Abstract: Background and Aim: The optimum storage and transport of freshly harvested hemopoetic progenitor cells (HPC) in the liquid state is not specified in the JACIE and FACT guidelines. Depending upon transplant centre, there is a range of reported ideal temperatures (1°C to 24°C) for HPC storage and transport but little data exists to justify the recommendations. Due to the limitations of Trypan Blue viability assays and CFU-GM colony assays, we used a no-lyse, CD34 assay (Sartor et al, Bone Marrow Transplantation 2005) to determine the optimum storage and transport temperature for maintaining viability of CD34+ stem cells in freshly harvested HPC. Method: Samples were aseptically removed from 46 fresh HPC harvests (34 PBSC & 12 BM) and stored at refrigerated temperature (2°– 8°C), room temperature (18°– 24°C) and 37°C, for up to 72 hours. Samples were analysed for viable CD34+ cells/ml at 0, 24, 48 and 72 hours. Results: The mean viable CD34+ yield prior to storage was 7.7x106/kg (range: 0.7 – 30.3). No viable CD34+ cells remained after storage at 37°C for 24 hours. The mean % loss of viable CD34+ cells at refrigerated and room temperatures can be summarized as follows: Conclusion: These results demonstrate that the optimum temperature to maintain the viability of CD34+ stem cells for up to 72 hours during storage and transport of freshly harvested HPC is 2°– 8°C. Mean % loss or gain of CD34+ cells on storage Time Refrigerated Temperature Room Temperature N Mean Range N Mean Range 24 hrs 39 −9.4 +15 to −42 23 −21.9 +17 to −59 48 hrs 31 −19.4 +7 to −69 20 −30.7 +3 to −68 72 hrs 29 −28.0 +4 to −53 18 −43.3 +11 to −70

Abstract: Recovery of neutrophil numbers after peripheral blood stem cell transplantation (PBSCT) is closely associated with graft CD34+ cell dose. Predicting the speed of platelet recovery is more difficult but would be of value given that a significant minority of patients experience delayed platelet recovery and bleeding complications after transplantation. In this study we retrospectively analysed the graft composition of 29 patients who underwent autologous transplantation, using blood stem cells mobilized with cyclophoshamide and G-CSF, to assess the utility of c-mpl expression on CD34+ cells as a predictor of platelet engraftment (ie, time to platelet count greater than 20 x 109/L for three consecutive days without the need for platelet transfusion). Absolute CD34+ cells and CD34 subsets expressing c-mpl were enumerated using a published single platform viable CD34 flow cytometry assay (BMT, 36: 199–204,2005). Of the 29 patients, 7 required at least 21 days for platelet engraftment. These patients received a median graft dose of 5.7 x 104 CD34+CD110+ cells/kg compared with a median dose of 13.4 x 104 cells/kg received by patients who experienced platelet engraftment within 21 days of transplant (p=0.013). In contrast, there was no difference in the number of CD34+ cells/kg infused (4.0 v 4.9 x 106/kg for & gt; or & lt; 21 days for platelet engraftment respectively, p=0.23). There was a poor correlation between the absolute number of CD34+ cells and the number of CD34+CD110+ cells in the graft (r2 = 0.48). Similarly there was no correlation between the percentage of CD34+ cells expressing c-mpl and the speed of platelet engraftment (8.1 v 5.8%) for & gt; or & lt; 21 days for platelet engraftment respectively, p=0.39). Patients with & gt;21 days for platelet engraftment received platelet transfusions more often than those with & lt;21 days for platelet engraftment (median 9 v 2 transfusions, p & lt;0.001). The absolute number of CD34+/CD110+ cells/kg infused at time of transplantation appears to be an important factor identifying patients at risk of delayed ( & gt;21 days) platelet engraftment. Those with & lt;6 x 104 CD34+/CD110+ cells/kg are at particularly high risk of delayed platelet engraftment, requiring multiple transfusions after transplantation.

Abstract: Although recent data suggests that osteoblasts play a key role within the hematopoietic stem cell (HSC) niche, the mechanisms underpinning this remain to be fully defined. The studies described herein examine the role in hematopoiesis of Osteopontin (Opn), a multidomain, phosphorylated glycoprotein, synthesized by osteoblasts, with well-described roles in cell adhesion, inflammatory responses, angiogenesis, and tumor metastasis. We demonstrate a previously unrecognized critical role for Opn in regulation of the physical location and proliferation of HSCs. Within marrow, Opn expression is restricted to the endosteal bone surface and contributes to HSC transmarrow migration toward the endosteal region, as demonstrated by the markedly aberrant distribution of HSCs in Opn–/– mice after transplantation. Primitive hematopoietic cells demonstrate specific adhesion to Opn in vitro via β1 integrin. Furthermore, exogenous Opn potently suppresses the proliferation of primitive HPCs in vitro, the physiologic relevance of which is demonstrated by the markedly enhanced cycling of HSC in Opn–/– mice. These data therefore provide strong evidence that Opn is an important component of the HSC niche which participates in HSC location and as a physiologic-negative regulator of HSC proliferation.

Abstract: Women are conferred with greater immunologic and survival benefits compared to men. Female sex steroids contribute to this sexual dimorphism. Furthermore, during human pregnancy when female sex hormones are elevated, neutrophil apoptosis is delayed. This study examines the specific effects of estradiol and progesterone on neutrophil apoptosis and function in healthy adult men and women. We also examined the contribution of these hormones to the persistence and resolution of an inflammatory response. Spontaneous apoptosis was significantly decreased in women compared with men. Physiologic doses of estradiol and progesterone caused a further delay in spontaneous apoptosis in both men and women but did not diminish Fas antibody-induced apoptosis. The delay in apoptosis was mediated at the level of the mitochondria with decreased release of cytochrome c, which may alter caspase cleavage and activity. There were no associated alterations in neutrophil CD11b, but production of reactive oxygen intermediates (ROIs) in women was increased. Thus, female sex hormones mediate delayed neutrophil apoptosis in both sexes and enhance female intracellular production of ROIs. Modulating hormonal responses may be an effective therapeutic tool in combating inflammatory diseases. (Blood. 2003;102:2653-2659)

Abstract: Patients with JMML have a variable clinical course. Many have relentless myeloproliferation, irrespective of the initial therapy, and die rapidly if not successfully given a bone marrow transplant (BMT). Others partially respond to therapy with reduction in their leukocytosis and organomegaly, but with continued cytopenias. Finally, some children have a much more indolent clinical course, requiring little or even no therapy. A number of cytogenetic abnormalities are found in JMML, particularly monosomy 7. Molecular abnormalities have also been described including mutations in PTPN11, NRAS and KRAS, but it is not clear whether the karyotype and genotype are related to the phenotype. To address this issue, we studied 33 cases diagnosed between 1992 to 2007. All fulfilled the minimal diagnostic criteria for JMML. Three had Noonan syndrome (NS), and 1 a constitutional trisomy 8 mosaicism (CT8M). The remaining 29 had no known genetic syndrome. The median age at presentation was 15 months (0–96 months) and 22 (69%) were under 2 years of age. Patients were retrospectively allocated to 1 of 3 clinical groups. Group I (18 patients, 55%) had aggressive disease with minimal or no response to initial therapy. Group II (8 patients, 24%) had a partial response to therapy but persistent severe cytopenias or persistence of a monosomy 7 clone. All patients in Group I and II were scheduled to receive a BMT; this was carried out in 16 of 18 Group I patients and 7 of 8 Group II patients. A further 7 cases (Group III, 21%) had indolent disease with a median follow-up of 5 years (1–12 years). It is noteworthy that 2 of the 3 patients with NS were in this category. There was no difference at presentation in the clinical or diagnostic parameters between the 3 clinical groups. Cytogenetic analysis was available in 32 patients with 20 (63%) having a normal karyotype, 9 (28%) monosomy 7, 2 complex abnormalities and 1 CT8M. The presence of monosomy 7 was restricted to Groups I and II, but as this cytogenetic finding was used as an indication for BMT, limited conclusions can be drawn about the natural history of this subset. All Group III patients had a normal karyotype. Mutation screening using WAVE DHPLC analysis revealed 12 patients (36%), including the 3 NS patients, with PTPN11 mutations, 6 (18%) with NRAS and 8 (24%) with KRAS mutations. The total incidence of mutations was similar in the 3 clinical groups being 78%, 88% and 71% in Groups I, II and III respectively. KRAS mutations were not present in Group III patients, but this was not significant. Six of the 33 patients in this series, all in Group I, have transformed to an acute leukemia. Two had cytogenetic abnormalities although none had monosomy 7, 1 had a PTPN11 mutation, 2 an NRAS and 2 a KRAS mutation. Four out of 14 patients with a RAS mutation underwent transformation compared to 1 out of 12 of those with a PTPN11 mutation (p = 0.18). Of note, 1 patient with a KRAS G12S mutation was in Group II, which differs from the indolent course reported for this mutation by others. These results indicate that neither cytogenetic abnormalities nor specific mutations in PTPN11, NRAS or KRAS predict the clinical course of JMML. This study also raises the possibility that the clinical course is determined, in part, by cooperating mutations or polymorphisms that have not yet been identified.

Abstract: Monosomy 7 (−7) and deletion 7q \del(7q)] are rare in childhood acute myeloid leukemia (AML). We retrospectively collected data on 258 children with AML or refractory anemia with excess blasts in transformation (RAEB-T) and −7 or del(7q) with or without other cytogenetic aberrations \± other] . Karyotypes included −7 (n = 90), −7 other (n = 82), del(7q) (n = 21), and del(7q) other (n = 65). Complete remission (CR) was achieved in fewer patients with −7 ± other compared with del(7q) ± other (61% versus 89%, P 〈 .001). Overall, the 5-year survival rate was 39% (SE, 3%). Survival was superior in del(7q) ± other compared with −7 ± other (51% versus 30%, P 〈 .01). Cytogenetic aberrations considered favorable in AML \t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q22;q21), t(9;11)(p22;q23)] (n = 24) were strongly associated with del(7q) and a higher 5-year survival rate compared with del(7q) without favorable cytogenetics (75% versus 46%, P = .03). Patients with −7 and inv(3),−5/del(5q), or + 21 had a 5-year survival rate of 5%. Stem cell transplantation analyzed as a time-dependent variable had no impact on overall survival. However, patients not achieving CR had a 31% survival rate after stem cell transplantation. Childhood AML with chromosome 7 aberrations represents a heterogeneous group of disorders with additional cytogenetic aberrations having a major prognostic impact which should be reflected in future risk-group stratification.

Abstract: We previously demonstrated that outcome of pediatric 11q23/MLL-rearranged AML depends on the translocation partner (TP). In this multicenter international study on 733 children with 11q23/MLL-rearranged AML, we further analyzed which additional cytogenetic aberrations (ACA) had prognostic significance. ACAs occurred in 344 (47%) of 733 and were associated with unfavorable outcome (5-year overall survival [OS] 47% vs 62%, P 〈 .001). Trisomy 8, the most frequent specific ACA (n = 130/344, 38%), independently predicted favorable outcome within the ACAs group (OS 61% vs 39%, P = .003; Cox model for OS hazard ratio (HR) 0.54, P = .03), on the basis of reduced relapse rate (26% vs 49%, P 〈 .001). Trisomy 19 (n = 37/344, 11%) independently predicted poor prognosis in ACAs cases, which was partly caused by refractory disease (remission rate 74% vs 89%, P = .04; OS 24% vs 50%, P 〈 .001; HR 1.77, P = .01). Structural ACAs had independent adverse prognostic value for event-free survival (HR 1.36, P = .01). Complex karyotype, defined as ≥ 3 abnormalities, was present in 26% (n = 192/733) and showed worse outcome than those without complex karyotype (OS 45% vs 59%, P = .003) in univariate analysis only. In conclusion, like TP, specific ACAs have independent prognostic significance in pediatric 11q23/MLL-rearranged AML, and the mechanism underlying these prognostic differences should be studied.

Abstract: The first three authors contributed equally. The last three authors share senior authorship. Background: Although there has been an increased recognition of the contribution of germline variants to development of myeloid neoplasms, only two large-scale case-control genome-wide association studies (GWASs) have been conducted to identify variants that predispose to AML. Importantly, these studies were dedicated to AML predisposition in general, without investigation of molecularly distinct AML subtypes. Thus, we performed the first dedicated meta-analysis combining the two GWASs to investigate predisposing variants to cytogenetic AML subsets characterized by recurrent translocations and inversions. Methods: Two sets of adult de novo AML patients treated on Alliance for Clinical Trials in Oncology (Alliance) protocols, and two sets of adult de novo AML patients reported to CIBMTR (2000-11) from DISCOVeRY-BMT cohorts were compared with four sets of population-matched non-leukemic individuals of European ancestry. Illumina Infinium arrays were used for genotyping. The haplotype reference consortium was used for imputation and comparisons were performed using SNPtest and METAL with fixed-effects, for CBF-AML (n=251, including t(8;21), n=115; inv(16), n=136) and AML with 11q23/KMT2A translocations (n=177). Blood or bone marrow samples from subsets of these patients and additional AML patients with other cytogenetic abnormalities were used for total transcriptome RNA sequencing with Illumina instruments. Results: Two risk loci reached genome-wide significance in AML patients with 11q23/KMT2A translocations (Fig 1A). The most significant single nucleotide polymorphism (SNP) in the 4q21.3 risk locus, rs17668899[A] (P = 2.32 x 10-8, odds ratio [OR] = 3.92 [2.43-6.32]) is in intron 6 of the AFF1 gene (also called AF4) (Fig 1B), within an enhancer that interacts with the AFF1 transcription start site (Fig 1C, left). KMT2A-translocated AML patients with the risk allele had higher blast expression of AFF1 compared to those homozygous for the non-risk allele, although the trend did not reach significance (Fig 1D). Notably, AFF1 encodes a subunit of the super-elongation-complex (SEC) that acts as Pol II-associated master regulator of global transcription elongation. AFF1 is a common translocation partner of KMT2A in patients with acute lymphoblastic leukemia with t(4;11)(q21;q23), and is required for KMT2A-mediated leukemogenesis. We observed significantly higher AFF1 expression in both KMT2A-translocated AML and cytogenetically normal (CN) AML compared to CBF-AML (Fig 1E). The suggested role of AFF1/SEC is consistent with recent studies showing an important role for DOT1L, H3K79 methylation, and transcriptional elongation in NPM1-mutant AML (the most common subtype of CN-AML). Outcome analysis showed higher expression of AFF1 associated with shorter disease-free (DFS) in patients & lt; 60 years treated on Alliance studies (hazard ratio [HR] = 1.36, P=0.04; Fig 1F). The second KMT2A-translocated AML risk locus was located at 22q13.31, and the most significant SNP was rs62231468[A] (P = 4.95 x 10-9, OR = 3.25). rs62231468 is immediately 5' of the LDOC1L gene (a retrotransposon GAG-related gene, also called RTL6), and analysis of expression quantitative trait loci (eQTL) showed association of rs62231468[A] with higher LDOC1L expression, consistent with its location in an active enhancer (Fig 1C, right). The association between rs62231468[A] and higher LDOC1L expression was validated in leukemic blast expression from a set of 449 AML patients of any cytogenetic subset (Fig 1G). Notably, higher LDOC1L expression was associated with shorter DFS and overall survival (OS) in Alliance patients & lt; 60 years (DFS, HR = 1.25, P=0.03; OS, HR = 1.46, P & lt;0.001; Fig 1H-I). Analysis of patients with CBF-AML identified rs71568004[C] as more common in CBF-AML patients compared to controls (P = 3.84 x 10-8 , OR = 3.05 [2.05-4.53] ). This SNP is ~50kb 5' of the MARCKS gene located at 6q21, but genomic context analysis did not reveal any clear associations with MARCKS expression. Conclusions: Our first assessment of risk alleles for cytogenetic subsets of AML identified two novel independent risk loci associated with 11q23/KMT2A-translocated AML, and one risk locus associated with CBF-AML. These data suggest an important, subtype-specific role for transcriptional elongation in AML and that functional studies of retro transposition elements should be undertaken in leukemogenesis. Figure Disclosures Walker: Karyopharm: Current Employment, Current equity holder in publicly-traded company; Vigeo Therapeutics: Consultancy. Powell:Rafael Pharmaceuticals: Consultancy, Other: Advisor, Research Funding; Jazz Pharmaceuticals: Consultancy, Other: Advisor, Research Funding; Genentech: Research Funding; Novartis: Research Funding; Pfizer: Research Funding. Kolitz:Pfizer: Membership on an entity's Board of Directors or advisory committees; Magellan: Membership on an entity's Board of Directors or advisory committees. Pasquini:Bristol Myers Squibb: Consultancy; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Other; Novartis: Research Funding; Kite: Research Funding. McCarthy:Karyopharm: Consultancy, Honoraria; Magenta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Genentech: Consultancy, Honoraria; Starton: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Juno Therapeutics, a Bristol-Myers Squibb Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board , Research Funding is to Roswell Park, Research Funding. Stone:AbbVie: Consultancy, Research Funding; Actinium: Consultancy; Agios: Consultancy, Research Funding; Argenx: Consultancy, Other: Data and safety monitoring board; Arog: Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; Biolinerx: Consultancy; Celgene: Consultancy, Other: Data and safety monitoring board; Jazz: Consultancy; Novartis: Consultancy, Research Funding; Otsuka: Consultancy; Pfizer: Consultancy; Trovagene: Consultancy; Takeda: Consultancy; Daiichi-Sankyo: Consultancy; Elevate: Consultancy; Gemoab: Consultancy; Janssen: Consultancy; Macrogenics: Consultancy; Hoffman LaRoche: Consultancy; Stemline: Consultancy; Syndax: Consultancy; Syntrix: Consultancy; Syros: Consultancy. Byrd:Trillium: Research Funding; Novartis: Research Funding; Kartos Therapeutics: Research Funding; Syndax: Research Funding; Vincera: Research Funding; Acerta Pharma: Research Funding; Janssen: Consultancy; Leukemia and Lymphoma Society: Other; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company, Janssen, Novartis, Gilead, TG Therapeutics: Other; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, Novartis, Janssen: Speakers Bureau. Eisfeld:Karyopharm: Current Employment, Current equity holder in publicly-traded company; Vigeo Therapeutics: Consultancy.

Abstract: Abstract 762 Pediatric AML is a heterogeneous disease. We showed that differential outcomes of 11q23/MLL-rearranged AML depend on the fusion partner involved in the translocation in a large international retrospective study from 11 collaborative groups comprising 756 children (Balgobind et al, Blood 2009). In the current analysis we focused on the clinical characteristics and prognostic impact of additional cytogenetic aberrations (ACA). All patients with complete karyotypes (n=733) were centrally reviewed and classified for type and number of aberrations. Cases with 2 or more aberrations (including 11q23/MLL-rearrangement), were included in the ACA group (n=344/733, 47%). Numerical and structural ACA were divided into gains and losses of full or partial chromosomes, and balanced translocations were defined by the breakpoints. A complex karyotype was defined as 3 or more aberrations. ACA occurring in at least 10 patients were considered for statistical analysis, including differences in presenting characteristics (chi-square or Fisher's exact tests) and survival estimates (Kaplan-Meier method and Cox proportional hazards model for Event free survival (EFS), 5 year estimates and 95% confidence intervals (CI) are given). Multivariate analysis included the fusion partners with independent prognostic significance, as identified by Balgobind et al. Patients with ACA were found to be older (median age, 3.0 y vs 1.8 y, p=.001) and had a higher frequency of FAB M7 phenotype (4.5 % vs 1.1 %, p=.007) than those without ACA. For the complete cohort (n=733) estimates of EFS and overall survival (OS) were .44 and .56, and cumulative incidence of relapse (CIR) was .35 (standard errors .03). Patients with ACA showed significantly poorer clinical outcome than cases without ACA (EFS .38 vs .48, p=.002; OS .47 vs .62, p 〈 .001; CIR .52 vs .38, p 〈 .001). The most frequent specific ACA that was identified was trisomy 8 (130/344 cases, 38%). Patients with trisomy 8 were older (median age, 4.4 y vs 1.9 y, p 〈 .001), presented with lower WBC counts (median 2.3 vs 27.1*109/l, p 〈 .001), were found more frequently in association with t(9;11)(p22;q23) (58% vs 42%, p=.01) and had a higher frequency of FAB M5 (78% vs 61%, p=.01) compared to patients without trisomy 8 cases. Trisomy 8 appeared to independently predict better clinical outcome within the ACA group (EFS .53 vs .29, p 〈 .001; OS .61 vs .39, p=.003; CIR .35 vs .62, p 〈 .001. and Hazard Ratio (HR) .57, CI .36-.92, p=.02). Trisomy 19 was found in 37/344 cases (11%). Trisomy 19 independently predicted poor clinical outcome in ACA cases. This effect appears to be mainly determined by refractory disease rather than relapse (probability of complete remission 62% vs 87%, EFS .17 vs .40, p=.003; OS .24 vs .50, p 〈 .001; CIR .54 vs .51, p=.88; HR 1.77, CI 1.13–2.78, p=.01). Structural ACA were identified in 204 cases. Analyses in which all structural ACA were grouped together showed that they are of independent prognostic significance compared to only numerical aberrations (EFS .32 vs .47, p=.02; OS .42 vs .56, p=.10; CIR .59 vs .41, p=.003; HR 1.36, CI 1.07–1.80, p=.01). However, no specific structural ACA was present in more than 10 patients, precluding a more detailed analysis. Complex karyotype was found in 192/733 (26%) patients. Outcome was worse in these patients than those without complex karyotype (EFS .37 vs .46, p=.02; OS .45 vs .59, p=.003; and CIR .53 vs .42, p 〈 .001), however, no independent prognostic significance was shown. In the context of the newly identified prognostic factors, the translocation partners 10p12, 6q27, 1q21 and 10p11.2 still showed independent prognostic value (HR 1.36, 2.29, .12 and 2.12 respectively). In conclusion, here we show that in addition to fusion partners, ACA have independent prognostic significance in pediatric 11q23/MLL-rearranged AML. Trisomy 8 was identified as an independent indicator of better prognosis in pediatric 11q23/MLL-rearranged AML. The presence of any ACA other than trisomy 8 predicts for worse clinical outcome. More specifically, trisomy 19 and structural aberrations were independent negative prognostic factors. Complex karyotype was a frequent finding and was a negative prognostic factor in univariate analysis only. This study shows that MLL-translocation partner and additional cytogenetic aberrations are important for patient stratification. Future studies should aim to understand the biology underlying these prognostic differences. Disclosures: Smith: Pfizer, Inc:.

Abstract: Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (± 5%), with large differences across subgroups (11% ± 5% to 92% ± 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P 〈 .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.