ABSTRACT
INTRODUCTION: Surgical complications occur in up to third of children, limiting the benefits of tunneled central venous catheters (tCVCs) in children. We aimed to identify risk factors for complications related to catheter implantation. METHODS: All children and adolescents undergoing tCVC implantation at a single center over a period of 9 years were analyzed. Infection, thrombosis, dislocation, and catheter dysfunction were defined as complications. Both patient-related (ie, age, sex, vessel characteristics, revision surgery) and surgical factors (ie, sex of surgeon, surgical experience) were analyzed for their association with complications. RESULTS: A total of 1024 catheters were inserted, 887 ports and 137 broviac catheters. In terms of patient-related factors, Broviac catheters, and nononcological patients had a higher complication rate. The use of the internal jugular vein and revision surgery was associated with significantly increased complications in patients with port catheters. Experience of the surgeon correlated with various outcome parameters. Implantation performed by an attending were associated with lower complication rates in comparison to those performed by residents. Within the resident group, insertions performed by experienced residents had more complications compared with those performed by residents during their first years. CONCLUSION: The study suggests that the outcome of tCVCs insertion is affected by the type of catheter used, the utilized vessel and above all by surgical experience. Residents had significantly increased complication rates in comparison to board-certified surgeons and amongst resident's outcome got worse with increasing experience of the residents. The presence of an experienced attending did not compensate for this effect. To improve the outcome of tCVCs, strategies like direct feedback after every procedure to achieve proficiency should be implanted in residency programs.
Subject(s)
Catheterization, Central Venous , Central Venous Catheters , Thrombosis , Adolescent , Humans , Child , Central Venous Catheters/adverse effects , Retrospective Studies , Catheterization, Central Venous/adverse effects , Risk Factors , Thrombosis/etiology , Catheters, IndwellingABSTRACT
Infantile myofibromatosis is a rare benign congenital tumour that often regresses spontaneously but may pose therapeutic challenges in its widespread visceral form. We present the case of a full-term neonate with generalized infantile myofibromatosis including ubiquitous subcutaneous and muscular nodules, a tumour in the mastoid and disseminated intestinal involvement. The intestinal tumours led to a mechanical ileus with intestinal perforation within the first days of life. After partial small bowel resection and necessary proximal jejunostomy the boy was dependent on total parenteral nutrition. Chemotherapy with vinblastine and methotrexate was started and was temporarily supplemented with imatinib. Feeding stayed impossible despite tumour shrinkage. At the age of 4.5 months, restoration of intestinal continuity with further stricturoplasties was performed which - for the first time - allowed complete oral feeding. Chemotherapy was continued for further two months. Currently, the child is in good general condition with growth and further disease regression. This report suggests that massive visceral involvement of infantile myofibromatosis may require extensive intestinal surgery, as conservative therapy cannot resolve the disease and its sequelae.
Subject(s)
Myofibromatosis , Infant, Newborn , Male , Child , Humans , Infant , Myofibromatosis/diagnosis , Myofibromatosis/surgery , Myofibromatosis/congenital , Imatinib Mesylate/therapeutic useABSTRACT
The WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue notes instances of Burkitt lymphoma/leukemia (BL) with IG-MYC rearrangement displaying a B-cell precursor immunophenotype (termed herein "preBLL"). To characterize the molecular pathogenesis of preBLL, we investigated 13 preBLL cases (including 1 cell line), of which 12 were analyzable using genome, exome, and targeted sequencing, imbalance mapping, and DNA methylation profiling. In 5 patients with reads across the IG-MYC breakpoint junctions, we found evidence that the translocation derived from an aberrant VDJ recombination, as is typical for IG translocations arising in B-cell precursors. Genomic changes like biallelic IGH translocations or VDJ rearrangements combined with translocation into the VDJ region on the second allele, potentially preventing expression of a productive immunoglobulin, were detected in 6 of 13 cases. We did not detect mutations in genes frequently altered in BL, but instead found activating NRAS and/or KRAS mutations in 7 of 12 preBLLs. Gains on 1q, recurrent in BL and preB lymphoblastic leukemia/lymphoma (pB-ALL/LBL), were detected in 7 of 12 preBLLs. DNA methylation profiling showed preBLL to cluster with precursor B cells and pB-ALL/LBL, but apart from BL. We conclude that preBLL genetically and epigenetically resembles pB-ALL/LBL rather than BL. Therefore, we propose that preBLL be considered as a pB-ALL/LBL with recurrent genetic abnormalities.
Subject(s)
Burkitt Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cells, B-Lymphoid/pathology , Proto-Oncogene Proteins c-myc/genetics , V(D)J Recombination , Adolescent , Adult , Aged , Burkitt Lymphoma/diagnosis , Burkitt Lymphoma/pathology , Child , Child, Preschool , DNA Methylation , Female , Gene Rearrangement, B-Lymphocyte , Humans , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cells, B-Lymphoid/metabolism , Retrospective Studies , Translocation, Genetic , Young AdultABSTRACT
BACKGROUND: Reduced toxicity conditioning for hematopoietic stem cell transplantation of patients with hemophagocyticlymphohistiocytosis (HLH) results in favorable survival, however at the expense of relevant rates of mixed chimerism. Factors predisposing to mixed chimerism remain to be determined. PROCEDURE: Patients with primary HLH transplanted 2009-2016 after treosulfan- or melphalan-based conditioning regimens were analyzed in a retrospective multicenter study for survival, engraftment, chimerism, and adverse events. Mixed chimerism was considered substantial if < 25% donor chimerism occurred and/or if secondary cell therapy was administered. Donor type, graft source, type of alkylating agent, type of serotherapy, and remission status were analyzed as potential risk factors in a multivariable logistic regression model. RESULTS: Among 60 patients, engraftment was achieved in 95%, and the five-year estimated overall survival rate was 75%. Prevalence of any recipient chimerism was 48%. Substantial recipient chimerism was recorded in 32% of patients. Secondary post-HSCT cell therapy was administered in 30% of patients. A human leukocyte antigen (HLA)-mismatched donor (< 10/10) was the only significant risk factor for the occurrence of substantial recipient chimerism (P = 0.01; odds ratio, 5.8; CI 95%, 1.5-26.3). CONCLUSION: The use of an HLA-matched donor is the most important factor to avoid substantial recipient chimerism following treosulfan -or melphalan-based conditioning in primary HLH.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chimerism/chemically induced , Graft vs Host Disease/etiology , Lymphohistiocytosis, Hemophagocytic/drug therapy , Transplantation Conditioning/adverse effects , Adolescent , Busulfan/administration & dosage , Busulfan/analogs & derivatives , Child , Child, Preschool , Female , Follow-Up Studies , Graft vs Host Disease/pathology , HLA Antigens/immunology , Hematopoietic Stem Cell Transplantation/methods , Humans , Infant , Lymphohistiocytosis, Hemophagocytic/pathology , Lymphohistiocytosis, Hemophagocytic/therapy , Male , Melphalan/administration & dosage , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , Tissue Donors , Transplantation, HomologousABSTRACT
Osteonecrosis (ON) was prospectively assessed in 557 children and adolescents in the Berlin-Frankfurt-Münster Stem Cell Transplantation in children with acute lymphoblastic leukaemia 2003 trial. Median age at haematopoietic stem cell transplantation (HSCT) was 10·3 years (range 0·5-26). Cumulative incidence of symptomatic ON (sON) was 9% at 5 years (standard deviation 1%), median time from HSCT to diagnosis of sON was 12·4 months (range 1-126). Multivariate analysis identified age at HSCT [10-15 years vs. <10 years: hazard ratio (HR) 3·73, P = 0·009; >15 years vs. <10 years: HR 5·46, P = 0·001], diagnosis of sON prior to HSCT and chronic graft-versus-host disease (yes versus no: HR 2·696, P = 0·015) as significant independent risk factors for the development of sON.
Subject(s)
Hematopoietic Stem Cell Transplantation , Osteonecrosis/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Child , Child, Preschool , Disease Progression , Female , Graft vs Host Disease/etiology , Humans , Incidence , Infant , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Risk Factors , Transplantation, Homologous , Young AdultABSTRACT
For reasons not yet understood, nearly all infants with acute lymphoblastic leukemia (ALL) are diagnosed with the B-cell type, with T-ALL in infancy representing a very rare exception. Clinical and molecular knowledge about infant T-ALL is still nearly completely lacking and it is also still unclear whether it represents a distinct disease compared to childhood T-ALL. To address this, we performed exome sequencing of three infant cases, which enabled the detection of mutations in NOTCH2, NOTCH3, PTEN, and KRAS. When analyzing the transcriptomes and miRNomes of the three infant and an additional six childhood T-ALL samples, we found 760 differentially expressed mRNAs and 58 differentially expressed miRNAs between these two cohorts. Correlation analysis for differentially expressed miRNA-mRNA target pairs revealed 47 miRNA-mRNA pairs, with many of them previously described to be aberrantly expressed in leukemia and cancer. Pathway analysis revealed differentially expressed pathways and upstream regulators related to the immune system or cancerogenesis such as the ERK5 pathway, which was activated in infant T-ALL. In summary, there are distinct molecular features in infant compared to childhood T-ALL on a transcriptomic and epigenetic level, which potentially have an impact on the development and course of the disease. © 2016 Wiley Periodicals, Inc.
Subject(s)
Biomarkers, Tumor/genetics , Epigenesis, Genetic/genetics , Gene Expression Profiling , Gene Expression Regulation, Leukemic , MicroRNAs/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Transcriptome/genetics , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , High-Throughput Nucleotide Sequencing , Humans , Infant , Infant, Newborn , Male , PrognosisABSTRACT
BACKGROUND: An alloimmune response to red blood cell (RBC) transfusion in neonates is a rare event. Several guidelines recommend limited pretransfusion testing in neonates. The evidence for these recommendations is based on small studies with sample sizes of between 30 and 90 infants. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study among consecutive patients who received transfusions at a single university medical center. All non-alloimmunized patients who had received their first RBC transfusion between 1994 and 2013 and who underwent at least one antibody screening follow-up visit between 7 and 365 days after transfusion were included. RESULTS: The incidence of alloimmunization in the control group of 17,084 adult patients age 45 years or older who had received a median of 5 RBC units (interquartile range, 2-12 RBC units) was 3.55% (n = 607 alloimmunized patients). After transfusion of 40 RBC units, the cumulative incidence of alloimmunization in adult controls was 10.24% (95% confidence interval, 7.71%-13.17%). In total, 1641 neonates and children up to age 3 years received a median of 4 RBC units (interquartile range, 2-7 RBC units) in a median of two RBC transfusion episodes (interquartile range, one to five RBC transfusion episodes). Two children developed anti-M and anti-E antibodies post-transfusion at the ages of 181 and 611 days, respectively. CONCLUSION: To our knowledge, this study presents the largest longitudinal cohort study of RBC alloimmunization in neonates. Antibodies against RBC antigens were not detected within the first 6 months of life. Repeat antibody screening and cross-matching during the first months of life can be safely omitted.
Subject(s)
Blood Group Antigens/immunology , Erythrocytes/immunology , Isoantibodies/immunology , Age Factors , Blood Group Incompatibility/immunology , Child, Preschool , Cohort Studies , Erythrocyte Transfusion/adverse effects , Humans , Infant , Infant, Newborn , Middle Aged , Practice Guidelines as Topic , Retrospective StudiesABSTRACT
BACKGROUND: The risk of early death (ED) by bleeding/leukostasis is high in patients with AML with hyperleukocytosis (>100,000/µl). Within the pediatric AML-BFM (Berlin-Frankfurt-Münster) 98/04 studies, emergency strategies for these children included exchange transfusion (ET) or leukapheresis (LPh). Risk factors for ED and interventions performed were analyzed. PATIENTS: Two hundred thirty-eight of 1,251 (19%) patients with AML presented with hyperleukocytosis; 23 of 1,251 (1.8%) patients died of bleeding/leukostasis. RESULTS: ED due to bleeding/leukostasis was highest at white blood cell (WBC) count >200,000/µl (14.3%). ED rates were even higher (20%) in patients with FAB (French-American-British) M4/M5 and hyperleukocytosis >200,000/µl. Patients with WBC >200,000/µl did slightly better with ET/LPh compared to those without ET/LPh (ED rate 7.5% vs. 21.2%, P = 0.055). Multivariate WBC >200,000/µl was of strongest prognostic significance for ED (P(χ(2) ) <0.0001). CONCLUSION: Our data confirm the high risk of bleeding/leukostasis in patients with hyperleukocytosis. ET/LPh shows a trend toward reduced ED rate due to bleeding/leukostasis and is recommended at WBC >200,000/µl, and in FAB M4/M5 even at lower WBC.
Subject(s)
Blood Transfusion , Leukapheresis , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/therapy , Child , Child, Preschool , Female , Hemorrhage/etiology , Hemorrhage/mortality , Hemorrhage/prevention & control , Humans , Infant , Leukemia, Myeloid, Acute/mortality , Leukostasis/etiology , Leukostasis/mortality , Leukostasis/prevention & control , Male , Proportional Hazards Models , Risk FactorsABSTRACT
Peripheral T-cell lymphomas (PTCL) other than anaplastic large-cell lymphoma are rare in children, and the role of hematopoietic stem cell transplantation (HSCT) has not been clarified yet. In a retrospective analysis of registry-data of the European Society for Blood and Marrow Transplantation we analyzed 55 patients aged < 18 years who received allogeneic (N = 46) or autologous (N = 9) HSCT for PTCL. Median age at HSCT was 13.9 years; 33 patients (60%) were in first remission, and 6 (19%) in progression at HSCT. Conditioning was myeloablative in 87% of the allogeneic HSCTs and in 27 (58.7%) based on total body irradiation. After allogeneic HSCT the 5-year overall- and progression-free survival was 58.9% (95% CI 42.7-71.9) and 52.6% (95% CI 36.8-66.1), respectively. 5-year relapse incidence was 27.6% (95% CI 15.1-41.6), the non-relapse mortality rate was 19.8% (95% CI 9.7-32.6). Five of the six patients with progression at HSCT died. Seven of nine patients after autologous HSCT were alive and disease-free at last follow-up. Our data suggest a role of allogeneic HSCT in consolidation-treatment of patients with high-risk disease, who reach at least partial remission after primary- or relapse-therapy, whereas patients with therapy-refractory or progressive disease prior to transplantation do not profit from HSCT.
Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, T-Cell, Peripheral , Humans , Hematopoietic Stem Cell Transplantation/methods , Child , Adolescent , Male , Female , Lymphoma, T-Cell, Peripheral/therapy , Lymphoma, T-Cell, Peripheral/mortality , Child, Preschool , Retrospective Studies , Infant , Transplantation Conditioning/methods , Disease-Free Survival , Survival RateABSTRACT
Data on incidence, characteristics, and prognosis in stage I childhood anaplastic large cell lymphoma are scarce. Of 463 patients enrolled in the international ALCL99 trial, 36 (8%) had stage I disease and were treated with a prephase chemotherapy, followed by either 3 chemotherapy courses in case of initial complete resection (6 patients) or otherwise by 6 courses of chemotherapy (30 patients). Disease localization was to the peripheral lymph nodes in 26, soft tissue mass in 8, and solitary bone and bronchial disease in 1 patient each. Of the 6 patients with complete resection, none experienced relapse, whereas of the 30 remaining stage I patients, 9 (30%) relapsed, including in all cases a new site of disease involvement and including 3 of 5 anaplastic lymphoma kinase-negative patients. In summary, the failure rate for incompletely resected stage I disease was similar to that for patients with stage II and stage III/IV disease. Whether anaplastic lymphoma kinase negativity contributed to this moderate outcome has to be proven prospectively. This study was registered at www.clinicaltrials.gov as NCT00006455.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large-Cell, Anaplastic/drug therapy , Lymphoma, Large-Cell, Anaplastic/pathology , Child , Female , Humans , International Agencies , Lymphoma, Large-Cell, Anaplastic/mortality , Male , Neoplasm Staging , Prognosis , Prospective Studies , Survival RateABSTRACT
Anaplastic lymphoma kinase-positive anaplastic large T-cell lymphoma is characterized by morphological variability. Morphological variants (non-common subtype) are associated with a poor outcome. They display abundant reactive bystander cells admixed with the lymphoma cells. So far, the difficulty in distinguishing lymphoma cells from bystander cells by visual inspection has prevented detailed and reliable immunophenotypic analysis using conventional immunohistochemistry. To overcome these limitations, we analyzed 124 cases of pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma treated within clinical trials using immunofluorescence multi-staining and digital image analysis combining antibodies against anaplastic lymphoma kinase to specifically identify lymphoma cells with antibodies against CD30, CD3, CD5, CD8, Ki67 and phosphorylated STAT3. Non-common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas express CD8 more frequently than common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas (35.4% and 5.6%, respectively; P=0.0002). CD8 expression was associated with a poorer outcome. Importantly, in a multivariate analysis including clinical risk factors, histological subtype and CD8 expression, CD8-positivity proved to be an independent prognostic predictor of worse outcome (hazard ratio for survival 3.38, P=0.042).
Subject(s)
CD8 Antigens/biosynthesis , Gene Expression Regulation, Neoplastic , Lymphoma, Large-Cell, Anaplastic/diagnosis , Lymphoma, Large-Cell, Anaplastic/enzymology , Receptor Protein-Tyrosine Kinases/biosynthesis , Adolescent , Anaplastic Lymphoma Kinase , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Infant , Lymphoma, Large-Cell, Anaplastic/therapy , Male , Treatment OutcomeABSTRACT
(1) Background: Embryonal abdominal tumors are one of the most common entities of solid childhood cancer. The present study investigates the Health-Related Quality of Life (HRQoL) and the mental health of children to obtain a comprehensive picture of their health status and uncover a possible gap in healthcare. (2) Methods: The sample consisted of 54 children who were treated for embryonal abdominal tumors and a control group of 46 children who received uncomplicated outpatient surgery. The HRQoL and the mental health were assessed by the parent proxy reports of the questionnaires Pediatric Quality of Life Inventory (PedsQL) and Strengths and Difficulties Questionnaire (SDQ). (3) Results: Children with embryonal abdominal tumors showed significantly lower HRQoL and mental health values compared to the norm data. The index group showed lower values in the social subscales of HRQoL and mental health compared to the control group. (4) Conclusions: Embryonal abdominal tumors affect the well-being of children. There is still a gap in healthcare due to children's HRQoL and mental health, especially regarding social development. It is essential to further advance the psychological care of children and improve their chances to develop social relationships.
ABSTRACT
BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication because of the reactivation of the Epstein-Barr virus (EBV). Although after solid organ transplantation (SOT) EBV is typically of recipient origin, after hematopoietic stem cell transplantation (HSCT) donor-derived B cells are usually the source of the EBV-induced lymphoproliferation. OBSERVATION: We report a unique presentation of an EBV-associated PTLD in a 13-year-old boy who underwent 2 subsequent HSCTs from 2 different-sex donors for BCR-ABL-positive acute lymphoblastic leukemia (ALL) and relapses of leukemia, respectively. The PTLD tissue was analyzed for the origin of both B cells and T cells of the lesion. Chimerism analysis done with short tandem repeat systems (STR) showed no autologous signals; approximately 50% of the cells were from the first and second donors, respectively. XY-fluorescence in situ hybridization showed a B-cell PTLD originating from the first donor surrounded by T cells from the second donor. CONCLUSION: This case shows that EBV-infected B cells from a first donor can be the source of a PTLD after a second myeloablative HSCT from a different donor.
Subject(s)
Epstein-Barr Virus Infections/etiology , Fusion Proteins, bcr-abl/genetics , Hematopoietic Stem Cell Transplantation/adverse effects , Lymphoproliferative Disorders/etiology , Postoperative Complications/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , B-Lymphocytes/virology , Epstein-Barr Virus Infections/drug therapy , Epstein-Barr Virus Infections/virology , Humans , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/virology , Male , Postoperative Complications/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/virology , Recurrence , Tissue Donors , Transplantation, HomologousABSTRACT
INFORM is a prospective, multinational registry gathering clinical and molecular data of relapsed, progressive, or high-risk pediatric patients with cancer. This report describes long-term follow-up of 519 patients in whom molecular alterations were evaluated according to a predefined seven-scale target prioritization algorithm. Mean turnaround time from sample receipt to report was 25.4 days. The highest target priority level was observed in 42 patients (8.1%). Of these, 20 patients received matched targeted treatment with a median progression-free survival of 204 days [95% confidence interval (CI), 99-not applicable], compared with 117 days (95% CI, 106-143; P = 0.011) in all other patients. The respective molecular targets were shown to be predictive for matched treatment response and not prognostic surrogates for improved outcome. Hereditary cancer predisposition syndromes were identified in 7.5% of patients, half of which were newly identified through the study. Integrated molecular analyses resulted in a change or refinement of diagnoses in 8.2% of cases. SIGNIFICANCE: The pediatric precision oncology INFORM registry prospectively tested a target prioritization algorithm in a real-world, multinational setting and identified subgroups of patients benefiting from matched targeted treatment with improved progression-free survival, refinement of diagnosis, and identification of hereditary cancer predisposition syndromes.See related commentary by Eggermont et al., p. 2677.This article is highlighted in the In This Issue feature, p. 2659.
Subject(s)
Neoplasms , Child , Humans , Neoplasms/diagnosis , Neoplasms/drug therapy , Neoplasms/genetics , Precision Medicine , Progression-Free Survival , Prospective Studies , RegistriesABSTRACT
The proximal DNA damage response kinase ATM is frequently inactivated in human malignancies. Germline mutations in the ATM gene cause Ataxia-telangiectasia (A-T), characterized by cerebellar ataxia and cancer predisposition. Whether ATM deficiency impacts on tumor initiation or also on the maintenance of the malignant state is unclear. Here, we show that Atm reactivation in initially Atm-deficient B- and T cell lymphomas induces tumor regression. We further find a reduced T cell abundance in B cell lymphomas from Atm-defective mice and A-T patients. Using T cell-specific Atm-knockout models, as well as allogeneic transplantation experiments, we pinpoint impaired immune surveillance as a contributor to cancer predisposition and development. Moreover, we demonstrate that Atm-deficient T cells display impaired proliferation capacity upon stimulation, due to replication stress. Altogether, our data indicate that T cell-specific restoration of ATM activity or allogeneic hematopoietic stem cell transplantation may prevent lymphomagenesis in A-T patients.
Subject(s)
Lymphoma/immunology , T-Lymphocytes/immunology , Alleles , Animals , Ataxia Telangiectasia Mutated Proteins/metabolism , Cell Proliferation , Etoposide/pharmacology , Hematopoietic Stem Cell Transplantation , Lymphoma/metabolism , Mice , Mice, Knockout , T-Lymphocytes/metabolism , Transplantation, Homologous , Treatment OutcomeABSTRACT
Although allogeneic hematopoietic stem-cell transplantation (HSCT) provides high cure rates for children with high-risk acute lymphoblastic leukaemia (ALL), relapses remain the main cause of treatment failure. Whereas donor killer cell immunoglobulin-like receptor (KIR) genotype was shown to impact on relapse incidence in adult myeloid leukaemia similar studies in paediatric ALL are largely missing. Effect of donor KIR genotype on transplant outcome was evaluated in 317 children receiving a first myeloablative HSCT from an HLA-matched unrelated donor or sibling within the prospective ALL-SCT-BFM-2003 trial. Analysis of donor KIR gene polymorphism revealed that centromeric presence and telomeric absence of KIR B haplotypes was associated with reduced relapse risk. A centromeric/telomeric KIR score (ct-KIR score) integrating these observations correlated with relapse risk (hazard ratio (HR) 0.58; P = 0.002) while it had no impact on graft-versus-host disease or non-relapse mortality. In multivariable analyses ct-KIR score was associated with reduced relapse risk (HR 0.58; P = 0.003) and a trend towards improved event-free survival (HR 0.76; P = 0.059). This effect proved independent of MRD level prior to HSCT. Our data suggest that in children with ALL undergoing HSCT after myeloablative conditioning, donor selection based on KIR genotyping holds promise to improve clinical outcome by decreasing relapse risk and prolonged event-free survival.