Selin Aytac

Alternative algorithm for L-asparaginase allergy in children with acute lymphoblastic leukemia

BACKGROUND L-asparaginase is a crucial chemotherapeutic agent for the treatment of acute lymphoblastic leukemia. The alternatives to L-asparaginase are not available in many parts of the world, including Turkey. OBJECTIVE We sought to evaluate the utility of premedication with or without a desensitization protocol in children with acute lymphoblastic leukemia and systemic hypersensitivity reactions to Escherichia coli-asparaginase. METHODS In this prospective study patients with systemic hypersensitivity reactions to E coli-asparaginase for whom we were unable to ascertain/provide other alternatives to asparaginase were either premedicated, desensitized, or both to receive their chemotherapy as E coli-asparaginase according to the severity of the hypersensitivity reaction. RESULTS Nineteen patients (13 male patients) with a mean age of 7.4 +/- 4.7 years experienced a systemic hypersensitivity reaction to E coli-asparaginase during a 4-year period. Polyethylene glycol-asparaginase could be used for 3 patients. Eight of the remaining 16 children, who had experienced anaphylaxis, were premedicated and desensitized with E coli-asparaginase, and in 7 patients treatment was tolerated. The other 8 patients, with acute allergic reactions to E coli-asparaginase, were premedicated first, and 5 of them showed no reaction subsequently. Three of them demonstrated systemic hypersensitivity reactions again (anaphylaxis, n = 3), and premedication and desensitization with E coli-asparaginase resulted in anaphylaxis. Polyethylene glycol-asparaginase was administered uneventfully to the patients who could be provided it. CONCLUSION E coli-asparaginase could be administered to more than half of the patients who had a hypersensitivity reaction, and all of these patients were able to receive their planned doses of asparaginase. In countries with shortages of alternative asparaginase preparations, our approach might be a suitable option.

Use of Recombinant Factor VIIa for Bleeding in Children with Glanzmann Thrombasthenia

Glanzmann thrombasthenia is a very rare inherited platelet function disorder in which bleeding may be extremely difficult to stop. Recombinant factor VIIa is one of the alternative treatments for bleeding. The authors report here their experience with the use of factor VIIa, which may be useful for arresting bleeding in Glazmann thrombasthenia.

PIPERACILLIN/TAZOBACTAM PLUS AMIKACIN VERSUS CARBAPENEM MONOTHERAPY AS EMPIRICAL TREATMENT OF FEBRILE NEUTROPENIA IN CHILDHOOD HEMATOLOGICAL MALIGNANCIES

A prospective, randomized clinical trial was conducted to compare the efficacy of piperacillin/tazobactam and amikacin combination with carbapenem monotherapy for the empirical treatment of febrile neutropenic episodes of children with acute lymphoblastic leukemia or acute myeloblastic leukemia. Patients aged 2–16 years with hematological malignancies who had febrile neutropenia were randomly assigned to receive piperacillin/tazobactam (80 mg/kg piperacillin/10 mg/kg tazobactam, q6h) combined with amikacin (PTA) (7.5 mg/kg, q12h) or meropenem or imipenem (20 mg/kg, q8h) (C). Response to antimicrobial therapy, evaluated for etiological agents, was measured. Duration of fever, neutropenia, and hospitalization, mortality, and the need for additional antibiotics or antifungal drugs were compared for the treatment success between the two groups. Out of 87 febrile neutropenic episodes that were evaluable for comparison, 46 patients received PTA and 41 patients were treated with carbapenems (imipenem or meropenem). Overall, the microbiologically documented infection rate was 21.9%, with Staphylococcus epidermidis as the most common cause of bacteremia. The rate of treatment modification was 56.5% in the PTA group and 53.6% in the carbapenem group with no statistical difference (p >. 05). There was no infection-related mortality during the study period.There was no difference between the two regimens for durations of fever, neutropenia, and hospitalization (p >. 05 for all categories). PTA was as effective as carbapenem monotherapy as an initial empirical regimen in febrile neutropenic episodes of pediatric hematological malignancies.

Central Nervous System Involvement in Turkish Children With Primary Hemophagocytic Lymphohistiocytosis

This report mainly presents the clinical and laboratory findings in a group of 15 primary hemophagocytic lymphohistiocytosis patients with central nervous system involvement (group 1) and compares some of the findings with those of 13 hemophagocytic lymphohistiocytosis patients without central nervous system involvement (group 2). Statistical analysis showed that age and sodium level at diagnosis were significantly higher while alanine aminotransferase and bilirubin levels were significantly lower in group 1 than group 2 (P < .05). There were no statistically significant differences between the 2 groups in the other clinical, laboratory, and overall survival parameters. Three patients in group 1 initially had central nervous system involvement in the absence of systemic findings, which led to the initial misdiagnosis of these patients as central nervous system disorders other than hemophagocytic lymphohistiocytosis.

Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) Levels and IL-6, TNF-Polymorphisms in Children With Thrombosis

Infection has an important role in the pathogenesis of thrombosis and it becomes more prominent in childhood cases, in whom the infection frequency is higher. It has been suggested that patients with high tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels might be at increased risk of developing thrombotic complications owing to the effects of these cytokines on the coagulation pathway. Functional polymorphisms in the promoter regions of the genes coding for TNF-α and IL-6 are associated with increased plasma levels of these cytokines. The aims of this study were to evaluate the serum levels of acute phase reactants, such as C-reactive protein, and of cytokines (TNF-α and IL-6) and to investigate the association between the TNF-α-308 G/A and IL-6-174 G/C polymorphisms in Turkish pediatric patients with thrombosis. Fifty-eight children with thrombosis (group 1) and 89 controls (group 2) were included in the study. Patients who had a history of infection within the 15 days before thrombosis were classified as group 1a and those who had no infection history before thrombosis were classified as group 1b. Serum TNF-α did not differ significantly between the groups. However, the IL-6 level was higher in group 1a than in group 1b (P<0.05). The genotype distribution and allele frequencies of TNF-α G/A polymorphism were significantly higher in the thrombotic children without infection and in the control group than in the thrombotic children with an infection history (P<0.05). The IL-6-174 C/C genotype was significantly higher in thrombotic children with an infection history (P<0.05); there were no differences between the groups in mean allele frequency (Table 2). On the basis of our results, patients with a history of infection seem to have higher C-reactive protein and IL-6 levels and IL-6-174 C/C genotype. Furthermore, venous thrombosis is more frequent in this group than arterial thrombosis (P<0.05).

Recurrent pediatric thrombosis: the effect of underlying and/or coexisting factors.

The objective of this study was to evaluate the underlying diseases, thrombus localization, and other risk factors in pediatric patients with recurrent thrombosis in order to obtain a sense of early awareness of the possible recurrences. We retrospectively evaluated both inherited and acquired thrombophilic risk factors in children with recurrent thrombosis that were diagnosed and treated at Hacettepe University, School of Medicine, Department of Pediatric Hematology, Ankara, Turkey. Both congenital and acquired risk factors associated with recurrent thrombosis, and treatment modalities were analyzed in detail. Among 569 children with thrombosis, 32 (5.6%) presented with recurrent thrombosis. Median age at first presentation in these 32 patients [11 women (34.4%) and 21 men (65.6%)] was 132 months. In all, 29 (90.6%) of the 32 patients had an underlying chronic disorder: the most common of which was congenital heart disease [n = 11 (34.4%)]. At presentation intracardiac localization, including the entrance of the inferior and superior vena cava, was observed in 10 of the patients (31.2%). Thrombosis recurred at the same location in 15 (47%) patients and at a different location in 17 (53%). Median time interval between the first and second episode of thrombosis was 6.5 months (range: 1–180 months). Considering both acquired and congenital thrombophilic factors, three (9.3%) patients, four (12.5%) patients, and 14 (43.8%) patients had five, four, and three risk factors, respectively. More than half of the patients had elevated plasma FVIII (>150 IU/dl) and D-dimer (>0.5 mg/ml) levels. Thrombectomy was performed in three patients with organized, chronic intracardiac thrombus. Tissue plasminogen activator (t-PA) was used more frequently to treat recurrence than the first event (15.6 vs. 28.1%) and consequently the complete resolution rate was higher (40 vs. 77.7%) at the second event. Thrombi partially resolved in 11 of the patients during the initial episode and in 10 patients during recurrence (34 vs. 32%). In all, 29 (87.5%) patients were using prophylaxis at the time of recurrence. [coumadin (n = 16), low molecular weight heparin (n = 12) and aspirin (n = 1)]. In total, four patients (12.5%) died because of their underlying disorders and six (18.7%) developed postthrombotic syndrome during the follow-up. Recurrent thrombosis should be expected, especially in cases with congenital heart disease, incomplete thrombus resolution, and elevated plasma FVIII/D-dimer levels. In the light of this knowledge we suggest aggressive treatment for pediatric patients with a high risk of recurrent thrombosis.

Long term biweekly 1 mg oral vitamin B12 ensures normal hematological parameters, but does not correct all other markers of vitamin B12 deficiency. A study in patients with inherited vitamin B12 deficiency

Parenteral vitamin B12 is considered the treatment of choice for vitamin B12 deficiency, but also treatment with 1–2 mg daily oral vitamin B12 is recommended.[1][1],[2][2] Recently, alternative regimes have been proposed, such as an oral dose of 1 mg vitamin B12 daily for ten days, weekly for four

Anaphylactic reaction to polyethylene-glycol conjugated-asparaginase: premedication and desensitization may not be sufficient.

In hypersensitive reactions to native L‐asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG‐ASP) is preferred. Anaphylaxis with PEG‐ASP is rare. An 8‐year‐old girl and a 2.5‐year‐old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L‐asparaginase hypersensitivity and substitution with PEG‐ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG‐ASP infusion. Both patients developed anaphylaxis with peg‐asparaginase. These are the first reported cases of anaphylactic reaction to PEG‐ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG‐ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions.

DEFERASIROX USE AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PEDIATRIC PATIENTS WITH β-THALASSEMIA MAJOR: Preliminary Results

There are limited data on the posttransplantation pharmacological treatment of iron overload in ex-thalassemic patients and the current approach is phlebotomy. The authors chelated 2 ex-thalassemic patients after hematopoietic stem cell transplantation with deferasirox for 6 and 24 months. Although serum ferritin levels decreased, cardiac and hepatic iron load, measured by T2* magnetic resonance imaging (MRI), showed decrease in iron overload in these organs. The drug was tolerated well by both patients and no adverse effect on donor hematopoiesis was observed. This preliminary study demonstrates that deferasirox is well tolerated in these patients and will be a good potential therapy when more data have been obtained from larger studies.

Number of erythrocyte transfusions is more predictive than serum ferritin in estimation of cardiac iron loading in pediatric patients with acute lymphoblastic leukemia.

BACKGROUND Transfusions with packed erythrocytes is a common practice in pediatric patients with acute lymphoblastic leukemia (ALL) who are on chemotherapy. Since there is no physiological excretion mechanism for iron, the iron related to erythrocyte transfusions accumulates and may contribute to late cardiac, hepatic and endocrine complications in these patients. PROCEDURE In order to evaluate the iron burden among pediatric patients with ALL and define the risk factors associated with higher iron loading, we evaluated 79 pediatric patients with ALL (36 were off-therapy). Cardiac and hepatic T2* were ordered to a total of 22 (28%) patients who were either transfused with erythrocytes ≥ 10 times (n=11; 50%), had serum ferritin (SF) ≥ 1000 ng/ml (n=2; 9.1%) or both (n=9; 40.9%). RESULTS Half of the patients who were screened by T2* MRI had hepatic T2*<7 ms and six (27%) of the patients had cardiac T2*<20 ms, indicating iron loading. Patients who had serum ferritin <1000 vs ≥ 1000 ng/ml had median cardiac T2* values of 28.3 ms (15-40) vs 21 (7.9-36), (p=0.324); whereas hepatic T2* of 10.8 (5.32-27) vs 4.7 (2.2-36), (p=0.017). Patients who had erythrocyte transfusion <10 vs ≥ 10 times had median cardiac T2* values of 34 ms (28-38) vs 23 (7.93-40), (p=0.021); whereas hepatic T2* of 13.6 (6.6-36) vs 5.32 (2.2-27), (p=0.046). CONCLUSIONS Our results indicate that pediatric patients with ALL should be screened for transfusional iron load and the amount of erythrocyte transfusions seems to be a more reliable indication than serum ferritin levels to detect cardiac iron loading in these patients.