Michael K Palmer

Histologic patterns of neuroblastoma related to prognosis and clinical staging.

Eighty‐three tumors have been examined histologically. They have been graded according to evidence of maturation; the grades have been related to prognosis and clinical staging, and the results submitted to statistical analysis. Fourteen of these patients are still alive at least 3 years after diagnosis; their tumors show a high level of histologic differentiation. The histologic grades are also related to the age of the patient and the site of the tumor. We have also assessed the degree of lymphocytic infiltration within the tumors, but no significant relationship between this and prognosis could be established.

Malignant melanoma in children and adolescents

Thirty‐one children and adolescents with malignant melanoma were treated at the Christie Hospital and Holt Radium Institute between 1945 and 1977. Locations of primary lesions included head‐neck 14, trunk nine, and extremity eight. Twenty‐five patients had clinically localized tumor at diagnosis, four had regional disease, and two had generalized tumor. Surgery was the primary modality of therapy. Fifteen patients survive without active disease from two years to more than 18 years, and 16 patients died of disease.

The spatial organization of the hierarchical proliferative cells of the crypts of the small intestine into clusters of ‘synchronized’ cells

Abstract. A statistical analysis of the distribution of [3H]TdR‐labelled cells in longitudinal and transverse sections of crypts from the ileum of the mouse, indicated that there was a strong tendency for labelled or unlabelled cells to be associated in short vertical runs and lateral clumps, suggesting the presence of clusters of labelled cells on the sides of the crypts. A model is discussed for the cellular spatial organization of the crypt that proposes a vertical alignment of the cells within branches of the proliferative cell lineage. The model would predict vertical alignment of partially synchronized cells as well as some lateral clumping.

Relationship between the pretreatment proliferative activity of marrow blast cells and prognosis of acute lymphoblastic leukaemia of childhood.

Pretreatment marrow blast cells were studied in 38 boys and 27 girls (aged 1-14) with acute lymphoblastic leukaemia by flow cytometry after staining with propidium iodide.The percentage of blast cells in the S phase of the cell cycle ranged from 1% to 40% (median 6%). A correlation was found between the percentage of cells in S and the morphological classification of the French American British Cooperative Group (FAB), presence of T or B cell markers, haemoglobin concentration, blast size, bone pain, platelet count, and an inverse correlation with coarse granule and block staining with Periodic-acid-Schiff (PAS).63 of the 65 children attained complete remission. During the first 24 months of follow up there were fewer relapses (P = 0·054), and deaths (P = 0·004) in those children with 6% or fewer blasts in S phase. The difference was most marked in the first 12 months with 4 relapses out of 33 in the group with 6% or fewer cells in S compared with 13/30 in the group with > 6% cells in S.In order to investigate the prognostic significance of the pretreatment proliferative studies in greater detail, remission duration was correlated with 17 presenting features. Each feature was correlated individually and then the simultaneous effect of all the features was assessed by stepwise multiple regression.Only 3 features of the disease at diagnosis were individually correlated with duration of remission. These were% cells in S (P < 0·001), log white cell blood count (WBC) (P < 0·01) and the presence of T- or B-cell surface markers (P < 0·05). However, the multiple regression analysis showed that cell markers were not an independent prognostic feature, whereas the percentage cells in S and log WBC were independently and significantly correlated with duration of first remission (P < 0·001 in each case).

A score at diagnosis for predicting length of remission in childhood acute lymphoblastic leukaemia

Thirty-two variables at diagnosis of acute lymphoblastic leukaemia (ALL) were studied in an unselected population-bases series of 209 children. Twelve variables had individually a statistically significant effect on the duration of first remission. A multivariate analysis using data on the 199 children who went into complete remission showed that all significant variation in remission times could be explained by only 3 variables acting simultaneously. These were the total white blood count (WBC) at diagnosis, the Franco-American-British (FAB) classification of blast morphology and the percentage of lymphoblasts with PAS+ coarse granules or blocks. A simple scoring system (for WBC add 1 if less than 20 X 10(9)/1, add 2 if 20 - 50 X 10(9)/1, add 3 if greater than or equal to 50 X 10(9)/1; for L2 or L3 leukaemia add 1; for PAS+ less than 5% add 1) separated patients into risk groups with widely different median lengths of first remission. Application of the risk score improves the prediction of the outcome of treatment, and the clinical trials, allows more accurate stratification, less extensive data collection and simpler analysis.

Adjuvant low dose radiation in childhood T cell leukaemia/lymphoma (report from the United Kingdom Childrens' Cancer Study Group--UKCCSG).

From November 1977 to July 1983, 82 children with T leukaemia/lymphoma entered a randomised trial of combination chemotherapy and radiotherapy. Twenty-five were designated T lymphoma and 57 T leukaemia, 28 having greater than 100 x 10(9)1(-1) blasts in peripheral blood at diagnosis. Twenty-seven patients with mediastinal primaries who were treated on the companion non-Hodgkin lymphoma (NHL) trial were comparable in all respects to the T lymphoma patients and the results of treatment were therefore combined and analysed together. Overall 4-year survival (48-53%) and failure-free survival (FFS) (37-40%) were similar in all groups except the 28 with T leukaemia and WCC greater than 100 X 10(9)1(-1) (20% and 13%). There was a significant advantage in FFS for patients randomised to receive low dose mediastinal radiation, and this was most marked in patients with T lymphoma (66% vs 18%, P = 0.006).

Prognostic significance of pretreatment serum β2-microglobulin levels in multiple myeloma

Pretreatment serum beta 2m levels were estimated in 65 patients with multiple myeloma. After correction for changes in renal function, the level of beta 2m attributable to multiple myeloma (beta 2m-m) no longer correlated with the serum creatinine, but showed a strong correlation with the total body myeloma cell mass (P = 0.002). There was an inverse correlation between beta 2m-m and the Karnofsky performance status of patients at presentation (P = 0.001). Patients with a pretreatment beta 2m-m level of less than the median value of 2.94 mg/l survived significantly longer than those with a raised level (P = 0.0008).

Routine bone marrow examination in the management of acute lymphoblastic leukaemia of childhood.

Eighty-four children with acute lymphoblastic leukaemia (ALL) who had relapsed in bone marrow were studied to assess whether treatment would be more successful if relapse was detected before the disease became clinically evident. Patients whose relapse was detected by routine bone marrow examination before the disease became apparent were compared with those whose relapse was suspected from clinical examination or peripheral blood findings. In the former there was a lower percentage of blast cells in the marrow (p less than 0.02) and the patients suffered less from complications of the disease, but there was no difference in the incidence or duration of second remissions between the two groups.

The prognostic significance of mediastinal bulk in patients with stage IA-IVB Hodgkin's disease: A report from the Manchester Lymphoma Group

Three hundred and two previously untreated patients with Stage IA-IVB Hodgkins disease were reviewed to determine the prognostic significance of mediastinal involvement. Mediastinal bulk disease was defined as either a maximal mediastinal width of 7.5 cm or more, or a ratio of the maximum width of mediastinal disease to the maximum chest diameter of greater than or equal to 0.33, or a ratio of the maximum width of mediastinal disease to the chest diameter at T5-T6 greater than or equal to 0.33, or as an area of mediastinal disease greater than or equal to 100 cm2. Bulk disease outside the chest was defined as a mass of lymph nodes measuring 5 cm or more in any axis. The presence of mediastinal bulk disease was of adverse prognostic significance for remission duration and survival in patients with Stage IA-IIB Hodgkins disease, but for patients with more advanced disease the effect of mediastinal bulk on remission duration and survival was not statistically significant. The mediastinal bulk variable which most significantly related to prognosis was the ratio of the maximum mediastinal disease to the chest diameter at T5-T6.

Bone marrow fibrosis in acute lymphoblastic leukaemia of childhood.

A prospective study of bone marrow fibrosis was made in a group of 40 children with acute lymphoblastic leukaemia to see whether it affected the prognosis or course of the disease. Secondary myelofibrosis (SMF) was present at diagnosis in 57% of the cases. It was not statistically significantly related to the prognosis or course of the disease. Thus, although trephine biopsy occasionally provided useful information in different diagnosis and when aspiration was difficult, it provided little information of use for management.