Clinical, Genetic, and Outcome Characteristics of Pediatric Patients with Primary Hemophagocytic Lymphohistiocytosis.

OBJECTIVE: In this study, we sought to describe the clinical, laboratory, and genetic character- istics of patients diagnosed with primary hemophagocytic lymphohistiocytosis. Thus, we aimed to evaluate the early diagnosis and appropriate treatment options for pediatric hemophago- cytic lymphohistiocytosis patients. MATERIALS AND METHODS: Medical records of 9 patients diagnosed with primary hemophago- cytic lymphohistiocytosis between November 2013 and December 2019 were analyzed retro- spectively. Clinical, genetic, and laboratory characteristics, family histories, initial complaints, physical examination findings, age at diagnosis, treatment choices, and clinical follow-up of all patients were investigated. RESULTS: The mean age at diagnosis was 11 months (range: 1.5 months to 17 years). Genetic analysis was performed in all patients, and a disease-related mutation was detected in 8 (89%) of them. Among clinical features, 6 (66%) patients had fever, 5 (56%) had splenomegaly, 4 (44%) had lymphadenopathy, 4 (44%) had skin rash, and 4 (44%) had neurological findings. Hemophagocytosis was observed in the bone marrow samples of 6 (66%) patients. Disease remission was achieved in 7 (78%) patients. Hematopoietic stem cell transplantation was per- formed in 7 (78%) patients. CONCLUSION: Hemophagocytic lymphohistiocytosis may present with different clinical symptoms that can cause a significant diagnostic delay. The only curative treatment option in primary hemophagocytic lymphohistiocytosis patients is hematopoietic stem cell transplantation. The chemotherapy should be started as early as possible, in order to achieve a disease remission. Patients should be referred to the appropriate bone marrow transplant center for hematopoi- etic stem cell transplantation as soon as they reach the disease remission.

Chronic Neutropenia in Childhood: Laboratory and Clinical Features.

OBJECTIVES: To describe the clinical characteristics of patients with chronic neutropenia. METHODS: Data of 36 patients with chronic neutropenia, who were followed up in the authors' clinic between May 2013 and May 2020, were analyzed retrospectively. Patients were diagnosed based on their clinical and laboratory characteristics. RESULTS: A total of 36 patients (23 females, 13 males) were included in the study. The mean age at diagnosis was 9.85 ± 9.17 mo while the mean follow-up time was 21.83 ± 20.03 mo. The mean absolute neutrophil count (ANC) at admission was 462.5 ± 388.8 cells/mm3 (median = 375 cells/mm3), and the lowest and highest ANC mean was 241.2 ± 262.1 cells/mm3 (median = 125 cells/mm3), and 1362.9 ± 1127.9 cells/mm3 (median = 925 cells/mm3), respectively. Idiopathic neutropenia was found in 28 (77.8%) patients, autoimmune neutropenia in 6 (16.7%) patients, and congenital neutropenia in 2 (5.6%) patients. Neutrophil normalization was observed in 19 (52.8%) of the patients. CONCLUSIONS: Chronic neutropenia is a heterogeneous picture that presents with different clinical symptoms in childhood. The cause of neutropoenia in children is usually benign and resolves spontaneously but especially in those with severe neutropoenia genetic examination should be performed.

HLA - matched related donor hematopoietic stem cell transplantation in a patient with polynucleotide kinase 3-phosphatase mutation developed acute myeloid leukemia.

BACKGROUND: PNPK gene mutations result in DNA repair disorders and have a spectrum of neurodevelopmental manifestations. To date, cancer predisposition has not been described in patients with PNKP mutations. OBSERVATION: Here, we report a patient with PNKP mutation, who developed AML at age of five and underwent reduced-intensity HSCT. CONCLUSION: Although many DNA repair disorders are known to have increased risk of malignancy, association between PNKP mutations and malignancy is not well-described. This report is the first description of a PNPK mutation patient developing a malignancy and undergoing curative HSCT.

Different Kinetics and Risk Factors for Isolated Extramedullary Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Leukemia.

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of post-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR compared with systemic relapse. The 5-year cumulative incidence of systemic relapse (either bone marrow [BM] only or BM combined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; P = .013). Complete response (CR) 2+/active disease at transplantation (hazard ratio [HR], 3.1; P < .001) and prior EM disease (HR, 2.3; P = .007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5; P = .043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% versus 15.3%; P = .089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, whereas those experiencing their iEMR at first relapse developed further systemic relapse and iEMR at approximately similar frequencies. A second iEMR was more common after a first iEMR than after a first systemic relapse (58.8% versus 13.0%; P = .001) and was associated with poor outcome. iEMR has a poor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes.

Unusual Clinical Presentation of Hodgkin Lymphoma in a Child: Both Spinal Cord Compression and Hydronephrosis.

BACKGROUND: Hodgkin lymphoma (HL) is predominantly a nodal disease with extranodal presentation being uncommon. Presentation with neurological symptoms is not uncommon in adult patients with HL. Subdiaphragmatic involvements are less common especially in childhood. In the literature, there has been no case which presented with both spinal cord compression and bilateral hydronephrosis in pediatric patients with HL. OBSERVATION: We report a 9-year-old boy diagnosed with HL who presented with bilateral hydronephrosis and epidural involvement. CONCLUSION: Differential diagnosis of abdominal mass in patients presenting with spinal cord compression and/or hydronephrosis should include HL. Retrograde J ureteral stenting is the treatment of choice for malignant ureteral obstruction.

Clinical Efficacy of Ruxolitinib Monotherapy and Haploidentical Hematopoeitic Stem Cell Transplantation in a Child with Philadelphia Chromosome-like Relapsed/Refractory acute lymphoblastic leukemia.

INTRODUCTION: (Ph-like) ALL is a subset of leukemia which has a gene expression profile similar to Ph+disease, but without the presence of BCR-ABL1 translocation. CASE DESCRIPTION: We reported an exceptional case of a child with relapsed Ph-like ALL with IKZF1 gene deletion treated with high-dose ruxolitinib as monotherapy, after multi-agent chemotherapy. He remains in continued MRD-negative leukemia remission with full donor chimerism at 12 months post-HSCT. DISCUSSION: The circumstance that makes our case featured is the usage of ruxolitinib as monotherapy. This report, we believe, is a pioneering report for a frequent disease with a high risk of failure for the outcome.

A child with a severe headache: Answers.

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Eltrombopag for treatment of thrombocytopenia after allogeneic hematopoietic cell transplantation in children: Single-centre experience.

Delayed recovery of thrombocytopenia is a well-known complication after allogeneic HSCT. Eltrombopag (ELT), a thrombopoietin receptor agonist (TRAs), induces platelet maturation and release. Mostly conducted in adults, some of the previous studies have shown that ELT seems to enhance platelet recovery for post-allogeneic HSCT thrombocytopenia, appears efficacious, and offers transfusion independence. To evaluate the safety and efficacy of ELT in pediatric patients with prolonged isolated thrombocytopenia (PIT) or secondary failure of platelet recovery (SFPR) after alloHSCT. Retrospective analysis of childhood patients who received treatment with ELT for persistent thrombocytopenia after alloHSCT between May 2016 and August 2019. We evaluated the safety and efficacy of ELT in 18 childhood patients with PIT or SFPR after alloHSCT. Eltrombopag (50 mg/d) treatment was started in all patients, above 6 years of age and 20 kg weight, who had thrombocytopenia despite neutrophil engraftment on the 30th day of HSCT. Our objective was to decrease the need for platelet transfusion and have a platelet count of more than 50 000/µL. The overall response rate was 77.7%. The median time to achieve a platelet level above 30 000/µL and 50 000/µL was 21 and 44 days, respectively. In four patients, platelet count never reached 30 000/mm3 . In two patients, the treatment was discontinued due to grade 3 hepatotoxicity. Our study supports the efficacy and relative safety of ELT use for the treatment of PIT and SFPR seen after alloHSCT in children.

Prognostic factors for survival in children who relapsed after allogeneic hematopoietic stem cell transplantation for acute leukemia.

BACKGROUND: Post-transplant relapse has a dismal prognosis in children with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data on risk factors, treatment options, and outcomes are limited. PROCEDURE: In this retrospective multicenter study in which a questionnaire was sent to all pediatric transplant centers reporting relapse after allo-HSCT for a cohort of 938 children with acute leukemia, we analyzed 255 children with relapse of acute leukemia after their first allo-HSCT. RESULTS: The median interval from transplantation to relapse was 180 days, and the median follow-up from relapse to the last follow-up was 1844 days. The 3-year overall survival (OS) rate was 12.0%. The main cause of death was disease progression or subsequent relapse (82.6%). The majority of children received salvage treatment with curative intent without a second HSCT (67.8%), 22.0% of children underwent a second allo-HSCT, and 10.2% received palliative therapy. Isolated extramedullary relapse (hazard ratio (HR): 0.607, P = .011) and relapse earlier than 365 days post-transplantation (HR: 2.101, P < .001 for 0-180 days; HR: 1.522, P = .041 for 181-365 days) were found in multivariate analysis to be significant prognostic factors for outcome. The type of salvage therapy in chemosensitive relapse was identified as a significant prognostic factor for OS. CONCLUSION: A salvage approach with curative intent may be considered for patients with post-transplant relapse, even if they relapse in the first year post-transplantation. For sustainable remission, a second allo-HSCT may be recommended for patients who achieve complete remission after reinduction treatment.

Late diagnosis of leukocyte adhesion deficiency type II and Bombay blood type in a child: a rare case report.

Leukocyte adhesion deficiency type II (LAD II) is a rare, autosomal, recessive inherited immunodeficiency disease that induces frequent and recurrent infections, persistent leukocytosis, severe mental and growth retardation, and impaired wound healing. The Bombay blood group is a rare blood group phenotype that is characterised by the deficiency of H, A, and B antigens on the surface of red cells. LAD II and the Bombay blood group are always seen together, because both of them are associated with a global defect in the common pathway of fucose metabolism. Here we report the case of an 11-year-old boy with LAD II, who presented with the Bombay blood group. Agglutination with strength of 4+ was detected in all cross-matching due to erythrocyte transfusions for our patient. Therefore, the Bombay blood group was incidentally determined due to deficient expression of the CD15 adhesion molecules on the surface of the leukocytes according to the results of flow cytometry. Upon detecting the Bombay blood type, LAD II was then diagnosed as a result of flow cytometry and the clinical findings of mental retardation and history of recurrent infections such as abscesses.

Graft-versus-host disease in a child with neuroblastoma after autologous stem cell transplantation.

In the pediatric population, hematopoietic stem cell transplantation (HSCT) is used to treat a wide variety of diseases, both malignant and nonmalignant. For many of these diseases, HSCT is a well-established treatment. Acute graft-versus-host disease (GVHD) continues to be a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Graft versus host disease is a common complication of allo-SCT which is induced by donor T cell recognition of recipient alloantigens. The occurrence of autologous GVHD suggests that inappropriate recognition of host self-antigens may occur. GVHD in patients who received autologous HSCT is extremely rare compared to patients who received allogeneic HSCT. We present the case of a 4-year-old girl with metastatic neuroblastoma who spontaneously developed autologous GVHD after autologous HSCT.

Non-typhoidal Salmonella bacteraemia in paediatric leukaemia patients.

Non-typhoidal Salmonella (NTS) is an important pathogen that causes gastroenteritis, bacteraemia, and focal infections. Herein, we present our experience with bloodstream infections caused by Salmonella in paediatric leukaemia patients, which has been reported for the first time in both Europe and the US. According to our research, NTS might be a cause of serious infections in paediatric haematology-oncology patients. Following a low bacterial diet and increasing the hygiene of both the children and their surroundings would be beneficial in preventing these infections.

Pediatric langerhans cell histiocytosis: single center experience over a 17-year period.

This study aimed to analyze children with the diagnosis of Langerhans cell histiocytosis (LCH) who were diagnosed and treated between 1998-2015. Medical records were evaluated retrospectively for clinical and laboratory features, treatment details, and outcome. There were 20 patients, the median age of diagnosis was 37 months, M/F ratio: 1.5. Nine had single system (SS), 11 had multisystem (MS) LCH. Spontaneous regression occurred in three infants with skin limited LCH. Eight patients had risk organ involvement in MS-LCH group. The curettage alone was performed in only one case. Patients received LCH-II/ LCH-III based chemotherapy schema. Radiotherapy was performed to vertebral disease and residual craniofacial bone disease in four cases. The regression and relapse rates were 100% and 33% for SS-LCH. The regression and relapse rates were 73%, and 18% for MS-LCH. Two infants with MS-LCH died despite chemotherapy. Pulmonary and liver involvements affected outcome adversely in MS-LCH. Multidisciplinary treatment approaches are needed.

Comparison of the BD GeneOhm VanR assay and a chromogenic agar-based culture method in screening for vancomycin-resistant enterococci in rectal specimens of pediatric hematology-oncology patients.

VRE species are an increasingly important and universal problem in intensive care units and hematology-oncology departments due to the spread of glycopeptide resistance. Rapid and accurate identification of VRE is therefore crucial. The intent of this study was to compare the diagnostic performance of a real-time PCR test, the BD GeneOhm VanR assay (GeneXpert vanA/ vanB, Cepheid, USA), with conventional cultures for screening hospitalized immunocompromised hematology-oncology patients for VRE. Three hundred and six duplicate rectal swab specimens were obtained from 120 pediatric hematology-oncology patients. PCR and conventional culture-based studies were performed. One hundred and twenty patients, 46 female and 74 male, participated in the study. The mean age of the patients was 7.5±4.7 years. A total of 51 specimens from 306 samples were found to be positive for vanA or vanB. Mean turnaround time for PCR was 0.5±0.2 days. Compared to the culture method, the RT-PCR assay had an overall sensitivity of 91.8% (34/37) and a specificity of 93.6%. The positive predictive value and negative predictive value were 66.6% and 98.8%, respectively. This study demonstrates that RT-PCR is a suitable alternative to culture-based procedures for rapid and accurate identification of VRE in hematology-oncology patients, as the overall performance of PCR is comparable to that of a chromogenic agar-based culture method for VRE screening, especially for detection of VRE-negative patients.

A 7-year study of the distribution of nosocomial candidemia in children with cancer.

Candidemia is an important cause of morbidity and mortality in cancer patients. The incidence of candidemia has been reported to have shifted toward nonalbicans species. The aim of this study was to determine the distribution of Candida species resulting in bloodstream infections or catheter-related blood stream infections (CRBSIs) in pediatric hematology-oncology (PHO) patients over a 7-year-period. Medical and computerized microbiology laboratory records of all positive blood fungal cultures during the study period were analyzed retrospectively. The ratio of non-albicans Candida species (81.4%) was nearly four times higher than that of C. albicans candidemia (18.5%). Overall, C. parapsilosis caused the majority (61.4%) of candidemia episodes, followed by C. tropicalis (14.8%), C. famata (2.9%), C. ciferrii (1.4%) and C. glabrata (0.7%). The rate of CRBSIs was significantly higher in C. Parapsilosis candidemia. The overall rate of 30-day mortality in 135 candidemia episodes was 4.44%. Nearly half of the C. parapsilosis candidemia was associated with CRBSIs, suggesting its importance in PHO, in which several types of central venous catheters have been used.

Comparing the Quality of Life of Patients With Hemophilia and Juvenile Idiopathic Arthritis in Which Chronic Arthropathy Is a Common Complication.

INTRODUCTION: Hemophilia is a genetic disorder in which recurrent joint bleeding causes arthropathy. Inflammation and degeneration play roles in the pathogenesis of hemophilic arthropathy. Patients with juvenile idiopathic arthritis (JIA) experience a similar inflammatory degenerative joint disease. A comparison of different patients with common pathogenetic features may identify unique features helpful in terms of the follow-up. AIM: We compared the quality of life (QoL) of patients with hemophilia and JIA, and healthy controls, using a generic QoL scale, Kidscreen and Disabkids Questionnaires (KINDL). Differences among groups were evaluated in terms of sociodemographic characteristics and clinical parameters affecting the QoL. METHODS: We included 33 hemophilia patients, 19 JIA patients, and 32 healthy individuals aged 4 to 18 years. Sociodemographic characteristics (the age, the maternal educational status, the place of residence, the size of the household, the household income, divorced parents) were noted, and the KINDL was administered to all participants. Clinical parameters associated with arthropathy (the functional independence score [FISH], the hemophilia joint health score [HJHS], the arthropathic joint count, and the painful joint count) were documented. Differences in frequencies and medians among the groups were evaluated using the χ, the Mann-Whitney U, and the Kruskal-Wallis tests. RESULTS: All KINDL dimensions were above 50, reflecting "good conditions" in the 2 patient groups. No difference between patients with hemophilia and JIA was evident in terms of the clinical parameters of FISH, the HJHS, or the arthropathic or painful joint counts (P>0.05). Sociodemographically, only the frequency of literate mothers was lower in patients with hemophilia than in those with JIA and healthy controls (P=0.03). Patients with JIA scored more higher on the KINDL dimension of chronic illness than those with hemophilia (P=0.02). The FISH score correlated with the total QoL score in both patients with hemophilia and JIA (r=0.39, P=0.03 and r=0.48, P=0.04, respectively). CONCLUSIONS: Although no difference was evident between the patient groups in terms of clinical parameters associated with arthropathy, JIA patients coped better with illness than those with hemophilia. JIA patients had a higher proportion of literate mothers than hemophilia patients; this may affect a patient's ability to cope with issues relating to chronic illness. Implementation of an educational program for mothers of hemophilia patients, during follow-up, may improve the patient's QoL. Also, hemophilia patients should be assisted to improve their QoL in the dimensions of self-esteem and schooling. Lastly, the evaluation of functional disability by FISH in hemophilia patients is important because the FISH score correlated with the total QoL score, as revealed by KINDL. In JIA patients also, functional disabilities caused by arthropathy affected the QoL.