Ehrlichiosis infection in a 5-year-old boy with neutropenia, anemia, thrombocytopenia, and hepatosplenomegaly.

Ehrlichiosis should be considered in the differential diagnosis of any patient with recent fever, pancytopenia, hepatosplenomegaly, and history of tick exposure. We present a previously healthy 5-year-old boy who was referred to the Hematology-Oncology Clinic to consider a bone marrow etiologic process after his pediatrician discovered progressive neutropenia, anemia, thrombocytopenia, and hepatosplenomegaly accompanied by 2 days of fever. Bone marrow aspirate and biopsy were nonrevealing. Because of the history of a recent tick bite, a diagnosis of ehrlichiosis infection was considered and ultimately confirmed by IgG-specific serum testing. The patient's fever was treated symptomatically with acetaminophen, and symptoms resolved on their own without intervention. Ehrlichiosis is a tick-borne infection that occurs throughout the spring and summer, often causing findings that mimic a malignancy or serious hematologic disorder. The diagnosis should be considered in any person living in tick-infested areas and can be confirmed by polymerase chain reaction or serum antibody titers. Treatment with doxycycline can lead to rapid clinical improvement if the diagnosis is made early.

The role of preoperative chemotherapy in the treatment of infantile fibrosarcoma.

Infantile fibrosarcoma (IFS) is a rare tumor most often affecting the extremities of infants and young children. Unlike its adult counterpart, IFS has a low potential for metastatic spread, and surgical extirpation alone has therefore resulted in an excellent prognosis. The amputation rate, however, exceeds 50%. The dramatic response in 2 recent cases to preoperative chemotherapy, given in an attempt to avoid amputation, prompted this report and a review of the literature.

Use of the platelet histogram maximum in evaluating thrombocytopenia.

The purpose of this study was to compare the mean platelet volume (MPV) and the highest peak of the platelet volume distribution curve (maximum of the platelet histogram) with regard to their ability to discriminate between thrombocytopenia due to decreased platelet production or increased platelet destruction. A total of 156 children were studied. Twenty-eight had a diagnosis of idiopathic thrombocytopenic purpura (ITP) and 128 had a low platelet count due to decreased production. MPV and maximum of the platelet histogram were obtained by using the Coulter Counter Max M (Coulter Diagnostics, Hialeah, FL). A comparison of the sensitivity and specificity for the MPV and the maximum of the histogram has been made using the method of the receiver operating characteristic curves. The results show that the maximum of the histogram is superior to the MPV and is a highly effective test for the evaluation of thrombocytopenia. We recommend the use of the maximum rather than the MPV to help distinguish between ITP and thrombocytopenia secondary to decreased platelet production.

Predictive sensitivity of human cancer cells in vivo using semipermeable polysulfone fibers.

An in vivo experimental model was developed to predict efficiently and accurately chemosensitivity of human tumors. Human cancer cells either from cultured cell lines or from patients' tumors were injected directly into semipermeable polysulfone fibers subsequently implanted into immunocompetent rats. Results suggest utility of this novel model system for predicting tumor sensitivity to a wide range of anticancer agents and for potentially guiding the treatment of cancer patients in the clinical setting.

Limb defects and congenital anomalies of the genitalia in an infant with homozygous alpha-thalassemia.

We describe an infant with homozygous alpha-thalassemia, genital abnormalities, and terminal transverse limb defects, whose limbs demonstrate evidence of loss of tissue and abnormal morphogenesis. We propose these defects were due to either severe fetal anemia or to vascular occlusion by abnormal erythrocytes, resulting in hypoxia of the developing distal limbs and genitalia.

Adolescent decision-making: giving weight to age-specific values.

Adults who give proxy consent for medical treatment for adolescents must decide how much weight to give to adolescents' own preferences. There is evidence that some adolescents choose treatments different from what adults see as most reasonable. It is argued that adolescents choose according to age-specific values, i.e. values they hold, as adolescents, and which fulfil important developmental needs. Because not fulfilling these needs may do serious psychological damage, it is urged that proxies give weight to these values, up to the limit where it would endanger or profoundly limit future life.

Typhlitis in a patient with acute lymphoblastic leukemia prior to the administration of chemotherapy.

PATIENTS AND METHODS: A 3-year-old girl with acute lymphoblastic leukemia developed typhlitis immediately after diagnosis and before the institution of chemotherapy. PURPOSE: Typhlitis is a necrotizing colitis that develops in immunodeficient patients with severe neutropenia. Most patients are leukemic children who are receiving or have received chemotherapy. Typhlitis in the absence of chemotherapy is rare. We report a fatal case of typhlitis in an untreated leukemic patient. RESULTS: This case emphasizes the multifactorial pathogenesis of typhlitis, which may occur in the absence of chemotherapy. CONCLUSIONS: Typhlitis should always be considered as a potential cause of acute sepsis and abdominal pain in a leukemic patient.

Immunophenotypic characteristics of cerebrospinal fluid cells in children with acute lymphoblastic leukemia at diagnosis.

The presence of meningeal involvement in children with acute lymphoblastic leukemia (ALL) may have important prognostic and therapeutic implications. Conventional methods of diagnosing central nervous system (CNS) leukemia rely on the interpretation of cerebrospinal fluid (CSF) cell morphology, which may produce ambiguous results in the presence of minimal leukemic involvement. A methodology has been developed for immunophenotyping small numbers of CSF cells while preserving cell morphology. CSF samples from 33 children with CD10 (common ALL antigen [CALLA]) positive ALL were examined at initial presentation using both conventional morphology and this combined immunohistopathologic technique. Six (18%) of the samples contained lymphoblasts or cells considered morphologically suspicious for leukemic involvement. Nine additional samples (27% of the total) had normal CSF morphology, but contained increased numbers of CALLA positive cells. Twelve of the 33 samples were also examined for the simultaneous presence of nuclear terminal deoxynucleotidyl transferase (TdT) and demonstrated increased numbers of cells positive for both TdT and CD10. These data suggest that a large proportion of children with ALL may have abnormalities of CSF cells at initial diagnosis consistent with the presence of occult leukemic involvement.

Telling the truth in the face of medical uncertainty and disagreement.

The pediatric oncologist often must face medical uncertainty and differing opinions among consultants. This raises a dilemma about telling the truth: Does the ethical requirement for telling the truth include informing parents about uncertainties and disagreements, or does the obligation to protect from emotional burden justify withholding information? Answering this question requires an analysis of the nature of medical disagreements. It is argued that disagreements that arise because of medical uncertainties are not disagreements about facts, but disagreements in attitude, where appeal to expertise is not possible. Thus, treatment recommendations must be offered carefully, in order to avoid imposing values on patients. Physicians should make clear the reasoning behind their recommendations, as well as areas of uncertainty. This approach offers the only possibility for parents to give informed consent and to participate in responsible decision making for their child that is consistent with their own values.

Effect of L-asparaginase administration on coagulation and platelet function in children with leukemia.

The use of L-asparaginase during remission induction in patients with leukemia is associated with coagulation abnormalities, which may present either as thrombosis or hemorrhage. However, because of the multiple pharmacologic and hematologic variables present in these patients, the exact contribution of L-asparaginase to these coagulation abnormalities is unclear. We studied platelet function and plasma coagulation parameters in 12 pediatric patients with acute lymphoblastic leukemia (ALL) receiving daily L-asparaginase as a single agent when in complete remission. Changes in the prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen, while statistically significant, remained within or close to the normal range during the study. Platelet function also remained normal during the study. In contrast, levels of protein C antigen decreased to a mean of 42%, a significant change from pretreatment values. Levels of antithrombin III (AT III) were likewise depressed to 15 mg/dL (34% of pretreatment value). Despite these changes in the levels of physiologic inhibitors of coagulation, this schedule of L-asparaginase administration was associated with only rare clinical thrombosis, and this study suggests that the development of this complication may be dependent on the presence of additional factors.

A method for the detection of multiple surface antigens on small heterogeneous cell populations.

A technic using fluorescent immunospheres was developed to identify simultaneously two surface antigens on individual lymphocytes while preserving Wright's stained cell morphology. Small numbers (10,000-20,000) of cells were studied from peripheral blood or bone marrow samples from normal control subjects and from patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). Samples were studied for surface antigens using OKT-11, OK-Ia-1, B1, and J5. Comparison was made with results obtained from the same patients by indirect immunofluorescence. Correlation between results obtained with immunospheres and indirect immunofluorescence was excellent (r = 0.97). In addition, 35 cerebrospinal fluid samples from children with ALL were tested using the immunosphere method alone. Results obtained with spinal fluid lymphocytes agreed with previously reported results using similar methodology. It is concluded that the use of fluorescent microspheres provides a method for the combined evaluation of cell morphology and surface antigens on small, heterogeneous cell populations.

Pharmacokinetics and toxicity of frequent intermediate dose methotrexate infusions.

Serum methotrexate (MTX) levels were measured in 12 children (ages 2-18 years) who received a total of 56 24-h infusions of intermediate-dose methotrexate (500 mg/m2) at 1- to 3-week intervals. Mean peak serum MTX concentration 1/2 h following a bolus of 167 mg/m2 MTX (1/3 total dose) was 25.9 X 10(-6) M, mean plateau serum MTX concentration was 7 X 10(-6) M (over 8-24 h), and mean MTX clearance was 74 ml/min/m2. No significant changes in these values were noted with increasing number of infusions, suggesting that no metabolic adaptation occurred in the manner in which the body handled the MTX when it was given repeatedly in this fashion. However, adolescent patients (greater than or equal to 15 years) demonstrated a trend toward increased MTX clearance and decreased serum MTX concentration with greater than or equal to 5 infusions. In general, toxicity was minimal and did not increase with an increasing number of infusions. Significant toxicity was found only in adolescent patients, in spite of no documented difference in either MTX serum concentrations or clearance rates between adolescent and preadolescent patients.

Use of monoclonal antibodies to identify cerebrospinal fluid lymphoblasts in children with acute lymphoblastic leukemia.

The identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of children with acute lymphoblastic leukemia (ALL). We adapted a latex sphere rosetting technique to allow us to identify simultaneously cell surface markers and cell morphology in 199 CSF samples from 34 patients and 14 control subjects. In patients without leukemic meningitis, the majority of CSF lymphocytes (69%) were found to be mature T cells positive for OKT11. A much smaller number of cells (8%) were found to be B cells positive for la. In these children, only 3% of CSF lymphoid cells expressed the common acute lymphoblastic leukemia antigen (CALLA). Similar results were found in the control subjects. By contrast, 28 CSF samples from nine children with varying numbers of CSF lymphoblasts had much greater proportions of CALLA- and la-positive CSF cells (24% to 96%). Leukemic meningitis was present in one of these patients and later developed in four others. However, three patients with small numbers of lymphoblasts present but with low proportions of CALLA-positive CSF cells (less than 5%) subsequently had normal CSF examinations. We found the use of this rosetting technique valuable in providing information complementary to that obtained from cell morphology alone about the possible malignant nature of small numbers of lymphoblast-like CSF cells seen on cytocentrifuge preparations in children with ALL.