Lack of bone lesions at diagnosis is associated with inferior outcome in multisystem langerhans cell histiocytosis of childhood.

Skeletal involvement is generally, but not universally, characteristic of Langerhans cell histiocytosis (LCH). We investigated whether the presence of bone lesions at diagnosis is a prognostic factor for survival in LCH. Nine hundred and thirty-eight children with multisystem (MS) LCH, both high (386 RO+) and low (RO-) risk, were evaluated for bone lesions at diagnosis. Risk organ (RO+) involvement was defined as: haematopoietic system (haemoglobin <100 g/l, and/or white blood cell count <4·0 × 10(9) /l and/or platelet count <100 × 10(9) /l), spleen (>2 cm below the costal margin), liver (>3 cm and/or hypoproteinaemia, hypoalbuminaemia, hyperbilirubinaemia, and/or increased aspartate transaminase/alanine transaminase). Given the general view that prognosis in LCH worsens with increasing extent of disease, the surprising finding was that in MS+RO+ LCH the probability of survival with bone involvement 74 ± 3% (n = 230, 56 events) was reduced to 62 ± 4% (n = 156, 55 events) if this was absent (P = 0·007). An even greater difference was seen in the subgroup of patients with both liver and either haematopoiesis or spleen involvement: 61 ± 5% survival (n = 105; 52 events) if patients had bony lesions, versus 47 ± 5% (n = 111; 39 events) if they did not (P = 0·014). This difference was retained in multivariate analysis (P = 0·048). Although as yet unexplained, we conclude that bone involvement at diagnosis is a previously unrecognized favourable prognostic factor in MS+RO+ LCH.

Development of treatment and clinical results in childhood AML in Austria (1993-2013).

BACKGROUND: Since the early 1990s, three consecutive pediatric acute myeloid leukemia (AML) trials have been performed in Austria (AML-Berlin-Frankfurt-Münster (BFM) 93, AML-BFM 98, and AML-BFM 2004) in close cooperation with the international BFM study center. Herein, we review the pertinent patient characteristics, therapy, and outcome data. PATIENTS AND METHODS: From January 1993 to April 2013, 249 children and adolescents (193 protocol patients) diagnosed with AML were enrolled in the three BFM studies. Patients were mainly treated in one of five pediatric hematology/oncology centers distributed over Austria. RESULTS: Many characteristics and outcome parameters were not statistically different between the three trials. Almost similar proportions of patients were stratified into two risk groups: standard risk (SR) (approximately 37 % overall) and high-risk (HR) (61 %). MLL rearrangements were found in 23 % of patients overall as the most frequent genetic aberration subtype. Complete remission (CR) was achieved by 84-95 % of patients. The most important type of event was leukemic relapse (5-year cumulative incidence 40 ± 8 %, 21 ± 5 %, and 39 ± 6 %; p = 0.058), with a trend to a higher rate specifically in SR patients of study AML-BFM 2004 compared with AML-BFM 98. Importantly, the frequency of death from causes other than relapse sequelae declined over the years (AML-BFM 93: 5/42 12 %, AML-BFM 98: 5/57 9 %, and AML-BFM 2004: 5/94 5 %). Altogether, event-free survival at 5 years varied insignificantly (48 ± 8 %, 61 ± 7 %, and 50 ± 6 %; p = 0.406). Nevertheless, survival (pSU) apparently improved from BFM 93 to subsequent studies, both overall (57 ± 8 %, 75 ± 6 %, and 62 ± 6 %; p = 0.046) and regarding the HR group (5-year-probability of survival (pSU) 40 ± 10 %, 66 ± 8 %, and 52 ± 8 %; p = 0.039). CONCLUSION: Treatment of pediatric AML in Austria renders survival rates in the range of international best practice. However, unambiguous statistical comparison of treatment periods is eventually hampered by small numbers and inequalities of recruitment. Hence, only internationally collaborative trials will allow developing treatment further to achieve higher cure rates with fewer events.

Outcome of children and adolescents with a second or third relapse of acute lymphoblastic leukemia (ALL): a population-based analysis of the Austrian ALL-BFM (Berlin-Frankfurt-Münster) study group.

We analyzed outcome of a population-based cohort of 74 children with second and third acute lymphoblastic leukemia (ALL) relapse and aimed to identify prognostic factors. Duration of previous remission and site of relapse appeared of prognostic relevance as patients with a second remission duration >1.5 years and isolated extramedullary relapse did better. Neither patient with a second bone marrow relapse who underwent previous allogeneic transplantation nor patients with T-cell ALL survived. Overall, 7 of 74 (9%) patients are in long-term remission. Stem cell transplantation seemed to be the only curative option for systemic relapse of B-cell precursor ALL as all 4 surviving patients with a second/third relapse involving the bone marrow received a transplant. Conclusively, patients with a second ALL relapse are ideal candidates for phase I/II trials exploring new innovative drugs.

Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH)-III tested risk-adjusted, intensified, longer treatment of multisystem LCH (MS-LCH), for which optimal therapy has been elusive. Stratified by risk organ involvement (high [RO+] or low [RO-] risk groups), > 400 patients were randomized. RO+ patients received 1 to 2 six-week courses of vinblastine+prednisone (Arm A) or vinblastine + prednisone + methotrexate (Arm B). Response triggered milder continuation therapy with the same combinations, plus 6-mercaptopurine, for 12 months total treatment. 6/12-week response rates (mean, 71%) and 5-year survival (84%) and reactivation rates (27%) were similar in both arms. Notably, historical comparisons revealed survival superior to that of identically stratified RO+ patients treated for 6 months in predecessor trials LCH-I (62%) or LCH-II (69%, P < .001), and lower 5-year reactivation rates than in LCH-I (55%) or LCH-II (44%, P < .001). RO- patients received vinblastine+prednisone throughout. Response by 6 weeks triggered randomization to 6 or 12 months total treatment. Significantly lower 5-year reactivation rates characterized the 12-month Arm D (37%) compared with 6-month Arm C (54%, P = .03) or to 6-month schedules in LCH-I (52%) and LCH-II (48%, P < .001). Thus, prolonging treatment decreased RO- patient reactivations in LCH-III, and although methotrexate added no benefit, RO+ patient survival and reactivation rates have substantially improved in the 3 sequential trials. (Trial No. NCT00276757 www.ClinicalTrials.gov).

Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells.

Langerhans cell histiocytosis (LCH) is an enigmatic disease defined by the accumulation of Langerhans cell-like dendritic cells (DCs). In the present study, we demonstrate that LCH cells exhibit a unique transcription profile that separates them not only from plasmacytoid and myeloid DCs, but also from epidermal Langerhans cells, indicating a distinct DC entity. Molecular analysis revealed that isolated and tissue-bound LCH cells selectively express the Notch ligand Jagged 2 (JAG2) and are the only DCs that express both Notch ligand and its receptor. We further show that JAG2 signaling induces key LCH-cell markers in monocyte-derived DCs, suggesting a functional role of Notch signaling in LCH ontogenesis. JAG2 also induced matrix-metalloproteinases 1 and 12, which are highly expressed in LCH and may account for tissue destruction in LCH lesions. This induction was selective for DCs and was not recapitulated in monocytes. The results of the present study suggest that JAG2-mediated Notch activation confers phenotypic and functional aspects of LCH to DCs; therefore, interference with Notch signaling may be an attractive strategy to combat this disease.

Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold.

BACKGROUND: Common cold is caused by a variety of respiratory viruses. The prevalence in children is high, and it potentially contributes to significant morbidity. Iota-carragenan, a polymer derived from red seaweed, has reduced viral load in nasal secretions and alleviated symptoms in adults with common cold. METHODS: We have assessed the antiviral and therapeutic activity of a nasal spray containing iota-carrageenan in children with acute symptoms of common cold. A cohort of 153 children between 1-18 years (mean age 5 years), displaying acute symptoms of common cold were randomly assigned to treatment with a nasal spray containing iota-carrageenan (0.12%) as verum or 0.9% sodium chloride solution as placebo for seven days. Symptoms of common cold were recorded and the viral load of respiratory viruses in nasal secretions was determined at two consecutive visits. RESULTS: The results of the present study showed no significant difference between the iota carrageenan and the placebo group on the mean of TSS between study days 2-7. Secondary endpoints, such as reduced time to clearance of disease (7.6 vs 9.4 days; p = 0.038), reduction of viral load (p = 0.026), and lower incidence of secondary infections with other respiratory viruses (p = 0.046) indicated beneficial effects of iota-carrageenan in this population. The treatment was safe and well tolerated, with less side effects observed in the verum group compared to placebo. CONCLUSION: In this study iota-carrageenan did not alleviate symptoms in children with acute symptoms of common cold, but significantly reduced viral load in nasal secretions that may have important implications for future studies. TRIAL REGISTRATION: ISRCTN52519535, http://www.controlled-trials.com/ISRCTN52519535/

Pulmonary involvement in pediatric-onset multisystem Langerhans cell histiocytosis: effect on course and outcome.

OBJECTIVES: To assess the effect of pulmonary involvement on the course and outcome of multisystem Langerhans cell histiocytosis (MS-LCH) in children. STUDY DESIGN: We conducted a retrospective analysis of 420 consecutive patients with MS-LCH. In this analysis, the term "risk organs" is defined as involvement of the liver, spleen, and/or hematopoietic system. The effect of pulmonary involvement on survival was assessed with multivariate Cox regression with adjustment for risk organs involvement and age. RESULTS: Pulmonary involvement in MS-LCH was present at diagnosis in 102 patients (24%). Of the 318 patients without pulmonary involvement at diagnosis, it developed in 28 within a median of 10 months (range, 1 month-5.5 years). The 5-year overall survival rate in patients without risk organ involvement at diagnosis was 96% in patients without pulmonary involvement and 94% in those with pulmonary involvement. In patients with risk organ involvement at diagnosis, the 5-year overall survival rate was 73% in patients without pulmonary involvement and 65% in patients with pulmonary involvement. In multivariate analysis, pulmonary involvement at diagnosis had no significant impact on survival rats (P = .109, hazard ratio = 1.5). CONCLUSIONS: In multivariate analysis, pulmonary involvement was not an independent prognostic variable and should therefore be excluded from the definition of risk organ involvement in MS-LCH.

Lethal pulmonary complications after pediatric allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) in children is accompanied by a transplant-related mortality of 10% to 30%, which is the result of lethal pulmonary complications (LPCs) in many cases. METHODS: We retrospectively assessed prevalence and risk factors of LPC following 234 allogeneic HSCTs in 228 patients for malignant or nonmalignant diseases at a single institution. RESULTS: Pulmonary complications (PCs) were observed following 81 of 234 transplants (35%). LPCs were observed in 4% of HSCT within 100 days and in 14% within 5 years after HSCT. Late PCs after day 100 were lethal in 56% (22/39) of the patients with PCs, who are 11% (22/202) of all evaluable patients still alive after day +100. Causes of LPC after day 100 were viral (10 cases), bacterial (1 case), fungal (5 cases) pulmonary infection, or noninfectious (6 cases) PCs. Abnormal pretransplant pulmonary function test was not associated with an increased risk of LPC. Children older than 10 years and those undergoing a second HSCT had an increased incidence of overall LPC. T-cell depletion and mismatched donor HSCT (P = 0.001), but not age, were associated with an increased risk of lethal viral pneumonia. CONCLUSIONS: Transplant-related mortality up to 5 years after HSCT in children was associated with LPC in 14%. There were more late (>100 days) than early LPCs, predominantly due to infectious etiologies and affecting children >10 years of age.

Long-term outcome of hypothalamic pituitary tumors in Langerhans cell histiocytosis.

BACKGROUND: Hypothalamic-pituitary (HP) disease is the most common CNS manifestation of Langerhans cell histiocytosis (LCH) frequently leading to diabetes insipidus (DI) and anterior pituitary hormone deficiencies (APD). On MRI, loss of the normal posterior pituitary signal and thickening of the pituitary stalk have been described, as well as neurodegenerative signal changes associated with neuropsychological disabilities in some patients. The influence of therapy on the long-term course of HP tumors and neurodegeneration (ND) is not well-understood. PROCEDURE: In this retrospective survey we focused on patients with LCH and HP disease with clinical and MRI data available at diagnosis of HP disease and at least three follow up investigations. We collected clinical and MRI follow-up information for central review and analysis. RESULTS: We identified 22 patients with HP tumors (HPT) registered at the LCH study center. Many different treatment regimens were applied for variable periods, with more than one regimen in most patients. Regression of the tumor was seen in the majority, but all patients had APD or ND on MRI at last follow up. In none of the patients APD and ND regressed or resolved. A deterioration of radiological ND was noted in 17 patients leading to overt clinical neuropsychological impairment in five. CONCLUSIONS: Patients with HPT appear to be at high risk to develop permanent neuroendocrine consequences. Coordinated studies for patients with LCH and HP disease including thorough MRI monitoring and neuropsychological tests are needed.

Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol.

Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis. We report the final results of HLH-94, the largest prospective diagnostic/therapeutic HLH study so far. The treatment includes immunosuppressive and cytotoxic therapy aiming at clinical remission, followed by HSCT in patients with familial, persistent, or recurrent disease. Altogether, 249 patients fulfilled inclusion criteria and started HLH-94 therapy (July 1994-December 2003); 227 (91%) were followed-up for ≥ 5 years. At 6.2 years median follow-up, estimated 5-year probability of survival was 54% ± 6%. Seventy-two patients (29%) died before HSCT, 64 within 1 year, 97% of whom had active disease. In 124 patients who underwent HSCT, 5-year survival was 66 ± 8%; tendency to increased survival (P = .064) in patients with nonactive disease at HSCT. Patients with familial disease had a 5-year survival of 50% ± 13%; none survived without HSCT. Patients deceased during the first 2 months more often had jaundice, edema, and elevated creatinine. Forty-nine patients (20%) were alive without signs of HLH activity and off-therapy > 1-year without HSCT; they presented at older age (P < .001), were more often female (P = .011), and less often had CNS disease (P < .001) or hepatomegaly (P = .007). To conclude, HLH-94 chemoimmunotherapy has considerably improved outcome in HLH. Collaborative efforts are needed to further reduce early mortality, HSCT-related mortality, and neurologic late effects.

Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study.

The prognostic value of MRD in large series of childhood T-ALL has not yet been established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative assessment of MRD for stratification, based on immunoglobulin and TCR gene rearrangements as polymerase chain reaction targets: Patients were considered MRD standard risk (MRD-SR) if MRD was negative at day 33 (time point 1 [TP1]) and day 78 (TP2), analyzed by at least 2 sensitive markers; MRD intermediate risk (MRD-IR) if positive either at day 33 or 78 and < 10(-3) at day 78; and MRD high risk (MRD-HR) if ≥ 10(-3) at day 78. A total of 464 patients with T-ALL were stratified by MRD: 16% of them were MRD-SR, 63% MRD-IR, and 21% MRD-HR. Their 7-year event-free-survival (SE) was 91.1% (3.5%), 80.6% (2.3%), and 49.8% (5.1%) (P < .001), respectively. Negativity of MRD at TP1 was the most favorable prognostic factor. An excellent outcome was also obtained in 32% of patients turning MRD negative only at TP2, indicating that early (TP1) MRD levels were irrelevant if MRD at TP2 was negative (48% of all patients). MRD ≥ 10(-3) at TP2 constitutes the most important predictive factor for relapse in childhood T-ALL. The study is registered at http://www.clinicaltrials.gov; "Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia," protocol identification #NCT00430118 for BFM and #NCT00613457 for AIEOP.

Osteosarcoma in very young children: experience of the Cooperative Osteosarcoma Study Group.

BACKGROUND: This study was conducted to investigate presentation, treatment, and outcome in very young children with osteosarcoma. METHODS: The authors retrospectively analyzed the data of 2706 consecutive COSS patients with newly diagnosed osteosarcoma and identified 28 (1.0%) patients aged younger than 5 years at diagnosis. Demographic, diagnostic, tumor, treatment-related variables, response, and survival data were analyzed. RESULTS: Of the 28 preschoolers, 27 presented with high-grade central osteosarcoma of an extremity, and 1 had a secondary osteosarcoma of the orbit. This analysis focused on the 27 patients with extremity tumors. The size of the primary was large (≥one-third of the involved bone) in 20 of 27 patients. Primary metastases were detected in 4 of 27 children. All patients received multiagent chemotherapy, and 11 of 18 analyzed tumors responded well (>90% necrosis) to neoadjuvant chemotherapy. Limb-sparing surgery was performed in 9 cases, ablative procedures were performed in 15, and, in 3 cases, no local surgery was performed. With a median follow-up of 4 years (6.2 years for survivors), 13 patients were alive. Four patients never achieved a complete remission, and 11 developed recurrences; 14 of these 15 patients died. Five-year overall and event-free survival probabilities were 51% (standard error of the mean [SE], 10%) and 48% (SE, 10%). Better survival was correlated with good response to chemotherapy and later time period of diagnosis. CONCLUSIONS: Osteosarcoma is extremely rare in preschool children. These patients often have large tumors that may require mutilating resections. Prognosis is in the range of that reported for older patients.

Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: evidence for a drug-induced regulatory phenomenon. Results of the AIEOP-BFM-ALL-FLOW-MRD-Study Group.

BACKGROUND: Changes of antigen expression on residual blast cells of acute lymphoblastic leukemia (ALL) occur during induction treatment. Many markers used for phenotyping and minimal residual disease (MRD) monitoring are affected. Glucocorticoid (GC)-induced expression modulation has been causally suspected, however, subclone selection may also cause the phenomenon. METHODS: We investigated this by following the phenotypic evolution of leukemic cells with flow cytometry from diagnosis to four time points during and after GC containing chemotherapy in the 20 (of 360 consecutive) B-cell precursor patients with ALL who had persistent MRD throughout. RESULTS: The early expression changes of CD10 and CD34 were reversible after stop of GC containing chemotherapy. Modulation of CD20 and CD45 occurred mostly during the GC phase, whereas CD11a also changed later on. Blast cells at diagnosis falling into gates designed according to "shifted" phenotypes from follow-up did not form clusters and were frequently less numerous than later on. CONCLUSIONS: Our data support the idea that drug-induced modulation rather than selection causes the phenomenon. The good message for MRD assessment is that modulation is transient in at least two (CD10 and CD34) of the five prominent antigens investigated and reverts to initial aberrant patterns after stop of GC therapy, whereas CD20 expression gains new aberrations exploitable for MRD detection.

Prognostic relevance of dic(9;20)(p11;q13) in childhood B-cell precursor acute lymphoblastic leukaemia treated with Berlin-Frankfurt-Münster (BFM) protocols containing an intensive induction and post-induction consolidation therapy.

The presence of a dicentric chromosome dic(9;20) has been reported to have an unfavourable prognosis in children with B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). As outcome may be influenced by type and composition of treatment, we analyzed 19 BCP-ALL patients with dic(9;20) who have been treated with ALL-BFM (Berlin-Frankfurt-Münster) protocols that included a 4-drug induction and subsequent consolidation therapy. All patients were good responders to prednisone and in complete remission after induction therapy. Eight patients had no molecular disease after induction and another eight patients had levels < or =10(-4) after consolidation therapy. After a median follow-up of 3.4 years, probabilities of 5-year event-free and overall survival were 75 +/- 11% and 94 +/- 6%, respectively. Of note, there was a tendency for extramedullary disease in case of relapse (two of three relapses with central nervous system involvement). In conclusion, in the context of ALL-BFM protocols dic(9;20)-positivity appeared to have a favourable prognosis, which could be due to a dose- and time-intensified induction and induction consolidation therapy. Given that in vitro studies have shown high cellular sensitivity of dic(9;20)-positive leukemic blasts to l-asparaginase and cytarabine, it is reasonable to speculate that both drugs, as given early during BFM-like induction and consolidation therapy, may have contributed to this good outcome.

Cytochemically myeloperoxidase positive childhood acute leukemia with lymphoblastic morphology treated as lymphoblastic leukemia.

SUMMARY: Cytochemical myeloperoxidase (MPO) positivity represents the gold standard for discrimination between lymphatic and myeloid blasts. Rarely, cytochemical MPO reaction may be positive in >or=3% of blasts with clear lymphoblastic morphology. We present 5 patients with cytochemically MPO-positive acute leukemia classified as lymphoblastic by cytomorphology and lymphoblastic (n=3) or biphenotypic (n=2) by immunophenotyping, who entered first-line treatment for lymphoblastic leukemia. The former 3 are in first remission and both with biphenotypic leukemia relapsed with acute myeloid leukemia. The study primarily shows that cytochemical MPO expression in childhood acute leukemia revealing typical lymphoblastic morphology and phenotype does rarely exist. Although a small number of patients studied, cytochemical MPO expression in acute leukemia does not seem to require myeloid leukemia treatment in case of otherwise lymphoblastic cytomorphology and phenotype.

Prognostic relevance of TLX3 (HOX11L2) expression in childhood T-cell acute lymphoblastic leukaemia treated with Berlin-Frankfurt-Münster (BFM) protocols containing early and late re-intensification elements.

TLX3 expression (TLX3+) in childhood T-cell acute lymphoblastic leukaemia (T-ALL) seems to be associated with a poor prognosis when treated with regimens that lack early and/or late re-intensification therapy elements. Because such elements are essential components of the ALL-BFM (Berlin-Frankfurt-Münster) protocols, we evaluated whether TLX3+ T-ALL patients benefit from this type of therapy. Thirty-one/131 childhood T-ALL cases (24%) enrolled into four population-based Austrian ALL-BFM therapy studies were TLX3+. The male to female ratio was 3.5:1 and median age and leucocyte count at diagnosis were 8.7 years and 58.9 x 10(9)/l, respectively. Twenty-four patients (77%) were good responders to prednisone. All were in complete remission after induction therapy. After a median observation time of 4.9 years (range 0.4-16.1 years) 28/31 TLX3+ cases remained in first complete remission after chemotherapy with one after additional stem cell transplantation. Although molecular disease was frequently present after a 4-drug induction therapy, final treatment outcome was excellent indicating that TLX3+ T-ALL cases may benefit from a BFM-type of ALL therapy with early and late re-intensification elements. Moreover, the fact that 2/3 relapses were also NUP214-ABL1+ suggests that these cases might represent the particular risk-prone TLX3+ subgroup that could benefit from a targeted tyrosine kinase inhibitor therapy.

Subcutaneous anti-D globulin application is a safe treatment option of immune thrombocytopenia in children.

Subcutaneous (sc) administration of anti-D seems to offer the same efficacy as intravenous administration but with less side effects. Here we report our experience with sc anti-D for pediatric immune thrombocytopenia (ITP). A total of 12 children with a median age of 11.2 years had been treated by sc anti-D. They received a median of 2 sc anti-D applications (range 1-31) with a dosage of 250-375 IE/kg body weight. Only in one out of a total of 102 single applications, a minimal and self-limited side effect (chills) had been observed. The mean platelet count was almost doubled after sc anti-D (p < 0.0001). After a median follow-up of 11.4 months, all patients are alive without major bleeding and stay well. We conclude that sc anti-D: is not only an efficient means of treating ITP in children but is also a safe and convenient one.

Stool polymerase chain reaction for Helicobacter pylori detection and clarithromycin susceptibility testing in children.

BACKGROUND & AIMS: This study was undertaken in a pediatric gastroenterology clinic to retrospectively evaluate a real-time polymerase chain reaction (PCR) for the detection and clarithromycin susceptibility testing of Helicobacter pylori using stool specimens. METHODS: All consecutive children who underwent a gastroscopy between March 2006 and February 2009 and also having been examined by stool PCR were enrolled. Rapid urease test, histology, and culture were the reference methods for the detection of H pylori and E-test for susceptibility testing, respectively. RESULTS: A total of 143 children (mean age, 10.8 y; range, 2.8-17.9; males:females, 1:1.5) were evaluable. Sensitivity, specificity, and test accuracy for the detection of H pylori were 83.8%, 98.4%, and 90.2%, respectively. Sensitivity, specificity, and accuracy for the detection of clarithromycin resistance were 89.2%, 100%, and 94.0%, respectively. CONCLUSIONS: Stool PCR was a reliable and useful noninvasive tool for detection and clarithromycin susceptibility testing of H pylori in a pediatric population with a high prevalence of clarithromycin-resistant strains.