Posted on Authorea 11 Sep 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159986215.56704311 — This a preprint and has not been peer reviewed. Data may be preliminary. 03 ewsmngdi u eiti ntbcueo urn aoal ucmsfrAoecnsand Adolescents for outcomes favorable current of protocols. November because COG in unit pediatric breath with of pediatric treating shortness our ALL and in with cough, (AYA) fever, managed Adults with Young was presented He syndrome Down with 2013. male year-old 30 chemotherapy salvage A R3 ALL of cycles PRESENTATION two marrow CASE bone receiving late only infections. a had after systemic who years severe (DS-ALL) 2 ALL to and for due syndrome remission Down with sustained man and year-old 37 relapse a of cause an disease case precipitating a whose except describe without leukemia We infections, myeloid days severe acute 35 mutant to for duplication remission secondary tandem treatment- spontaneous therapy internal underwent FLT3 2-year of relapsed a cessation with following patient and older remission patients infection sustained non-DS severe ALL with in latter. leukemia after after 15% the outcome remission in with of spontaneous 2% comparing factor with attained 7% 26% prognostic of of independent mortality an relapse related be of to incidence proven cumulative 40% was about itself of DS relapse. adults in outcomes. prognosis survival suboptimal worse long-term a even have overall ALL poor relapsed with with still but cure-rates children, attained in successfully have 1-3 90-95% (ALL) leukemia approximately lymphoblastic of acute for regimens treatment current The is infection severe combined chemotherapy INTRODUCTION partial to due relapse ALL rare. after prognosis. remission poor long-term a Transient has MRD mortality. positive treatment-related with and ALL relapse Relapsed of rate higher a has DS-ALL late for remission with message in patient clinical remained DS-ALL patient Key infections. a The systemic severe describe chemotherapy. to We reinduction due R3 discontinued mortality. ALL was treatment-related British therapy after per and years treated relapse two was approximately of who rate relapse marrow higher bone a have patients DS-ALL Abstract 2020 11, September 1 Hu Zhongbo R3 British partial only chemotherapy despite remission lymphoblastic sustained acute with relapsed leukemia and syndrome Down with Patient HRibwBbe n hlrnsHospital Children’s and Babies Rainbow UH tsilrmisasgicn hleg oipoetesria fptet ihrlpe L.Patients ALL. relapsed with patients of survival the improve to challenge significant a remains still It . 5 L ainswt Shv ihrrt frlpeadtetetrltdmraiy iha 8-year an with mortality, related treatment and relapse of rate higher a have DS with patients ALL 1 rse VanHeyst Kristen , 1 ins Dalal Jignesh , 6 hr r eea aerprso ainswt ekmawho leukemia with patients of reports case several are There ,4 1, onsnrm ains(S ihrlpe L have ALL relapsed with (DS) patients syndrome Down . 1 7-9 1 hr r orprso ain ihrelapsed with patient a of reports no are There . n iaHackney Lisa and , 11 10 i opeebodcut(CBC) count blood complete His . 1 Posted on Authorea 11 Sep 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159986215.56704311 — This a preprint and has not been peer reviewed. Data may be preliminary. lhuhhg oeMtxnrn lsCtrbn eeeetv naheigrmsini refractory year in a remission half achieving about in only was effective remission were the Cytarabine of plus duration Mitoxantrone the leukemia, dose high relapse Although experience ALL complications. with infectious patients severe subgroups relapse develop adult high-risk The in of rate, 25-30%) patients. relapse 50% ALL (about high higher of have to substantially cure but 40% the children, for estimated in obstacles ALL childrenAn important of in most 10-15% the 90% about still above is are reaching rate cases ALL adult of and survival ALL leukemia-free patientrelapsed with remission the long-term unfortunately current Despite and therapy marrow further bone no and for DISCUSSION treatment opted his later. with Family stopping weeks presented to after 7 he team disease. away years Unfortunately, treatment relapsed passed continued 2 outpatient. and marrow with about an family bone consistent as thrombocytopenia his repeat was closely and a by followed psychosis disease, made and was relapsed onset was overload, He of acute decision fluid MRD. diagnosis a negative broviac, his point, after demonstrate his weeks to this of 50 Once At removal but About MRD. Methotrexate necessitating chemotherapy. lesion. negative during to dosed stop infection lung demonstrate intermediate held by cavitary related to with was complicated persistent continued delirium attempted chemotherapy was a months developed was his course three chemotherapy also illness, after hospital stable, He marrow severe this clinically bone to more A defect. Due became wall he period. bowel hospitalization. bowel month small prolonged abnormal splenic three small of complete and a area focal near illness segmental for revealed a severe and also concern his liquefaction bi- imaging and of severe CT signs enhancement While with and albicans. wall deficits MRD. pneumonia, perfusion Candida negative renal necrotizing revealed had right BAL marrow sepsis, infarct, bone developed effusions. his he pleural which chemotherapy, lateral after Intensification 15-19), Vin- for day rescue, hospitalized 100mg/m2/dose 440mg/m2/dose Leucovorin Cyclophosphamide Etoposide with 9, 15-19, day 1, 8 2500U/m2/dose day day day PEG-asparaginase Methotrexate 8). 3, 1000mg/m2/dose (Intrathecal day and methotrexate 1.5ng/m2/dose protocol 1 cristine R3 1-5, ALL day day per Methotrexate 6mg/m2/day chemotherapy Intrathecal Dexamethasone Consolidation from receive 18; to 1.5mg/m2/dose 1). and continued (Table He Vincristine 3 0.2% day was 1-2, (Dexamethasone MRD 2500U/M2 day was 29 protocol PEG-asparaginase 10mg/m2/dose day CNS R3 weekly; Post-reinduction Mitoxantrone ALL 21. then chromosome per 15-19, 3, chemotherapy of & day trisomy Reinduction positive 1-5 constitutional with marrow also his day was treated with bone and consistent was beside 20mg/m2/day cells repeat blasts, 9p relapse of a 82% chromosome This 63.5% with in on diagnosis, negative. marrow positive CDKN2A initial translocation bone of CRLF2 the cellular deletion showed 90% after FISH for a years relapse. showed marrow thrombocytopenia four and bone of was obtained late achieved level was which he lowest he count biopsy which his 2017, platelet and and At for his September aspirate 17 treatment, 112x10ˆ9/L. failure his in Day and multi-organ of complicated 48x10ˆ9/L at 90x10ˆ9/L end included the between marrow a Following which to DVT, ranged M1 of had associated and line one a He normalized PICC sepsis, with (MRD). never and of ICU, response disease Medical episodes early the residual in few rapid minimal was factor a risk a negative including NCI had with to course He due Induction treatment arm after syndrome old. Down remission years AALL1131, complete 10 protocol above risk blasts. high age for COG negative 17 for per was day treated fluid was on patient cerebrospinal ETV6 two obtained The Diagnostic with nuc sample 21 signals. showed trisomy marrow RUNX1 AALL1131 constitutional three study for bone and (COG) pattern B-precursor CD10 a signal Group signals with normal CD19, from Oncology consistent a Children’s FISH was was CD34, the which which but ish(ETV6x2,RUNX1x3)[250] per co-expressed cytometry, successful as flow which chemotherapy and not by Induction blasts g/dL, CD33 was during 73% dim 8.3 analysis confirmed of of biopsy with Cytogenetic expression and hemoglobin ALL. leukemia aspirate aberrant 10ˆ9/L, marrow lymphoblastic with x Bone TdT acute 1.4 blasts. and circulating of of occasional count diagnosis with (WBC) 10ˆ9/L the cell x 32 blood of white count platelet a with pancytopenia showed 6 atal u opo oeac oat-ekmadrugs. anti-leukemia to tolerance poor to due partially 16 2 17 n tl bu 0 fALpa- ALL of 50% about still and 15 16 Sptet ihALeven ALL with patients DS . Sptet oefrequently more patients DS 3 14 13, ,12 1, , . Posted on Authorea 11 Sep 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159986215.56704311 — This a preprint and has not been peer reviewed. Data may be preliminary. orce ain aaadrvsdtemnsrp.J:wsivle noealspriino h ae.All paper. the of supervision overall manuscript. in final involved reviewed, the was LH: approved KAV, JD: and manuscript. manuscript. read the the wrote revised authors: and and review, literature data a patient performed corrected data, patient the gathered ZH: CONTRIBUTIONS interest. AUTHORS’ of conflicts systemic no the declare with authors protocol The R3 ALL INTEREST per chemotherapy OF infections. of CONFLICTS severe phases multiple two his the to of related combination leading stress patients a leukemia cells to myeloid killer acute attributed blast in natural be series residual and case macrophages, the and cases lymphocytes, inhibit several effect T directly anti-leukemia of can immune- an activity an infection to duration increased with during through in combined released or weeks infection interleukin-2, proliferation ten or and averaged de- stress interferon-alpha, with during been effects alpha, production anti-leukemic reports has generating cortisol series infection thereby increased process severe case mediated to during and due leukemia cases was lymphoblastic few mechanism acute a of of in management remission scribed the transient in or breakthroughs Spontaneous major are therapies CD19- –cell and options T Inotzumab, more leukemia (CAR) Blinatumomab, relapsed time, antibody-targeted we receptor Currently, antibody Over which antigen toxicity. T-cell-engaging therapy, chimeric less parents. (CD3/CD19) of confer directed patient’s bispecific that relapse. cessation by ALL as approved disease for relapsed such was following with made therapies, patients and was protocol for multi- better available decision R3 developed becoming patient a ALL are also the experienced, the benefit He he per would chemotherapy that AALL1131. thought toxicity of inferior per significant phases survival chemotherapy the two overall initial Given after and his event-free infections five-year severe during the ple infections multiple both made had which patient DS-ALL DS-ALL, with in patients in protocols protocols. all pediatric in with pre- creased 15%) B-cell treated vs developing are (26% of they patients risk when non-DS increased than 20-fold relapse to of 10- incidence remained have but to relapse, well-known ALL. 56% first are cursor with his syndrome for MRD Down protocol low with R3 Patients the years. ALL in two the that nearly per with for chemotherapy remission of comparing phases in group two MRD receiving In high only R3. the after ALL in 27% lower per about 72% chemotherapy significantly was our versus continue with was rate for toxicities to years relapse group his chose second 5 a chemotherapy, given We was as at with high rate this group status. too discussed relapse MRD syndrome be had low second would Down We the (TRM) the his transplant. mortality years, and cell related 7 chemotherapy stem transplant after initial for his MRD even patients that group thought low relapse MRD and marrow and high patient bone the relapse in late marrow 23% the about bone ( of late follow-up MRD long-term with higher Consolidation. after ALL with after the Patients MRD B-precursor per negative as with and transplantation. treated patients Reinduction was He after protocol, 0.2% therapy). R3 ( front-line of of ALL MRD months end positive 36 the the had occurring after Per months and relapse 6 as protocol than (defined R3 more relapse ALL or marrow diagnosis bone first late with the have children after protocol to in considered R3 survival was overall ALL chemotherapy, and tial the progression-free in to response prior ALL significant relapsed therapy a confer salvage to to Mitoxantrone utilizes respond not do tients < .1)a h n fidcinhdfvrbeotoe ihceohrp ihu negigstem-cell undergoing without chemotherapy with outcomes favorable had induction of end the at 0.01%) 19 20 u aei nqei htteptetwssilcmlctdwt eea ytmcinfection systemic several with complicated still was patient the that in unique is case Our . 4 h ot iLgosuygopsoe htD-L ainshdhge -ercumulative 8-year higher had patients DS-ALL that showed group study Legno di Ponte The u ain,wohdabn arwrlpeaot2 otsatrtecmlto fhsini- his of completion the after months 20 about relapse marrow bone a had who patient, Our . 23 . 1 22 21, 6 27 26, urn O rtcl aemd oictost ii oiiis Our toxicities. limit to modifications made have protocols COG Current . iia hnmn n ehnsshv endsusdadrpre in reported and discussed been have mechanisms and phenomena Similar . > 11 .1)rqie loeecse-eltaslnain But transplantation. stem-cell allogeneic required 0.01%) ramn-eae otlt,piaiyfo neto,in- infection, from primarily mortality, Treatment-related 3 6 Y ainswt L aefvrbeoutcomes favorable have ALL with patients AYA . ,8 25 8, 7, 8 29 28, yoie,icuigtmrncoi factor- necrosis tumor including Cytokines, . u ain’ ogtr eiso may remission long-term patient’s Our . 18 19 h rts L 3protocol R3 ALL British The . h rgeso-resurvival progression-free The . -,24 7-9, h proposed The . Posted on Authorea 11 Sep 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159986215.56704311 — This a preprint and has not been peer reviewed. Data may be preliminary. 7 ann ,SplegO ilsS ta.Slaeteayo ercoyadrlpe ct ekmawith leukemia acute relapsed and refractory and of pathobiology therapy cytarabine. Salvage syndrome: dose Down’s al. high et 2126(99)00078-8 in and S, ALL mitoxantrone Gillis treat dose O, high I Shpilberg P, How Raanani J. 17. Whitlock Lym- CM, Acute Zwaan Adult A, of Vora Management management. S, the Izraeli in Innovations 16. and Progress leukaemia. H. Kantarjian lymphoblastic CH, Leukemia. acute Pui phoblastic E, childhood Jabbour Relapsed 15. CH. leukaemia. Pui lymphoblastic doi:10.1016/S1470-2045(12)70580-6 acute D, 2013;14(6):e205-17. childhood Bhojwani Progress in on risk 14. Report relapse Annual Predicting SP. 2019: Hunger Advances Haematol DT, Cancer Teachey Clinical 13. al. adults Oncology. et young Clinical N, of and Society Agarwal adolescents doi:10.1200/JCO.18.02037 American MJ, the older From Miller for Cancer SK, Against regimen Pal 10403. pediatric A CALGB 12. of al. Relapsed results et with AS, Patient leukemia: Advani Older doi:10.1182/blood-2018-10-881961 lymphoblastic SM, an acute in Luger Remission with W, Spontaneous Stock al. 11. et A, AML. Evans Mutant JH, ITD Mendler FLT3 case with P, A leukemia Vachhani leukemia: lymphoblastic lymphoblastic 10. acute acute of of remission Spontaneous remission K. Schaefer-Eckart Spontaneous K, report. Wendelin T, al. of Hores et Remission 9. E, Spontaneous Celiker of M, Case Erguven mass. Rare mediastinal A, A Yoruk L. 8. Giordano D, doi:10.1097/MPH.0000000000000906 Dighe 2018;40(3):e176-e178. Apr V, Angelova . Leukemia. 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