sem Perinatol. 1999;23:274\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRossoff J, Akpan I, Platanias LC. Spontaneous remission in congenital leukemia. Leuk Lymphoma. 2018;59:2271\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoenen EA, Zwaan CM, Reinhardt D, Harrison CJ, Haas OA, de Haas V, Mihal V, De Moerloose B, Jeison M, Rubnitz JE, Tomizawa D, Johnston D, Alonzo TA, Hasle H, Auvrignon A, Dworzak M, Pession A, van der Velden VH, Swansbury J, Wong KF, Terui K, Savasan S, Winstanley M, Vaitkeviciene G, Zimmermann M, Pieters R, van den Heuvel-Eibrink MM. Pediatric acute myeloid leukemia with t(8;16)(p11; p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Munster AML-study group. Blood. 2013;122:2704\u0026ndash;271.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","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":"Neonatal leukemia, Congenital leukemia, Leukemia, Acute lymphoblastic leukemia","lastPublishedDoi":"10.21203/rs.3.rs-4852511/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4852511/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eBackground\u003c/b\u003e Even though Leukemia is one of the commonest causes of childhood cancer its occurrence in the newborn period is very uncommon, specially when presenting with non-specific symptoms.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCase Presentation\u003c/b\u003e A 10 days old female Ethiopian infant was referred from a tertiary hospital to the Neonatal intensive care unit of Gondar university comprehensive specialized hospital after they found a markedly elevated leukocyte count while working her up for early onset neonatal sepsis as she was experiencing persistent vomiting since the first day of delivery. Physical examination was only notable for palpable spleen 3cm below the left costal margin. Further evaluation with peripheral morphology and bone marrow aspiration revealed numerous blast cells and a diagnosis of acute lymphoblastic leukemia.\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusion\u003c/b\u003e Neonatal leukemia, a rare disease in newborns, may present with unusual symptoms. It should be considered among the differential diagnosis when accompanied by the presence of abnormalities in blood counts and other suggestive features.\u003c/p\u003e","manuscriptTitle":"Neonatal Leukemia: A Case report of a rare disease with an atypical presentation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-23 12:27:02","doi":"10.21203/rs.3.rs-4852511/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":"cc7c08c4-74e5-46cc-8e29-1d96728693d3","owner":[],"postedDate":"August 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-23T12:43:28+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-23 12:27:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4852511","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4852511","identity":"rs-4852511","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}