N. B. McWilliams

864 CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA WITH B-CELL PHENOTYPE (B-ALL)

B-ALL is uncommon in children and is associated with a poor prognosis. No distinctive clinical features have been identified. At present B-ALL is defined immunologically by the presence of surface immunoglobulins (slg+) on leukemic lymphoblasts. Since 1976 6/56 (11%) of our newly diagnosed ALL patients have been sIg+ and their data are presented below.Blasts from all six patients expressed Ia-like antigens, a normal B cell alloantigen; 2/6 reacted with rabbit antiserum specific for human thymic lymphocytes; and 1/6 had a common ALL antigen characteristic of null cell ALL. Receptors for the lectin peanut agglutinin (PNA) were present on 3/5 tested and these 3 patients have died. 2/5 did not express PNA receptors and remain in remission at 36+ and 29+ months.We conclude that: (1) B-ALL is immunologically heterogenous with some patients simultaneously expressing a common ALL antigen or certain T cell characteristics and (2) the presence of receptors for PNA appears to have prognostic significance in B-ALL.

CONTROLLED CLINICAL TRIAL OF PREDNISONE IN CHILDHOOD IDIOPATHIC THROMBOCYTOPENIA PURPURA (I.T.P.)

Twenty-seven children, 13 girls and 14 boys, from 1-17 years of age (mean 6,0 years) with acute I.T.P. were randomized to receive prednisone 2 mg/Kg/day for 3 weeks or no therapy. A history of preceding infection was obtained in 84.6% of the treated group and 92.8% of the controls.. Initial mean platelet count for all patients (± SEM) was 21,000/cu mm ± 4,000 and did not differ significantly in the 2 groups (p>.05). Median follow-up time for the entire group was 17 months.The median time to attain a platelet count of ≧150,000 was 21 days in the treated group vs. 60 days in the controls (p = .03) There was no relationship between initial platelet count, age and time to response. Of the 24 patients evaluable for long term outcome 5/11 (45.4%) of controls failed to achieve a normal platelet count and required treatment, including splenectomy in 1. In the treated group 2/13 (15.4%) relapsed and 1 required splenectomy.We conclude that early steroid treatment in acute I.T.P in children restores normal platelet counts significantly sooner than in those not treated and should be instituted at the time of diagnosis to prevent early complications.

805A PROGNOSIS AFTER 3-YEAR SURVIVAL IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

The appropriate duration of therapy for childhood ALL remains controversial.82 children(M:F, 47:35) with ALL were diagnosed between 1965-1975. Forty (49%)children, including 18 males,remained in complete continuous remission (CCR) at 3 years. Between the third and fifth years of therapy, 3 males and 3 females relapsed. The sites of initial relapse were the CNS in 5(4 had received CNS prophylaxis) and a simultaneous marrow and testicular relapse in the sixth. Five were initially high risk patients by age(<2 or >8 years)or white count(≥30,000/mm3) criterian. One additional child died, in remission, of varicella complications.33 patients (40%) remained in CCR at least 5 years. They had received chemotherapy for a median of 61 mos. Followup times off therapy ranged from 6-178 mos (median 36+ mos). One boy in this group subsequently relapsed in the marrow 16 months after therapy ended.We conclude that the relapse rate of 17.5% (7/40) after 3 years of CCR is comparable to the 20% relapse rate reported by St. Jude Childrens Research Hospital (NEJM 300:269, 1979), although our patients received therapy for an additional 2+ years. Continuing therapy beyond 3 years would therefore seem to subject patients to continued potential morbidity without improving ultimate prognosis.

601 IMMUNE STATUS OF CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) IN PROLONGED REMISSION (CR)

With the marked improvement in survival in childhood ALL, it is increasingly important to correlate immune status with longterm disease control. 24 ALL patients, 7 in CR for 5-12 yrs. and off therapy for a x of 3.5 yrs., and 17 in CR on therapy for a x of 2.8 yrs. (.3-5 yrs.) were studied.The mean % of sheep RBC rosettes (T-cell) on therapy (53%) and off therapy (50%) was similar to controls (60%). Complement receptor lymphocytes (B-cell) averaged 25.6 and 15.6% in patients off and on therapy, respectively, a significant difference (p< .05), but still WNL. Mouse RBC receptors, detecting a B-cell subgroup, were deficient in 93% of patients on and 40% of patients off therapy (p<.01). Stimulation by T (PHA, CON-A) and B (Saureus) cell mitogens was comparable (all p>.05) in the 3 groups of children after 3 or 6 days of culture. In 2 patients who relapsed, a marked reduction in all mitogen stimulation was noted at a time when there was no clinical evidence of relapse. None of the patients had cells reactive with either the antisera detecting la like or leukemia associated antigens (LAA), including the 2 in the pre-relapse state.We conclude that these patients in prolonged CR have normal T-cell % and function. Maintenance therapy, however, does reduce a B-cell marker while mitogen response remains intact. Preliminary data suggest that mitogen response may be more sensitive than the reappearance of LAA in detecting impending relapse.

Granulocyte yields in leukaphereses without steroids and hydroxyethyl starch (HES)

16 febrile, neutropenic patients, 3–77 years of aqe, received a total of 49 granulocyte transfusions (mean = 3,.06/pt) between May and December 1976. Granulocytes were used in addition to antibiotics for treatment of sepsis, either suspected or proved. Granulocytes were collected by semi-continuous centrifugation utilizing the Haemonetics Model 30 Blood Processor with ACD as the anticoagulant. Corticosteroids and HES, a rouleausproducing agent reported to improve the separation and collection of granulocytes, were not used in the leukaphereses. The mean volume of blood processed/transfusion was 2.92 liters (± 0.50) with a mean total WBC yield of 2.13 × 109/liter blood processed (LBP), (± 0.58 × 109). The mean yield of granulocytes/LBP was 0.63 × 109 (± 0.36 × 109). This granulocyte yield was markedly below values reported using HES and steroids in this system (3.5 × 109/LBP). The granulocyte yield we obtained was actually less than that obtained from simple phlebotomy of 500 ml of fresh whole blood (mean 1.67 × 109/500 ml ± 0.38 × 109). A good clinical response was achieved in only 5/16 patients (31%), and this was below the expected rate of response of at least 60%.We conclude that the yield of granulocytes collected without steroids and HES is inadequate and emphasize the necessity for continually monitoring granulocyte yields in leukaphereses.

COMPLETE RESPONSE OF INOPERABLE HEPATOBLASTOMA TO ADRIAMYCIN

Total surgical excision of hepatoblastoma, an uncommon malignancy of early childhood has been the only favorable therapy for this disease. The tumor is poorly responsive to both radiation and standard chemotherapy.The case described is that of an 8 month old white male who presented with a huge abdominal mass. Laparotomy disclosed replacement of the entire liver with nodular tumor masses. Biopsy revealed mixed hepatoblastoma consisting of embryonal malignant epithelial cells and osteoid formation. No distant metastases were evident. Alpha-fetoprotein was negative.1500 r Co60 was delivered to the liver over 25 days without change in tumor size. This was followed after 2 weeks rest by 5 courses of Adriamycin 30 mg/m2 in 3 daily doses at 3 week intervals or at marrow recovery. Serial physical examinations showed marked reduction in tumor size following chemotherapy. Radiologically, surgical clips migrated laterally and right upper guadrant calcification appeared. Five months after chemotherapy a second laparotomy was performed. The liver appeared normal and biopsies revealed no tumor. Adriamycin has been shown to have significant activity against a variety of tumors including osteogenic sarcoma. It is possible that the osteoid elements in this tumor were also sensitive as demonstrated by the calcifications seen radiographically. Further Adriamycin trials are warranted in this tumor.