Chronic neutrophilic leukemia, an extremely rare cause of neutrophilia in childhood: Cure with hematopoietic stem cell transplantation.

CNL is a rare myeloproliferative disorder frequently seen in older adults. A significant proportion of patients show progression to AML. Here, we report the case of a patient with FA who was monitored for leukopenia but who developed leukocytosis during the follow-up and was diagnosed with CNL probably after an acquired CSF3R mutation. Because the patient had FA, which could accelerate the progression to AML, an HSCT was performed, which resulted in cure. This patient (aged 12 years) is one of the youngest patients reported to develop CNL as well as the first FA patient with a diagnosis of CNL.

Effects of stem cell transplantation on bone mineral density and vitamin D status in children with thalassemia major.

HSCT is a curative treatment in TM, but conditioning and immunosuppressive treatment may affect bone metabolism. In this retrospective study, we aimed to compare BMD, vitamin D status, and growth in children with TM who underwent HSCT to those in children with TD TM. Twenty-three children with TM who underwent HSCT (mean age 7.1 years [1.03-14.7]) and 24 children with TD thalassemia (mean age 9.8 years [1.6-14]) were recruited. Lumbar spine BMD of TD thalassemia patients was higher than those in patients who had HSCT at both baseline and second-year assessments (P=.009, P<.001, respectively). However, BMD Z scores or serum 25-OH vitamin D levels were not different in two groups. Being >10 years of age was a significant risk factor for low BMD, height, and weight Z score for both groups. Patients who underwent HSCT with Pesaro risk class II or III had higher risk for low BMD compared to those risk class I patients (P=.044). In conclusion, children with TM who were >10 years at HSCT are at risk for low BMD and growth retardation. HSCT had no effect on BMD deficit in children with TM.

Factors associated with bone marrow stem cell yield for pediatric allogeneic stem cell transplantation: The impact of donor characteristics.

The aim of this study was to investigate the effects of donor characteristics on CD34+ cell yield in BM harvest. Between April 2010 and November 2013, consecutive donors who underwent BM harvesting in our BM transplantation unit were retrospectively investigated. Donors were classified into two groups: those who donated BM without mobilization (steady-state BM donors) and those who received G-CSF for stem cell mobilization (G-CSF-primed BM donors). Donor characteristics (age, gender, race, body weight, BMI, and laboratory factors including donor's leukocyte, platelet, and monocyte) and their relationship with total nuclear cell and CD34+ cell numbers has been evaluated. A total of 64 healthy related donors (29 males/35 females, median age 11.2 years; 49 [76.6%] younger than 18 and 36 [56.3%] younger than 12 years) were included in the study. The median CD34+ cell yield in the harvest was 0.12×106 /L (0.02-0.21) in SS-BM donors and 0.18×106 /L (0.09-0.67) in GP-BM donors (P=.03). Median of CD34+ cell count given to recipients was 2.6×106 /recipient body weight (1.3-19.3) in SS-BM yields and 3.8×106 /recipient body weight (1.1-10.2) in GP-BM yields, respectively. Multiple regression analysis showed that donor height and pre-G-CSF platelet were the most important parameters to obtain a sufficient BM harvest. Our data suggest that the shorter donors and the donors with higher thrombocyte counts may offer more hematopoietic stem cell. The height and thrombocyte count of the donors should be taken into consideration before planning the targeted CD34+ cell count especially for pediatric donors.

Ophthalmologic Findings in Children with Leukemia: A Single-Center Study.

OBJECTIVES: Ophthalmologic disease in patients with acute leukemia occurs due to primary leukemic infiltration (involvement), or secondary to the disease and its treatment. In recent years the life expectancy of acute leukemia patients has increased with the advent of modern therapies. The present study aimed to determine the incidence of ocular manifestations in children with acute leukemia. MATERIALS AND METHODS: The study included 120 patients diagnosed with acute leukemia at Baskent University Hospital, Pediatric Hematology Department between 1995 and 2010. All the patients were examined by an ophthalmologist via direct and indirect ophthalmoscopy. RESULTS: Among the patients, 83 (69.2%) were diagnosed with acute lymphoblastic leukemia, 35 (29.1%) with acute myeloblastic leukemia, and 2 (1.7%) with mixed-lineage leukemia. In all, 58 ophthalmic manifestations were noted in 41 patients (34.2%). In our patients, 12 ophthalmologic involvements were present at admission and 46 ocular findings occurred during follow-up. The incidence of these manifestations increased with age. CONCLUSION: Ophthalmologic manifestations were not correlated with gender, hematological parameters at disease onset, type of leukemia, or the frequency of relapse and survival. To more clearly determine the effect of ophthalmologic manifestations on the prognosis of leukemia, larger scale and multi-center studies are needed.

Comparison of prophylactic use of intravenous immunoglobulin versus Pentaglobin® in pediatric patients after hematopoietic stem cell transplantation.

There are few studies evaluating the use of IgM-enriched IVIG (Pentaglobin(®) ) in HSCT recipients. This study aimed to compare the efficacy of prophylactic use of IVIG versus prophylactic use of Pentaglobin(®) within the first 100 days after allogeneic HSCT. We performed a prospective, randomized study of the use of prophylactic IVIG versus prophylactic use of Pentaglobin(®) in patients after allogeneic HSCT. The first dose of IVIG or Pentaglobin(®) was given before conditioning regimen and after transplant was given on day +1, +8, +15, and +22. And then, it was given if IgG level was below 400 mg/dL. Twenty-seven patients in IVIG group and 32 patients in Pentaglobin(®) group were included in the study. There were no significant differences in the duration of neutropenia, hospitalization, fever, and in the number of pyrexial episode, septicemia, bacteremia, local infection, CMV infection, acute GVHD, VOD, and adverse events between the IVIG group and Pentaglobin(®) group. Randomized placebo-controlled trials are needed to conclude that utilization of IVIG or Pentaglobin(®) has no beneficial effect in HSCT.

Clinical outcomes and graft characteristics in pediatric hematopoietic stem cell transplantation: Effect of granulocyte-colony stimulating factor priming.

In this study, we aimed to determine the effect(s) of G-CSF priming on graft and transplantation parameters and compare these findings with those obtained without priming. A total of 64 pediatric patients transplanted from HLA-matched family donors were enrolled in the study. Twenty-nine patients received G-CSF primed marrow (G-BM group) and 35 patients received steady state bone marrow (S-BM group). Number of total nucleated cells (TNC) and CD34(+) cells, CFU-GM colony number, neutrophil and platelet engraftment times, total length of stay in hospital, overall and disease free survival, and occasions of acute and chronic GvHD has been compared between these two groups. Granulocyte colony stimulating factor primed bone marrow (G-BM) yielded higher numbers of CD34(+) cells, TNCs, and CFU-GM colony numbers compared to those obtained in S-BM. The neutrophil engraftment time, platelet engraftment time, length of stay in hospital, overall survival and disease free survival were not different between G-BM and S-BM groups. Also the cumulative incidence of grades II-IV acute and chronic GvHD were similar. It was observed that the use of G-CSF did not increase the risk of acute or chronic GvHD. We concluded that use of G-CSF for stem cell mobilization is an effective and safe method in children.

A case of transient cortical blindness associated with hypercapnia as a result of extremely enlarged adenoid tissue.

Adenotonsillar hypertrophy is common among children, but it can lead to serious complications if left untreated. Among the well-known complications are obstructive sleep apnea syndrome, growth failure, cor pulmonale, and hypertension. One complication of adenotonsillar hypertrophy that has not been previously reported in the English-language literature is transient cortical blindness. We describe such a case, which occurred in a 6-year-old boy who presented with a sudden loss of vision and subsequent unconsciousness. He had experienced hypercapnia and was resuscitated via endotracheal tube ventilation. Laboratory and radiologic assessments found no pathology except for extremely enlarged adenoid tissue. Once the patient was stabilized, an urgent adenotonsillectomy was performed. The patient recovered well, and his vision and respiratory symptoms resolved. Severe hypertrophy of the adenoid tissue can cause hypercapnia and acidosis secondary to upper airway obstruction. The possibility of adenoid hypertrophy and hypercapnia should be kept in mind in cases of transient cortical blindness. Aggressive treatment, including early intubation and adenoidectomy, may lead to a rapid resolution of symptoms.

Homozygosity for HBA1: c.179G > A: Hb Adana in an infant.

Hb Adana (HBA1: c.179G > A) is a very rare, unstable form of α-globin variant that results from deficient synthesis of functional α chains. We present a 2-month-old boy with hypochromic microcytic anemia, and remarkable anisocytosis, target cells and basophilic stippling on his peripheral blood smear. α-Globin gene analysis of the patient determined homozygosity for HBA1: c.179G > A, a mutation known as Hb Adana. On his follow-up visit, hemoglobin (Hb) levels were stable at 9.0-9.5 g/dL and mean corpuscular volume (MCV) was 62.2-62.5 fL without the need for a blood transfusion. Clinical and hematological findings of our case were comparable to Hb H (ß4) or ß-thalassemia intermedia (ß-TI)-like phenotypes, despite the fact that he carried an α1 gene mutation. Heterozygosity for the HBA1: c.179G > A mutation may also lead to microcytosis only as seen in his parents. According to our current knowledge, this is the first described case with homozygosity for the Hb Adana mutation, carried on the α1 gene. The relatively mild presentation of the case highlights the milder phenotypic consequences of nondeletional α mutations in the α1 vs. the α2 gene.

Aplastic anemia and Hoyeraal-Hreidarsson syndrome.

A 2-year-old girl patient was admitted with intractable diarrhea, respiratory infections, and seizures. She was the first child of the first-degree parents. She was born at term with a birth weight of 2300 g. Physical examination revealed weight 6800 g, height 76 cm, and head circumference 41 cm, below the third percentile. Findings included sparse and dull hair, nail dystrophy, and proximally located thumbs (Figure). Aphthous lesions were observed on the oral mucosa. Neurologic examination disclosed poor head control. She could not sit without support and had hyper-reactive deep tendon reflexes.

Massive splenic infarction and portal vein thrombosis in children with chronic myeloid leukemia.

Massive splenic infarction and portal vein thrombosis (PVT) due to chronic myeloid leukemia (CML) is extremely rare. We describe 2 children who were presented with massive splenic infarction and PVT in the course of CML. Massive splenic infarction and PVT treated with splenectomy in one and with medical treatment in another in whom PVT resolved by cytoreductive treatment, led to downsizing of spleen or splenectomy. Splenic infarct and PVT should be considered in CML patients with long-lasting severe abdominal pain despite appropriate medical attempts. Splenectomy should be spared for persistent symptoms and complications.

Cushing syndrome related to leukemic infiltration of the central nervous system: a case report and a possible role of LIF.

BACKGROUND: Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome (CS) in the presence of leukemic central nervous system infiltration is very rare. CASE: A 3.8-year-old girl who had been treated for B-cell acute lymphoblastic leukemia (ALL) for 1.5 years was admitted to our hospital with excessive weight gain and depression for the last 2 months. Prior to her admission, she was on maintenance with the ALL-BFM95 study protocol for 10 months that does not contain corticosteroids. On physical examination, central obesity and moon face appearance were determined. Laboratory tests revealed high morning ACTH, cortisol level, and 24-h urinary free cortisol level. Morning cortisol level was 33.94 nmol/L after a 2-day (4 × 0.5 mg) dexamethasone suppression test. A lumbar puncture revealed leukemic cells in the cerebrospinal fluid. No pituitary adenoma was detected on magnetic resonance imaging. We diagnosed the patient with ACTH-dependent CS related to leukemic infiltration of the central nervous system. CONCLUSION: Central nervous system infiltration should be considered in leukemic patients who have developed CS. We believe increased leukemia inhibitory factor levels may be a factor for CS in our patient with ALL.

Effects of Zinc Sulfate Supplementation in Treatment of Iron Defi ciency Anemia.

OBJECTIVE: In this study, we aimed to compare the effect(s) of zinc sulphate on growth and serum iron variables when it is given with ferrous sulphate in iron deficiency anemia (IDA). MATERIALS AND METHODS: Patients (n=79) were randomly divided into two groups. In one group (n=40) 4 mg/kg/d ferrous sulfate was given orally. In the other group (n=39), in addition to ferrous sulfate, 5 mg/d oral zinc sulfate was given. RESULTS: Compared to the initial values statistically significant increase in mean height, weight, and head circumference has been observed in both groups after 3 months. However, there was no statistical difference between two groups concerning mean height, weight, and head circumference at the beginning (83.43±11.3 cm vs 84.62±12.77 cm; 12.36±3.08 kg vs 12.72±3.87 kg; 47.33±2.15 cm vs 47.26±2.73 cm, respectively), at the first month, (84.82±10.97 vs 85.97±12.28; 12.78±3.09 vs 13.09±3.87; 47.76±2.10 vs 47.61±2.67, respectively), and at the third month, (86.4±11.12 vs 87.69±12.13; 12.9±3.06 vs 13.35±3.81; 48.22±1.89 vs 48.07±2.45, respectively). There were no statistical differences between mean hematological parameters of the groups at the beginning, at the first month, and at the third month, either (mean hb of Group 1: 8.78±1.12 g/dL; 11.27±1.09 g/ dL; 12.05±1.00 g/dL respectively and of Group 2: 9.10±1.07 g/dL; 11.12±0.85 g/dL; 11.80±0.79 g/dL, respectively). Mean ferritin and zinc values of the groups were statistically insignificant at the beginning (Mean ferritin: 4.96±4.03 µg/dL vs 4.52±2.94 µg/dL, zinc: 88.64±15.35 ng/mL vs 86.84±17.34 ng/mL). Their increase was statistically significant at the third month (mean ferritin: 15.91±9.57 µg/dL vs 15.25±10.47 µg/dL; zinc: 88.02±15.10 ng/mL vs 95.25±16.55 ng/mL). CONCLUSION: In our study neither positive nor negative effect of zinc administration on IDA treatment was demonstrated. Therefore, in the treatment of IDA zinc together with iron should be used at different times if there is coexistent zinc deficiency. CONFLICT OF INTEREST: None declared.

Low serum lipocalin levels in patients with iron deficiency anemia.

In the recent literature, there are studies on the relationship between anemia and lipocalin, but there is no study regarding the relationship between lipocalin and iron deficiency anemia (IDA) up to date. In this study, we aimed to observe lipocalin levels at admission, and after iron therapy in children with IDA. We also compared our findings to those in healthy children. Sixty-one children admitted in our outpatient clinic were included in the study. Thirty of these children had IDA (study group) and the rest were healthy (control group). Thirty patients, meeting the IDA criteria, received oral ferrous sulfate of 4 mg/kg/d. As soon as the hemoglobin value reached >11 g/dL, half dose of oral ferrous sulfate therapy was continued for another month. Serum lipocalin levels before and after iron therapies were compared. Hematologic parameters and serum lipocalin levels were also compared between the 2 groups. Mean values of serum lipocalin were 31.01±14.46 and 74.77 ng/dL in patients with IDA at admission and at third month of therapy, respectively (P<0.0001). The same figure was 57.35±39.51 ng/dL in the control group. Before treatment, mean values of lipocalin levels in patients with IDA was significantly lower than the control group (P=0.001); however, such a difference was not detected after 3 months of therapy (P=0.102). We suggest that decreased serum lipocalin levels in our patients during iron insufficiency were caused by iron deficiency rather than anemia.

The association of serum lipocalin-2 levels with metabolic and clinical parameters in obese children: a pilot study.

OBJECTIVE: We aimed to evaluate the association between serum lipocalin-2 level and clinical and metabolic parameters in obese children. METHODS: The study included obese children with a body mass index (BMI) >95th percentile who presented to Kecioren Teaching and Research Hospital with the complaint of weight gain and healthy children with a BMI <85th percentile. The height and weight of the patients were measured for compartment of anthropometric data. Fasting blood glucose, insulin, lipid profile, and serum lipocalin-2 level were measured to evaluate the laboratory parameters. RESULTS: The study included 33 obese and 34 healthy nonobese children. Comparison of data on the obese subjects with those of the healthy subjects shows differences in BMI, BMI-SDS, triglyceride, insulin, and homeostasis model assessment index-insulin resistance levels between the two groups were statistically significant (p < 0.05), whereas serum lipocalin-2 was not statistically significant (p >0.05). There was no statistically significant difference in serum lipocalin-2 levels when obese and control groups were reclassified as prepubertal and pubertal ( p >0.05). CONCLUSIONS: In this study, we did not find any relationships among serum lipocalin-2 level, anthropometric parameters, or metabolic parameters. According to the results of this study, we do not suggest routine investigation of serum lipocalin-2 level in obese subjects for risk stratification of the obesity-related complications.

Successful treatment of ICE-rituximab chemotherapy and subsequent bone marrow transplantation in a patient with early-relapse Burkitt leukemia and inverted duplication of 1q.

Although childhood acute lymphoblastic leukemias are of good prognosis than leukemias of adulthood, some chromosomal abnormalities may have negative effects on their prognosis. Inverted duplication (1q) is a chromosomal abnormality with negative effect on outcome of Burkitt leukemia and lymphomas. We report a case of CD20 Burkitt leukemia with inverted duplication (1q) mutation, who had an early relapse during NHL-BFM 95 treatment. Two courses of ICE-rituximab treatment were administered after relapse and a successful HLA-full match bone marrow transplantation was carried out. He is in follow-up for 18 months without any problem after the bone marrow transplantation. We suggest the usage of ICE protocol combined with rituximab in childhood CD20 Burkitt leukemia with poor prognostic criteria such as inverted duplication (1q) mutation.

Extended spectrum of human glucose-6-phosphatase catalytic subunit 3 deficiency: novel genotypes and phenotypic variability in severe congenital neutropenia.

OBJECTIVE: To delineate the phenotypic and molecular spectrum of patients with a syndromic variant of severe congenital neutropenia (SCN) due to mutations in the gene encoding glucose-6-phosphatase catalytic subunit 3 (G6PC3). STUDY DESIGN: Patients with syndromic SCN were characterized for associated malformations and referred to us for G6PC3 mutational analysis. RESULTS: In a cohort of 31 patients with syndromic SCN, we identified 16 patients with G6PC3 deficiency including 11 patients with novel biallelic mutations. We show that nonhematologic features of G6PC3 deficiency are good predictive indicators for mutations in G6PC3. Additionally, we demonstrate genetic variability in this disease and define novel features such as growth hormone deficiency, genital malformations, disrupted bone remodeling, and abnormalities of the integument. G6PC3 mutations may be associated with hydronephrosis or facial dysmorphism. The risk of transition to myelodysplastic syndrome/acute myeloid leukemia may be lower than in other genetically defined SCN subgroups. CONCLUSIONS: The phenotypic and molecular spectrum in G6PC3 deficiency is wider than previously appreciated. The risk of transition to myelodysplastic syndrome or acute myeloid leukemia may be lower in G6PC3 deficiency compared with other subgroups of SCN.