Hematopoietic stem cell transplantation

Transcription

1 Online Clinicl Investigtions Improved outcomes for stem cell trnsplnt recipients requiring peditric intensive cre Rnjit S. Chim, MD; Rodney C. Dniels, MD; Mi-Ok Kim, PhD; Dndn Li, MS; Derek S. Wheeler, MD; Stell M. Dvies, MBBS, PhD; Sont Jodele, MD Objectives: Survivl for hemtopoietic stem cell trnsplnt ptients requiring peditric intensive cre unit dmission my be improving. This study ws conducted to review outcomes for ptients undergoing hemtopoietic stem cell trnsplnttion requiring dmission to our peditric intensive cre unit nd to identify vribles impcting survivl. Design: Retrospective dtbse review. Setting: Peditric intensive cre unit nd bone mrrow trnsplnt service of children s hospitl. Ptients: Ptients undergoing hemtopoietic stem cell trnsplnttion t our center from July 2004 through June 2010 requiring peditric intensive cre unit dmission during the sme period. Mesurements nd Min Results: Thirty-five percent of ptients (155 of 448) undergoing hemtopoietic stem cell trnsplnttion required 319 dmissions over this period. Of these 155 ptients, 63% (97 of 155) were dischrged live following their most recent dmission with 100-dy survivl of 51% (79 of 155). Forty-five percent (69 of 155) of ptients were still live on long-term followup. Intubtion nd mechnicl ventiltion were required for 57% (88 of 155) of ptients, with 39% (34 of 88) of ptients surviving their lst peditric intensive cre unit dmission. Renl support ws utilized for 25% (38 of 155) of ptients with 34% (13 of 38) survivl to peditric intensive cre unit dischrge. Admissions surviving to peditric intensive cre unit dischrge hd significntly lower Peditric Risk of Mortlity II scores, shorter peditric intensive cre unit length of sty, lower utiliztion of intubtion nd mechnicl ventiltion with fewer ventiltor dys, nd lower use of renl support when compred to nonsurvivors. Of note, ech prior peditric intensive cre unit dmission significntly reduced the odds of peditric intensive cre unit survivl. Conclusions: We report 63% survivl to peditric intensive cre unit dischrge, with 45% surviving t medin follow-up of over 2 yrs for ll hemtopoietic stem cell trnsplnttion ptients dmitted to our peditric intensive cre unit over 6-yr period. Our dt suggest improved survivl outcomes for this high risk ptient popultion. (Peditr Crit Cre Med 2012; 13:e336 e342) Key Words: bone mrrow trnsplnt; mechnicl ventiltion; outcomes, peditric intensive cre unit; stem cell trnsplnt; survivl Hemtopoietic stem cell trnsplnttion (HSCT) is lifesving therpeutic option for children with multiple hemtologic, oncologic, nd immunologic disorders. A proportion of children undergoing HSCT develop complictions tht necessitte dmission to the peditric intensive cre unit (PICU). The proportion of children requiring PICU dmission following HSCT is vrible, with up to 44% of children undergoing HSCT requiring PICU dmission in some From the Divisions of Criticl Cre Medicine (RSC, RCD, DSW), Biosttistics nd Epidemiology (M-OK, DL), nd Bone Mrrow Trnsplnttion nd Immunodeficiency (SMD, SJ), Cincinnti Children s Hospitl Medicl Center, University of Cincinnti College of Medicine, Cincinnti, OH. The uthors hve not disclosed ny potentil conflicts of interest. For informtion regrding this rticle, E-mil: rnjit. chim@cchmc.org Copyright 2012 by the Society of Criticl Cre Medicine nd the World Federtion of Peditric Intensive nd Criticl Cre Societies DOI: /PCC.0b013e318253c945 series (1, 2). Historiclly, outcomes for this cohort of ptients hve been poor. A recent met-nlysis suggested wide rnge of overll PICU mortlity, rnging between 25% nd 91% (1). Despite improvement in single-center outcomes, overll severity-djusted outcomes for children requiring PICU dmission hve chnged little over time, especilly for children tht develop orgn filure (3). However, the literture describing overll PICU outcomes for children in this cohort is not representtive of current outcomes, s ll published studies utilize dt prior to 2004 (1). Hence, it is importnt to scertin PICU outcomes in this cohort utilizing contemporry dt from children requiring intensive cre following HSCT. Our institution is mongst the lrgest centers performing HSCT in children. Children undergoing HSCT t our center represent high-risk group, s most grfts come from unrelted donors, mny with significnt humn leukocyte ntigen mismtch. We performed retrospective review to determine outcomes for children who hd undergone HSCT requiring dmission to our PICU. Furthermore, we sought to identify clinicl vribles t PICU dmission tht were ssocited with poor prognosis. We hypothesized tht overll survivl to PICU dischrge hs improved when compred to published dt for children hving undergone HSCT. MATERIALS AND METHODS We performed retrospective review nd nlysis of outcomes for ll ptients dmitted to the PICU following HSCT from July 1, 2004, through June 30, 2010, t our institution, with pprovl from our Institutionl Review Bord. Due to the retrospective nture of our study, the need for informed consent ws wived. Ptients were identified using our PICU nd HSCT dtbses. We reviewed ll ptients who underwent HSCT t our institution during this time frme nd who subsequently required dmission to the PICU during this sme period. Ptients were excluded if they underwent HSCT nd/or PICU dmission prior to July 2004 or fter June 2010, underwent HSCT t nother institution, or were dmitted to the e336 Peditr Crit Cre Med 2012 Vol. 13, No. 6

2 PICU for performnce of procedure. For this review we included HSCT ptients dmitted to the intensive cre unit (ICU) following surgicl procedures for postopertive cre. Our institution is free-stnding children s hospitl nd serves s referrl center for ptients requiring HSCT. Ptients undergoing HSCT re cred for in specilized unit by physicins from the bone mrrow trnsplnt service. Admission to our PICU is not bsed upon specific criteri or clinicl scoring system. Rther, the merit of ech dmission is determined by review of ech ptient s cse nd clinicl need, nd the decision for dmission is mde jointly by the bone mrrow trnsplnt service nd criticl cre tem. Of note, HSCT ptients requiring ny inotrope/vsopressor support, ventiltory support (including noninvsive ventiltion), or initition of renl support (continuous or intermittent) re dmitted to the PICU. While in the PICU, these ptients re cred for by multidisciplinry tem consisting of intensivists nd bone mrrow trnsplnt physicins, s well s clinicl phrmcists, socil workers, nursing stff, respirtory therpy stff, nd nutrition specilists. We bstrcted dt directly from the medicl records nd PICU/HSCT dtbses nd entered the dt directly into pssword-protected Microsoft Excel spredsheets. Dt bstrcted included demogrphic prmeters such s dte of birth, sex, rce, nd ethnicity s well s clinicl dt pertining to ech ptient s HSCT nd PICU course. Specific HSCT dt included dte of trnsplnt, ge t trnsplnt, trnsplnt number, primry disese requiring trnsplnt, trnsplnt type, stem cell source, nd type of grft versus host disese prophylxis. PICU dt included ge t PICU dmission, dmission number, reson for ICU dmission (medicl vs. surgicl), Peditric Risk of Mortlity (PRISM) II score, PRISM clculted risk of mortlity, nd ICU length of sty s well s the need for invsive mechnicl ventiltion, renl support (intermittent or continuous), nd inotrope/ vsopressor usge. Admissions requiring invsive mechnicl ventiltion were ctegorized s hving primry or secondry respirtory filure. Primry respirtory filure included dmissions needing invsive mechnicl ventiltion for irwy obstruction, lung disese, fluid overlod, nd bdominl distension, wheres secondry respirtory filure included dmissions needing invsive mechnicl ventiltion for shock including crdic rrest, seizures, encephlopthy, nd opertive procedures. We compred PICU dmission nd intervention chrcteristics between those who survived to PICU dischrge nd those who did not survive to PICU dischrge. Sttisticl Anlysis. Ctegoricl nd continuous dt were compred utilizing chi-squre or Mnn Whitney rnk-sum tests, respectively. For model building, mechnicl ventiltion (invsive), inotrope/vsopressor usge, nd renl support (intermittent or continuous) were utilized s surrogtes for orgn filure, wheres PICU length of sty nd number of prior PICU Tble 1. Demogrphics nd survivl of hemtopoietic stem cell trnsplnttion ptients dmitted to the peditric intensive cre unit dmissions were used s surrogtes of morbidity. Using these vribles, we estimted the likelihood of survivl to PICU dischrge s well s survivl to 100 dys following the lst PICU dmission. Since HSCT ptients could hve hd multiple PICU dmissions resulting in multiple survivl outcomes tht re correlted mong themselves, we used generlized liner mixed effects model with n uto regressive order of 1 in order to ccount for multiple visits tht my belong to one ptient s well s the intercorreltion of survivl outcomes. We ssessed the odds of survivl to PICU dischrge utilizing simple nd multiple generlized liner mixed effects model regression nlysis to ssess the effect of ech vrible seprtely nd ll vribles concurrently. The odds of surviving to 100 dys following the lst PICU dmission for ll ptients were ssessed using logistic regression model for survivl probbility. Since multiple ptients in our cohort hd greter thn one PICU dmission nd vrying durtion of follow-up fter their lst PICU dischrge, we normlized risk fctors ccumulted during multiple PICU dmissions for the length of follow-up time. Lstly, we lso documented those ptients who were currently live (defined s of Jnury 1, 2011). Thess dt represent period of 6 months from the lst ptient included in our cohort. In ll nlyses, p vlue <.05 ws considered significnt. Sttisticl nlysis ws performed using SAS softwre (Cry, NC) version 9.2. RESULTS Demogrphic Totl n = 155 (%) Between July 1, 2004, nd June 30, 2010, 448 ptients received HSCT t our Peditric Intensive Cre Unit Survivl n = 97 (%) Mle 93 (60) Femle 62 (40) Dignosis Nonmlignnt 99 (64) 55 (56) Bone mrrow filure 29 (19) 17 (59) Genetic/metbolic disorder 6 (4) 4 (67) Immune disorders 64 (41) 34 (53) Mlignnt 56 (36) 42 (75) b Stem cell source Allogeneic 134 (86) 79 (59) Unrelted dult donor 96 (62) 56 (58) Unrelted cord blood 18 (12) 10 (56) Mtched sibling donor 18 (12) 12 (67) Mismtched sibling donor 1 (0.6) 0 (0) Hploidenticl prent 1 (0.6) 1 (100) Autologous 21 (14) 18 (86) c Conditioning regimen Myelobltive 98 (63) 64 (65) Nonmyelobltive d 57 (37) 33 (58) Peditric intensive cre unit survivl for lst peditric intensive cre unit dmission during the study period; b p =.004 when compred to ptients with nonmlignnt disorders; c p =.04 when compred to ptients undergoing llogeneic trnsplnt; d nonmyelobltive conditioning includes reduced intensity conditioning nd no conditioning of which there ws only one ptient. institution. Of these, 155 ptients (35%) required PICU cre, ccounting for 319 totl PICU dmissions over this 6-yr period. The most frequent resons for HSCT were immune disorders (41%) nd mlignncy (36%) (Tble 1). The medin ge t the time of HSCT ws 6 yrs (interqurtile rnge [IQR] 1.8, 14.3), nd 60% of ptients were mle (Tble 1). Nerly 85% of the cohort received stem cells from nother person (llogeneic trnsplnts), nd the mjority of the grfts were from n unrelted donor (Tble 1). Conditioning regimens were myleobltive in 63% of ptients; of these, nerly 50% received totl body irrdition (Tble 1). Over 6 yrs we observed n increse in stem cell trnsplnt ctivity t our center; this ws ssocited with mrked increse in PICU dmissions for ptients hving undergone HSCT t our institution (Fig. 1A). The mjority of ptients required one to two dmissions to the PICU (men dmissions/ptient 2 ± 1.5, mode 1); however, 45 ptients (29%) required more thn two dmissions. Of the 319 dmissions, only 9% (29) were for postopertive mngement. The medin time to dmission following trnsplnt ws 38 dys (IQR 8.3, 145) with medin ge of 6.6 yrs (IQR 2.5, 16.4). The medin PRISM II score for this cohort t PICU dmission ws 8 (IQR 4, 14) with medin length of sty in the PICU of 4 dys (IQR 2, 11), both being Peditr Crit Cre Med 2012 Vol. 13, No. 6 e337

3 Figure 1. A, Hemtopoietic stem cell trnsplnttion (HSCT) dmissions to the peditric intensive cre unit (PICU) nd number of ptients undergoing HSCT by fiscl yer. Ech br depicts the numbers of HSCT dmissions tht survived nd did not survive to PICU dischrge for tht fiscl yer. *Percentge of HSCT dmissions surviving to PICU dischrge; # number of ptients undergoing HSCT. B, Line grph demonstrting trend of medin Peditric Risk of Mortlity (PRISM) II score nd mechnicl ventiltion use (% ge) for HSCT dmissions to the PICU by fiscl yer over the study period. significntly higher (p <.001) when compred to non-hsct dmissions over the sme period (medin PRISM II score 4 [IQR 1, 7] nd medin length of sty 2 dys [IQR 2,4]). To scertin if this trend of incresed dmissions ws not consequence of lower severity of illness, we ssessed the yerly utiliztion of invsive mechnicl ventiltion over this period s n index of severity of illness. As expected, there ws vrition in the yerly need for mechnicl ventiltion; however, yerly dmission mortlity did pper to be ssocited with the percentge of dmissions needing mechnicl ventiltion (Fig. 1). Furthermore, there ws miniml vrition in PRISM II score over this period (Fig. 1B). Tken together these dt suggest tht the improved survivl to PICU dischrge is not consequence of dmissions hving lower severity of illness. We specificlly ssessed mechnicl ventiltion, inotrope use, nd renl support for HSCT dmissions during this period. Mechnicl ventiltion ws needed for 57% (88 of 155) of ptients nd 39% (124 of 319) of dmissions, s some ptients were dmitted more thn once. Nerly 60% (73 of 124) of dmissions needed mechnicl ventiltion for primry respirtory filure, while 40% (50 of 124) were intubted nd ventilted for secondry respirtory filure. For the dmissions requiring mechnicl ventiltion, the medin ventiltor dys were 6.5 dys (IQR 2, 15). Renl support ws required for 25% (38 of 155) of ptients. This resulted in 55 episodes of renl support in the PICU out of 319 dmissions. The modlities utilized during these 55 episodes were intermittent hemodilysis (n = 24), continuous renl replcement therpy (n = 11), or both (n = 20). Inotropes nd vsopressors were utilized in 61% (95 of 155) of ptients. Overll 37% (119 of 319) of dmissions required the use of n inotrope or vsopressor gent. The utiliztion of PICU interventions (mechnicl ventiltion, inotrope use, nd renl support) mongst HSCT recipients ws not impcted by underlying primry disese (mlignnt vs. nonmlignnt) nd trnsplnt chrcteristic (llogeneic vs. utologous trnsplnt, myelobltive vs. nonmyelobltive conditioning) (Tble 2). However, there ws trend towrd lower utiliztion of PICU interventions in ptients who underwent utologous trnsplnt when compred to llogeneic trnsplnts. We compred PICU dmission nd intervention chrcteristics mongst dmissions surviving to those not surviving to PICU dischrge. When compred to nonsurvivors, dmissions surviving to PICU dischrge hd significntly lower PRISM II score (7 vs. 13.5, p <.001) nd spent significntly fewer dys (3 vs. 12.5, p <.001) in the PICU (Tble 3). Additionlly, HSCT dmissions surviving their PICU sty hd significntly lower utiliztion of mechnicl ventiltion (28% vs. 90%, p <.001) nd fewer ventiltor dys (5 vs. 10.5, p <.001) when compred to nonsurvivors (Tble 3). Importntly, 58% (72 of 124) of dmissions requiring ventiltion survived to PICU dischrge. This trnslted to 39% (34 of 88) of ptients who required ventiltion during ny dmission surviving through their lst PICU dischrge, with 34% (30 of 88) surviving t lest 100 dys fter their lst PICU dischrge. Furthermore, we observed n 80% (12 of 15) survivl for ptients who received mechnicl ventiltion, but did not require inotrope support or renl support; we noted 32% (11 of 34) survivl for those ptients who were ventilted nd required renl support s well. Survivors to PICU dischrge hd significntly lower use of renl support (12% vs. 41%, p <.001) nd inotropes/vsopressors (28% vs. 79%, p <.001) when compred to nonsurvivors (Tble 3). Of the 38 ptients who required renl support, 34% (13 of 38) survived ll their PICU dmissions, with 29% (11 of 38) surviving t lest 100 dys fter their lst e338 Peditr Crit Cre Med 2012 Vol. 13, No. 6

4 Tble 2. Chrcteristics nd use of peditric intensive cre unit interventions for hemtopoietic stem cell trnsplnttion ptients Hemtopoietic Stem Cell Trnsplnttion Chrcteristic dmission. This corresponded to 56% survivl (31 of 55) to PICU dischrge for ll dmissions requiring renl support. For those dmissions tht required the use of n inotrope or vsopressor gent, we observed 61% (73 of 119) survivl to PICU dischrge. Overll survivl for HSCT ptients following lst PICU dischrge ws 63% (97 of 155) (Fig. 2). This trnslted to 82% (261 of 319) of HSCT dmissions surviving to PICU dischrge; in comprison, survivl to PICU dischrge for non-hsct dmissions over the sme period ws significntly higher t 97.5% (p <.001). On further follow-up, 51% (79 of 155) of HSCT ptients were live t 100 dys, nd nerly 45% (69 of 155) of ptients were live t medin follow-up of 2.5 yrs fter their lst PICU dischrge (IQR, 1, 3.5; rnge, 6 months to 6 yrs) (Fig. 2). In contrst, 98% of HSCT ptients not dmitted to the PICU over the sme period were live t 100 dys following trnsplnt. On further follow-up, 88% were live t 1 yr. PICU survivl ws significntly higher for ptients who underwent HSCT for dignosis of mlignncy compred to those with nonmlignnt disorders (75% vs. 56%, p =.004) (Tble 1); this higher Mechnicl Ventiltion Use (%) Tble 3. Hemtopoietic stem cell trnsplnttion dmissions chrcteristics nd interventions of peditric intensive cre unit nonsurvivors nd survivors Nonsurvivors n = 58 Inotrope Vsopressor Use (%) Survivors n = 261 Renl Support (%) Mlignnt disorder (n = 56) 29 (52) 33 (59) 11 (19) Nonmlignnt disorder (n = 99) 59 (60) 62 (63) 27 (27) Allogeneic trnsplnt (n = 134) 80 (60) 85 (63) 35 (26) Autologous trnsplnt (n = 21) 8 (38) 10 (48) 3 (14) Myelobltive conditioning (n = 98) 57 (58) 65 (66) 24 (24) Nonmyelobltive conditioning (n = 57) 31 (54) 30 (53) 14 (25) Number of ptients. Age t peditric intensive cre unit Admission (yrs) 8.8 ( ) b 6.5 ( ) b.3 Peditric Risk of Mortlity II score 13.5 (9 21) b 7 (3 12.3) b <.001 Peditric intensive cre unit length of sty (dys) 12.5 (5 23) b 3 (2 7) b <.001 Mechnicl ventiltion use (%) 52 (90) 72 (28) <.001 Ventiltor dys 10.5 (3 20) b 5 (2 11) b.012 Inotrope/vsopressor use (%) 46 (79) 73 (28) <.001 Renl support (%) 24 (41) 31 (12) <.001 Intermittent hemodilysis 3 21 Continuous renl replcement therpy 9 2 Both 12 8 p vlue reflects the difference between dmissions tht survived nd did not survive to peditric intensive cre unit dischrge by Mnn Whitney rnk-sum test for continuous dt nd chi-squre test for ctegoricl dt; b medin vlue with interqurtile rnge (25 75 percentile). mortlity for nonmlignnt disorders my reflect inclusion of lrge proportion of ptients undergoing HSCT for immune disorders, most commonly hemophgocytic lymphohistiocytosis. Additionlly, ptients who received utologous trnsplnts hd significntly higher PICU survivl when compred to those receiving n llogeneic trnsplnt (86% vs. 59%, p =.04) (Tble 1). In contrst, PICU survivl ws not ffected by the type of conditioning regimen (Tble 1). In order to determine the risk fctors tht impcted survivl to PICU dischrge, we used need for interventions such s mechnicl ventiltion, hemodynmic support, nd renl support s surrogtes for orgn filure. Furthermore, we used PICU length of sty nd number of prior PICU dmissions s surrogtes of morbidity. The odds of survivl to PICU dischrge were significntly higher for ptients not requiring mechnicl ventiltion or renl support (Tble 4). Similrly, ech prior PICU dmission following HSCT decresed the odds of PICU survivl significntly (odds rtio 0.8, p =.014) (Tble 4). However, PICU length of sty did not pper to hve significnt effect on the odds of PICU survivl p once djusted for the effects of the other risk fctors (Tble 4). These results suggest tht the odds of PICU mortlity for HSCT ptients re likely dependent on orgn filure nd mybe independent of PICU length of sty. For ptients who survived their lst PICU dmission during this period, we determined risk fctors tht impcted 100-dy survivl following their lst PICU dischrge. Since ptients in our cohort hd multiple dmissions nd vrying durtion of follow-up following their lst PICU dischrge, we normlized risk fctors ccumulted during multiple PICU dmissions for the length of follow-up time. After normlizing for risk fctors nd follow-up time, the 100- dy odds of survivl were significntly lower for ptients requiring mechnicl ventiltion, renl support, or combintion of mechnicl ventiltion nd renl support during their lst PICU dmission (Tble 5). Notbly, the use of inotropes/ vsopressors did not impct 100-dy survivl following lst PICU dischrge. DISCUSSION Our study describes outcomes for lrge contemporry cohort of stem cell trnsplnt ptients from single center requiring PICU dmission over 6-yr period. We observed n incresing number of dmissions for ptients undergoing HSCT t our institution over this period, in prllel with incresed trnsplnt ctivity in our progrm. For this ptient cohort, we report 63% survivl to PICU dischrge with n overll survivl of 45% t medin follow-up of over 2 yrs. We believe these dt re encourging nd show better outcomes thn previous reports. These dt indicte tht ggressive PICU support cn be beneficil for HSCT ptients, nd tht ptients cn survive even prolonged PICU stys. The primry impetus for our nlysis ws pucity of recent dt describing outcomes for ptients requiring dmission to PICU following HSCT. The frequency of PICU dmission fter HSCT is vrible in literture reports. A recent met-regression nlysis tht nlyzed dt from 23 retrospective studies spnning 15-yr period in children demonstrted n dmission rte between 5% nd 44% (1). In ddition, recent single center nlysis observed n PICU dmission rte of 35% for children undergoing stem cell trnsplnttion for primry immunodeficiency over 5-yr period (4). Hence, our dt seem to be in keeping Peditr Crit Cre Med 2012 Vol. 13, No. 6 e339

5 Figure 2. Survivl for hemtopoietic stem cell trnsplnttion (HSCT) ptients requiring peditric intensive cre unit (PICU) dmission. Flowchrt depicts survivl for 155 HSCT ptients requiring PICU dmission during the study period. Survivl depicted t PICU dischrge, 30 dys, 100 dys, nd to dte following lst PICU dischrge during the study period. Tble 4. Fctors ffecting peditric intensive cre unit survivl Risk Fctor with recent published dt wherein third of ptients undergoing HSCT required PICU dmission t some time following their trnsplnt. In our report, Odds Rtio (95% Confidence Intervl) Simple generlized liner mixed effects model regression nlysis Ventiltor use (no vs. yes) 22.8 ( ) <.001 Renl support (no vs. yes) 5.2 ( ) <.001 Inotrope/vsopressor use (no vs. yes) 9.8 ( ) <.001 PICU length of sty c 0.81 ( ) c.002 Mechnicl ventiltion durtion c 0.61 ( ) c <.001 Prior PICU dmission d 0.82 ( ) d.01 Multiple generlized liner mixed effects model regression nlysis Ventiltor use (no vs. yes) 19.1 ( ) <.001 Renl support (no vs. yes) 2.8 ( ).013 Ventiltor + renl support (no/no vs. yes/yes) 53.1 ( ) PICU length of sty c 0.98 ( ) c.63 Prior PICU dmission d 0.77 ( ) d.014 PICU, peditric intensive cre unit. Odds rtio (OR) for PICU survivl with 95% confidence intervls; b p vlue represents sttisticl significnce for ech vrible independent of the others (simple generlized liner mixed effects model regression) or djusted for the effects of the others (multiple generlized liner mixed effects model regression); c OR represents chnge in odds of survivl by the reported fctor for ech dditionl week of PICU sty or mechnicl ventiltion: e.g., the odds of survivl differ by OR x for x dditionl weeks; d OR represents chnge in odds of survivl by the reported fctor for ech prior dmission: e.g., the odds of survivl differ by OR x for x dditionl prior dmissions. the vst mjority of ptients hd only one or two dmissions, with postopertive dmissions ccounting for <10% of dmissions. Mechnicl ventiltion ws p b needed in 57% of ptients dmitted to the ICU, which is comprble to published studies (2, 5, 6). Renl support ws utilized for 25% of ptients, resulting in 55 episodes of renl support during the study. The use of mechnicl ventiltion, inotropes, nd renl support were similr mongst ptients undergoing trnsplnt for mlignnt vs. nonmlignnt disorders nd myelobltive vs. nonmyelobltive conditioning. Similr use ws lso seen in ptients receiving llogeneic or utologous trnsplnt; however, this lck of difference is possibly confounded by the reltively few ptients in our cohort receiving utologous trnsplnts. Overll, we observed n 82% survivl to PICU dischrge for these 319 dmissions. This trnslted to 63% (97 of 155) of HSCT ptients surviving their lst PICU dmission, with 51% (79 of 155) being live t 100 dys. On longer followup, 45% were still live. This suggests tht in our cohort the mjority of deths occur in the PICU or within 100 dys of dischrge. All similr studies published over the lst decde hve hd fr fewer ptients, nd with lower survivl to PICU dischrge. The rnge of survivl to PICU dischrge for ptients in these studies vries between 30% nd 47% (2, 5 10). Only single smll study tht evluted dt over 4-yr period for 33 ptients demonstrtes similr survivl rte (2). In our study, 81% (79 of 97) of ptients tht survived to PICU dischrge were still live 100 dys lter. This is n importnt improvement in survivl compred to 54% observed by Kche et l (2) in their cohort. However, the lck of specific dmission criteri for our cohort leves open the possibility tht dmissions of ptients with lower severity of illness my hve ffected our outcomes. Unlike prior studies, we followed ptients in our cohort longer, with medin follow-up of nerly 2.5 yrs. Hence, our dt demonstrte n improvement in survivl for ptients requiring PICU dmission following HSCT, nd tht the improved outcome leds to long-term survivl. We were prticulrly interested in outcomes for HSCT ptients who needed mechnicl ventiltion nd/or renl support during their PICU sty, s historiclly outcomes for these ptients hve been poor. At our center nerly 40% of the 88 ptients ventilted t ny time over the 6-yr study period survived through their lst PICU dmission, with 34% surviving t lest 100 dys fter e340 Peditr Crit Cre Med 2012 Vol. 13, No. 6

6 Tble 5. Multiple logistic regression nlysis: Interventions ffecting 100-dy survivl following lst peditric intensive cre unit dischrge djusted for normlized risk fctors ccumulted over prior peditric intensive cre unit dmissions Intervention b Odds Rtio (95% Confidence Intervl) p Ventiltor use (no vs. yes) 5.3 ( ) <.001 Renl support (no vs. yes) 3.1 (1 9.3).048 Ventiltor + renl support (no/no vs. yes/yes) 16.3 ( ) Risk fctors ccrued during prior dmissions over the study period were normlized for the time period over which the peditric intensive cre unit dmissions occurred nd were included s explntory vribles; b intervention must hve occurred during the ptients lst peditric intensive cre unit dmission within the study period PICU dischrge. Since multiple studies report mechnicl ventiltion outcomes by dmissions rther thn by ptient numbers (some ptients were dmitted more thn once), we observed 58% survivl to PICU dischrge for HSCT dmissions requiring mechnicl ventiltion. These numbers represent improvements over historicl reports. Vn Gestel et l (9) demonstrted men ICU survivl of 29% for HSCT ptients requiring mechnicl ventiltion in their metregression nlysis. Our results re similr if not better thn recent studies reporting 45% nd 58% survivl for HSCT dmissions requiring mechnicl ventiltion (11 13). For ptients needing renl support t our center, survivl to PICU dischrge nd 100-dy survivl following lst PICU dischrge were 34% nd 29%, respectively, not dissimilr to the Continuous Renl Replcement Therpy Registry Group recently reporting 45% ptient survivl to PICU dischrge for HSCT ptients requiring continuous renl replcement therpy (13). While this survivl is improved reltive to our results, the severity of illness nd underlying disorder leding to these ptients HSCT is not reported nd, therefore, mkes correltions to our cohort difficult. However, more comprble study by Rjsekrn et l (14) demonstrted 33% ICU survivl for HSCT ptients undergoing continuous renl replcement therpy. A combintion of mechnicl ventiltion nd renl support ws used in 34 of our ptients, with 32% survivl to ICU dischrge. These dt contrst with recent study reporting tht 17% of such ptients survived to PICU dischrge (15). Tken together, our survivl dt for HSCT ptients needing mechnicl ventiltion nd/or renl support revel n improvement compred to published dt. However, the need for mechnicl ventiltion nd/or renl support significntly diminished the likelihood of PICU nd 100-dy survivl for these ptients. These findings re not surprising to helthcre providers cring for these ptients, s prior studies hve demonstrted worsening outcomes for HSCT ptients with multiple orgn filure (9, 10). The number of prior PICU dmissions for HSCT ptients t our center proportionlly decresed their odds of survivl. However, prior studies hve not studied this or hve demonstrted no effect of dmission number on PICU survivl (4). The reson for this difference is uncler; however, repeted PICU dmissions my be mrker of incresed complictions following trnsplnt. Notbly, the PICU length of sty did not impct PICU survivl. While we describe improved outcomes for this cohort of ptients, we could identify no single intervention or chnge in mngement tht could ccount for the improved outcomes observed in our high-risk ptient popultion. Although difficult to evlute nd quntify in retrospective study, we believe tht our multidisciplinry pproch to the mngement of HSCT ptients, with both tems present on rounds, plys n importnt role in our observed outcomes. Ultimtely it is most likely tht improved outcomes re most likely result of the dditive effect of multiple smll chnges in mngement of these ptients from both the trnsplnt nd intensive cre stndpoint. CONCLUSIONS In conclusion, our study demonstrtes 63% survivl to ICU dischrge with 45% long-term survivl for HSCT ptients needing PICU cre. Our study bolsters the belief tht outcomes for this cohort of ptients re improving nd chllenges previously held dogms of universlly poor outcomes for HSCT ptients requiring dmission to the PICU. We suggest tht ggressive, well-coordinted, multidisciplinry cre cn led to long-term survivl. REFERENCES 1. vn Gestel JP, Bollen CW, vn der Tweel I, et l: Intensive cre unit mortlity trends in children fter hemtopoietic stem cell trnsplnttion: A met-regression nlysis. Crit Cre Med 2008; 36: Kche S, Weiss IK, Moore TB: Chnging outcomes for children requiring intensive cre following hemtopoietic stem cell trnsplnttion. Peditr Trnsplnt 2006; 10: Brtton SL, Vn Duker H, Sttler KD, et l: Lower hospitl mortlity nd complictions fter peditric hemtopoietic stem cell trnsplnttion. Crit Cre Med 2008; 36: Cole TS, Johnstone IC, Perce MS, et l: Outcome of children requiring intensive cre following hemtopoietic SCT for primry immunodeficiency nd other non-mlignnt disorders. Bone Mrrow Trnsplnt 2012; 47: González-Vicent M, Mrín C, Mdero L, et l: Risk score for peditric intensive cre unit dmission in children undergoing hemtopoietic stem cell trnsplnttion nd nlysis of predictive fctors for survivl. J Peditr Hemtol Oncol 2005; 27: Cheuk DK, H SY, Lee SL, et l: Prognostic fctors in children requiring dmission to n intensive cre unit fter hemtopoietic stem cell trnsplnt. Hemtol Oncol 2004; 22: Tomske M, Bosk A, Eyrich M, et l: Risks of mortlity in children dmitted to the peditric intensive cre unit fter hemtopoietic stem cell trnsplnttion. Br J Hemtol 2003; 121: Lms A, Otheo E, Ros P, et l: Prognosis of child recipients of hemtopoietic stem cell trnsplnttion requiring intensive cre. Intensive Cre Med 2003; 29: Diz MA, Vicent MG, Prudencio M, et l: Predicting fctors for dmission to n intensive cre unit nd clinicl outcome in peditric ptients receiving hemtopoietic stem cell trnsplnttion. Hemtologic 2002; 87: Jcobe SJ, Hssn A, Veys P, et l: Outcome of children requiring dmission to n intensive cre unit fter bone mrrow trnsplnttion. Crit Cre Med 2003; 31: Tmburro RF, Brfield RC, Shffer ML, et l: Chnges in outcomes ( ) for peditric oncology nd hemtopoietic stem cell trnsplnt ptients requiring invsive mechnicl ventiltion. Peditr Crit Cre Med 2008; 9: vn Gestel JP, Bollen CW, Bierings MB, et l: Survivl in recent cohort of mechniclly ventilted peditric llogeneic hemtopoietic stem cell trnsplnttion recipients. Biol Blood Mrrow Trnsplnt 2008; 14: Peditr Crit Cre Med 2012 Vol. 13, No. 6 e341

7 13. Flores FX, Brophy PD, Symons JM, et l: Continuous renl replcement therpy (CRRT) fter stem cell trnsplnttion. A report from the prospective peditric CRRT Registry Group. Peditr Nephrol 2008; 23: Rjsekrn S, Jones DP, Avent Y, et l: Outcomes of hemtopoietic stem cell trnsplnt ptients who received continuous renl replcement therpy in peditric oncology intensive cre unit. Peditr Crit Cre Med 2010; 11: Elbhlwn L, West NK, Avent Y, et l: Impct of continuous renl replcement therpy on oxygention in children with cute lung injury fter llogeneic hemtopoietic stem cell trnsplnttion. Peditr Blood Cncer 2010; 55: e342 Peditr Crit Cre Med 2012 Vol. 13, No. 6