G. E. van Zanen

Detection of Minimal Residual Acute Lymphoblastic Leukemia by Immunological Marker Analysis: Possibilities and Limitations

The detection of small numbers of malignant cells is a major problem at diagnosis and during follow-up of malignancies (1). The possibilities and limitations of methods for the detection of minimal residual disease in general depend on their specificity (malignant cells have to be identified among many normal cells), sensitivity (detection limit of the method) and reproducibility. Although the method as such may have an excellent reproducibility, the cell sample may not always be representative for the whole cell population.

Detection of Minimal Residual Disease in TdT Positive T Cell Malignancies by Double Immunofluorescence Staining

Identification of small numbers of residual malignant cells is one of the major goals in cancer research. Detection of minimal disease enables better staging of the malignant process and provides information about residual disease. As a consequence individual adjustment of the therapy as well as avoidance of under- or overtreatment of the patient is possible.

Incidence of childhood leukaemia in The Netherlands (1973-1980)

The childhood leukaemia incidence rate for the Netherlands was estimated at 3.11 per 100.000 children (aged 0-15 year) per year, based on a complete nation-wide childhood leukaemia registry comprising the period 1973-1980. Acute lymphocytic leukaemia (ALL) accounted for 82.4% of the patients, acute non-lymphocytic leukaemia for 13.6% and chronic myeloid leukaemia for 2.9%. ALL occurred more frequently in boys (sex ratio 1.2). The highest ALL rate was observed in the 3-4 year age group. These figures corresponded with the data of the Manchester Childrens Tumour Registry. Neither the incidence rates according to year of diagnosis nor the incidence rates according to year of birth showed a significant trend with time. The total leukaemia incidence rate in urban areas was somewhat higher than in rural areas. While the direct comparison of the incidence rate between these areas is not significant, the trend over the three categories of urbanisation is significant.

C-Group Chromosome Abnormalities in Bone Marrow Cells of Three Children with Dyshaematopoiesis of Unknown Origin

Clinical and cytogenetic findings in three children with dyshaematopoiesis and bone marrow aneuploidy are described. Monosomy 7 was found in immature cells of one 10‐year‐old boy with myelofibrosis following a 3 years evolution of severe thrombocytopenia and anaemia. Trisomy 8 was found in 80% of the bone marrow metaphases of a 5 1/2year‐old girl with aplastic anaemia and Australia antigen positivity. During a 3 year observation period the number of cells with trisomy 8 regressed and eventually disappeared. Improvement of her clinical condition is present but still limited. Trisomy 8 was also found in all bone marrow cells of an 8‐year‐old girl with an undefined myeloproliferative disorder. Her disease was apparently related to collagen‐vascular disorders like periarteritis or other necrotizing angiitis and presented bvith periods of exacerbation and periods of chronic evolution. Periods of exacerbation were accompanied by excessive myeloid proliferation. Repeated bone marrow cytogenetic analysis during the acute and chronic phases showed trisomy 8 in all the metnphases analysed. During the last episode of acute illness, further clonal evolution was observed, characterized by a translocation (8; 17).

Time space distribution of childhood leukaemia in the Netherlands.

In the western part of the Netherlands during 1973-80 leukaemia was diagnosed in 293 patients aged under 15 years. An overall incidence rate of 2.91 per 100000 person years was calculated. No seasonal influence on months of birth or months of diagnosis of these patients could be traced by the method of Edwards. Time space clustering was looked for by both methods of Mantel and Knox. No significant time space clustering of date and place of diagnosis of childhood leukaemia was found in all types of leukaemia, acute lymphocytic leukaemia (ALL), ALL in boys and girls, ALL in children under 6 years at diagnosis, and in acute non-lymphocytic leukaemia.

The Small Subpopulation of T Cell Marker+/Tdt+ Cells in the Human Bone Marrow may Represent Prothymocytes

Most normal haematopoietic differentiation stages have malignant counterparts in the form of a leukaemia or non-Hodgkin lymphoma (NHL) (Foon et al., 1982). The acute lymphoblastic leukaemias (ALL) may be regarded as the malignant counterparts of normal immature lymphoid cells (Janossy et al., 1980, 1981). These ALL can be characterized immunologically by use of several markers such as: terminal deoxynucleotidyl transferase (TdT), the HLA-DR non-polymorphic antigen, the common ALL antigen (cALL), cytoplasmic immunoglobulin μ heavy chain (cIgM), surface membrane Ig (SmIg) and the T cell markers Tp41, T11, T1, T6, T4, T8 and T3 (Foon et al., 1982; Vodinelich et al., 1983).

Characterization and Monitoring of the Malignant Cells in the Elastic and Chronic Phase of Chronic Myeloid Leukemia

A 13-year-old-boy presented with a lymphoid blast crisis of chronic myeloid leukemia, without a preceding chronic phase. The lymphoid and myeloid leukemic cell populations were studied with double immunofluorescence staining. The myeloid cells were positive for the monoclonal antibodies VIM-D5 (myeloid marker) and B13 (mature myeloid marker) and negative for VIL-A1 (cALL marker), HLA-DR and terminal deoxynucleotidyl transferase (TdT). The lymphoid cells were positive for the monoclonal antibodies VIL-A1 and HLA-DR and for TdT; these cells were negative for VIM-D5. The fate of the myeloid and lymphoid leukemic cells in bone marrow and blood was monitored during therapy. By using VIM-D5 and VIL-A1 as marker the two leukemic cell populations were separated by means of the FACS. Both cell types carried a complex Ph1 translocation t(4;9;22). The lymphoid leukemic cells showed additional aberrations.