Nalini Mukhopadhyay

Lymphocytic leukemia in children: Prognostic significance of clinical and laboratory findings at time of diagnosis**

Forty-eight children with untreated acute lymphocytic leukemia were evaluated with regard to their clinical presentation and the surface membrane characteristics, mitogen responsiveness, and cytochemical staining features of their lymphoblasts. The presence at diagnosis of 20% or more bone marrow lymphoblasts possessing T-cell surface markers was associated with the development of early relapse and death. Age, sex, initial peripheral leukocyte count (WBC), lymph node enlargement or the presence of hepato- or splenomegaly bore no statistically significant relationship to the patients lymphoblast type, and only a WBC in excess of 10(5)/microliter correlated with a poor prognosis. Leukemic T-cells were found to be periodic acid-Schiff negative from nearly all patients, helping to distinguish such patients from the larger group of children whose leukemic cells were PAS positive, but negative for T-cell membrane features. In those patients who had multiple relapses, the surface membrane characteristics, staining features, and mitogen responses of their lymphoblasts remained constant. This suggests that relapse occurs in the same clone of malignant cells present at diagnosis and that the above features may be reliably used to evaluate and classify patients beyond the time of diagnosis.

T and B cells and immune competence in human fetal liver cells.

Abstract Mononuclear cells obtained from the fetal liver of seven human fetuses between 10 and 14 weeks of gestation had very few T cells as detected by spontaneous sheep erythrocyte rosette formations. Cells bearing surface membrane-bound immunoglobulin were rare, while cells bearing a receptor for the third component of complement could be detected in all of the specimens and were found to be within normal values in two specimens. The response of these cells to mitogens and allogeneic lymphocytes was poor, while the stimulatory ability of these cells in the mixed lymphocyte reaction could be detected in these cells. In the cocultivation of fetal liver mononuclear cells with peripheral blood lymphocytes obtained from a patient with severe combined immunodeficiency disease, the responsiveness for phytohemagglutinin increased threefold over control values.

Cytotoxic and soluble mediator responses by complement (C3) receptor-bearing lymphocytes from patients with B-cell immunodeficiency diseases

Abstract Peripheral blood lymphoid subpopulations from congenital (X-linked) agammaglobulinemic and selective IgA-deficient patients were assessed for nonspecific cytotoxicity and lymphotoxin (LT) effector responses. Complement receptor-bearing lymphocyte-mediated cytotoxicity and culture supernatant LT responses were quantitated using 51 Cr-labeled human melanoma target cells. All patients appeared to have normal numbers of T and B cells as defined by E and EAC rosetting while agammaglobulinemic patients were deficient in cells bearing surface membrane-associated immunoglobulin (SmIg). T cells and enriched B cells obtained by T-cell depletion gave negligible nonspecific cytolytic responses. In contrast, complement (C3) receptor-bearing lymphocytes (CRL) from B-cell-immunodeficient patients and normal donors gave significant cytolytic and supernatant lymphotoxin responses when activated by EAC rosetting. Evidence is presented that CRL from immunodeficient patients with total or partial B-cell deficiencies can still express C3 receptor-induced nonspecific cytotoxicity and lymphotoxin effector responses. The absence of serum and membrane-associated immunoglobulins did not impair the expression of C3 receptor-induced responses.

948 GENERATION OF CONCANAVALIN A (Con-A)-INDUCIBLE SUPPRESSIVE FACTORS IN ACUTE LYMPHOCYTIC LEUKEMIA (ALL)

Leukemic blasts (LB) obtained at diagnosis from 6 non-T, non-B, and 2 T-cell patients with ALL were studied for their ability to suppress or enhance the proliferative capacity of normal allogeneic peripheral blood lymphocytes (PBL). LB or control lymphocytes (Ly), preincubated at 37°C for 48 hrs with 100 μg/ml Con-A (Ca) or without Con-A (Co), were treated with mitomycin-C. One hundred thousand Ca- or Co-treated LB or Ly were added to 1 × 105 PBL and cultured with or without supernatants of preincubated cultures in the presence of phytohemagglutinin, Con-A, and pokeweed mitogen. The response of PBL in the presence of supernatants from LB or Ly was markedly suppressed for all stimulations (P = <.001). However, in the absence of supernatants, 2 patients with non-T, non-B ALL and 1 T-cell ALL suppressed the PBL response for all mitogens (% suppression range 10-73.9; control range 19.3-81.1). One T cell and 4 non-T, non-B ALL showed enhancement (range 11.6-232.0). We conclude that T-cell factors are bifunctional molecules recognizing the stimulant by one end, selecting the cell type by the other end, leading to suppression or augmentation with their restriction specificity.