Infantile cytomegalovirus-associated autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) is a hematologic disorder that is rarely seen in infants and young children. Most cases are associated with viral or bacterial infection, but the immunologic events leading to hemolysis are poorly understood. We describe two infants with severe cytomegalovirus (CMV)-associated warm antibody AIHA. One case was immunohematologically analyzed and showed suggestive evidence that endogenous anti-CMV IgG antibodies were the pathogenic antibodies leading to hemolysis, implicating a possible causal relationship between AIHA and CMV infection. Both patients were ultimately treated with intravenous CMV immune globulin, with subsequent improvement. These cases suggest that investigation for the presence of CMV in infantile AIHA is warranted and that CMV immune globulin should be considered as a therapeutic option.

Beneficial effect of intravenous dexamethasone in children with mild to moderately severe acute chest syndrome complicating sickle cell disease.

Acute chest syndrome (ACS) in patients with sickle cell disease (SCD) has historically been managed with oxygen, antibiotics, and blood transfusions. Recently high-dose corticosteroid therapy was shown to reduce the duration of hospitalization in children with SCD and vaso-occlusive crisis. Therefore, we chose to assess the use of glucocorticoids in ACS. We conducted a randomized, double-blind placebo-controlled trial to evaluate the efficacy and toxicity of intravenous dexamethasone (0.3 mg/kg every 12 hours x 4 doses) in children with SCD hospitalized with mild to moderately severe ACS. Forty-three evaluable episodes of ACS occurred in 38 children (median age, 6.7 years). Twenty-two patients received dexamethasone and 21 patients received placebo. There were no statistically significant differences in demographic, clinical, or laboratory characteristics between the two groups. Mean hospital stay was shorter in the dexamethasone-treated group (47 hours v 80 hours; P = .005). Dexamethasone therapy prevented clinical deterioration and reduced the need for blood transfusions (P < .001 and = .013, respectively). Mean duration of oxygen and analgesic therapy, number of opioid doses, and the duration of fever was also significantly reduced in the dexamethasone-treated patients. Of seven patients readmitted within 72 hours after discharge (six after dexamethasone; P = .095), only one had respiratory complications (P = 1.00). No side effects clearly related to dexamethasone were observed. In a stepwise multiple linear regression analysis, gender and previous episodes of ACS were the only variables that appeared to predict response to dexamethasone, as measured by lengh of hospital stay. Intravenous dexamethasone has a beneficial effect in children with SCD hospitalized with mild to moderately severe acute chest syndrome. Further study of this therapeutic modality is indicated.

Low-dose recombinant human granulocyte colony-stimulating factor therapy in children with symptomatic chronic idiopathic neutropenia.

OBJECTIVES: To prospectively define the lowest possible doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) that would benefit selected children with chronic idiopathic neutropenia whose disease was severe enough to interfere appreciably with quality of life. STUDY DESIGN: The efficacy of low-dose rhG-CSF therapy was investigated in six children with symptomatic chronic idiopathic neutropenia. All patients received rhG-CSF, 5 micrograms/kg subcutaneously, as a single daily dose until an absolute neutrophil count (ANC) above 1.5 x 10(9)/L was observed. The rhG-CSF dosage interval and amount were then increased and decreased, respectively, in an alternating fashion until the lowest rhG-CSF dose that would maintain the ANC above 1.0 x 10(9)/L (1000/mm3) was reached. RESULTS: Although the minimal dose requirements varied, all patients were able to maintain a mean ANC > 1.0 x 10(9)/L during a mean follow-up period of 14 months at doses ranging from 1.0 microgram/kg once weekly to 5.0 micrograms/kg every other day. Administration of rhG-CSF resulted in resolution of all preexisting chronic infections, reduction in the frequency of new infectious episodes, and discontinuation of prophylactic antibiotics. In all patients the ANC decreased to pretreatment values when further reduction or discontinuation of rhG-CSF therapy was attempted. By identifying the minimal effective dose in each patient, we were able to reduce the treatment cost by a mean of 81% compared with daily dosage at 5 micrograms/kg. CONCLUSIONS: Recombinant human granulocyte colony-stimulating factor therapy at low doses (< or = 5 micrograms/kg) every 2 to 7 days to symptomatic children with chronic idiopathic neutropenia is effective and no more costly than supportive treatment with antibiotics.

Diagnosis and management of chronic neutropenia during childhood.

The approach to the diagnostic evaluation of a patient with neutropenia can be guided largely by clinical history and physical examination and does not always require an extensive laboratory evaluation. Based on the history and bone marrow morphology, most children with chronic neutropenia can be classified and managed. Most patients with chronic neutropenia are free of infections and are able to maintain a normal lifestyle with no or minimal medical intervention. On the other hand, for patients with recurrent or severe infections, careful follow-up and institution of treatment are mandatory. The Food and Drug Administration has approved the use of rhG-CSF in patients with chronic neutropenia. As mentioned previously, the use of colony-stimulating factors has dramatically improved the outcome for many patients with the more severe neutropenia; however, this cytokine is expensive, so treatment should be reserved for more severely affected patients and not given just because the ANC is low. Although concerns exist regarding leukemogenic effects or eventual loss of the progenitor cell compartment driven by the continuous stimulation of rhG-CSF, at this moment, the long-term data available suggest that the chronic administration of rhG-CSF is safe.

Relapse of precursor B-cell acute lymphoblastic leukemia as an isolated central nervous system mass lesion 9 years after initial diagnosis.

Seven years after completion of chemotherapy for acute lymphoblastic leukemia, diagnosed at the age of 5 years, a black female presented with signs of increased intracranial pressure. Neuroimaging showed a large enhancing extra-axial occipital tumor mass. The resection specimen showed morphologic, cytogenetic, and immunophenotypic features consistent with relapse of the primary leukemia. Bone marrow examination was negative for malignancy. The long duration of complete remission followed by the formation of a mass in the central nervous system are highly unusual features of recurrent acute lymphoblastic leukemia.

High-dose intravenous methylprednisolone therapy for patients with Diamond-Blackfan anemia refractory to conventional doses of prednisone.

OBJECTIVES: To assess the efficacy and toxicity of very high doses of glucocorticoids in patients with congenital pure red cell aplasia (Diamond-Blackfan anemia) who did not respond to standard doses of prednisone. STUDY DESIGNS: We prospectively treated eight patients with transfusion-dependent Diamond-Blackfan anemia with high intravenous doses of methylprednisolone. All patients had previously not responded to one or more oral courses of prednisone in standard doses and were dependent on erythrocyte transfusions. Every patient initially received methylprednisolone at a dose of 30 mg/kg per day, followed by slow tapering for 4 weeks, but none responded. All patients then received a second treatment course starting at 100 mg of methylprednisolone per kilogram per day, again followed by slow tapering of the dosage. RESULTS: Three patients had a complete response that has been sustained for 21+, 31+, and 41+ months, respectively. One patient had a partial response. Toxic effects included a rise in serum alanine aminotransferase activity in all patients, transient diabetes mellitus in one child, and three episodes of bacteremia in two patients with intravenous access devices. CONCLUSIONS: We conclude that very high doses of methylprednisolone may induce sustained remission in some patients with transfusion-dependent Diamond-Blackfan anemia refractory to standard-dose prednisone therapy.

Fatal hemolysis induced by ceftriaxone in a child with sickle cell anemia.

A 2-year-old boy with sickle cell anemia had a massive, fatal hemolytic reaction after administration of an intravenous dose of ceftriaxone. Laboratory studies demonstrated the presence of an IgM antibody against ceftriaxone, binding to and destroying the patient's erythrocytes by an immune complex mechanism. This rare complication should be considered in the differential diagnosis when hemoglobinuria develops in a child after administration of ceftriaxone or a similar agent.

Aminophylline for methotrexate-induced neurotoxicity.

Methotrexate, a mainstay treatment for children with acute lymphoblastic leukaemia, can cause neurotoxicity, with paralysis, seizures, somnolence, anorexia, and headaches. The pathophysiology of this reaction is unknown. It has been suggested that the anti-inflammatory effect of methotrexate in patients with arthritis is due to adenosine release brought on by inhibition of purine synthesis. Since adenosine is a central nervous system depressant, we wondered whether adenosine release in the central nervous system could account for some of the neurotoxicity due to methotrexate, and whether that toxicity could be lessened by displacement of adenosine from its receptor by aminophylline. 6 patients (age 3-16 years) who had methotrexate-induced neurotoxicity unresponsive to standard treatment received 2.5 mg/kg aminophylline. In addition, the concentration of adenosine in the cerebrospinal fluid (CSF) from 11 children completing a 24-h systemic methotrexate protocol was compared with that in 8 newly diagnosed patients and 12 who had not received any treatment for at least a week. 4 of 6 patients with toxic signs and symptoms attributed to methotrexate and unrelieved by steroids, epidural blood patch, promethazine, 5-hydroytryptamine antagonists, paracetamol, and narcotics, had complete resolution of neurotoxicity after or during a 1-h infusion of aminophylline; 2 others had a pronounced improvement but persistent nausea. CSF adenosine concentrations of patients receiving methotrexate, even when there was very slight or no toxicity, were greatly increased compared with control subjects (mean values of 217 and 51 nmol/L, median 175 and 52 nmol/L). Subacute methotrexate neurotoxicity may be mediated by adenosine and relieved by aminophylline.

Acute basophilic leukemia in a child. Anaphylactoid reaction and coagulopathy secondary to vincristine-mediated degranulation.

BACKGROUND: Acute de novo basophilic leukemia (ABL) is uncommon in adults, and extremely rare in children. To the authors' knowledge, there have been no previous reports of anaphylactoid reactions from basophilic degranulation in children with this condition. METHODS: This report describes the clinicopathologic profile and complications of a patient with de novo ABL. RESULTS: Immediately after the first induction dose of intravenous vincristine, the patient developed an anaphylactoid reaction and disseminated intravascular coagulation with massive pulmonary hemorrhage. A normal serum tryptase level suggested that this life-threatening event was secondary to tumor lysis (basophilic degranulation), rather than to a mast-cell mediated anaphylactic reaction to vincristine. This interpretation is supported by the coagulation studies, which suggested release of heparin from the blast granules. CONCLUSIONS: Although de novo ABL is rare, it should be considered when cytoplasmic basophilic granules are seen in the leukemic cells of patients with what otherwise appears to be undifferentiated leukemia, and the pertinent diagnostic procedures should be undertaken. During the treatment of ABL, potential complications related to basophilic degranulation should be anticipated, and antihistamine prophylaxis may be of value.

Adjuvant chemotherapy for treatment of unresectable and metastatic angiomatoid malignant fibrous histiocytoma.

Angiomatoid malignant fibrous histiocytoma (AMFH) is a low grade soft tissue sarcoma usually treated with surgery alone. Only one adult patient has been treated with systemic chemotherapy. The authors report a case of unresectable, metastatic AMFH treated initially with vincristine, doxorubicin, dactinomycin, and cyclophosphamide. A complete response at the metastatic site and a marked reduction in the size of the primary tumor allowed complete surgical excision 7 months after treatment was initiated. The patient remains disease free 19 months after being diagnosed. It was concluded that systemic chemotherapy may be effective in patients with AMFH.

Splenic rupture in hemophilia.

PURPOSE: Little information is available regarding splenic injury in patients with hemophilia. We describe here the management of splenic rupture in five of our patients with hemophilia and summarize the literature describing this complication. PATIENTS AND METHODS: Two human immunodeficiency virus-seropositive patients were managed medically and did not require splenectomy. A third patient had a high titer inhibitor to both porcine and human factor VIII and required emergency splenectomy. Two boys had not been previously diagnosed with hemophilia until they underwent splenectomy after abdominal trauma. RESULTS: All five patients survived. CONCLUSIONS: These cases demonstrate that nonsurgical management of splenic injury in patients with hemophilia can be performed safely and that splenectomy can be successfully performed despite a high titer of factor VIII inhibitor.

Hypoprothrombinemia and severe hemorrhage associated with a lupus anticoagulant.

We recently encountered a previously healthy 3-year-old girl who had severe bleeding resulting from a severe deficiency of prothrombin. A lupus anticoagulant was identified by several different methods. The patient was successfully treated with glucocorticoids. This rare complication of a lupus anticoagulant should be considered in the differential diagnosis of a previously well child who suddenly has hemorrhage.