Disparities in pediatric leukemia early survival in Argentina: a population-based study

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1 Investigción originl / Originl reserch Pn Americn Journl of Public Helth Disprities in peditric leukemi erly survivl in Argentin: popultion-bsed study Gild Gribotti, 1 Florenci Moreno, 2 Veronic Dussel, 3 nd Lilin Orelln 4 Suggested cittion Gribotti G, Moreno F, Dussel V, Orelln L. Disprities in peditric leukemi erly survivl in Argentin: popultion-bsed study. Rev Pnm Slud Public. 2014;36(4): bstrct Key words Objective. To identify disprities using recursive prtitioning (RP) in erly survivl for children with leukemis treted in Argentin, nd to depict the min chrcteristics of the most vulnerble groups. Methods. This secondry dt nlysis evluted 12-month survivl (12-ms) in children dignosed between 2000 nd 2008 with lymphoid leukemi (LL) nd myeloid leukemi (ML) nd registered in Argentin s popultion-bsed oncopeditric registry. Prognostic groups bsed on ge t dignosis, gender, socioeconomic index of the province of residence, nd migrtion to different province to receive helth cre were identified using the RP method. Results. Overll 12-ms for LL nd ML cses ws 83.7% nd 59.9% respectively. RP detected mjor gps in 12-ms. Among 1 10-yer-old LL ptients from poorer provinces, 12-ms for those who did nd did not migrte ws 87.0% nd 78.2% respectively. Survivl of ML ptients < 2 yers old from provinces with low/medium socioeconomic index ws 38.9% compred to 62.1% for those in the sme ge group from richer provinces. For 2 14-yer-old ML ptients living in poor provinces, ptient migrtion ws ssocited with 30% increse in 12-ms. Conclusions. Mjor disprities in leukemi survivl mong Argentine children were found. Ptient migrtion nd socioeconomic index of residence province were ssocited with survivl. The RP method ws instrumentl in identifying nd chrcterizing vulnerble groups. Helthcre disprities; leukemi; child; developing countries; survivl nlysis; Argentin. Leukemi comprises bout 30% of ll cncer cses occurring in children younger thn 15 yers old in resourcerich countries. Advnces in tretment hve mrkedly improved survivl. In countries with highly developed helth 1 Centro Regionl Universitrio Briloche, Universidd Ncionl del Comhue, Briloche, Argentin. Send correspondence to: Gild Gribotti, gribottig@comhue-conicet.gob.r 2 Argentine Hospitl Oncopeditric Registry, Instituto Ncionl del Cáncer, Buenos Aires, Argentin. 3 Instituto de Efectividd Clínic y Snitri, Buenos Aires, Argentin. 4 Instituto de Cálculo, Universidd de Buenos Aires, Buenos Aires, Argentin. services, five-yer survivl rtes for children with cute lymphoid leukemi nd cute non-lymphocytic leukemi re pproximtely 80% nd 50% respectively (1, 2). While outcomes in countries with limited resources re less well known, becuse of the scrcity of popultion-bsed cncer registries (3), reports suggest tht three-yer survivl in tht setting is worse, nd cn be s low s 54.2% for cute lymphoid leukemi (4, 5). The poorer outcomes re generlly ttributed to restricted vilbility of helth services, delyed dignosis, lck of therpeutic strtegies, tretment bndonment, nd indequte supportive cre (4, 6, 7). One of the few peditric cncer registries in Ltin Americ is the Argentine Hospitl Oncopeditric Registry (Registro Oncopediátrico Hospitlrio Argentino, ROHA). This popultion-bsed registry ws creted in the yer 2000 nd hs reched n estimted coverge of 92%; ROHA s incidence nd survivl dt hve helped to inform helth policies nd drive the development of ntionl peditric cncer progrm (8, 9). 248 Rev Pnm Slud Public 36(4), 2014

2 Gribotti et l. Disprities in peditric leukemi erly survivl in Argentin Originl reserch Dt from ROHA indicte tht in Argentin the rtes for three-yer survivl of lymphoid leukemi (LL) nd myeloid leukemi (ML) were 69% nd 40% respectively, with significnt vritions (of up to 15 points) cross the country (10). These differences rise within context of pprent uniformity. In this upper-middle income country, cncer tretment is provided free of chrge nd is highly centrlized: 85% of children with cncer receive cre in public institutions nd 47% re treted in one of three tertiry-level peditric hospitls (10). All centers use the sme tretment protocol. About 49% of ptients need to migrte to nother province for dignosis nd therpy (10). Moving nd lodging expenses re usully covered by the province of residence or through helth insurnce. Once child is trnsferred to specilized institution, ll therpy is usully dministered by the new institution. Consequently, mny ptients spend long periods (up to two yers) wy from their homes (11, 12). Identifiction of the most vulnerble groups of peditric cncer ptients in terms of their survivl is necessry to further develop the ntionl peditric cncer progrm nd to reduce cncerrelted disprities within the country. Argentin s high-qulity registry llows for this type of nlysis. Recursive prtitioning (RP) is sttisticl method idelly suited for splitting the study popultion into different groups by ptient survivl rtes, nd for identifying prognostic fctors relted to the course of disese. Breimn et l. (13) estblished the theoreticl nd prcticl frmework of RP methods within the specific context of clssifiction nd regression trees. Erly dpttion of RP methods to helth science dt ws crried out by Gordon & Olshen (14) nd Cimpi et l. (15). Zhng & Singer (16) provide comprehensive list of references bout RP in helth sciences. Unlike the Cox proportionl hzrds model trditionlly used to nlyze survivl dt, the RP method is non-prmetric pproch tht does not rely on ssumptions bout the survivl function. In ddition, the RP splitting lgorithm llows for identifiction of the most relevnt prognostic fctors for given subset of subjects, rther thn estimting effects cross ll subjects, s in the Cox model. Survivl throughout the 12-month period fter dignosis depends primrily on the helth system s bility to provide rpid dignosis nd dequte supportive cre. Therefore, mortlity during this period cn be voided by improving infrstructure, equipment, nd trining of personnel t the treting institutions, or by developing good referrl policies. The gol of this study is to identify disprities using RP in erly survivl for children with leukemis treted in Argentin, nd to depict the min chrcteristics of the most vulnerble groups. MATERIALS AND METHODS This is secondry dt nlysis using dt from Argentin s popultion-bsed oncopeditric registry, the ROHA. Dt ROHA registers ll cncer cses dignosed in children nd dolescents 0 19 yers old nd living in Argentin. To dte, more thn cses hve been registered. Cses re collected through network of centers tht covers the entire country. Vitl sttus is updted by the centers on n nnul bsis nd supplemented with deth certificte informtion. A detiled description of ROHA dt cquisition strtegies nd registry qulity hs been described elsewhere (8). ROHA records type of tumor; gender; birth, dignosis, deth, nd lst contct dte; dignosing institution; referrl hospitl; nd province of residence. Clssifiction of type of tumor is bsed on the Interntionl Clssifiction of Disese for Oncology (17) nd the Interntionl Clssifiction of Childhood Cncer (18). To protect ptient confidentility, the dtbses were de-identified for this nlysis. Children dignosed between 2000 nd 2008 with LL or ML, before ge 15, were included in this study. Cses identified by deth certifictes only were excluded. The study outcome ws the time from dignosis to deth from ny cuse. Ptients who lost contct with the clinicl center were clssified s lost to followup; for these ptients, the study outcome ws the durtion of observtion from dignosis to lst contct. Survivl t 12 months fter dignosis ws evluted in reltion to ge t dignosis, gender, socioeconomic index of the province of residence, nd cncer-relted migrtion. The Extended Humn Development Index (EHDI) for the yer 2006, which combines helth, eduction, nd living stndrds informtion, ws used s socioeconomic index for ech of the 23 provinces nd the cpitl city of Buenos Aires (19, 20). The EHDI uses vlues between 0 nd 1, with lower vlues corresponding to lower socioeconomic sttus. A dichotomous vrible clled ptient migrtion ws defined s Yes if the child ws referred to hospitl in province different from his/her residence nd No if he/she ws not. Sttisticl methods Cox proportionl hzrds models were fitted to evlute ech of the four fctors studied s prognostic indictors of 12-month survivl (12-ms): 1) ge in yers t time of dignosis (0, 1 4, 5 9, nd 10 14); 2) gender; 3) ptient migrtion ( Yes or No); nd 4) EHDI for the province of residence, nlyzed s continuous vrible. The RP lgorithm ws used to split the study popultion into subgroups by survivl experience nd chrcterize them. The nlysis ws bsed on the pproch proposed by Therneu & Atkinson (21). The response vrible considered ws survivl in the first 12 months fter dignosis. The predictor vribles were the sme s those described for the Cox models, except for ge (in yers), which ws entered s continuous vrible. In the first step of the process, RP divides the whole set of ptients into two subgroups bsed on responses to question involving one of the explntory vribles (e.g., Is ge t dignosis 1 yer or more? ). Allowble questions involve one predictor (x): if x is ordered, the question is Is x c? for given vlue c; if x is ctegoricl, the question is Is x in S? where S is ny subset of ctegories of x. The question tht defines the prtition is utomticlly selected mong ll llowble questions bsed on rule tht mximizes mesure of the improvement cused by the new prtition. In this study, the reduction in the devince ws used s the mesure of improvement. This process ws repeted in ech subgroup until the subgroups reched minimum size. Ech step resulted in subgroups tht were more homogeneous in terms of survivl experience thn the groups t the previous step. In the lst step of the RP lgorithm ( pruning ), n pproprite tree size ws selected (21). The resulting model cn be represented s binry tree whose leves or terminl Rev Pnm Slud Public 36(4),

3 Originl reserch Gribotti et l. Disprities in peditric leukemi erly survivl in Argentin nodes correspond to the prtition of the dt. The RP strtegy cretes groups of observtions with survivl experiences tht re considered similr nd cn thus be summrized by the Kpln Meier estimtor. For ech subgroup identified by the RP method, the Kpln Meier curve nd estimted survivl t 12 months (plus the corresponding 95% confidence intervls (CIs)) were reported. The finl tree my contin terminl nodes with similr survivl experience, which cn be combined or mlgmted to form the finl groups (13, 16, 21). This dditionl step ws crried out by creting ctegoricl vrible with ctegories corresponding to the nodes of the tree nd using RP gin, on just tht vrible, to define terminl nodes with distinct survivl experiences. All nlyses were performed with the R pckge (22). RP ws crried out using rprt (23). Tble 1. Chrcteristics of children dignosed with lymphoid leukemi (LL) nd myeloid leukemi (ML), Argentin, LL ML (n = 3 212) (n = 775) Chrcteristic No. (%) No. (%) Age t dignosis (yers) (4) 97 (13) (44) 241 (31) (30) 188 (24) (23) 249 (32) Mle (55) 403 (52) Ptient migrtion (35) 330 (43) EHDI of the province of residence Low (EHDI 0.672) 668 (21) 154 (20) Medium (0.672 < EHDI 0.75) (51) 409 (53) High (EHDI > 0.75) 897 (28) 212 (27) Lost to follow-up in < 12 months 204 (6) 33 (4) Alive 12 months fter dignosis (84) 472 (61) EHDI: Extended Humn Development Index for 2006 (19, 20). Figure 1. Extended Humn Development Index (EHDI) for provinces, Argentin, 2006 RESULTS Source: (19, 20). CABA: Ciudd Autónom de Buenos Aires (Argentin s cpitl city). Between there were LL nd 832 ML cses reported to ROHA. Of those, 125 (3.7%) LL nd 57 (6.9%) ML cses identified only through deth certifictes were excluded, leving LL nd 775 ML ptients s the finl study smple. The medin follow-up time ws 35.3 months mong children with LL nd 15.8 months for those with ML. Events occurring fter one yer of dignosis were not tken into considertion in the nlysis. A totl of 204 (6%) LL ptients nd 33 (4%) ML ptients lost contct with the clinicl center within one yer of their dignosis. Distribution of losses ws similr by gender nd ge groups; no pprent pttern ws found in reltion to EHDI. Ptient chrcteristics re presented in Tble 1. The EHDI of Argentine provinces rnged between nd (Figure 1). In Tble 1, the province EHDI is clssified in three ctegories: low, medium, nd high (tertiles). The city of Buenos Aires (Ciudd Autónom de Buenos Aires or CABA, s shown in Figure 1) hd the highest concentrtion of both specilized oncologists nd tertiry-level centers. The estimted Kpln Meier 12-ms nd 95% CIs were 83.7% (95% CI: 82.4%, 85.0%) for children dignosed with LL, nd 59.9% (95% CI: 56.5%, 63.5%) for those with ML. Tble 2 presents hzrd rte rtios from univrite Cox proportionl hzrds models of the vribles studied. For LL ptients, ge nd EHDI were the only fctors significntly ssocited with erly survivl. Their hzrd of deth decresed by 19% ((1 0.81) 100) s EHDI incresed by 0.1, resulting in 47% (95% CI: 22%, 65%) decrese in hzrd between the province with the low- 250 Rev Pnm Slud Public 36(4), 2014

4 Gribotti et l. Disprities in peditric leukemi erly survivl in Argentin Originl reserch Tble 2. Hzrd rte rtios (HRR) for lymphoid leukemi (LL) nd myeloid leukemi (ML) in children bsed on univrite Cox proportionl models, Argentin, LL ML (n = 3 212) (n = 775) Chrcteristic HRR (95% CI ) Age t dignosis (in yers; reference = 10 14) (2.27, 4.09) 2.12 (1.51, 2.98) (0.37, 0.58) 1.29 (0.96, 1.74) (0.48, 0.76) 1.16 (0.84, 1.60) Gender (reference = femle) 0.96 (0.80, 1.14) 0.91 (0.72, 1.14) Ptient migrtion (reference = No ) 0.94 (0.78, 1.13) 0.76 (0.60, 0.96) EHDI of the province of residence b 0.81 (0.72, 0.92) 0.84 (0.71, 0.99) CI: confidence intervl. b Extended Humn Development Index (EDHI) for 2006 (19, 20). The HRR represents vrition cused by n increse of 0.1 in the EDHI. est EHDI nd the one with the highest EHDI. ML ptients erly survivl ws significntly ssocited with ge, ptient migrtion, nd EHDI. Their hzrd of deth decresed by 16% ((1 0.84) 100) s EHDI incresed by 0.1, resulting in 43% (95% CI: 3%, 66%) decrese in hzrd between the province with the lowest EHDI nd the one with the highest EHDI. Recursive prtitioning Lymphoid leukemi. Figure 2 shows summry of the nlysis for LL ptients, including the nlysis tree nd the estimted 12-ms curves for the eight terminl nodes, nd the one for ll LL ptients. As shown in the nlysis tree, the first split ws bsed on ge (0 versus 1 14 yers). Children < 1 yer old formed prticulrly poor prognostic group; estimted 12-ms ws 46.8% (Group 8 (G8)). The group of older children ws subdivided further by ge: 1 10 yers versus yers. Estimted 12-ms for children yers old ws 75.0% (G7). The 1 10-yer-old group ws subdivided in the next step bsed on Figure 2. Recursive prtitioning (RP) nlysis for ptients dignosed with lymphoid leukemi: RP tree,b (left) nd 12-month Kpln Meier survivl curves for groups defined by terminl nodes of RP lgorithm c (right), Argentin, Age< 5 Age 2 Age 5 PM=yes G1 d/n: 73/975 s: 92.3 (90.6, 94.0) EHDI PM=no Age< 2 G2 G3 d/n: 26/295 d/n: 82/567 s: 91.1 s: 84.9 (87.9, 94.4) (81.9, 88.0) G4 d/n: 32/162 s: 79.4 (73.3, 86.0) Age< 11 EHDI< PM=yes G5 d/n: 23/178 s: 87.0 (82.2, 92.1) Age 1 Age 11 PM=no G6 d/n: 68/328 s: 78.2 (73.7, 82.9) Age< 1 G7 d/n: 143/590 s: 75.0 (71.5, 78.7) G8 d/n: 61/117 s: 46.8 (38.5, 57.0) 12 month survivl Overll G1 G5 G2 G6 G3 G Time in months G: group; d/n: number of deths / smple size; s: Kpln Meier 12-month survivl estimte; EHDI: Extended Humn Development Index for 2006 (19, 20); PM: ptient migrtion. b Including 95% confidence intervls. c Overll: overll 12-month survivl curve. Rev Pnm Slud Public 36(4),

5 Originl reserch Gribotti et l. Disprities in peditric leukemi erly survivl in Argentin Figure 3. Twelve-month Kpln Meier survivl curves for groups of lymphoid leukemi ptients obtined fter pplying the mlgmtion lgorithm, Argentin, month survivl Overll G: 1, 2 G: 4, 6, 7 G: 3, 5 G: Time in months Overll: overll 12-month survivl curve; G1 G8: groups of lymphoid leukemi ptients bsed on terminl nodes of RP lgorithm. EHDI. The group of children 1 10 yers old living in the poorer provinces (EHDI < 0.654) ws subdivided by whether they migrted or not (G5 nd G6). Those who did not migrte (G5) hd lower estimted 12-ms thn those who migrted (G6) 78.2% compred to 87.0%. The 1 10-yer-old group living in provinces with EHDI ws subdivided ccording to ge in three groups: 1 yer old (G4, 12-ms 79.4%); 2 4 yers old (G1, 12-ms 92.3%); nd 5 10 yers old; the ltter group hd 91.1% or 84.9% 12-ms depending on whether they migrted or not (G2 or G3 respectively). The min gp in 12-ms for LL identified by the RP method (n 8.8% difference) ws ssocited with non-migrtion versus migrtion for cre groups G5 nd G6 respectively. As shown in Figure 2, some of the survivl curves ppered to be similr. Therefore, the mlgmtion lgorithm to merge nodes with similr prognosis ws run. The four survivl curves obtined fter mlgmtion re shown in Figure 3. The worst prognosis ws for children < 1 yer old (G8). The other group with prognosis below verge nd n estimted 12-ms of 76.6% (95% CI: 74.1, 79.2) resulted from the ggregtion of three clusters: 1-yer-old children from provinces with EHDI 0.65 (G4), children 1 10 yers old from poor provinces (EHDI < 0.65) who did not migrte (G6), nd ptients yers old (G7). Myeloid leukemi. The result of the RP pproch for ML ptients is represented in Figure 4; overll 12-ms ws 59.9%. The EHDI of the province of residence plyed n importnt role in ML erly survivl. Two prticulrly poor prognostic groups were identified: the first (G6) ws composed of children < 2 yers old from provinces with EHDI < 0.73; estimted 12-ms ws 38.9%. The second (G4) ws composed of children 2 14 yers old from provinces with EHDI 0.70 who did not migrte; estimted 12-ms ws 40.8%. Therefore, RP identified two mjor gps in the 12-ms experience. The first ws between G5 nd G6 nd ws ssocited with poverty (62.1% versus 38.9%). The second ws between G3 nd G4 nd ws ssocited with ptient migrtion (70.8% versus 40.8%). The mlgmtion process resulted in three prognostic groups. The group with the worst prognosis hd 12-ms of 39.7% (95% CI: 33.8, 46.8) nd included the two poor prognostic groups mentioned bove (G4 nd G6). The intermedite group included those dignosed t < 2 yers old from provinces with EHDI 0.73 (G5) nd those dignosed t 2 14 yers old from provinces with EHDI 0.75 (G2); 12-ms ws 61.1% (95% CI: 54.8, 68.1). Children dignosed t 2 14 yers old from provinces with EHDI between 0.7 nd 0.75 (G1) nd those from provinces with EHDI < 0.7 tht migrted (G3) exhibited the best survivl experience 12-ms of 72.7% (95% CI: 68.0, 77.7). 252 Rev Pnm Slud Public 36(4), 2014

6 Gribotti et l. Disprities in peditric leukemi erly survivl in Argentin Originl reserch Figure 4. Recursive prtitioning (RP) nlysis for ptients dignosed with myeloid leukemi: RP tree,b (left) nd 12-month Kpln Meier survivl curves for groups defined by terminl nodes of RP lgorithm c (right), Argentin, EHDI< G1 d/n: 67/257 s: 73.2 (68.0, 78.9) EHDI EHDI PM=yes G2 d/n: 59/157 s: 60.7 (53.3, 69.1) EHDI< G3 d/n: 22/76 s: 70.8 (61.3, 81.9) Age 2 Age< 2 PM=no G4 d/n: 56/97 s: 40.8 (32.0, 52.1) EHDI 0.73 EHDI< 0.73 G5 G6 d/n: 22/59 d/n: 77/129 s: 62.1 s: 38.9 (50.7, 76.0) (31.3, 48.4) 12 month survivl Overll G1 G Time in months G2 G5 G3 G6 G: group; d/n: number of deths / smple size; s: Kpln Meier 12-month survivl estimte; EHDI: Extended Humn Development Index for 2006 (19, 20); PM: ptient migrtion. b Including 95% confidence intervls. c Overll: overll 12-month survivl curve. DISCUSSION This study provides popultion-bsed estimtes on peditric leukemi erly survivl in Ltin Americn country. Mjor gps in 12-ms for leukemi cncer mong Argentine children were reveled using the RP pproch. Beyond the lredy-estblished reltionship between ge nd LL survivl which is one of the grounds for clssifying LL s stndrd-risk (1 9 yers of ge) or high-risk (older children nd infnts) (24) the RP nlysis identified n dditionl vulnerble group mong the stndrd risk group: children from poorer provinces (EHDI < 0.65) who received tretment in their province hd 9% reduction in 12-ms compred to those who migrted for tret ment. Interestingly, survivl of those who migrted ws similr to those from richer provinces. A similr reltionship ws observed for ML cses. Among ML ptients dignosed t < 2 yers old, RP identified lrge erly survivl gp: children from provinces with EHDI 0.73 hd 12-ms 60% higher thn those living in poorer provinces. For ML ptients 2 14 yers old living in poor provinces (EHDI < 0.698), ptient migrtion ws ssocited with 30% increse in 12-ms. While the univrite Cox nlysis lso showed tht EHDI ws significntly ssocited with survivl, the result of the RP nlysis llows for more precise identifiction of the subpopultions with lrger survivl gps. Further, ptient migrtion, which the RP pproch identified s n importnt prognostic fctor, did not pper s relevnt fctor in the Cox nlysis when considering the popultion s whole. The RP pproch utomticlly ctegorizes EHDI, ge t dignosis, nd other explntory vribles into groups, gurnteeing tht the survivl pttern for specific group of ptients will be homogeneous within tht group. This is dvntgeous compred to the trditionl Cox model pproch, in which ctegoriztion hs to be decided priori by the investigtor nd there is no gurntee of homogeneity within the clss. In ddition, the recursive nture of the RP method llows for the identifiction of prognostic fctors tht exert their influence in subsets of Rev Pnm Slud Public 36(4),

7 Originl reserch Gribotti et l. Disprities in peditric leukemi erly survivl in Argentin subjects rther thn cross ll subjects, s in the Cox model. In the current study, ge t dignosis ws included in the nlysis s numericl vrible mesured in yers. The strt defined by the RP technique were similr to those commonly used in peditric oncology. The current findings re similr to those in the existing literture. Regionl differences in survivl ptterns for childhood cncers hve lso been documented in Europen popultions (25, 26) nd ttributed to differences in ccess to nd qulity of helth cre. Vlsecchi et l. (4), in multi-center retrospective study of hospitl dmitted ptients, found significnt differences in three-yer overll peditric cncer survivl cross severl Centrl Americ nd Cribben countries, lrgely due to tretment bndonment. In Argentin, the lower survivl rtes observed in the poorer provinces my hve less to do with tretment bndonment, which is not significnt problem in the country, nd more to do with differences in the vilbility of supportive cre services. This clim would be supported by the observtion of better survivl mong those who migrte for tretment. Despite the fct tht ll tretment centers use the sme protocols, hospitls in provinces with low EHDI re ill-equipped in terms of infrstructure, equipment, nd trined providers. This disprity becomes prticulrly relevnt in the erly tretment period, the focus of the nlysis reported here, given tht initil leukemi tretments re intensive nd much of their success depends on the provision of dequte supportive cre. The positive effect of migrtion on erly survivl ws only observed mong the groups with more fvorble prognosis for both LL nd ML. This result ws difficult to interpret bsed on the informtion vilble for this study. The ROHA records did not include informtion such s prognostic fctors other thn ge; clinicl sttus t the time of the referrl; nd other possible resons for the referrl. As most provinces in Argentin lck forml referrl polices, ptients cn be referred to other helth fcilities for myrid of resons rnging from officil recommendtions for specil procedures (e.g., stem cell trnsplnts) to fmilies decision to migrte for tretment (which my hve to do with their socioeconomic sttus, nother fctor ffecting survivl). Therefore, the effects of migrtion on survivl my be relted to complex interctions tht could not be explored in this study. Further reserch is wrrnted to confirm the results reported here nd to understnd the phenomen. In the mentime, the current findings my be used to guide trgeted interventions for determining preestblished criteri for ptient trnsfers to highcomplexity hospitls, developing regionl centers nd networks, nd improving infrstructure nd trining to help ensure dequte supportive cre. These types of interventions my help nrrow the gp of inequlity between richer nd poorer regions. The evidence suggests tht gret progress cn be mde towrd reducing the helth gp by improving prevention, erly detection, tretment, nd pllitive cre (27, 28). In the United Sttes, wreness of cncer disprities hs stimulted the cretion nd strengthening of federl progrms to decrese inequlities in cncer burden (29, 30). In Ltin Americ, the implementtion of peditric cncer progrms in severl res with limited economic resources hs resulted in improved outcomes (7, 28, 31). Trgeting the lrgest contributors to the overll burden of mortlity, such s lte dignosis, indequte support of tretment, nd tretment bndonment, will do the most to reduce inequlities mong Argentin s popultion. In recent yers, workshops, twinning progrms, nd publictions to improve erly detection of peditric cncer ptients nd build locl cpcity hve been developed in Argentin (32, 33). In this regrd, RP could become useful tool for defining vulnerble subgroups of ptients tht my be prticulrly benefited by improvements in both short- nd longterm policies. Strengths nd limittions To the best of the uthors knowledge, this is the first popultion-bsed study reporting on survivl of Ltin Americn children dignosed with leukemi. Nevertheless, the study hs number of limittions. First, lthough the completeness nd qulity of the ROHA dt is high, the registry only includes limited number of dt items. Some importnt determinnts of cncer survivl, such s lte dignosis, clinicl stge t dignosis, tretment bndonment, nd immunologicl subtype, re not vilble in the ROHA records, which limited the richness of the conclusions of this study. Despite these constrints, this study 1) highlights importnt gps in leukemi survivl in Argentine ptients nd 2) provides evidence of the usefulness of the RP strtegy to identify inequlities. It is evident tht with dtbse including lrger number of vribles this methodology could contribute to more ccurte understnding of fctors ssocited with disprities in this popultion. Second, this study lcked socioeconomic informtion t the fmily level. Therefore, the 2006 EHDI for the province of residence ws used. The uthors consider this ggregted socioeconomic mesure n cceptble proxy for level of cre of the helth system. As mentioned bove, the qulity of peditric oncology dignosis nd cre vilble in poor province is, in generl, well below the top-level cre ccessible in richer provinces. Conclusions This study found importnt disprities in leukemi survivl mong Argentine children. The findings point to ptient migrtion s one of the fctors benefiting 1 10-yer-old LL ptients nd 2 14-yer-old ML ptients living in poor res. A low-cost, simple mesure, such s implementing protocol for referring ptients to highly specilized helth centers, my help reduce this gp. Actions llowing ptients to complete tretment in their home province, resulting in reduction of the time spent by the child nd the fmily fr from their home, would lso be beneficil. This study lso 1) shows tht the RP methodology is vluble tool for evluting helth inequlities nd 2) highlights the fct tht popultionbsed registries re indispensble for guiding decision-mking in cncer cre. Acknowledgments. The uthors thnk Benedetto Terrcini for his indepth revision of the mnuscript nd vluble suggestions nd comments, which helped improve this report. They lso thnk the network of peditric units nd popultion-bsed cncer registries tht contribute to Argentin s Hospitl Oncopeditric Registry (Registro Oncopediátrico Hospitlrio Argentino, ROHA). 254 Rev Pnm Slud Public 36(4), 2014

8 Gribotti et l. Disprities in peditric leukemi erly survivl in Argentin Originl reserch Funding. Support for this study ws provided by the Ntionl Cncer Institute (Instituto Ncionl del Cáncer, INC) nd the Ntionl Agency for Scientific nd Technologicl Development (Agenci Ncionl de Promoción Científic y Tecnológic, ANPCYT) in Buenos Aires. GG nd LO were prtilly supported by ANPCYT grnt no. PRH 1-1, PICT The funding sources hd no role in the study design, dt collection, nlysis, interprettion, or writing of this report. Conflicts of interest. None. REFERENCES 1. Coebergh J, Reedijk A, de Vries E, Mrtos C, Jkb Z, Stelirov-Foucher E, et l. Leukemi incidence nd survivl in children nd dolescents in Europe during Eur J Cncer. 2006;42(13): Ries LA, Smith MA, Gurney JG, Linet M, Tmr T, Young JL, et l., editors. Cncer incidence nd survivl mong children nd dolescents: United Sttes SEER Progrm Bethesd (MD): Ntionl Cncer Institute, SEER Progrm; Formn D, Bry F, Brewster DH, Gombe Mblw C, Kohler B, Piñeros M, et l., editors. Cncer incidence in five continents. Vol. X. Lyon: Interntionl Agency for Reserch on Cncer; Vlsecchi MG, Tognoni G, Bonill M, Moreno N, Bez F, Pcheco C, et l. Clinicl epidemiology of childhood cncer in Centrl Americ nd Cribben countries. Ann Oncol. 2004;15(4): Mushtq N, Fdoo Z, Nqvi A. Childhood cute lymphoblstic leukemi: experience from single tertiry cre fcility of Pkistn. J Pk Med Assoc. 2013;63(11): De Angelis C, Pcheco C, Lucchini G, Arguello M, Conter V, Flores A, et l. The experience in Nicrgu: childhood leukemi in low income countries the min cuse of lte dignosis my be medicl dely. Int J Peditr. 2012;2012: Metzger ML, Howrd SC, Fu LC, Peñ A, Stefn R, Hncock ML, et l. Outcome of childhood cute lymphoblstic leukemi in resource-poor countries. Lncet. 2003;362(9385): Moreno F, Lori D, Abrit G, Terrcini B; ROHA network. Childhood cncer: incidence nd erly deths in Argentin, Eur J Cncer. 2013;49(2): Moreno F, Schvrtzmn E, Scopinro M, Diez B, Grcí Lombrdi M, Lori D, et l. Registro Oncopediátrico Argentino: resultdos Buenos Aires: Fundción Kleidos; Avilble from: fundcionkleidos.org/roh_publicciones/ roh2008.pdf Accessed on 17 November Moreno F, Dussel V, Abrit G, Lori D, Orelln L. Registro Oncopediátrico Hospitlrio Argentino: incidenci , supervivenci , tendenci de mortlidd Buenos Aires: Instituto Ncionl del Cáncer; Avilble from: bes/grficos/ cnt-20-registroon copeditricohospitlrioargentino_sobre vid CncerInfntil_2012.pdf Accessed on 17 November Tozino R, Wlter J, Brulc A, Nvi M, Quintn S, Flores A. Perfil socioeconómico y de l tención de pcientes oncológicos provenientes de cinco provincis en un hospitl de tención terciri. Arch Argent Peditr. 2004;102(4): Scopinro MJ, Csk SJ. Peditric oncology in Argentin: medicl nd ethicl issues. Lncet Oncol. 2002;3(2): Breimn L, Friedmn J, Olshen R, Stone C. Clssifiction nd regression trees. Belmont (CA): Wdsworth Interntionl Group; Gordon L, Olshen RA. Tree-structured survivl nlysis. Cncer Tret Rep. 1985;69(10): Cimpi A, Chng C-H, Hogg S, McKinney S. Recursive prtitioning: verstile method for explortory dt nlysis in biosttistics. In: McNeil IB, Umphrey GJ, editors. Biosttistics. New York: Reidel; Pp Zhng H, Singer BH. Recursive prtitioning nd pplictions. 2nd ed. New York: Springer; Fritz A, Percy C, Jck A, Shnmugrtnm K, Sobin L, Prkin DM, et l., editors. Interntionl Clssifiction of Diseses for Oncology. 3rd ed. Genev: World Helth Orgniztion; Stelirov-Foucher E, Stiller C, Lcour B, Ktsch P. Interntionl Clssifiction of Childhood Cncer, 3rd ed. Cncer. 2005;103(7): Progrm de ls Nciones Unids pr el Desrrollo. Informe ncionl sobre desrrollo humno Desrrollo humno en Argentin: tryectos y nuevos desfíos. Buenos Aires: PNUD; pp. 20. United Ntions Development Progrmme. Humn development report The rel welth of ntions: pthwys to humn development. New York: UNDP; Therneu TM, Atkinson EJ. An introduction to recursive prtitioning using the RPART routines. Rochester (MN): Myo Foundtion; Avilble from: reserch/documents/biostt-61pdf/doc Accessed on 17 November R Core Tem. R: lnguge nd environment for sttisticl computing. Vienn: R Foundtion for Sttisticl Computing; Avilble from: Accessed on 17 November Therneu T, Atkinson B. Rprt: recursive prtitioning. Vienn: Comprehensive R Archive Network, Vienn University of Economics nd Business Administrtion; Avilble from: pckges/rprt/rprt.pdf Accessed on 17 November Hunger SP, Lu X, Devids M, Cmitt BM, Gynon PS, Winick NJ, et l. Improved survivl for children nd dolescents with cute lymphoblstic leukemi between 1990 nd 2005: report from the Children s Oncology Group. J Clin Oncol. 2012;30(14): Stelirov-Foucher E, Stiller C, Ktsch P, Berrino F, Coebergh JW, Lcour B, et l. Geogrphicl ptterns nd time trends of cncer incidence nd survivl mong children nd dolescents in Europe since the 1970s (the ACCISproject): n epidemiologicl study. Lncet. 2004;364(9451): Gtt G, Corzziri I, Mgnni C, Peris-Bonet R, Rozzi P, Stiller C, et l. Childhood cncer survivl in Europe. Ann Oncol. 2003;14 Suppl 5:v Frmer P, Frenk J, Knul FM, Shulmn LN, Alleyne G, Armstrong L, et l. Expnsion of cncer cre nd control in countries of low nd middle income: cll to ction. Lncet. 2010;376(9747): Howrd SC, Pedros M, Lins M, Pedros A, Pui CH, Ribeiro RC, et l. Estblishment of peditric oncology progrm nd outcomes of childhood cute lymphoblstic leukemi in resource-poor re. JAMA. 2004;291(20): Hynes MA, Smedley BD, editors. The unequl burden of cncer: n ssessment of NIH reserch nd progrms for ethnic minorities nd the mediclly underserved. Wshington: Ntionl Acdemy Press; Avilble from: php?isbn= Accessed on 17 November Foley KM, Gelbnd H, editors. Improving pllitive cre for cncer. Wshington: Ntionl Acdemy Press; Avilble from: php?isbn= Accessed on 17 November Sl A, Brr RD, Mser G; MISPHO Consortium. A survey of resources nd ctivities in the MISPHO fmily of institutions in Ltin Americ: comprison of two ers. Peditr Blood Cncer. 2004;43(7): Ministerio de Slud (AR). Cuándo sospechr cáncer en niños? Buenos Aires: Registro Oncopediátrico Hospitlrio Argentino, MSAL; Avilble from: grficos/ cnt-32-cscn--guibj. pdf Accessed on 17 November Scopinro M, Lvdo G, Lun P, Grynszpncholc E. El progrm de cooperción entre los servicios de hemtooncologí de los hospitles Jun P. Grrhn (HPG) y del Niño Jesus (HNJ). Med Infnt. 2007;14(2): Avilble from: stories/volumen/2007/xiv_2_162.pdf Accessed on 17 November Mnuscript received on 14 My Revised version ccepted for publiction on 7 November Rev Pnm Slud Public 36(4),

9 Originl reserch Gribotti et l. Disprities in peditric leukemi erly survivl in Argentin resumen Dispriddes en l supervivenci temprn l leucemi infntil en Argentin: un estudio poblcionl Plbrs clve Objetivo. Determinr medinte prticionmiento recursivo ls dispriddes en l supervivenci temprn de los niños con leucemi trtdos en Argentin, y presentr ls crcterístics principles de los grupos más vulnerbles. Métodos. Análisis de dtos secundrios en el que se evluó l supervivenci los 12 meses de niños dignosticdos entre el 2000 y el 2008 de leucemi linfoide (LL) y leucemi mieloide (LM), e inscritos en el registro oncopediátrico poblcionl de Argentin. Medinte el método de prticionmiento recursivo se determinron los grupos pronósticos con bse en l edd en el momento del dignóstico, el sexo, el índice socioeconómico de l provinci de residenci y l migrción un provinci diferente pr recibir tención de slud. Resultdos. L supervivenci globl los 12 meses correspondiente los csos de LL y LM fue de 83,7 y 59,9%, respectivmente, y el método detectó brechs importntes en l supervivenci. Entre los pcientes de 1 10 ños con LL de ls provincis más pobres l supervivenci los 12 meses de los que migrron y de los que no lo hicieron fue de 87,0 y 78,2%, respectivmente. L supervivenci de los pcientes con LM menores de dos ños que residín en ls provincis con un índice socioeconómico bjo o medio fue de 38,9%, en comprción con 62,1% en los pcientes del mismo grupo etrio que residín en ls provincis más rics. En los pcientes con LM de 2 14 ños de edd que residín en ls provincis pobres, l migrción se soció con un umento de 30% en l supervivenci los 12 meses. Conclusiones. Se observron importntes dispriddes en l supervivenci de los niños rgentinos con leucemi. L supervivenci se soció con l migrción y el índice socioeconómico de l provinci de residenci. El método de prticionmiento recursivo contribuyó l determinción y crcterizción de los grupos vulnerbles. Dispriddes en tención de slud; leucemi; niño; píses en desrrollo; nálisis de supervivenci; Argentin. 256 Rev Pnm Slud Public 36(4), 2014