Robert Festa

Leukemia in a black child with Bloom's syndrome: somatic recombination as a possible mechanism for neoplasia.

A 5 1/2‐year‐old black child with Blooms syndrome developed acute lymphocytic leukemia (ALL). Blooms syndrome is associated with chromosomal aberrations, and affected individuals have an increased incidence of leukemia and solid tumors. The skin on our patient had adjacent areas of decreased and increased pigmentation similar to the “twin‐spots” seen in Drosophila. “Twin‐spots” are the manifestation of somatic cell DNA recombination and provide evidence that clones of cells in Blooms syndrome have become homozygous for a particular gene. Somatic cell recombination is proposed as a mechanism to explain the increased incidence of neoplasia in Blooms syndrome and supports the hypothesis that cancer may be a recessive disorder at the cellular level.

920 PLASMA PROTEIN C LEVELS IN PATIENTS WITH SICKLE CELL DISEASE (SCD)

Vitamin-K=dependent protein C (PC) functions as a potent anticoagulant. Thrombo-embolism has been reported in kindreds with congenitally low PC levels suggesting that PC has an important role in hemostasis and that even a moderate reduction in this plasma protein may be associated with increased risk of thrombosis. Since thrombotic phenomena have important robs in the vaso-occlusive manifestations in SCD, PC was determined in 32 SCD during steady state and in controls (C).The SCD had significantly lower PC levels as compared to controls. Six SCD were also studied during vaso-occlusive crisis (VOC). During VOC there was marked decrease in PC as compared to levels during steady state (49.5 ± 6.4 and 66.1 ± 10.0, respectively. P < 0.01). Decreased levels of PC during VOC increased to initial levels or higher with clinical improvement. It is postulated that the decreased levels of PC in SCD are probably secondary to increased consumption as well as decreased production because of altered liver functions. This data suggests that decreased levels of PC may increase the risk of thrombosis in these patients.

HEAD TRAUMA IN CHILDREN WITH HEMOPHILIA

Central nervous system bleeding is the main cause of death in hemophilia accounting for 34% of all deaths. Between January 1981 and December 1983, 26 children with hemophilia ranging in age from 1 to 17 years (mean of 7.5 ± 4.5) had 67 hospital admissions for head trauma. Eighteen had Factor VIII, seven Factor IX deficiency and one Von Willebrands Disease. Of the 26 children, 17 had severe hemophilia and 2 had Factor VIII inhibitors. All patients had scalp hematoma; 3 had lacerations at the site of the hematoma; 1 had severe cerebral concussion; 3 had a history of possible loss of consciousness; 12 had headache; 1 had vomiting and 4 had dizziness on admission. All patients received factor replacement therapy within 12 hours of trauma and factor levels were maintained over 50% for 2 to 9 days (mean 2.7 ± 1.1) and all recovered without sequelae. Eightteen patients had skull x-rays on 38 occasions, all of which were negative. Six patients had EEGs, all of which were normal. Of 20 patients who had CT scans on 25 occasions, all were negative. Hemophilia patients treated with adequate factor replacement following head trauma have an excellent prognosis and in the absence of persistent neurological signs or symptoms probably do not require CT examination.

ADEQUACY OF CHEMOPROPHYLAXIS ALONE IN PREVENTION OF CENTRAL NERVOUS SYSTEM (CNS) LEUKEMIA IN CHILDREN WITH STANDARD RISK ACUTE LYMPHOCYTIC LEUKEMIA (S-ALL)

The neurotoxicity resulting from the combination of cranial irradiation and intrathecal methotrexate (IT MTX) for prophylaxis of CNS leukemia led to the use of IT MTX alone in S-ALL (WBC<50,000/mm3). From July 1978 to February 1983 thirty-nine children with S-ALL (14 boys, 25 girls; ages 1-6/12 to 14-5/12 years; WBC 900-37,200/mm3) received IT MTX alone for CNS prophylaxis. All the patients received the same induction, consolidation and maintenance multi-drug systemic treatment and IT MTX alone for CNS prophylaxis. Therapy was discontinued at 3 years in those patients remaining in complete continuous remission. With a median observation period of 32+ months the following relapse rate was observed: a) isolated CNS: 3 patients (7.6%) at 11, 22, and 35 months; b) simultaneous CNS and bone marrow (BM): 1 patient (2.5%); c) BM alone: 13 patients (33%). The isolated CNS relapse rate of 7.6% utilizing IT MTX alone in S-ALL compares favorably with studies utilizing a combination of cranial irradiation and IT MTX. We conclude that the administration of IT MTX during induction and maintenance therapy provides adequate CNS prophylaxis for S-ALL and justifies the ommission of cranial irradiation in these children.

PARTIAL EXCHANGE TRANSFUSION (PET) FOR TREATMENT OF PRIAPISM IN CHILDREN WITH SICKLE CELL DISEASE (SCD)

Sixteen episodes of priapism in 6 children with SCD, aged from 9 to 15 years (mean 12.0 ± 2.5) were treated with 2 or 3 PET. In 14 episodes (4 patients) PET was started within 6 to 8 hours from the onset. Marked clinical improvement occurred within 1.3 ± 0.5 days and complete recovery followed each episode. In 2 episodes (2 patients) PET was started at 17 and 20 hours from the onset. In these 2 cases there was only partial response to PET and needle aspiration of corpora cavernosum and glandular A-V fistula were performed at the 3rd and 5th day of the onset, respectively.Priapism is a serious complication of SCD and may result in impotence. Conservative measures generally are not effective and impotence (partial or complete) is a frequent sequal to surgical procedures. Treatment with PET is successful alternative therapy at the early onset of priapism.

THE PERIODIC ACID-SCHIFF (PAS) REACTION AND PROGNOSIS IN CHILDHOOD ACUTE LYMPHOCYTIC LEUKEMIA (ALL)

The degree of PAS positivity was determined by counting 200 blast cells in the initial bone marrow specimen of 38 children with ALL. Each cell was scored on a 0 to 5 scale according to the number of PAS-positive granules per cell (0–4), or the presence of 1 or more large blocks per cell (5). The patients were stratified into 3 groups according to their mean PAS score. Fourteen children had a low score (mean 65, range 3–150), 12 were intermediate (mean 315, range 153–445), and 12 were high (mean 692, range 465–860). The mean white blood count (WBC) at diaanosis was higher in the low-score group compared to the high-score group, but the difference was not significant (p>0.05); 5/14 low-score patients had an initial WBC below 20,000/mm3, and 3/12 high-score patients were above 20,000/mm3. There were no significant differences among the groups with respect to age, hemoglobin and platelet levels at dignosis or presence of a mediastinal or abdominal mass. However, 13 of 14 low-score patients were male, compared to 4/12 and 6/12 in the intermediate and high groups (p<0.05). In addition, 7 of 13 low-score patients were in relapse by 6 months from diagnosis (3/7 had an initial WBC below 20,000/mm3), compared to none of the inermediate and only 1 of the high patients (p<0.05). These results suggest that a low PAS score is related to a poor prognosis in childhood ALL, regardless of the level of the initial WBC. Females tend to have higher PAS scores than males, and also seem to have a better prognosis.

ABNORMALLY LOW P50 IN PATIENTS WITH MALIGNANCIES

Oxygen equilibrium curves of red cell suspensions were measured on 34 anemic children with malignant disease and 10 non-anemic control subjects, and the results were compared to the levels of 2,3-diphosphoglycerate(DPG). The P50 and DPG levels for normal controls were in a narrow range (P50=29.1±0.7mm Hg, DPG=4.448±.329 umoles/ml RBC), while many of the children with cancer undergoing chemotherapy showed abnormally low P50 values in view of the anemia (Hct.=21 1±4.0%). One group which consisted primarily of patients with acute leukemia in relapse did not respond to the anemia with an increase in P50(28.8±1.8mm Hg) or in DPG levels (4.678±.449 umoles/ml RBC). Another group comprised primarily of patients with solid tumors with progressive disease and acute leukemia receiving intensive chemotherapy demonstrated no increase in P50(28.1±0.9mm Hg) in spite of elevated DPG levels(6.493±.868 umoles/ml RBC). Upon retrospective analysis, the low P50 values with or without elevated DPG levels were found to be related in part to the chemotherapy, frequency of prior transfusion, and bone marrow status of the child. Studies on 15 additional children requiring transfusion showed that patients with poor bone marrow function, due either to intensive chemotherapy or malignant cell infiltration, did not exhibit the rapid recovery in P50 to normal values following transfusions with old blood. These studies indicate that children with malignancies and poor bone marrow activity requiring repetitive transfusion should be given relatively fresh blood.