Bone marrow fibrosis in childhood acute lymphoblastic leukaemia.

Bone marrow trephine biopsy specimens were obtained at diagnosis from 63 of 76 consecutively presenting children with acute lymphoblastic leukaemia (ALL). The association between marrow fibrosis and presenting features, including immunophenotype, was analysed. Reticulin was increased in 45 of 56 cases in which blasts expressed B lineage markers, but in only one of seven with T-ALL. A weak association was also found between marrow fibrosis and splenomegaly in those with common ALL. Marrow fibrosis is apparently associated with some examples of ALL of B cell lineage, but precisely which subtypes and whether the phenomenon is clinically important remain to be determined.     

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.     

Morphological heterogeneity in childhood B cell acute lymphoblastic leukaemia.

Considerable heterogeneity of lymphoblast morphology in childhood B cell acute lymphoblastic leukaemia has been observed. One case showed unusual monocytic features and emphasised the need for marker studies in the accurate definition of acute lymphoblastic leukaemia phenotypes. B cell acute lymphoblastic leukaemia is rare but may have been previously underestimated by morphological misinterpretation. Further information is required to determine if the different morphological features of this condition are of clinical and prognostic importance.     

The age incidence of childhood acute lymphoblastic leukaemia

A mathematical model of childhood acute lymphoblastic leukaemia (ALL) is presented which is based on the assumptions that: 1) malignant clones of lymphoblasts arise by spontaneous mutation; 2) this is normally prevented by repair systems which either cause intracellular DNA repair or eliminate the malignant clone; and 3) the repair systems are fallible and their performance decays at random with time. If the major drive to lymphocyte division is microbial antigens then the model produces a reasonable fit to published data on the age distribution of ALL. Furthermore the model offers an explanation for the apparent increase in the incidence of ALL which is associated with improved social conditions.     

Granular acute lymphoblastic leukaemia of childhood: a morphological phenomenon.

Three hundred and twenty consecutive children with lymphoblastic leukaemia (ALL), treated on the Medical Research Council UKALL VIII schedule, had their Romanowsky stained diagnostic marrows reviewed for the presence of azurophil granules in blast cell cytoplasm. Twenty patients (7%) had greater than 5% blasts showing this feature; 19 had the cell phenotype of "common ALL." Male children and those with French-American-British (FAB) L2 morphology predominantly showed this feature. There was also a strong correlation between granularity and non-diffuse acid phosphate positivity, but no obvious difference between the 20 patients in their response to treatment emerged during a minimum follow up of 15 months. The "granular" variant occurs in around 7% of children with ALL, but has no clear prognostic importance. Morphologists should be aware of its existence and incidence to avoid confusion with acute myeloid leukaemia.     

Variable detection of myeloid antigens in childhood acute lymphoblastic leukaemia.

AIMS--To determine whether the use of different sources of anti-CD13 and anti-CD33 monoclonal antibodies leads to discrepant results in childhood acute lymphoblastic leukaemia (ALL), which might contribute to the wide variation in the reported incidence of myeloid antigen expressing ALL in childhood. METHODS--Stored leukaemic cells from 10 children with previously defined myeloid positive ALL were examined. A range of commercially available anti-CD13 and anti-CD33 monoclonal antibodies, directly conjugated with phycoerythrin or fluorescein isothyocyanate, or both, was used. Positively reacting cells were detected by flow cytometry. RESULTS--There was a noticeable discordance between the different commercial sources of antibody and between the two fluorochromes in their ability to detect myeloid antigens, as well as variation in the intensity of staining. For CD13, one antibody reacted with eight cases and another with only four. Similarly, CD33 was detected in all 10 cases by one antibody and in only three by another. CONCLUSIONS--The lack of any consistent pattern of results suggests that various commercial antibodies against the same CD antigen might recognise different epitopes and that the number of molecules per cell might vary from case to case. These observations partly explain the variation in reported incidence and the failure to establish the clinical importance of myeloid positivity, and they highlight the importance of standardisation in multicentre studies in which immunophenotypic data are collected.     

Terminal deoxynucleotidyl transferase activity in childhood and adult acute lymphoblastic leukaemia.

The measurement of terminal deoxynucleotidyl transferase (TDT) activity in leukaemic blasts of 26 cases of acute lymphoblastic leukaemia (ALL) (13 children less than 14 years, 13 adults greater than 14 years) demonstrated significantly greater activities of the enzyme on a proportion of the adults. The predominant cytological sub-type in the adult patients was L2 (FAB classification) whereas L1 cytological sub-type dominated in the childhood group. There was no relation between TDT values and FAB sub-type but the highest activities in the childhood group were seen in patients assessed at the time of relapse. We conclude that continued use of quantitative TDT estimations may provide useful information in further characterising the currently recognised cytological and immunological sub-types in ALL.     

HLA status following fetal liver transplantation in aplastic anaemia and acute myeloid leukaemia

Fetal liver infusion (FLI) was tried as an alternate mode of therapy in 40 patients with aplastic anaemia and in 16 patients with acute myeloid leukaemia. The fetal HLA typing carried out on spleen and thymus cells revealed that, while it was more difficult to HLA type the thymus than the spleen cells, 'full house' antigens could be determined only in fetuses of 18 weeks or older. No special effort was made to transfuse HLA- matched or partially matched donor cells into the recipient. The recipients were HLA typed at varying time intervals following FLI in an attempt to document a possible chimerism. None of the patients revealed a 'shift' in their HLA antigen profile and there was no evidence of any donor cell engraftment. No relationship between the HLA match of donor and recipient, and the general condition, the prognosis or the total survival of the patient was evidenced. These data indicate that, even though fetal liver cells express HLA antigens, these cells are functionally incompetent to cause an apparent graft-versus-host disease in the host.     

Treatment of acute lymphoblastic leukaemia.

In acute lymphoblastic leukaemia the combination prednisone-vincristine induces more than 85% complete remissions. L-asparaginase which was used in complete remissions, seemed to increase their duration. Actually the best maintenance treatment consists in the combination of 6-mercaptopurine and methotrexate interrupted by reinductions. In other respects C.N.S. prophylaxis with intrathecal methotrexate and craniospinal irradiation is necessary. The well-known prognostic factors are: age, leucocytosis, tumoral syndrome, and cytological type: 216 cases of long remission have been observed. One group of these patients was treated by old methods: this represents 0.8 to 1% of the material, while 20% were treated by recent protocols with reinductions (20%).     

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.     

Immunological follow-up of acute lymphoblastic leukaemia.

In different treatment groups of children with acute lymphatic leukaemia and undifferentiated leukaemia, the lymphocyte count and a number of immunologic parameters were examined during the various stages of treatment. These parameters were related to the type of chemotherapy as well as the stages of treatment. This paper deals with the values of lymphocyte counts, of gamma globulin, IgG, IgM and IgA and the results of the DNCB skin tests, as a parameter for cellular immunity. IgG determined by acetate sheet electrophoresis showed no significnat change, while its significant reduction was shown during the periods of prophylactic reinduction with vincristine in the Pinkel VII scheme, The IgM level was significantly raised in the initial stage before treatment and in all periods of treatment both in the Pinkel VII group and in an earlier therapeutic group treated with methotrexate every two weeks and vincristine pulses every six weeks. IgA was raised in both groups before treatment but significantly reduced during the phases of maintenance and reinduction. About 50% of the P VII cases had negative DNCB skin tests during maintenance therapy, while all long-term survivors in the earlier methotrexate group had a positive skin test.     

Sex and acid phosphatase in childhood non-T lymphoblastic leukaemia.

A semiquantitative assessment of blast cell acid phosphatase activity, expressed as a score, was made in 41 unselected children with newly diagnosed and untreated non-T acute lymphoblastic leukaemia (ALL). Despite a wide range of enzyme activity in both sexes boys had significantly higher scores than girls, and, in view of the known association between males and T ALL on the one hand, and between acid phosphatase and T ALL on the other, these findings raise the possibility that boys may have a predisposition to a type of pre-T ALL which could contribute to the as yet unexplained difference in prognosis between the sexes.     

Small bowel enterocyte abnormalities caused by methotrexate treatment in acute lymphoblastic leukaemia of childhood.

Jejunal biopsy specimens from 10 children with acute lymphoblastic leukaemia on methotrexate treatment were compared with 10 from children being investigated for diarrhoea or failure to thrive. In association with methotrexate treatment on both light and electron microscopy, there were marked morphological abnormalities in the villus enterocytes. These consisted of a striking distention of the lateral basal intercellular spaces, cell vacuolation and patchy necrosis and was most marked when methotrexate treatment was given between 24 and 72 h before biopsy. Two mechanisms may be involved: an early direct toxic effect on the mature enterocyte coupled with interference with crypt cell generation, possibly causing ageing and loss of cells proximal to the normal extrusion zone. These pathological changes may account for the malabsorption in association with methotrexate treatment.     

Low molecular weight IgM in sera of children following bone marrow transplantation for severe aplastic anaemia and acute leukaemia.

Serum samples of 16 children, treated with allogeneic bone marrow grafts for either aplastic anaemia or leukaemia, were investigated longitudinally for the presence of pentameric (19S) and low molecular weight (LMW) (7S) IgM. From 2 months following grafting, serum IgM increased in all patients, gradually in seven cases and with a transient overshoot in the other nine. In eight patients, LMW-IgM was detected transiently in the serum within the period when total IgM was increasing, either with (five patients) or without (three patients) overshoot. These data indicate that, at a certain stage of the immunological reconstitution after transplantation as in normal ontogeny, rather immature cells of the B cell lineage are able to produce and secrete LMW-IgM.