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.

Nonimmune hydrops fetalis in two cases of consanguineous parents and associated with hereditary spherocytosis and hemophagocytic hystiocytosis.

Nonimmune hydrops fetalis may occur as a result of different etiological conditions and in about one-third of cases no cause could be identified. Here, we report two cases of nonimmune hydrops fetalis associated with hereditary spherocytosis and hemophagocytic hystiocytosis. We think that babies with hydrops fetalis born of consanguineous parents should be examined for hereditary diseases, and that these rare causes should be taken into account in problematic cases.

Perforation of the stomach due to chest tube complication in a patient with iatrogenic diaphragmatic rupture.

Diagnosis of diaphragmatic injury is difficult. A case of iatrogenic diaphragmatic rupture is reported in which perforation of a herniated stomach occurred following left lobectomy and partial resection of the diaphragm for lung cancer. On the second postoperative day, bile-stained fluid coming out from the chest tube revealed gastrointestinal leakage. This rare complication of chest tube insertion, early diagnosis and treatment are emphasized.

Primary hemophagocytic lymphohistiocytosis in Turkish children.

Nineteen children with hemophagocytic lymphohistiocytosis (HLH) were studied in the Department of Pediatric Hematology, Hacettepe University. Patients were divided into two groups. Group 1: Thirteen patients were classified as having a genetic etiology (7 familial, 6 presumed familial) on the basis of an affected sibling and consanguinity. There was a history of consanguineous marriage in 13 of the families. Seven of them had a history of a sibling with HLH. Group 2: Six patients were diagnosed with sporadic HLH. The age at presentation for familial patients was 0.7-84 months (mean 21.9 +/- 24.9 months), and for sporadic cases it was 2.5-48 months (mean 22.7 +/- 19.8 months). The clinical and laboratory data of these two groups were similar at diagnosis. Thirteen cases were diagnosed premortem by bone marrow aspiration. Splenic biopsy was performed in 2 patients. Four patients were diagnosed by postmortem examination. Elevated LDH levels were found in all patients tested. No significant differences for clinical and laboratory data were found between the two groups.

Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up.

Eight-year event-free survival (EFS) was evaluated in 205 patients with acute lymphoblastic leukemia (ALL), to consider the efficacy of high-dose methylprednisolone (HDMP) given during remission induction chemotherapy between 1 and 29 days. The St Jude Total XI Study protocol was used after some minor modifications in this trial. Patients were randomized into two groups. Group A (n = 108) received conventional dose (60 mg/m(2)/day orally) prednisolone and group B (n = 97) received HDMP (Prednol-L, 900-600 mg/m(2) orally) during remission induction chemotherapy. Complete remission was obtained in 95% of the 205 patients who were followed-up for 11 years; median follow-up was 72 months (range 60-129) and 8-year EFS rate was 60% overall (53% in group A, 66% in group B). The EFS rate of group B was significantly higher than of group A (P = 0.05). The 8-year EFS rate of groups A and B in the high-risk groups was 39% vs 63% (P = 0.002). When we compared 8-year EFS rate in groups A and B in the high-risk subgroup for both ages together /=10 years, it was 44% vs 74%, respectively. Among patients in the high-risk subgroup with a WBC count >/=50 x 10(9)/l, the 8-year EFS was 38% in group A vs58% in group B. During the 11-year follow-up period, a total of 64 relapses occurred in 205 patients. In group A relapses were higher (39%) than in group B (23%) (P = 0.05). These results suggest that HDMP during remission-induction chemotherapy improves the EFS rate significantly for high-risk patients in terms of the chances of cure.

The effects of high dose methylprednisolone on apoptosis in children with acute lymphoblastic leukemia.

Rapid leukemic cell kill at initial diagnosis of patients with acute lymphoblastic leukemia (ALL) has been shown to be associated with a favorable outcome. The aim of the present study was to investigate the effect of high dose methylprednisolone (HDMP) on in vivo blast cell apoptosis in children with ALL. Annexin V-binding and Fas (CD95), Fas ligand (FasL; CD95L), and Bcl-2 expression in PB blasts were determined in newly diagnosed children with ALL before and 4, 24, 96 h after initiation of HDMP treatment (n=20) or conventional dose steroids (CDS) (n=10) as the control group. A decrease in absolute blast count (from 40.8 x 09 to 21.4 x 109/l) associated with an increase in apoptosis (14.2 to 26.9%) (P < 0.05) was detected 4 h after initiation of HDMP. A significant increase in Fas and FasL expression was detected 96 h after HDMP. There was no significant change in apoptosis, Fas and FasL expression from baseline in the control group treated with CDS. The changes in Bcl-2 expression after treatment was not significant in both groups. The results of this preliminary study have shown that HDMP treatment was effective in inducing immediate (within 4 h) blast cell apoptosis. The contribution of Fas/FasL interaction in the rapid component of cell kill remains to be determined, as the increase in the expression of these molecules was evident later.

Clinical importance of serum vascular endothelial and basic fibroblast growth factors in children with acute lymphoblastic leukemia.

The aim of this study is to evaluate, for the first time serum levels of vascular endothelial growth factor (s-VEGF), and basic fibroblast growth factor (s-b FGF) in children with acute lymphoblastic leukemia (ALL), and its relation to clinical manifestations of the disease. Although VEGF and b FGF have been suggested to be reliable prognostic indicators and important tools for treatment approach in malignant haematopoietic and solid tumours, experience in childhood ALL has been limited to only one study on angiogenesis and urine b FGF. All 31 ALL patients included in the present study at the time of diagnosis and in remission, and all 10 control children had detectable serum levels of VEGF and b FGF. The median level of s-VEGF at the time of diagnosis was significantly lower than in the control group and at the time of remission (respectively p = 0.005, p = 0.0001). Twenty six of 31 patients had an increasing trend of s-VEGF levels in remission reaching control values compared with the levels obtained at diagnosis. S-b FGF median levels at the time of diagnosis were the same as those of the control group, significantly lower than the median s-b FGF values in remission (p = 0.001). In patients with lower platelet counts (< 50 x 10(9)/L) growth factors (VEGF and b FGF) were lower than in patients with higher platelet counts (p = 0.0009 and p = 0.002 respectively). In patients with hepatosplenomegaly (longitudinal size > 3 cm) b FGF levels were higher than patients without hepatosplenomegaly (P = 0.003). We concluded that the increment in both s-VEGF and s-b FGF in patients in remission may be related to the renewal of normal haematopoiesis. The increase in s-VEGF values in 26 out of 31 patients in remission compared to normal control values, may also suggest that there is clinical significance in ALL patients.

Megakaryocyte emperipolesis in a child with chronic neutropenia: an unusual coexistence.

The term emperipolesis defines the temporary presence of one cell within another's cytoplasm. In clinical use, megakaryocyte emperipolesis is the penetration of hematopoietic cells into the cytoplasm of megakaryocytes. The pathophysiological significance of megakaryocyte emperipolesis is uncertain. It has been described in association with neoplastic disorders, and in a few instances in idiopathic thrombocytopenic purpura, iron deficiency anemia, bleeding, and during the administration of recombinant human granulocyte colony-stimulating factor. However, megakaryocyte emperipolesis in a patient with chronic neutropenia has not been reported. In the current report, emperipolesis of hematopoietic cells within megakaryocytes in a boy with chronic neutropenia is described and the possible mechanisms are discussed.

Relapse in hairy cell leukemia due to isolated nodular skin infiltration.

Leukemic skin infiltration is quite uncommon in certain types of leukemia. Here, a child with hairy cell leukemia who developed isolated skin infiltration during remission is reported. The failure to diagnose the leukemic infiltration until the nodule reached a diameter of 2 cm is emphasized.

Acute tumour lysis syndrome following a single-dose corticosteroid in children with acute lymphoblastic leukaemia.

Acute tumour lysis syndrome (ATLS) is a well recognised complication of treatment of a variety of malignant disorders. It commonly occurs in patients with non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukaemia (ALL) with the administration of combined cytotoxic chemotherapy. It is rarely reported after single-agent corticosteroid therapy. We present two children with acute lymphoblastic leukaemia of T-cell lineage who developed acute tumour lysis syndrome after a single dose of prednisolone, and methylprednisolone at the beginning of the induction chemotherapy. In the first case (an 11-yr-old) ATLS had occurred after an oral dose of prednisolone as small as 12 mg and within 18 h. The second case was a 14-yr-old boy with ALL who developed ATLS following a single dose of methylprednisolone. A few similar cases in the English literature are summarised in the report. These cases indicate that acute tumour lysis syndrome may occur after a single dose of corticosteroids. One should be aware of this potentially life-threatening complication especially while prescribing corticosteroids to patients with NHL and leukaemia.

Chronic idiopathic neutropenia associated with gingival enlargement.

A girl with chronic idiopathic neutropenia who developed gingival enlargement at seven years of age is presented. Intraoral examination revealed generalized gingival inflammation with a tendency to bleeding and inflammatory gingival enlargement localized to the anterior region. A considerable amount of bacterial plaque was noted on the teeth. There were also 4-5 mm pocket depths around the first molars. Radiographic examination also indicated the presence of incipient bone loss around the first molars in both jaws. The patient, who was diagnosed as localized prepubertal periodontitis with generalized gingival inflammation and anterior gingival enlargement, accentuates the importance of evaluation of periodontal status in patients with chronic idiopathic neutropenia, to avoid the destruction of supporting structures of the dentition.

Two booster dose hepatitis B virus vaccination in patients with leukemia.

The aim of this study was to interpret the antibody response to hepatitis B (HB) vaccination following a two booster dose schedule in 94 acute lymphoblastic leukemia (ALL) patients. All patients were between 1-16 years of age with negative hepatitis B virus (HBV) serology and normal hepatic function. Fifty patients were vaccinated with Engerix B vaccine, and 44 patients were vaccinated with GenHevac B vaccine, with a schedule of 0, 1, 6 and 0, 1, 2, as well as booster doses, in 12 and 6 months respectively. A second booster was given as a fifth dose to 16 unresponsive patients in each vaccine group, 3 and 6 months after the first booster for Engerix B and GenHevac B vaccines respectively. Dosage was 20 microg HbsAg for all patients. Seroconversion rates with protective level antibody were 35.1% (n=33/94). The figures were 32.1% (n=16/50) and 38.6% (n=17/44) for Engerix B and GenHevac B vaccines, respectively. Seroconversion rate in patients younger than 10 years old was found to be higher (39.11%) than older patients (24%), but this was not statistically significant. This study indicates that one third of the leukemic children undergoing maintenence chemotherapy responded to HB vaccine with protective titers of anti-HBs. We recommend HB vaccination especially in developing countries.

Acute lymphoblastic leukemia in a child with Wilson disease.

Wilson disease is an autosomal recessively inherited disease of copper metabolism and is characterized by liver and central nervous system dysfunction. The heterozygote carrier state rate is about one in 90 persons and the incidence of the disease is about 30 in 1,000,000. Although leukemia is the most common form of childhood malignancies, the probability of the presence of Wilson disease and acute lymphoblastic leukemia in the same patient is very low. We report an unusual case of a child with Wilson disease who developed acute lymphoblastic leukemia in three months.

Acute parvovirus B19 infection mimicking juvenile myelomonocytic leukemia.

An 11-month-old patient with parvovirus infection mimicking juvenile myelomonocytic leukemia (JMML) is presented. The patient's history, presenting physical and laboratory features, was suggestive of JMML and consisted of fever, hepatosplenomegaly, lymphadenopathy, desquamation of the skin, anemia, leukocytosis with monocytosis and trilineage dysplastic findings of the peripheral blood and bone marrow. However, positive IgM titers for parvovirus B19 followed by seroconversion, negative cytogenetics and the benign follow-up of the patient suggested acute parvovirus infection as an etiologic factor for development of dysplastic features in the patient, and thus is recommended for consideration in the differential diagnosis of MDS. Although parvovirus B19 infection mimicking MDS has previously been shown in two patients with spherocytosis and one with subclinical immune deficiency; to our knowledge, the present report is the first describing the association of acute parvovirus B19 infection with dysplastic features mimicking myelodysplasia (MDS) in a child without a demonstrable underlying hematolymphoid disorder.

Dysplastic changes in idiopathic thrombocytopenic purpura and the effect of corticosteroids to increase dysplasia and cause hyperdiploid macropolycytes.

This study evaluates the dysplastic hematological changes in nine patients with idiopathic thrombocytopenic purpura (ITP) in 11 attacks, before and after corticosteroid treatment. The pretreatment blood smears of patients with ITP, displayed more neutrophils with bizarre nuclei (P < 0.001), Döhle or Döhle-like inclusions (P < 0. 01), irregular distribution of granules (P < 0.05), hypo-agranulation (P < 0.05), pseudo-Pelger-Huet-like cells (P < 0. 01), and nuclei with chromatine clumping (P < 0.01) than the normal children. The eosinophils of ITP patients were also dysplastic, before treatment. The pretreatment diameter of the neutrophils and the percentage of macropolycytes were greater than those of the patients with viral infections and normal group (P < 0.05 for all). The percentage of neutrophils with bizarre nuclei and nuclei with chromatine clumping and the diameter of neutrophils and macropolycyte percentage increased with corticosteroid therapy (P < 0.01, < 0.01, < 0.01, and < 0.05, respectively). The neutrophil diameter, percentage of macropolycytes, and number of neutrophils with bizarre nuclei decreased within 1-4 weeks after the therapy was stopped. In the neutrophils of two patients, diploidy and hyperdiploidy were established before and on the last day of therapy, respectively, and diploidy reversed after therapy was stopped. In conclusion, ITP patients display dysplastic findings in both neutrophils and eosinophils before treatment and corticosteroids cause transient significant increase in some of the dysplastic changes in neutrophils.