Carlos R. Suarez

Impact of chromosomal translocations on prognosis in childhood acute lymphoblastic leukemia.

The presence of a chromosomal translocation in the leukemic cells at diagnosis of acute lymphoblastic leukemia (ALL) in children is associated with a high risk for treatment failure. We have reexamined the relationship between translocations and prognosis in 146 children with ALL who received risk-based therapy such that high-risk patients were treated with intensive drug schedules. In univariate analysis, multiple factors were associated with a relatively poor event-free survival (EFS) including age less than 2 years or greater than 10 years (combined group), WBC count greater than 10 x 10(9)/L, French-American-British (FAB) morphologic classification L2, absence of common ALL antigen (CALLA, CD10) expression, absence of hyperdiploidy with a chromosome number of 50 to 60, and presence of the specific translocations t(4; 11)(q21;q23) or t(9;22)(q34;q11) (combined group). However, there was no disadvantage with respect to EFS in patients with translocations compared with those who lacked translocations (73% at 4 years in both groups). Furthermore, when patients with specific cytogenetic abnormalities for which the prognostic significance has been well established (hyperdiploid 50 to 60, t(4;11), and t(9;22] were removed from the analysis, the remaining group with other translocations had a better EFS than the remaining group lacking translocations, although this was not statistically significant (81% v 65% at 4 years, P = .24). In a multivariate analysis, a model including WBC count and FAB classification was the strongest predictor of EFS. The presence or absence of translocations was not an independent predictor of EFS and did not contribute to the ability of any model to predict EFS. In conclusion, when effective intensive therapy is used to treat childhood ALL with high-risk clinical features, categorization of patients on the basis of chromosomal translocations without attention to the specific abnormality is not useful as a prognostic factor.

Impact of long-term erythrocytapheresis on splenic function in patients with sickle cell disease.

Fifteen children with sickle cell disease undergoing long-term erythrocytapheresis were assessed for splenic regeneration using abdominal ultrasound and radionuclide spleen scans. Despite a significant level of reduction of hemoglobin S (HbS), none of the 15 patients showed evidence of splenic regeneration. Comparing our results with other published reports on hypertransfusion therapy in patients with sickle cell disease, it appears that the process of splenic regeneration in these patients is minimal and may depend partly on the intensity of transfusion therapy and the length of time that HbS has been maintained below 20%.

Elevated lead levels in a patient with sickle cell disease and inappropriate secretion of antidiuretic hormone.

A five-year-old girl with known sickle cell disease presented with severe hyponatremia and findings compatible with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). She was found to have lead levels in the Class III category. By exclusion, we postulated that the SIADH was in some way related to the high lead levels, since this was the only abnormality the patient exhibited. The toxic lead levels and the elevated vasopressin levels rapidly responded to dimercaprol and calcium EDTA chelation therapy.

Testing for Passovoy Defect in Children with Prolonged Activated Partial Thromboplastin Time (aptt)

Purpose: To investigate the value of testing for Passovoy defect using the commercially available Passovoy trait plasma (PTP) in children with prolonged activated partial thromboplastin time (APTT). Patients and Methods: We studied 13 children with prolonged APTT that corrected in a 1:1 mix with normal human plasma but not with PTP. In most children, a thorough laboratory investigation of the intrinsic pathway factors and von Willebrand factor was performed. Results: Five patients had bleeding manifestations and eight were asymptomatic. Measurement of von Willebrand factor and intrinsic pathway factors revealed abnormal values in eight patients (low von Willebrand activity in six patients, low factor XII in one patient, and the presence of lupus anticoagulant in one patient). Conclusion: Our data suggest inability to diagnose Passovoy defect based on a mixing study. This study also raises the question of whether Passovoy defect exists as a distinct coagulation disorder.

Pseudo-Chediak-Higashi anomaly in a child with a hepatic vascular malformation.

A case of a congenital hepatic vascular malformation in a child complicated by disseminated intravascular coagulation and hemolytic anemia is presented. Examination of the peripheral blood disclosed the presence in the leukocytes of giant intracytoplasmic inclusions resembling those of the Chediak-Higashi anomaly. Ultrastructural analysis characterized those inclusions as phagocytosed red cell debris, a result of mechanical destruction of the red cells.

Accidental Carbon Monoxide Poisoning

In this case report of an accidental automobile carbon monoxide poisoning, we identify the following risk factors: freezing temperature, young passenger age, location in the rear of the auto, smaller patient mass, and auto disrepair. The pathogenesis of carbon monoxide poisoning is reviewed. Emergency treatment and suggested criteria for hyperbaric oxygen use in pediatric patients are discussed.

Second malignant neoplasms (SMN) in childhood acute lymphoblastic leukemia (ALL): Primitive neuroectodermal tumor of bone (PNET) with p53 mutation

8173 Background: About 80% of children treated for ALL will be long term survivors. The estimated cumulative risk of a SMN is 2% to 3.3% 15 yrs after diagnosis. METHODS A review of the literature of 25,907 children treated for ALL revealed 274 SMN (1.07%). RESULTS The most frequently observed SMN are shown below: [Figure: see text] Others included CML(3), breast cancer (4), malignant histiocytosis (2), ovarian cancer (2), one case each of nephroblastoma, mucoepidermoid CA, bladder CA, malignant teratoma, leimyosarcoma of lung, and 22 unknown cases. In the lymphoma group there was an equal number of NHL and Hodgkins (10). In the AML/MDS group most were AML(26). Of all cases of SMN 62% recieved RT and the risk of a SMN appears to be dose related. Of significance is the fact that the overall survival rate for those patients with reported long term follow is 57.3% (101/176). The Ewings Family tumors and in particular PNET of bone are rare SMN. Of these 25,901 children treated for ALL there is only one case report of a PNET of bone. Our case of a chest wall PNET developing in an 8-yr-old boy one yr after completing therapy for standard risk ALL is the second case reported and the first one associated with germline and tumor cell p53 mutation. . Our patient did not receive RT and therefore can be excluded as a contributing factor. Exposure to anthracyclines and alkylating agents was minimal (75mg/m2 and 1gm/m2 of adriamycin and cytoxan respectively). CONCLUSIONS We conclude that germline p53 mutation played a major role in the development of this rarely observed SMN and that cases of SMN in pediatric patients should be evaluated for p53 mutation. Overall long term survival for patients with SMN after treatment for ALL is encouraging at 57% and determination of p53 may influence therapeutic and prognostic considerations. One percent of children treated for ALL will develop SMN, the decrease use of RT in children with ALL should result in even a lower number of SMN. No significant financial relationships to disclose.

Diagnosis of intrapericardial tumor in an infant by two-dimensional echocardiography

SummaryTwo-dimensional echocardiography is a useful noninvasive tool for diagnosing intrapericardial tumors as a cause of respiratory distress or abnormal cardiomediastinal shadow on chest x-ray. Early recognition of these tumors within the pericardium is important since surgical removal is often curative. Cardiac cineangiography is unnecessary to delineate further the tumor and should be reserved for those in which associated intracardiac defects are suspected.