The Combination of Clofarabine, Etoposide, and Cyclophosphamide

Posted on Authorea 16 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159493282.20139584 — This a preprint and has not been peer reviewed. Data may be preliminary. ercoyaueluei:Rslso oioe rsetv study prospective Toporski monitored Jacek with a children of for Results transplant leukemia: to acute bridge refractory a as efficacy cyclophosphamide limited and shows etoposide, clofarabine, of combination The ae fpdarcaueluei,bt hngvna igedu n ncmiainwt tpsd and etoposide with refractory combination in of in remissions and risk induce drug the single potently transplantation, a to of as shown given time when been the tumor both has the at leukemia, Clofarabine to effect acute remission correlated anti-leukemic pediatric morphological high. inversely of the least is very cases with HSCT at is together allogeneic without relapse of effect patients subsequent efficacy (GvL) In the graft-versus-leukemia However, the survivalburden. regimen. by Better conditioning mediated leukemia. the acute be of high-risk with part children precursor in in challenge. B survival and can improve unmet in (T-ALL) to an primarily leukemia seems represent lymphoblastic (HSCT) applied still transplantation acute are (AML) T-cell therapies leukemia refractory myeloblastic cell/immune whereas acute far, conventional (ALL), Thus of leukemia escalation lymphoblastic cases effective. many acute longer expectancy, in life because no short option, is reasonable a have chemotherapy only transplantation the cell remains patients treatment stem treatment. such palliative hematopoietic of to and allogeneic number resistance previous significant after a secondary relapsing (AL), or those leukemia primary acute with experience children still of survival in improvement Despite INTRODUCTION remission. our achieving with In of Also, patients chance observed. infections. some the was toxicity life-threatening increase in organ months not of significant responses and 7.5 does clinically risk induce No hepatitis probably and substantial CloEC can engraftment. adenovirus 6.5 in sustained repeating died CloEC fulminant resulting with and feasible Conclusions developed immunosuppressive, was relapsed child highly HSCT toxicity. children haploidentical is One study, Two common but most induction. course. leukemia the of acute CloEC was start refractory first to Infection after the months succumbed after enrollment. 7 two years remission after and disease 7.5 complete transplanted; graft-versus-host continuous well were skin in and died and acute died alive one no chemotherapy is and induction: off-protocol Two child engrafted to transplantation. received study. children One respond cell two transplanted the not stem All entered course; did disease children enable first leukemia. active Five progressive the to with transplantation. after control children underwent Seven progression disease and Results in courses sufficient toxicity. induction achieving and to by safety responded evaluate children survival to improve were cyclophosphamide to and objectives (HSCT). was etoposide, Secondary transplantation clofarabine, cell objective stem of hematopoietic primary courses Children haploidentical depleted induction Methods The a T-cell two for approach. conducted receive scheduled bridge-to-transplant We were to patients a leukemia. enrolled Responding as (CloEC). were refractory chemotherapy leukemia with clofarabine-based acute children of refractory in use with remission the explore induce effectively to study to prospective shown been has Clofarabine Background Abstract 2020 16, July 2 1 Turkiewicz Dominik and ka eUiest optlLbeii Skane Labmedicin Sk˚ane Hospital University Lund Sk˚ane Hospital University 1 ailvKr´ol Ladislav , 1 1 oen Dykes Josefina , 1 2 vneH˚akansson Yvonne , 1,2 hlrnfiigt civ eiso and remission achieve to failing Children 3 loeechmtpitcse cell stem hematopoietic Allogeneic 1 onlsPronk Cornelis , > rd a observed. was I grade 1 , Posted on Authorea 16 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159493282.20139584 — This a preprint and has not been peer reviewed. Data may be preliminary. h ohrwstefis hieadtefte eodcoc;i omsac a rsn,temte was mother the present, was mismatch observed, no was if mismatch choice; grafting. if second before mismatch: father –10 KIR the contraindication day on medical and to based no choice was was –12 first there selection day the if donor was from mother patients, mother the administered AML always the was For was mg/kg donor donation. 30 preferred for the of ALL, dose with total patients For a at days. (Fresenius) 21 ATG mg/m and was hypoplastic increased, 120 mg/m courses in 200 blasts melphalan CloEC blasts clofarabine the between and of 5% interval or consisted minimum [?] regimen occurred The with conditioning regeneration The Those course. until second week course. the a second to once the proceeded re-evaluated on then were started (BM) immediately criteria, marrow transplant were with the to bone Those course of responding first program. fulfillment not care Children in the palliative result of transplantation. the did pending entered responding that administered course not if was second Children and CloEC the of course, transplantation. course second to (third) the proceeded additional given and an were course course second first the the received to CloEC of course mg/m first 40 mg/m clofarabine 340 of cyclophosphamide consisted chemotherapy CloEC Re-induction Declaration. Helsinki the was European plan of it Re- the Treatment and principles Ethical and 2009-012437-30), the categories) Swedish number (NCT01025778) with age (EudraCT the clinicval.trials.gov accordance Database different by at in Trials approved to registered conducted Clinical was Authorities and (adjusted Regulating study 2009/83) assent Drug The a and Union no. cri- consent 70%; (File enrollment. institutional Informed Authority [?] for fulfilling view of required and donation. donation were status marrow patients/parents cell performance and stem from Karnofsky for blood available or func- for m member Lansky liver teria ml/min/1.73 family ULN; adequate haploidentical 90 2.5x [GFR]); adult [?] [?] 1.5 rate suitable clearance [?] phosphatase filtration creatinine alkaline bilirubin glomerular calculated serum transaminase; estimated by by output for cardiac indicated formula indicated Schwartz tion enrollment: function status for the renal Disease necessary by adequate were immunophenotyping enrollment. (calculated and criteria 25%; before examination eligibility [?] morphological attempt additional both SF following induction conventional by The remission after assessed enrollment. was failed relapsing and prior isolated Patients one inclusion chemoresistant least directly. for as at mandatory recruited defined was have be was to could refractoriness were HSCT AML, treatment allogeneic and after ALL relapse relapsing aged relapse, both Patients were marrow For institu- who bone our sAML), enrollment. combined to including or of referred AML adolescents time or and the (ALL children AL at comprised (r/r) study relapsed/refractory prospective with this tion for population target The haploidentical timed promptly population Target a to patients METHODS these the AND bridge PATIENTS to to due and approach AL, effect this r/r GvL of with enhanced children HSCT. potential pretreated an the heavily recipient. to determine for lead induction also and Transplantation remission also donor multidrug HSCT. may clofarabine-based the allogeneic and intensified between the precision of of disparity such risk timing the offers HLA reducing precise donors in short requires haploidentical The effect load responses with GvL responses. tumor clofarabine-induced the clofarabine-elicited clofarabine-containing of in of consolidation of by decrease potency potential multidrug duration a induced temporary the modality multiple increase a treatment responses this to theoretically even making Still, could Nevertheless, refractory relapse, HSCT are character. allogeneic clofarabine. in who an to transient patients before often exposed from are treatment been cells combinations primary not leukemic drug the thus in usually incorporated have children, been in regimes not leukemia has clofarabine acute countries, of Nordic the In cyclophosphamide. 2 n twsgvnbtendy 8ad– ro ogatn.Srteaywith Serotherapy grafting. to prior –1 and –8 days between given was it and , 2 dy n twsgvno v osctv as hlrnrsodn othe to responding Children days. consecutive five on given was it and /day, × > pe ii fnra UN;apraetransaminase/alanine aspartate (ULN); normal of limit upper otsatralgni ST rpiayidcinfailure. induction primary or HSCT, allogeneic after months 6 4-6 2 u i a oeaut h aeyadtxct of toxicity and safety the evaluate to was aim Our 2 rfldrbn 5 mg/m 150 fludarabine or > %bat ndy2 fe h beginning the after 21 day on blasts 5% 2 dy tpsd 0 mg/m 100 etoposide /day, 2 hoea1 mg/kg, 10 thiotepa , > n ? 1years 21 [?] and 1 2 dy and /day, 2 Posted on Authorea 16 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159493282.20139584 — This a preprint and has not been peer reviewed. Data may be preliminary. h eann v hlrnddntrsodt h rtcus fCoC n ftoennrsodr was non-responders those of in One blasts CloEC. leukemic have of to course found was first and the infection fungal to invasive respond cerebro-pulmonary possible not with did diagnosed the children after five transplantation remaining to The directly MRD-positive proceeding highly protocol, CloEC. the the of physician, protocol treating from course the the deviated first to by that decided remission according morphological treatment As treatment in CloEC. received the was second patient continued other the patient the the after and MRD-negative transplanted to MRD, The was for related MRD. and negative responded for deaths be ALL) to positive BCP- No proved with highly one (both and CloEC: protocol. patients of the seven course first the to the of according to Two chemotherapy observed. induction were induction first patients clofarabine-containing two the received in children treatment, All of 1. Table lines in more had presented CloEC or patients are to two remaining patients Response failed The the study. had of early the and Characteristics very to HSCT. relapse a directly i.e., had allogeneic refractory recruited patient including disease, subsequent was One active or CloEC. and of had treatment) first course on patients AML either first (while with All the T-ALL two before BCP-ALL). of and remission relapse of ) complete 16 achieved treatment T-ALL to never one previous 3 and and disease after aged BCP-ALL females sAML (four five one ALL and > and with males diagnosed novo two were de leukemia: patients (one acute the refractory of with Five patients years. seven included study The cohort Study used not was factor mon- colony-stimulating was for RESULTS granulocyte transplantation. copies specific Human after virus IgG recovery prophylaxis. number with neutrophil VOD the patients enhance guidelines. as institutional to All detected, used to was according not indicated. acyclovir DNA was prophylactic when received Defibrotide viral started viruses If simplex was empirical herpes EBV. treatment screened aggressive or varicella-zoster were and antiviral an patients appropriate AdV, prophylaxis although the and CMV, transplantation, as given, itored, for After and was weekly mandatory. prophylaxis prophylaxis was least antiemetic episodes antibacterial at neutropenia as No febrile both Together of syndrome. dexamethasone, treatment support. release received transfusion for patients cytokine used all for were CloEC, products blood the Irradiated with received guidelines. and children institutional PB to all in according transplantation, blasts after no and were Before criteria the patients, AML care For remission: Supportive morphological regeneration. indicated BM proceed patients of or treatment ALL signs the < for and continue to aspiration criteria whether BM response determine in to The evaluated was transplant. CloEC to of course each to Response Graft-versus- MMF response of vivo. of course Definition in short depletion a B-cell and performing 2.5x10 processing, exceeded of graft serotherapy, instead mg/m above-mentioned grafting 600 the after included +1 was prophylaxis harvest day host Biotec, second on (Miltenyi the administered whereas separation was cells, the cell CD34+ expressing immunomagnetic of cells collected αβ selection T for The entailed of twice. system harvest depletion harvested CliniMACS first for were The donors the all Germany). with hematologists. and Gladbach, adult G-CSF, processed of with were team mobilized independent were cells an cells by stem accepted blood and Peripheral evaluated, screened, were donors The chosen. el a e t5x10 x 5 at set was cells + 5 lssi Maspiration. BM in blasts 25% %o ekmcbat nbn arwa h ieo nolet n ain a rmr refractory primary had patient One enrollment. of time the at marrow bone in blasts leukemic of 5% 2 i ie rmdy– ody+8i h ubro residual of number the if +28 day to –1 day from given tid 4 k fdnrsbd weight. body donor’s of /kg 5 el/g igeds 35mg/m (375 dose single A cells/kg. αβ hiso elrcpo TR.Mxmmalwdds fTCR of dose allowed Maximum (TCR). receptor cell T of chains 3 Pneumocystis 2 nuoi n niuglprophylaxis antifungal and pneumonia fat-D0atbd (Rituximab) antibody anti-CD20 of ) αβ C oiieclsi h graft the in cells positive TCR < %o blasts of 5% Posted on Authorea 16 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159493282.20139584 — This a preprint and has not been peer reviewed. Data may be preliminary. neto nteCS ct rd knGH a igoe nol n ain.N hoi vDwas GvHD chronic No patient. one only in diagnosed fungal was invasive developed GvHD by patient caused skin one probably I to three, thrombosis grade 3 in sinus Acute Grade sagittal required CNS. VOD. showed was the developed one support in them and nutritional infection of cystitis, patients, none hemorrhagic two although II transplanted in patients, grade transaminases the four recorded in of All was elevations as three mucositis detected. noted gram-positive in 4 toxicities was observed Liver with reactivation were pancytopenia. EBV bilirubin patients profound no and/or of two biopsy- but them period with of pathogens, a in two diagnosed experienced viral patients; patients been patients, multiple all had in with transplanted patient observed infections were One infections four had Viral pathogens. the gram-negative mucormycosis. with cerebro-pulmonary invasive of patient verified one two in in and pathogens, observed was only and Septicemia No observed, was patient. mucositis one transplantation mild nutrition. only of - was parenteral in Toxicity case patient required 4 one course Liver One grade Only each infection). as recorded. after course. AdV classified were patient one second hyperbilirubinemia transaminases one and or the of reactivation VOD infections elevation CMV after of Viral (one transient four cases course to course. of second first limited the out the were seven after two after toxicities the patients infection in two of fungal in and invasive three observed cerebro-pulmonary CloEC in were possible registered of a were course with infections first diagnosed thrombocytopenia), bacterial and the verified neutropenia after Microbiologically 4 patients (grade patients. aplasia all marrow bone in profound observed was toxicity in common 3. most failure Table The liver in died of presented ultimately courses died are follow-up CloEC and and post-transplant - hepatitis post-transplant Toxicity and fulminant +128 transplantation AdV-induced and of developed Details +55 child remission. days One complete on leukemia. relapsed progressive children of Two 10 The transplantation. x 10 10.6 mothers. after x were to 102 donors 4.45 to first All from 5.0 ranged the remission. from cells of morphological to CD34+ in according start transplanted transplanted being after was of not one respectively, numbers despite and days, decision criteria, 151 physician’s proceed-to-transplant treating fulfilled and them the 78, of Three 76, CloEC. 43, of course HSCT the haploidentical and underwent children CloEC Four with Re-induction FLADx. patient to outcome 2. additional Transplant changed Table One was in criteria. summarized CloEC response are after the protocol-defined responses remission achieved chemotherapy, patients’ into children of went enrolled course who seven fourth the (sAML) was of the the percentage two after good, blast all, very remission In in still morphological reduction was fulfilling in further transplant. patient not to which being this proceeded despite after not of patient further given, physician, still condition without was was treating clinical Despite but child (FLADx) the the course showed observed. chemotherapy One third as by point the Inasmuch of decided time received course. course patient blasts. this as fourth this first of at after 30%; CloEC, evaluation the percentage of treatment below disease in after course palliative to and second decrease days the 80% only CloEC, 132 after second from with criteria and the blasts continued response second 57 after in three the condition disease received reduction those clinical progressive CloEC a of good of of very Two course died a first and in the responded. CloEC after them remission second achieve of the not none did but who children course, (FLADx), transplant. five tumor in cytarabine to the stipulated the and proceed previous of course finally fludarabine, on Three after could second daunorubicin, CloEC relapse and the liposomal in of remission with received study MRD-negative course continue instead achieved the to first patient and to unreasonable This the recruited it of protocol. was considered effect the physician who measurable treating sAML no the with month was 1 burden; patient disease there progressive one of transplantation, In died patient haploidentical CloEC. the first and treatment, the further declined after parents The blood. peripheral 3 k.Alcide hwdssandegatet n ain saieadwl . years 7.5 well and alive is patient One engraftment. sustained showed children All /kg. 4 6 k n residual and /kg αβ C+lymphocytes TCR+ Posted on Authorea 16 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159493282.20139584 — This a preprint and has not been peer reviewed. Data may be preliminary. L.Nvrhls,ti atclrgopo ainsmyb ffrdslaeimnteaywt either with immunotherapy salvage BCP- offered with diagnosed be those may were patients study our of in group CloEC to particular universal responding this a children be Nevertheless, to only seem the ALL. not AL: did cyclophosphamide r/r and for etoposide, treatment clofarabine, transplantation. of after combination weeks the based, conclusion, 4 MMF In limited, first was be the effectively prophylaxis during could depletion pharmacological only T-cell transplantation to the Ex-vivo given due the though transplantation and modality. even in of transplant GvHD, delay this timing relevant unnecessary of no clinically the was flexibility prevented cases, There the reflecting all children. the difficulties, In of logistical situations transplantation. changing observations, the after to previous adjusted nor and some phase CloEC state to both induction immunosuppressive Contrary together, the during to that, contributed patients. plausible patients) the is two mainly transplanted, in it and of being significant HSCT Still, was allogeneic before CloEC myelosuppression. (including died of and treatments courses who immuno- previous the children profound of toxicity all the the in However, to and, related disease. whereas observed, progressive to patients. were course, due toxicity first responding was CloEC the death in to after load suggest related response tumor deaths results no pre-transplant No Our showing the patients decrease hepatitis. was in further AdV patient repeated may of this be progressed, CloEC remission FLADx; not and repeating in to probably respond CloEC died should not from but CloEC did chemotherapy remission that changing T-ALL morphological by and salvaged in AML transplanted be with MRD could finally children them high The of a cohort. one having our although still in with survivor despite long-term (both CloEC only responders of HSCT 10 CloEC course haploidentical x two first after 1 the the effect Considering after GvL a already transplantation. despite the ( transplanted at condition that was load clinical third hope transplantation one tumor good the physician’s to BCP-ALL), high patient’s received treating proceeded a the patient the and overcome reflected One and criteria) might decision of already course. response burden, Two this transplanted second treatment required remission; was response. different the high morphological substantial them a fulfilling in a received of not not in one one (despite while result other protocol not protocol: the did off CloEC and course CloEC the course, first first from and the approach, the significantly if individualized after deviated CloEC an patients of repeating seven pursuit in physicians’ the confidence treating of acceptable the lack by an limited a combination showing was the data with group chose published patient We AL, promising HSCT). demanding relapsing toxicities. on in for organ (even based pre-existing profile cyclophosphamide recommended toxicity have and is those often bridge including etoposide, and patients children, to clofarabine, effective pretreated such heavily of approach be and to given possible HSCT, to always previous known nearly only chemotherapy. Immunotherapy is with is patients re-induction the therapy HSCT. salvage agents, intensified the and The subsequent other was bridge toxicity. study, without acceptable with time potentially our or combination that can performed with in at that and therapy or HSCT load designed cell to cell we patients or blast when the of alone available reduction HSCT not effective procedure: was on salvage is HSCT, AL. a focus before refractory to main control with the disease children AL, the the for control r/r better procedure to curative the proven attempting that entails and accepted available applied currently transplantation. widely is cell most stem that the performing condition subsequently this and for disease immunotherapy best the disease. but therapy-resistant refractory for even in successful are particularly therapy, transplantation. cell or cell can antibodies children stem bispecific of ALL. of without majority use the with/or as and such chemotherapy effective, approaches, conventional are newest intensive children in by AML saved and ALL be both for protocols treatment Current 4. DISCUSSION Table in summarized are Toxicities observed. > % eoetaslnain h te o-epne a ncmlt opooia eiso u had but remission morphological complete in was non-responder other The transplantation. before 1%) 5 -4 ti tl noe usinwehrimnteayaoecnsffiet civ oglsigremission long-lasting achieve to suffice can alone immunotherapy whether question open an still is It oiieMDatrtefis oreadudtcal R fe h eodcus;ti sthe is this course; second the after MRD undetectable and course first the after MRD positive 6 oee,orrslssgetta h plcblt ftepooo o this for protocol the of applicability the that suggest results our However, 7 ubro muohrpe o / M r ne investigation, under are AML r/r for immunotherapies of number A 5 6,17 13-16 efudn infiatlvrtxct,neither toxicity, liver significant no found we 8 h etrteepce ucm.Tu in Thus outcome. expected the better the hsse eltaslnainsest be to seems transplantation cell stem Thus 17,18 lfrbn,bt alone both Clofarabine, 9-12 ti commonly is It 1,2 ned the Indeed, Posted on Authorea 16 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159493282.20139584 — This a preprint and has not been peer reviewed. Data may be preliminary. tcSe elTaslnainwtotAttyoyeGoui nCide ihCeoercoyAcute Chemorefractory with Hematopoi- Children Haploidentical in Cell-Depleted Globulin T Antithymocyte alphabeta Leukemia. without al. Myelogenous Transplantation et Cell Z, Shekhovtsova Stem M, etic Ilushina L, Shelikhova Clofarabine- Novel 12. a Using Neoplasms. Transplantation Malignant Donor Hematologic Haploidentical High-risk al. Very Oncol. et for A, Regimen Sunkara Conditioning G, containing unrelated Kang HLA-matched A, after Sharma high- outcomes 11. with of children Comparison for transplantation G. leukemia. cell Ozturk acute stem E, risk hematopoietic Ovali haploidentical HLA-haploidentical D, T-cell-depleted Atay vs alphabeta A, donor and Akcay Unrelated F, Erbey al. leukemia. 10. et acute B, with children Buldini leukemia. in M, myeloid HSCT Zecca acute depleted A, for Bertaina immunotherapy in 9. Advances ES. Chimeric Wang of A, Age Szeles Oncol. the A, in Przespolewski Hematopoietic (ALL) of 8. Role Leukemia the Lymphoblastic Therapy? is (CART) What Acute MJ. T-Cell Burke Pediatric Receptor K, Antigen Becktell for NS, (HCT) Bhatt Transplantation R, Phelan Cell L, leukaemia. Broglie A, lymphoblastic Taraseviciute single-course 7. acute as relapsed etoposide and refractory/multiple cyclophosphamide with Clofarabine, children Haematol. al. et for ME, therapy Bernardo AM, re-induction with Testi leukemia. F, children lymphoblastic Locatelli for acute 6. B-cell tool pediatric immunomodulatory in Immunotherapy an RJ. as 2019;80(6):400-408. Bram transplant KD, Wyatt cell 5. Stem JM. with Cunningham patients malignancies. pediatric JL, hematologic in LaBelle treatment blinatumomab after 4. Survival leukemia. lymphoblastic al. lymphoblastic acute et acute relapsed G, precursor Zugmaier with B-cell F, relapsed/refractory children Locatelli in L, Gore outcome 90. 3. Long-term BFM chemother- ALL-REZ multidrug the trial al. short-course intensified in of et and results leukemia G, stratification lymphoblastic apy: site-of-relapse Mann and acute R, time-point childhood after Ratei leukemia Relapsed G, Tallen al. outcome. et 2. and J, treatment factors, Arvidson prognostic S, countries: Soderhall in Nordic T, involved Oskarsson not were data. 1. but the of protocol analysis study and the management, REFERENCES collection, writing or in patients involved the were of (GZ-2010-10157). Genzyme selection clofarabine Sanofi providing by of trial investigator-sponsored Representatives this supported partly Genzyme Sanofi interest. ACKNOWLEDGMENTS of conflict no have authors The to needed are INTEREST studies further OF HSCT. although CONFLICT option such essential, viable that transplantation of a approach the potential remains an anti-leukemic planning HSCT in the T-cells, Haploidentical flexibility assess CloEC. (CAR) which to receptor in patients antigen such cases in exposing chimeric than or reasonable antibodies more seems CD19 engaging T-cell bi-specific 2018;40(8):e479-e485. 2018;14(10):963-978. 2009;147(3):371-378. eit Transplant. Pediatr ilBodMro Transplant. Marrow Blood Biol mScCi no dcBook. Educ Oncol Clin Soc Am lnOncol. Clin J 2018;22(4):e13192. ora fpdarchematology/oncology. pediatric of Journal Blood. 6 2010;28(14):2339-2347. 2019;25(5):e179-e182. 2018;132(24):2594-2607. 2013:10.1200/EdBook Haematologica. lo acrJ. Cancer Blood 2016;101(1):68-76. AM.2013.1233.e1347. 2018;8(9):80. α/β 2019;41(5):337-344. -el n B-cell- and T-cell- eit Hematol Pediatr J u Immunol. Hum Future rJ Br Posted on Authorea 16 Jul 2020 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.159493282.20139584 — This a preprint and has not been peer reviewed. Data may be preliminary. prospective-study bridge-to-transplant-for-children-with-refractory-acute-leukemia-results-of-a-monitored- combination-of-clofarabine-etoposide-and-cyclophosphamide-shows-limited-efficacy-as-a- Toporski.docx 4 TABLE file Hosted prospective-study bridge-to-transplant-for-children-with-refractory-acute-leukemia-results-of-a-monitored- combination-of-clofarabine-etoposide-and-cyclophosphamide-shows-limited-efficacy-as-a- Toporski.docx 3 TABLE file Hosted prospective-study bridge-to-transplant-for-children-with-refractory-acute-leukemia-results-of-a-monitored- combination-of-clofarabine-etoposide-and-cyclophosphamide-shows-limited-efficacy-as-a- Toporski.docx 2 TABLE file Hosted prospective-study bridge-to-transplant-for-children-with-refractory-acute-leukemia-results-of-a-monitored- combination-of-clofarabine-etoposide-and-cyclophosphamide-shows-limited-efficacy-as-a- Toporski.docx 1 refractory with TABLE patients pediatric in clofarabine of file study II refractory Hosted Phase with leukemia. patients al. lymphoblastic et pediatric acute BI, in relapsed Razzouk clofarabine PS, or of Gaynon study S, II Jeha Phase 18. trans- al. leukemia. allogeneic et myeloid M, after tested? acute Rytting relapse relapsed be B, of or interventions Razzouk timing S, should Jeha and when factors 17. and Risk whom al. for et ALL: DA, plant. Wall pediatric B, in Langholz Remission? Myeloid plantation MA, Complete Acute Pulsipher of for Transplantation Definition 16. Cell Disease-Based Hematopoietic Residual Allogeneic Minimal in a al. Oncol. Toward Outcome et Move Clin Clinical M, to With Othus Time Disease BL, Residual Wood Leukemia: Minimal D, of Meta-analysis. Araki A Association 15. Leukemia: al. Lymphoblastic et Acute H, Adult Higley and S, Pediatric Zhou Lymphoblastic DA, Acute Berry Relapsed on 14. With Based Transplantation Group. Children Stem-Cell Intermediate-Risk Hematopoietic for Allogeneic the Outcomes of in Improves Use Leukemia Response al. Disease et K, Residual Seeger Minimal G, Henze C, Eckert 13. 2015;50(9):1173-1179. 2016;34(4):329-336. vial at available at available at available at available lnOncol. Clin J https://authorea.com/users/342951/articles/469709-the- https://authorea.com/users/342951/articles/469709-the- https://authorea.com/users/342951/articles/469709-the- https://authorea.com/users/342951/articles/469709-the- lnOncol. Clin J ora fCiia Oncology. Clinical of Journal 2009;27(26):4392-4397. 7 2006;24(12):1917-1923. AAOncol. JAMA 2013;31(21):2736-2742. oeMro Trans- Marrow Bone 2017;3(7):e170580. J