In the effort to improve immunophenotyping and minimal residual disease (MRD) assessment in acute lymphoblastic leukemia (ALL), the international Berlin-Frankfurt-Münster (iBFM) Flow Network introduced the myelomonocytic marker CD371 for a large prospective characterization with a long follow-up. In the present study, we aimed to investigate the clinical and biological features of CD371-positive (CD371pos) pediatric B-cell precursor ALL (BCP-ALL). From June 2014 to February 2017, 1812 pediatric patients with newly diagnosed BCP-ALLs enrolled in trial AIEOP-BFM ALL 2009 were evaluated as part of either a screening (n = 843, Italian centers) or validation cohort (n = 969, other iBFM centers). Laboratory assessment at diagnosis consisted of morphological, immunophenotypic, and genetic analysis. Response assessment relied on morphology, multiparametric flow cytometry (MFC), and polymerase chain reaction (PCR)-MRD. At diagnosis, 160 of 1812 (8.8%) BCP-ALLs were CD371pos. This correlated with older age, lower ETV6::RUNX1 frequency, immunophenotypic immaturity (all P < .001), and strong expression of CD34 and of CD45 (P < .05). During induction therapy, CD371pos BCP-ALLs showed a transient myelomonocytic switch (mm-SW: up to 65.4% of samples at day 15) and an inferior response to chemotherapy (slow early response, P < .001). However, the 5-year event-free survival was 88.3%. Among 420 patients from the validation cohort, 27 of 28 (96.4%) cases positive for DUX4-fusions were CD371pos. In conclusion, in the largest pediatric cohort, CD371 is the most sensitive marker of transient mm-SW, whose recognition is essential for proper MFC MRD assessment. CD371pos is associated to poor early treatment response, although a good outcome can be reached after MRD-based ALL-related therapies.

• MeSH
• buněčný rodokmen MeSH
• dítě MeSH
• imunofenotypizace MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• pre-B-buněčná leukemie * genetika   mortalita   farmakoterapie   patologie   diagnóza   terapie   metabolismus   MeSH
• předškolní dítě MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• reziduální nádor * diagnóza   MeSH
• tetraspaniny genetika   metabolismus   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• tetraspaniny MeSH

We compared minimal/measurable residual disease (MRD) levels evaluated by routinely used real-time quantitative polymerase chain reaction (qPCR) patient-specific assays and by next-generation sequencing (NGS) approach in 780 immunoglobulin (IG) and T-cell receptor (TR) markers in 432 children with B-cell precursor acute lymphoblastic leukemia treated on the AIEOP-BFM ALL 2009 protocol. Our aim was to compare the MRD-based risk stratification at the end of induction. The results were concordant in 639 of 780 (81.9%) of these markers; 37 of 780 (4.7%) markers were detected only by NGS. In 104 of 780 (13.3%) markers positive only by qPCR, a large fraction (23/104; 22.1%) was detected also by NGS, however, owing to the presence of identical IG/TR rearrangements in unrelated samples, we classified those as nonspecific/false-positive. Risk group stratification based on the MRD results by qPCR and NGS at the end of induction was concordant in 76% of the patients; 19% of the patients would be assigned to a lower risk group by NGS, largely owing to the elimination of false-positive qPCR results, and 5% of patients would be assigned to a higher risk group by NGS. NGS MRD is highly concordant with qPCR while providing more specific results and can be an alternative in the front line of MRD evaluation in forthcoming MRD-based protocols.

• MeSH
• akutní lymfatická leukemie * diagnóza   genetika   terapie   MeSH
• dítě MeSH
• genová přestavba MeSH
• hodnocení rizik MeSH
• imunoglobuliny genetika   MeSH
• lidé MeSH
• pre-B-buněčná leukemie * diagnóza   genetika   terapie   MeSH
• receptory antigenů T-buněk genetika   MeSH
• reziduální nádor diagnóza   genetika   MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• imunoglobuliny MeSH
• receptory antigenů T-buněk MeSH

BACKGROUND: Blinatumomab, a CD3/CD19 BiTE® (bispecific T cell engager) molecule, was superior to high-risk third course consolidation chemotherapy (HC3) in prolonging event-free survival (EFS) in children with high-risk first relapse B-cell precursor acute lymphoblastic leukemia (B-ALL). Here, we report results from a post hoc measurable residual disease (MRD) analysis of this phase 3 study (NCT02393859). PROCEDURE: Children >28 days and <18 years with high-risk first-relapse B-ALL in cytomorphological complete remission (M1 marrow, <5% blasts) or with M2 marrow (≥5% and <25% blasts) after induction and two cycles of high-risk consolidation chemotherapy (baseline) were enrolled in this trial. Patients received one cycle of blinatumomab (15 μg/m2 /day, 4 weeks, continuous intravenous infusion) or HC3. The primary endpoint was EFS. In this post hoc analysis, patients with MRD <10-4 by PCR were grouped as having positive but not quantifiable (pbnq) or undetectable disease. RESULTS: A higher proportion of patients with MRD <10-4 had undetectable versus pbnq disease after blinatumomab (day 29) than after HC3 (p = 0.0367). Of the 22 patients with MRD ≥10-4 at baseline who achieved MRD remission after blinatumomab, 20 (91%) achieved MRD <10-4 remission by day 15. Patients treated with blinatumomab had improved EFS and overall survival compared with those treated with HC3 independent of end-of-induction or baseline (end-of-second consolidation) MRD levels. CONCLUSIONS: Blinatumomab was more efficacious than HC3 regardless of MRD status before treatment. These data support the role of blinatumomab in inducing deep MRD remission, negating the poor prognostic value of MRD.

• Klíčová slova
• MRD, acute lymphoblastic leukemia, blinatumomab, pediatric, prognosis,
• MeSH
• akutní lymfatická leukemie * farmakoterapie   MeSH
• akutní nemoc MeSH
• B-buněčný lymfom * farmakoterapie   MeSH
• Burkittův lymfom * farmakoterapie   MeSH
• dítě MeSH
• lidé MeSH
• pre-B-buněčná leukemie * terapie   MeSH
• prognóza MeSH
• protilátky bispecifické * terapeutické užití   MeSH
• recidiva MeSH
• reziduální nádor chemicky indukované   farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• Názvy látek
• blinatumomab MeSH Prohlížeč
• protilátky bispecifické * MeSH

• MeSH
• dítě MeSH
• genová přestavba * MeSH
• jaderné proteiny genetika   MeSH
• kojenec MeSH
• lidé MeSH
• míra přežití MeSH
• nádorové proteiny genetika   MeSH
• pre-B-buněčná leukemie genetika   mortalita   patologie   terapie   MeSH
• prognóza MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• jaderné proteiny MeSH
• nádorové proteiny MeSH
• NUTM1 protein, human MeSH Prohlížeč

Adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with t(4;11)(q21;q23);KMT2A/AFF1 is a poor-prognosis entity. This registry-based study was aimed to analyze outcome of patients with t(4;11) BCP-ALL treated with allogeneic hematopoietic stem cell transplantation (alloHSCT) in first complete remission (CR1) between 2000 and 2017, focusing on the impact of measurable residual disease (MRD) at the time of transplant. Among 151 patients (median age, 38) allotransplanted from either HLA-matched siblings or unrelated donors, leukemia-free survival (LFS) and overall survival (OS) at 2 years were 51% and 60%, whereas relapse incidence (RI) and non-relapse mortality (NRM) were 30% and 20%, respectively. These results were comparable to a cohort of contemporary patients with diploid normal karyotype (NK) BCP-ALL with equivalent inclusion criteria (n = 567). Among patients with evaluable MRD pre-alloHSCT, a negative status was the strongest beneficial factor influencing LFS (hazard ratio [HR] = 0.2, p < 0.001), OS (HR = 0.14, p < 0.001), RI (HR = 0.23, p = 0.001), and NRM (HR = 0.16, p = 0.002), with a similar outcome to MRD-negative NK BCP-ALL patients. In contrast, among patients with detectable pretransplant MRD, outcome in t(4;11) BCP-ALL was inferior to NK BCP-ALL (LFS: 27% vs. 50%, p = 0.02). These results support indication of alloHSCT in CR1 for t(4;11) BCP-ALL patients, provided a negative MRD status is achieved. Conversely, pre-alloHSCT additional therapy is warranted in MRD-positive patients.

• MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• dospělí MeSH
• histonlysin-N-methyltransferasa genetika   metabolismus   MeSH
• homologní transplantace MeSH
• indukce remise MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• lidské chromozomy, pár 4 genetika   MeSH
• míra přežití MeSH
• následné studie MeSH
• pre-B-buněčná leukemie genetika   patologie   terapie   MeSH
• příprava pacienta k transplantaci MeSH
• prognóza MeSH
• protoonkogenní protein MLL genetika   metabolismus   MeSH
• retrospektivní studie MeSH
• reziduální nádor genetika   patologie   terapie   MeSH
• transkripční elongační faktory genetika   metabolismus   MeSH
• translokace genetická MeSH
• transplantace hematopoetických kmenových buněk metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• AFF1 protein, human MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• histonlysin-N-methyltransferasa MeSH
• KMT2A protein, human MeSH Prohlížeč
• protoonkogenní protein MLL MeSH
• transkripční elongační faktory MeSH

AIM: Outcomes of children with high-risk (HR) relapsed acute lymphoblastic leukaemia (ALL) (N = 393), recruited to ALLR3 and ALL-REZ BFM 2002 trials, were analysed. Minimal residual disease (MRD) was assessed after induction and at predetermined time points until haematopoietic stem cell transplantation (SCT). METHODS: Genetic analyses included karyotype, copy-number alterations and mutation analyses. Ten-year survivals were analysed using Kaplan-Meier and Cox models for multivariable analyses. RESULTS: Outcomes of patients were comparable in ALLR3 and ALL-REZ BFM 2002. The event-free survival of B-cell precursor (BCP) and T-cell ALL (T-ALL) was 22.6% and 26.2% (P = 0.94), respectively, and the overall survival (OS) was 32.6% and 28.2% (P = 0.11), respectively. Induction failures (38%) were associated with deletions of NR3C1 (P = 0.002) and BTG1 (P = 0.03) in BCP-ALL. The disease-free survival (DFS) and OS in patients with good vs poor MRD responses were 57.4% vs 22.6% (P < 0.0001) and 57.8% vs 32.0% (P = 0.0004), respectively. For BCP- and T-ALL, the post-SCT DFS and OS were 42.1% and 56.8% (P = 0.26) and 51.6% and 55.4% (P = 0.67), respectively. The cumulative incidences of post-SCT relapse for BCP- and T-ALL were 36.9% and 17.8% (P = 0.012) and of death were 10.7% and 25.5% (P = 0.013), respectively. Determinants of outcomes after SCT were acute graft versus host disease, pre-SCT MRD (≥10-3), HR cytogenetics and TP53 alterations in BCP-ALL. CONCLUSION: Improvements in outcomes for HR ALL relapses require novel compounds in induction therapy to improve remission rates and immune targeted therapy after induction to maintain remission after SCT. TRIAL REGISTRATION: ALLR3: NCT00967057; ALL REZ-BFM 2002: NCT00114348.

• Klíčová slova
• Acute lymphoblastic leukaemia, High-risk, Minimal residual disease, Outcomes, Stem cell transplantation,
• MeSH
• časové faktory MeSH
• dítě MeSH
• doba přežití bez progrese choroby MeSH
• genová dávka MeSH
• hodnocení rizik MeSH
• karyotyp MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• lymfoblastická leukemie-lymfom z prekurzorových T-buněk diagnóza   genetika   mortalita   terapie   MeSH
• mladiství MeSH
• mutace MeSH
• nádorové biomarkery genetika   MeSH
• nemoc štěpu proti hostiteli etiologie   MeSH
• pre-B-buněčná leukemie diagnóza   genetika   mortalita   terapie   MeSH
• předškolní dítě MeSH
• přežití bez známek nemoci MeSH
• progrese nemoci MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• recidiva MeSH
• reziduální nádor MeSH
• rizikové faktory MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH

• MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genová přestavba MeSH
• histonlysin-N-methyltransferasa genetika   MeSH
• kojenec MeSH
• lidé MeSH
• onkogenní fúze * MeSH
• pre-B-buněčná leukemie genetika   patologie   terapie   MeSH
• protoonkogenní protein MLL genetika   MeSH
• retrospektivní studie MeSH
• zárodečné buňky patologie   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fúzní onkogenní proteiny MeSH
• histonlysin-N-methyltransferasa MeSH
• KMT2A protein, human MeSH Prohlížeč
• protoonkogenní protein MLL MeSH

BACKGROUND: ABL-class fusion genes other than BCR-ABL1 have been identified in approximately 3% of children with newly diagnosed acute lymphocytic leukaemia, and studies suggest that leukaemic cells carrying ABL-class fusions can be targeted successfully by tyrosine-kinase inhibitors. We aimed to establish the baseline characteristics and outcomes of paediatric patients with ABL-class fusion B-cell acute lymphocytic leukaemia in the pre-tyrosine-kinase inhibitor era. METHODS: This multicentre, retrospective, cohort study included paediatric patients (aged 1-18 years) with newly diagnosed ABL-class fusion (ABL1 fusion-positive, ABL2 fusion-positive, CSF1R fusion-positive, and PDGFRB fusion-positive) B-cell acute lymphocytic leukaemia enrolled in clinical trials of multidrug chemotherapy done between Oct 3, 2000, and Aug 28, 2018, in which tyrosine-kinase inhibitors had not been given as a first-line treatment. Patients from 14 European, North American, and Asia-Pacific study groups of the Ponte di Legno group were included. No patients were excluded, and patients were followed up by individual study groups. Through the Ponte di Legno group, we collected data on the baseline characteristics of patients, including IKZF1, PAX5, and CDKN2A/B deletion status, and whether haematopoietic stem cell transplantation (HSCT) had been done, as well as treatment outcomes, including complete remission, no response, relapse, early death, and treatment-related mortality, response to prednisone, and minimal residual disease (MRD) at end of induction therapy. 5-year event-free survival and 5-year overall survival were estimated by use of Kaplan-Meier methods, and the 5-year cumulative incidence of relapse was calculated by use of a competing risk model. FINDINGS: We identified 122 paediatric patients with newly diagnosed ABL-class fusion B-cell acute lymphocytic leukaemia (77 from European study groups, 25 from North American study groups, and 20 from Asia-Pacific study groups). 64 (52%) of 122 patients were PDGFRB fusion-positive, 40 (33%) were ABL1 fusion-positive, ten (8%) were CSF1R fusion-positive, and eight (7%) were ABL2 fusion-positive. In all 122 patients, 5-year event-free survival was 59·1% (95% CI 50·5-69·1), 5-year overall survival was 76·1% (68·6-84·5), and the 5-year cumulative incidence of relapse was 31·0% (95% CI 22·4-40·1). MRD at the end of induction therapy was high (≥10-2 cells) in 61 (66%) of 93 patients, and most prevalent in patients with ABL2 fusions (six [86%] of 7 patients) and PDGFRB fusion-positive B-cell acute lymphocytic leukaemia (43 [88%] of 49 patients). MRD at the end of induction therapy of 10-2 cells or more was predictive of an unfavourable outcome (hazard ratio of event-free survival in patients with a MRD of ≥10-2vs those with a MRD of <10-2 3·33 [95% CI 1·46-7·56], p=0·0039). Of the 36 (30%) of 119 patients who relapsed, 25 (69%) relapsed within 3 years of diagnosis. The 5-year cumulative incidence of relapse in 41 patients who underwent HSCT (17·8% [95% CI 7·7-31·3]) was lower than in the 43 patients who did not undergo HSCT (45·1% [28·4-60·5], p=0·013), but event-free survival and overall survival did not differ between these two groups. INTERPRETATION: Children with ABL-class fusion B-cell acute lymphocytic leukaemia have poor outcomes when treated with regimens that do not contain a tyrosine-kinase inhibitor, despite the use of high-risk chemotherapy regimens and frequent HSCT upon first remission. Our findings provide a reference for evaluating the potential benefit of first-line tyrosine-kinase inhibitor treatment in patients with ABL-class fusion B-cell acute lymphocytic leukaemia. FUNDING: The Oncode Institute, Pediatric Cancer Foundation Rotterdam, Dutch Cancer Society, Kika Foundation, Deutsche Krebshilfe, Blood Cancer UK, Associazione Italiana per la Ricerca sul Cancro, Cancer Australia, National Cancer Institute, National Institute of Health, and St Baldrick's Foundation.

• MeSH
• alografty MeSH
• dítě MeSH
• doba přežití bez progrese choroby MeSH
• fúzní onkogenní proteiny genetika   MeSH
• inhibitory proteinkinas MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• pre-B-buněčná leukemie * genetika   mortalita   terapie   MeSH
• předškolní dítě MeSH
• přežití bez známek nemoci MeSH
• protoonkogenní proteiny c-abl genetika   MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• tyrosinkinasy genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• Názvy látek
• ABL1 protein, human MeSH Prohlížeč
• ARG tyrosine kinase MeSH Prohlížeč
• fúzní onkogenní proteiny MeSH
• inhibitory proteinkinas MeSH
• protoonkogenní proteiny c-abl MeSH
• tyrosinkinasy MeSH

PURPOSE: Minimal residual disease (MRD) helps to accurately assess when children with late bone marrow relapses of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) will benefit from allogeneic hematopoietic stem-cell transplantation (allo-HSCT). More detailed dissection of MRD response heterogeneity and the specific genetic aberrations could improve current practice. PATIENTS AND METHODS: MRD was assessed after induction treatment and at different times during relapse treatment until allo-HSCT (indicated in poor responders to induction; MRD ≥ 10-3) for patients being treated for late BCP-ALL bone marrow relapses (n = 413; median follow-up, 9.4 years) in the ALL-REZ BFM 2002 trial/registry (ClinicalTrials.gov identifier: NCT00114348). RESULTS: Patients with both good (MRD < 10-3) and poor responses to induction treatment reached excellent event-free survival (EFS; 72% v 65%) and overall survival (OS; 82% v 74%). Patients with MRD of 10-2 or greater after induction had reduced EFS (56%), and their MRD persisted until allo-HSCT more frequently than it did in patients with MRD of 10-3 or greater to less than 10-2 (P = .037). Patients with 25% or more leukemic blasts after induction (early nonresponders) had the poorest prognosis (EFS, 22%). Interestingly, patients with MRD of 10-3 or greater before allo-HSCT (late nonresponders) still had an EFS of 50% and OS of 63%, which in principle justifies allo-HSCT in these patients. From a panel of selected candidate genes, TP53 alterations (frequency, 8%) were the only genetic alteration with independent prognostic value in any MRD-based response subgroup. CONCLUSION: After induction treatment, MRD-based treatment stratification resulted in excellent survival in patients with late relapsed BCP-ALL. Prognosis could be further improved in very poor responders by intensifying treatment directly after induction. TP53 alterations can be defined as a novel genetic high-risk marker in all MRD response groups in late relapsed BCP-ALL. Here we identified early and late nonresponders to be considered as events in future trials.

• MeSH
• dítě MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• mladiství MeSH
• pre-B-buněčná leukemie klasifikace   patologie   terapie   MeSH
• přežití bez známek nemoci MeSH
• protinádorové látky terapeutické užití   MeSH
• reziduální nádor genetika   patologie   MeSH
• transplantace hematopoetických kmenových buněk MeSH
• výběr pacientů MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protinádorové látky MeSH

OBJECTIVES: Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. This study evaluated outcomes of patients with B-cell precursor ALL with MRD of ≥10-4 Methods: Study population was from ALL study groups in Europe managed in national study protocols 2000-2014. MRD was measured by polymerase chain reaction or flow cytometry. Patients were age ≥15 years at initial ALL diagnosis. Patients were excluded if exposed to blinatumomab within 18 months of baseline or prior alloHSCT. RESULTS: Of 272 patients in CR1, baseline MRD was ≥10-1, 10-2 to <10-1, 10-3 to <10-2, and 10-4 to <10-3 in 15 (6%), 71 (26%), 109 (40%), and 77 (28%) patients, respectively. Median duration of complete remission (DoR) was 18.5 months (95% confidence interval [CI], 11.9-27.2), median relapse-free survival (RFS) was 12.4 months (95% CI, 10.0-19.0) and median overall survival (OS) was 32.5 months (95% CI, 23.6-48.0). Lower baseline MRD level (P ≤ .0003) and white blood cell count <30,000/µL at diagnosis (P ≤ .0053) were strong predictors for better RFS and DoR. Allogeneic hematopoietic stem cell transplantation (alloHSCT) was associated with longer RFS (hazard ratio [HR], 0.59; 95% CI, 0.41-0.84) and DoR (HR, 0.43; 95% CI, 0.29-0.64); the association with OS was not significant (HR, 0.72; 95% CI, 0.50-1.05). DISCUSSION: In conclusion, RFS, DoR, and OS are relatively short in patients with MRD-positive ALL, particularly at higher MRD levels. AlloHSCT may improve survival but has limitations. Alternative approaches are needed to improve outcomes in MRD-positive ALL.

• Klíčová slova
• Acute lymphoblastic leukemia, MRD, allogeneic stem cell transplant, minimal residual disease,
• MeSH
• alografty MeSH
• dospělí MeSH
• filadelfský chromozom MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• následné studie MeSH
• pre-B-buněčná leukemie * krev   mortalita   terapie   MeSH
• přežití bez známek nemoci MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH