Martin J. S. Dyer

REMISSION INDUCTION IN NON-HODGKIN LYMPHOMA WITH RESHAPED HUMAN MONOCLONAL ANTIBODY CAMPATH-1H

A genetically reshaped human IgG1 monoclonal antibody (CAMPATH-1H) was used to treat two patients with non-Hodgkin lymphoma. Doses of 1-20 mg daily were given intravenously for up to 43 days. In both patients lymphoma cells were cleared from the blood and bone marrow and splenomegaly resolved. One patient had lymphadenopathy which also resolved. These effects were achieved without myelosuppression, and normal haemopoeisis was restored during the course of treatment, partially in one patient and completely in the other. No antiglobulin response was detected in either patient. CAMPATH-1H is a potent lympholytic antibody which might have an important use in the treatment of lymphoproliferative disorders and additionally as an immunosuppressive agent.

Remission Induction in Patients with Lymphoid Malignancies Using Unconjugated CAMPATH-1 Monoclonal Antibodies.

CAMPATH-1 (CDw52) antigen is a heavily glycosylated, non-modulating glycoprotein expressed abundantly on the cell surface of nearly all normal and malignant lymphocytes but not on hemopoietic stem cells. A series of rat monoclonal antibodies (MAbs) with CDw52 specificity but of varying immunoglobulin isotype has been produced, and assessed for ability to deplete lymphoid cells in patients with lymphoproliferative disorders. Although all IgM, IgG2a and IgG2b rat MAbs were able to elicit lysis with human complement in vitro, only the IgG2b MAb (CAMPATH-1G) could elicit substantial lymphoid depletion in vivo. The efficacy of CAMPATH-1 G probably results from its ability to bind human Fc receptors and activate cell-mediated lysis of antibody-coated cells. Twenty-nine patients with lymphoid malignancies have received between 250 mg and 680 mg of CAMPATH-1G; nine of these attained complete remission A human MAb with CDw52 specificity has been produced by grafting the complementarity-determining regions (CDRs) of the rat MAb into human IgG1 heavy- and kappa light-chain genes. These constructs were transfected into a rat myeloma cell line. Sufficient human MAb (CAMPATH-1H) has been purified to treat two patients with non-Hodgkins lymphoma in leukemic phase. Although each patient only received approximately 100 mg of MAb, remission was induced in both patients with recovery of normal hemopoiesis during the course of therapy CDw52 MAbs are the first MAbs to demonstrate consistent anti-tumor effects in vivo and may have roles in the therapy of a wide range of lymphoid malignancies and as powerful immunosuppressive agents.

Translocation 5;21 and interstitial deletion of chromosome 7 in a case of chronic myelomonocytic leukemia

We report a case of chronic myelomonocytic leukemia with a translocation involving chromosome 5 and 21, namely, t(5;21)(q35.3;q22.1), and an interstitial deletion of the long arm of chromosome 7. High-resolution analysis at the 900-band stage has shown that the lesion in chromosome 7 is an interstitial deletion involving loss of the segments q22-q35 of the long arm of chromosome 7 and retaining the telomere.

T-Cell Receptor and Immunoglobulin Gene Rearrangements in Acute Myeloid and Undifferentiated Leukemias of Adults: Correlation with Weak Surface Expression of CD45 and CDw52 Antigens

We examined 150 cases of acute myeloid leukemia (AML) and 8 cases of acute undifferentiated leukemi (AUL) of adults for both phenotypic and genotypic evidence of commitment to the lymphoid lineages. There was no correlation between expression of lymphoid differentiation antigens and rearrangement of T-cell receptor (TCR) and immunoglobulin (Ig) DNA sequences. In particular 8 cases of CD7(+) AML were germline for all TCR α, β,μ, and δ Also none of the 11 cases with IgJH rearrangement expressed CD19 either on the cell surface or within the cytoplasm. Ten out of 13 cases with TCR/Ig gene rearrangement were either cytologically undifferentiated AML of FAB type M1 or AUL. None had clear immunophenotypic evidence for commitment to lymphoid lineages but 9 expressed only very small amounts of CD45 framework antigens and 7 expressed small amounts of CDw52 (CAMPATH-1). This phenotypic combination is otherwise seen only in precursor B cell ALL. TCR/Ig gene rearrangement in AML and AUL of adults appears to have become dissociated from the rest of the lymphoid differentiation program. Recognition of these cases may be facilitated by the weak expression of both CD45 and CDw52 antigens.