James T. Lowman

A reliable method for evaluating drug compliance in children with cancer

Poor drug compliance may cause a decreased survival of children with malignancies. Children who fail to take their medications are not receiving optimum amounts of chemotherapy and suboptimal therapy causes a shortened survival in children with cancer. This is a study of prednisone compliance in 52 children with cancer during three distinct phases of therapy. The patients were either known to be taking prednisone (on‐therapy group), off prednisone (off‐therapy group), or their compliance was unknown (unknown group). Evaluation of prednisone compliance was attempted by measuring hemoglobin level changes, weight changes, and random urinary 17‐ketogenic steroids. The results obtained show that while hemoglobin and weight changes are not helpful, a random urine 17‐ketogenic steroid assay is able to differentiate clearly those patients who are taking their prednisone. By the use of this assay it was found that 33% of patients who by protocol and instruction were supposed to be receiving prednisone were not complying. Separate analysis of adolescents revealed an even more alarming 59% noncompliance rate. This striking level of noncompliance strongly suggests that the survival of patients may be threatened by noncompliance.

Fusarium solani infection during treatment for acute leukemia.

Blunt abdomina l t r a u m a accounts for at least half the repor ted cases of pseudocyst of the pancreas in ch i ld ren? In some of the 30 per cent of repor ted cases in which the cause is not identified 4 unsuspected t r auma may actual ly be the cause. Abdomina l t r a u m a in school age chi ldren is usually the result of accidenta l i n ju ry -b i cyc l e handlebars, contact sports, or traffic accidents. The si tuation is somewhat different in the case of chi ldren under 3 years of age. I n this age group our experience leads us to believe that when a pseudocyst of the pancreas is found, and no acceptable explana t ion for its occurrence is for thcoming, the possibility of child abuse should be considered. We believe that t r auma t i c pseudocyst of the pancreas due to child abuse is more common than the l i te ra ture current ly indicates, and tha t some of the repor ted cases of pseudocyst of the pancreas in children, especially those repor ted in infants and toddlers, may in fact be the result of child abuse.

School Phobia in Children With Malignant Neoplasms

With the advent of improved therapy, many of the childhood malignant diseases have become chronic. This group of patients and their families demonstrate many problems usually not associated with the primary disease, but which can become incapacitating. School phobia was selected as one such problem for this study. The 11 cases reported here demonstrate the insidious and subtle nature of the onset of the disease. With aggressive management, some long-standing cases of school phobia could be reversed, but not all. In a group subjected to a prophylactic regime at the onset of their malignant neoplasm, there have been no new cases of school phobia. It is important for pediatricians caring for these children to search actively for the signs of school phobia and intervene as soon as possible.

Nonspherocytic Haemolytic Anaemia with Increased Red Cell Adenine Nucleotides, Glutathione and Basophilic Stippling and Ribosephosphate Pyrophosphokinase (RPK) Deficiency: Studies on Two New Kindreds

The second and third kindreds with hereditary haemolytic anaemia characterized by marked basophilic stippling of the erythrocytes, increased red‐cell GSH and adenine nucleotides, and ribosephosphate pyrophosphokinase (RPK, PRPP synthetase) deficiency are reported. In each affected subject increased auto‐haemolysis was not corrected by glucose additives in the autohaemolysis test. Despite the clearly hereditary nature of the syndrome, a heterozygous ‘carrier’ state could not be demonstrated in any family members. While autosomal recessive transmission is likely, the genetics remain obscure. The roles of substantial RPK deficiency as either a causative factor or an epiphenomenon is likewise not firmly established.

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.

In vitro sensitivity of normal granulocytic and lymphoma colonies to vinca alkaloids

Recently, a colony‐forming assay was developed in our laboratory for pediatric malignant lymphoid diseases. This assay supports the growth of lymphoma colonies (ML‐CFC) as well as normal granulocytic colonies (CFU‐C) and thus a direct comparison between the antineoplastic and myelosuppressive effects of a drug can be determined. To test specificity of this in vitro assay to structurally similar drugs, the inhibitory effects of three vinca alkaloids (vincristine, vindesine, vinblastine) on ML‐CFC (B‐, T‐, pre‐T‐cell types) and CFU‐C was determined. Our results demonstrate that all three vinca alkaloids were active agents in vitro and that a direct dose response effect occurred once a threshold dose was reached. Each vinca alkaloid had a different pattern of inhibitory effect on ML‐CFC and CFU‐C suggesting an inherent difference in drug metabolism by these cells. Also, based on the dose inhibiting 50% of colony formation, vinblastine was 94 times more inhibitory against malignant B‐cell ML‐CFCs than against granulocytic CFU‐C.