Transverse leukonychia (Mees' lines) due to daunorubicin chemotherapy.

Transverse bands of leukonychia are reported in a 7-year-old boy following a 10-day course of daunorubicin given for the treatment of lymphoblastic leukemia. A variety of other chemotherapies did not induce any nail changes in this patient.

Sensitizing for cis-diamminedichloroplatinum(II) action by hyperthermia in resistant cells.

cDDP-resistant Ehrlich ascites tumour (EAT) cells (ER cells) were tested for cellular content of total glutathione, heat sensitivity, cDDP sensitivity and synergistic effects of a combined treatment of heat and chemotherapy. In comparison with the non-resistant EAT cells (EN) the ER cells had an elevated level of glutathione. Treatment with D,L-buthionine-(S,R)-sulphoximine (BSO), resulting in almost complete depletion of cellular glutathione, did not cause drug sensitization. The ER cells were somewhat less heat sensitive compared with the EN cells. Heat chemosensitization was observed for the EN cells as well as for the ER cells. At 43 degrees C (but not at 42 degrees C) the thermal enhancement ratio (TER) for cDDP toxicity was significantly higher in the ER cells. The total number of cells killed by the combined treatment was less in the ER cells than in the EN cells. After analysing existing literature, combined with the current results, it is concluded that although cDDP-resistant cells can often considerably be chemosensitized by hyperthermia, in most cases the difference in cDDP sensitivity cannot be overcome totally. In those situations where cDDP-resistant cells are more sensitive to heat and also show a high TER, especially at clinically relevant temperatures, hyperthermia as added modality is indicated for clinical treatment.

The occurrence of high levels of acute behavioral distress in children and adolescents undergoing routine venipunctures.

While there is no question that children dislike needles, there are very little data available on the occurrence of high levels of distress experienced by children undergoing routine venipunctures. To provide some insight into this problem, trained observers evaluated distress in 223 different children and adolescents undergoing this procedure. An observational distress scale of 1 to 5 was developed; 1 = calm, 2 = timid/nervous, 3 = serious distress, but still under control, 4 = serious distress with loss of control, and 5 = panic. We observed a strong relation between distress and age but not between distress and gender. During the actual venipuncture, half the subjects (113/223) were scored as having high levels of distress (3 or more). Our subjects were also grouped into three age ranges: toddlers; 2 1/2 to 6 years, N = 70; preadolescents; 7 to 12 years, N = 55; and adolescents; 12 years and older, N = 98. The percent of subjects experiencing high levels of distress for each age group were: 83%, 51%, and 28%, respectively. We conclude that for venipunctures: 1) high levels of distress are common, and 2) age and not gender correlates with distress. Other correlations are discussed. Toddlers and pre-adolescents should be the targets for new interventions to reduce distress.

Physician/patient communication: a model considering the interaction of physicians' therapeutic strategy and patients' coping style.

During the last decade, several studies have demonstrated the importance of information-seeking versus information-avoiding coping styles of cancer patients receiving educational information from their physician. During the same period of time other studies have demonstrated important differences in the communicative style of oncologists providing educational information to their patients. However, the implications of the interaction of these two areas of research have not been systematically considered. We present here a hypothetical model concerning the implications of physicians with different communicative styles interacting with patients with different coping styles.

Longitudinal anthropometric study in children with acute lymphoblastic leukaemia.

In four groups of patients with acute lymphoblastic leukaemia, anthropometric variables were investigated every 3 months for 2 years. Group 1 (n = 7) was treated with a high-risk protocol, group 2 (n = 13) with a standard-risk protocol including cranial irradiation, group 3 (n = 13) with a standard-risk protocol without cranial irradiation and group 4 (n = 8) was followed after completion of treatment. A height retardation of 0.4-0.6 SD was observed during therapy in groups 1-3. A catch-up of 0.5 SD was found in group 4. The retardation of armspan was significantly larger than the retardation of sitting height when groups 1-3 were taken together. Head circumference was not affected. The anthropometric variables reflecting nutritional status showed a growth above normal during and after treatment. Corticosteroid medication and not cranial irradiation is the most likely explanation for our findings.

Anthropometric measurements at diagnosis of childhood cancer.

Height, weight, upper-arm circumference, sitting height, armspan, and head circumference were measured in 96 patients at diagnosis of a childhood malignancy. Height of both parents could be measured in 60 cases. Some individuals with acute lymphoblastic leukemia were very tall and some patients with a brain tumor were very small. In contrast, the mean values for height, sitting height, and midparent height were normal in all four groups of patients (with leukemia, solid tumor, brain tumors, and remaining malignancies). Armspan, however, was significantly longer in leukemia and solid tumor patients in comparison with healthy peers. These finding are not considered enough evidence for the existence of an association between tallness and childhood malignancy. Weight (for height) was significantly lower in solid tumor patients than in leukemia patients.

Prognostic factors in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.

Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43% (SE = 4%). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell-associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age less than or equal to 5 or less than or equal to 7 years, WBC level less than 10, less than 25, less than 50 or less than 100 x 10(3)/microL, and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level less than 50 x 10(3)/microL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows: (1) those with a WBC count less than 50 x 10(3)/microL who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66%, SE = 7%, EFS 4 years, n = 84); (2) those with (b1) WBC counts less than 50 x 10(3)/microL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts greater than 50 x 10(3)/microL with expression of the THY antigen had an intermediate prognosis (39%, SE = 7% EFS at 4 years, n = 94); (3) those with WBC counts greater than 50 x 10(3)/microL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19% at 4 years, SE = 8%, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P less than .001). The recursive partitioning was able to classify 241 (95%) of the patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Long term results of chemotherapy on the developing dentition: caries risk and developmental aspects.

The dental health of 45 children who had been placed on long term evaluation after chemotherapy treatment for malignancies was examined in this study. All children had received cytotoxic drugs during the period of tooth formation. It was found that they had more filled or diseased permanent teeth than control children. Their current caries activity as indicated by initial white spot lesions was also higher. Forty-three of the children showed evidence of disturbed amelogenesis. This had resulted in aesthetically displeasing grooves, pits and discoloration. Twenty-three of the children were counseled on the possibility of cosmetic dentistry. Delayed eruption and shortened, malformed roots were also found on several patients. It was concluded that these patients constitute a high risk dental care group.

Heterogeneity among the acute nonlymphocytic leukemias: value of immunophenotype for diagnosis, prognosis, and therapy.

Immunophenotyping of acute nonlymphocytic leukemia has confirmed previous observations on the heterogeneity of this disease. The lack of leukemia-specific monoclonal antibodies as well as antibodies reactive with early myeloid cells is reflected in poor correlation of morphologically and cytochemically defined FAB classes with the immunophenotype of the leukemic cells. Possible exceptions are the microgranular variant of FAB-M3, megakaryocytic leukemia (FAB-M7), and early erythroid leukemias (FAB-M6). The use of antibody panels can alleviate the differential diagnosis of acute lymphoid and myeloid leukemias, especially those occurring in infants, and the discrimination of FAB-L2 and FAB-M1. Also, the immunophenotyping of presumptive hybrid leukemias can help to resolve the many questions about these leukemias with a particularly poor prognosis. The challenge for multiinstitutional groups is to define those clinically relevant subgroups of acute nonlymphocytic leukemia in children that have general acceptance and could provide the basis for new treatment strategies.

[Regional isolation perfusion with cisplatinum in dogs with osteosarcoma of an extremity]. / Regionale geïsoleerde perfusie met cisplatinum bij honden met osteosarcoom van een extremiteit.

In the treatment of osteosarcoma, it is possible to differentiate between systemic therapy and local regional treatment. Systemic treatment of human patients with osteosarcomas consists in adjuvant chemotherapy. This has considerably improved the prognosis in these cases. The primary object in local regional treatment is to prevent local recurrences and to preserve function. As regards extremities, the aim is to preserve the limbs. In the present investigations, the value of regional chemotherapy by isolated regional perfusion with cis-platinum to dogs is studied. This approach was based on the hypothesis that considerable necrosis of tumours may be produced after perfusion with cis-platinum, thus making extremity-saving surgery possible. Isolated regional perfusion with cis-platinum (30 mg/litre of extremity volume) was performed in nine dogs with osteosarcomas of an extremity. A marked effect on the tumour was detectable on the basis of clinical, radiological and histological parameters. In the opinion of the present authors, regional perfusion with cis-platinum may contribute to extremity-saving treatment of osteosarcomas in dogs and human subjects. However, further studies will be required in order to achieve more adequate quantitation an improvement of local effects. In view of the synergy with cis-platinum, the latter may possibly be attained by the addition of hyperthermia (temperatures above 41.5 degrees C).

Tonsillar mapping of determinants found on normal lymphoreticular (T,B,K, immature and macrophage) and myeloblastic leukemia cells.

A monoclonal immunocytochemical method with 25 monoclonal antibodies was used to study the distribution in human tonsil of determinants expressed on T cells (mature and immature), Langerhans cells, B cells, killer/natural killer cells, macrophages, immature myeloid and lymphoblastic leukemia cells. Many of the respective determinants were found to have a discrete topographic distribution in normal reactive tonsil. The common acute lymphoblastic leukemia antigen and a determinant found on myeloblastic leukemia cells (My10) were not found in the specimens of the tonsil examined.

Experimental chemotherapy in children with cancer--a parent's view.

Parental attitude and the parents' perceptions of a child's responsibilities were measured by mailing a questionnaire to 156 parents of cured children of the Pediatric Oncology Center, University of Groningen. Simplistically, the questionnaire concerned parental judgment on (1) the role of the child in decisions about experimental therapy, (2) what information should be related to the child and by whom, (3) parental attitudes toward experimental therapy, and (4) the parents' opinions about ethical aspects of proposing experimental therapy. A high response rate (87.8%) was achieved. A majority of the respondents would allow a child take responsibility in deciding about experimental therapy. In their opinion the median age (16 years) at which a child should be allowed to give consent was higher than the median age (12 years) at which a child should merely be involved in the decision. Parents were more likely to overrule the child's decision if the child decided against experimental therapy than if the child chose the therapy (p less than 0.001). Parents found it more difficult to talk about death than about experimental therapy, and parents would be more willing to involve the physician in discussing experimental therapy than in discussing imminent death with a child (p less than 0.001). Many respondents (68%) felt that the child should be given both altruistic reasons and reasons of self-interest for participating in experimental therapy. About half of all of the respondents believed that a pediatric oncologist should always advise experimental therapy for the benefit of similarly afflicted patients.

Acid phosphatase positivity in childhood acute lymphocytic leukemia.

The Pediatric Oncology Group analyzed 103 cases of childhood acute lymphocytic leukemia (ALL) with an acid phosphatase stain and with a series of immunologic markers. As reported by others, the authors demonstrated a high correlation of acid phosphatase (AP) positivity and T-ALL. However, a subset of T-ALL was acid phosphatase negative, and some non-T, non-B, non-pre-B-ALL cases were AP positive. The predictive value of the AP test was, therefore, poor as a marker of T-ALL. AP-negative T-ALL cases appeared to be a distinctive subset of T-ALL, and AP negativity an intrinsic characteristic of this subset, rather than a failure of the test system. AP-positive n-ALL cases demonstrated no difference from AP-negative cases and, in particular, no evidence of early T-ALL differentiation.

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.

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.

Natural history of histiocytosis X: a Pediatric Oncology Group Study.

The best therapy for patients with histiocytosis X with disease involvement other than isolated bone lesions but without organ dysfunction is unclear. This retrospective study was undertaken to define the natural history of this group of patients. In 25 of the 92 studied patients, there was no progression of the disease after diagnosis. In 53 surviving patients, the disease either continuously progressed (40) or recurred intermittently (13). The onset of last disease activity was 24 months or less for 55% of these children. A fatal outcome occurred in 14 children. All of these children developed organ dysfunction and 11/14 died during or before the second year of disease. These three different outcomes could not be predicted from the parameters evaluated; however, the disease that never abated but was continuously active was associated with a suboptimal outcome, and the development of organ dysfunction was a grave prognostic sign.