G. Bennett Humphrey

Comparison of maintenance treatment regimens for first central nervous system relapse in children with acute lymphocytic leukemia. A pediatric oncology group study

Eighty‐seven children with central nervous system (CNS) leukemia were randomized to receive either induction intrathecal chemotherapy (ITC) and cranial irradiation (CRT) plus maintenance ITC, or induction ITC and craniospinal irradiation (CSpRT) with no maintenance ITC. Induction ITC consisted of six weekly injections of methotrexate, hydrocortisone, and arabinosylcytosine. Also, intensification of systemic induction and maintenance chemotherapy was given. CRT + ITC was given as CRT, 2400 rad in 12 fractions followed by ITC maintenance bimonthly for 2 years. Craniospinal irradiation consisted of CRT + 1400 rad in ten fractions to the spine. Randomization was stratified according to whether CNS leukemia occurred at initial diagnosis of acute lymphocytic leukemia (ALL) (Stratum I, 15 patients), during first bone marrow (BM) remission (Stratum II, 49 patients), simultaneous with first BM relapse (Stratum III, 12 patients), or during second BM remission (Stratum IV, 11 patients). The median follow‐up for patients who remain at risk is 15 + months. Eight children (seven on CRT + ITC, one on CSpRT) developed presumed therapy related encephalopathy. In Stratum II, 16 of 29 (55%) patients receiving CRT + ITC experienced adverse events: 3 deaths during continuous complete remission (CCR) and 13 relapses (2 CNS, 1 CNS + BM, 7 BM, 1 BM + testes, and 2 testes) as compared with only 5 relapses in 20 (25%) patients on CSpRT (1 CNS, 1 CNS + BM, 1 BM, and 2 testes). The children on both regimens were comparable for sex, race, age at initial ALL diagnosis, time from ALL diagnosis to first episode of CNS leukemia, systemic therapy both before and after CNS relapse, and number of blasts in the spinal fluid at diagnosis of CNS leukemia. The conclusion is that children with isolated CNS leukemia can achieve prolonged survival with aggressive therapy, and that CSpRT is possibly less toxic and more likely than is CRT + ITC to prevent subsequent BM and testicular relapse (P < 0.02), but not subsequent CNS relapse (P = 0.7). A possible systemic therapy effect of spinal irradiation is postulated to explain the superiority of CSpRT.

CNS prophylaxis in acute lymphoblastic leukemia: comparison of two methods a Southwest Oncology Group study.

Children with acute lymphoblastic leukemia were randomized to one of two treatment options for CNS prophylaxis. All patients received intrathecal therapy over a one‐year period with methotrexate, hydrocortisone and cytosine arabinoside. One‐half of the patients also received 2400 rad cranial radiation over 2 1/2 weeks. There was no significant difference in CNS relapse rate, length of hematologic remission or survival between the two groups. No further CNS relapses have been observed for the last four years. CNS relapse was associated with subsequent disease recurrence in the 67% of patients.

The French—American—British (FAB) classification of leukemia. The pediatric oncology group experience with lymphocytic leukemia

The Pediatric Oncology Group institutions initiated extensive subclassification of cases of acute lymphocytic leukemia (ALL) at diagnosis into laboratory‐designated categories. Included was a French‐American‐British (FAB) classification of all new patients, which was reviewed by a central six‐member committee. In addition, on the basis of immunologic criteria, patients were defined as having T‐, B‐, pre‐B‐, or “null” cell leukemia. Slides from 617 patients were reviewed. Five hundred forty‐six (88.5%) were classified as L1, 51 (8.3%) were classified as L2, 9 (1.5%) were classified as L3, and the remainder could not be assigned. Concordance within the committee was good: in 71% of the cases the committee was unanimous, and in an additional 17% only one member disagreed. In only 11 cases (1.8%) was diagreement such that a majority classification could not be assigned. Institutions assigned L2 more frequently. There was a strong correlation with L3 for B‐cell disease only. However, four patients had unequivocal B‐cell disease and unmistakable L1 morphologic type, whereas one and had L3 morphologic features and had non‐B‐cell disease. There was no correlation between the other immunologic markers or periodic acid‐Schiff stain and FAB classification, nor between L1 or L2 and risk factors. However, for the 248 null cell and pre‐B‐cell patients, L2 was more frequent among patients in the poor‐risk group (P = 0.008). The time to first failure was significantly shorter for patients with L3 morphologic type. The induction failure rate of L2 patients was significantly greater than that of L1 patients (P = 0.016). With analysis of the duration of remission and adjustment for risk factors, the impact of L2 morphologic characteristics on outcome was not significant (P = 0.18) in null cell patients. Even unadjusted for risk factors, there was no impact of L2 morphologic type on outcome in the pre‐B‐cell phenotype. It can be concluded that other risk factors overshadow the impact of L1 and L2 morphologic features in predicting duration of remission.

Cyclophosphamide-asparaginase-vincristine-prednisone induction therapy in childhood acute lymphocytic and nonlymphocytic leukemia

A remission‐induction regimen for childhood leukemia using cyclophosphamide, asparaginase, vincristine, and prednisone (CAVP) was compared to standard vincristine‐prednisone (VP) induction. The more intensive regimen was associated with a lower complete remission rate (81% vs 93%) and a higher early death rate from infection (15% vs 5%) for acute lymphocytic leukemia. In contrast, complete remission was achieved in 58% of children with acute nonlymphocytic leukemia treated with CAVP compared to 18% for VP. Early death rates were similar (27% vs 25%). These observations corroborate previous studies in childhood nonlymphocytic leukemia showing activity for asparaginase. Preliminary analysis of remission duration and survival for responders shows no advantage for those who survived the more intensive induction.

Overview on the Management of Adrenocortical Carcinoma (ACC)

The case material included in this volume includes 72 carcinomas, 30 adenomas and 12 cases diagnosed as ‘tumor’; this includes 22 cases analyzed in depth by Weatherby and Carney in their review of pathology [1]. The largest collection of cases and the most detailed clinical analysis is from France. LeFevre and co-workers were able to review 42 children treated between 1958 and 1980 [2].

Analysis of histiocytosis X infiltrates with monoclonal antibodies directed against cells of histiocytic, lymphoid, and myeloid lineage

Surface markers expressed on histiocytosis X (HX) cells were studied using 18 monoclonal antibodies (McAbs) and an in situ indirect immunoperoxidase technique. Specimens of skin (five biopsies from three cases) and lymph node (one case) were studied. Our study confirmed previous findings of an OKT6+ HLA DR+ Leu 3a+ phenotype of HX cells in skin and indicated that lymph node HX cells can also have this phenotype. A mixture of cells expressing T markers/T subset, monocyte/macrophage, and killer/natural killer (K/NK) markers was also present in two cases. However, one case with an aggressive course showed no detectable HNK 1+ (K/NK) or Leu 2A (suppressor) cells in the cutaneous infiltrates and no detectable HNK 1+ lymphocytes in an affected lymph node. The significance of these findings in relation to prognosis and therapy is discussed.

Pancreatic tumors in children

I. Selected Topics.- 1. Role of natural killer (NK) cells in resistance to tumors.- 2. Clonal evolution and childhood tumors.- 3. Cancer cell differentiation.- 4. Clinical significance of chromosome abnormalities in childhood and adult leukemia.- II. Pancreatic Malignancies.- 5. Genetic aspects of endocrine neoplasia.- 6. Tumors of the exocrine pancreas in childhood.- 7. Pre-operative evaluation of pancreatic tumors.- 8. Surgical therapy in pancreatic malignancies in children.- 9. Pancreatic carcinoma in children in Japan-Review of the Japanese literature.- 10. Pancreatoblastoma. Histopathologic criteria based upon a review of six cases.- 11. Solid and papillary epithelial neoplasms of the pancreas.- 12. Ectopic Cushings syndrome in an adolescent.- 13. Low grade papillary pancreatic neoplasm in an adolescent female.- 14. Cancer of the pancreas in children: Experience at the M.D Anderson Hospital and Tumor Institute.- 15. A case of metastatic insulinoma in an adolescent girl.- 16. Experience with endocrine and exocrine neoplasias in children.- 17. Childhood rare endocrine tumors.- 18. Overview of childhood pancreatic tumors.

Bleeding Disorder in an Infant Associated with Anicteric Hepatitis Acquired Prothrombin Deficiency

An 11-week-old infant had an acquired hemo static defect caused by malabsorption of vitamin K. Apparently the steatorrhea caused by anic teric hepatitis precipitated overt clinical man ifestations of vitamin K deficiency in this infant, whose dietary intake of vitamin K had been low.

Properdin factor B and acute lymphocytic leukemia (ALL).

One hundred‐sixty‐four ALL patients were compared to 545 controls for differences in phenotype and gene frequencies at the Properdin factor B locus. In addition, 90 of the ALL patients were immune phenotyped. A significant association with the Bf F allele and ALL was found, resulting in an estimated relative risk of 3.62. There was no difference in the Bf S phenotype between ALL patients and controls. However, those homozygous for the Bf S allele are at a significantly low risk of 0.30 for developing ALL. ALL patients with a non‐B/T cell type were 2.5 times more likely to be Bf SS homozygotes; in contrast, those patients with the pre‐B cell type were 2.5 more likely to be Bf FF homozygotes. These data suggest association of the Bf locus with an ALL protection and/or susceptibility gene(s).

960 THE ACCURACY OF IDENTIFYING T CELL LEUKEMIA USING E ROSETTING OF BONE MARROW LYMPHOBLASTS

The identification of sheep erythrocyte rosettes (ER) formed by acute lymphocytic leukemia (ALL) cells (blasts), at 4· C has permitted investigators to distinguish patients with presumed T cell ALL from those with non-T ALL (less than 10-20% ER(+) blasts). The identification of T antigen (T-ag) on the blasts, detected by monoclonal or carefully absorbed xenoantisera, now permits an analysis of how accurately ER positivity distinguishes T from non T ALL. Bone marrow blasts from 354 pediatric patients with untreated ALL were examined for ER and T-ag. The following chart summarizes the results:Using the reference point of ≥ 10% (20%) ER (+) blasts to define T cell disease would have led to the incorrect judgement that 37(10) T-ag (-) patients had T cell ALL, a 60%(16%) excess, while 19 (26) T-ag (+) patients would have been excluded, a 31%(42%) deficit. This degree of error in subclassification could substantially affect the results of descriptive studies on therapeutic trials in T cell leukemia, indicating the need for careful T-ag detection in classifying ALL.