Impaired antibody levels to tetanus toxoid and pneumococcal polysaccharides in acute leukemias.

Antibody levels to the protein antigen tetanus toxoid (TTx) and the carbohydrate antigens pneumococcal capsular polysaccharides (PCP) were studied by enzyme immunoassay in 14 patients with acute lymphocytic leukemia (ALL) and 32 patients with acute non lymphocytic leukemia (ANLL) before and three weeks after initiation of chemotherapy. The antibody levels to TTx were significantly lower in ALL patients than in controls. This was associated with elevated levels of sCD8 (soluble CD8) in the serum of 12 out of the 14 ALL patients. Patients with ANLL had normal antibody levels before chemotherapy. After chemotherapy ANLL patients with septic complications had a reduced increase of antibody titers to TTx than patients without sepsis. The average antibody titers to PCP decreased in patients with sepsis, while they increased slightly in patients without sepsis. We conclude that in contrast to ANLL patients ALL patients have preexisting decreased antibody levels to thymus dependent protein antigens, while antibody levels to thymus independent carbohydrate antigens are normal in both types of leukemias.

The clinical relevance of IgG subclasses in acute leukemias: low serum IgG as a risk factor for early death due to infection in acute myelogenous leukemia.

In order to investigate the clinical significance of IgG subclass levels in adult patients treated for acute lymphocytic (ALL) or myelogenous leukemias (AML), patients were tested before and in regular intervals during and after chemotherapy. Ten patients treated for acute lymphocytic leukemia had normal total IgG and IgG subclass levels that decreased under chemotherapy. This decrease was not associated with septic complications. In contrast, total IgG and subclass levels increased in most patients with acute myelogenous leukemia during chemotherapy and bone marrow aplasia. Those patients with newly diagnosed AML and low total serum IgG before treatment with intensive remission induction chemotherapy had, however, an increased risk of early death due to septic complications.

European experience with ifosfamide in lymphomas.

In malignant lymphomas, ifosfamide-containing regimens were at first used mainly in second-line therapy and response-adapted protocols. Currently, in combination with other drugs, ifosfamide is being used in several phase-III trials. As salvage therapy in non-Hodgkin's lymphoma (NHL), IMV-Bleo (ifosfamide, methotrexate, etoposide, bleomycin) produced a complete remission (CR) rate of 41% and seemed to be particularly effective in patients with suboptimal response to first-line treatment. IBEP (ifosfamide, bleomycin, etoposide, procarbazine), in combination with procarbazine and bleomycin was an effective non-cross-resistant alternative in CHOP (cyclophosphamide, hydroxydauomycin/doxorubicin, vincristine, prednisone)-refractory NHL. In a trial of response-oriented therapy in high-grade malignant lymphoma patients, the investigators concluded that consolidation therapy was necessary even in patients with rapid response to CHOP. Patients with NHL resistant to or relapsing from conventional chemotherapy or with MOPP-ABVD (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, decarbazine)-resistant Hodgkin's disease (HD) were treated with BMV-VIP [bleomycin, plus high-dose methylprednisolone plus ifosfamide, etoposide, plus methylprednisolone]. In high-grade malignant NHL, patients received three cycles of COP-BLAM (cyclophosphamide, vincristine, procarbazine, prednisone, bleomycin, doxorubicin). Those who achieved CR received two more cycles of COP-BLAM and IMV (ifosfamide, methotrexate, etoposide) as consolidation therapy. Patients in partial remission (PR) or with less of a response to COP-BLAM were switched to IMV. After reaching CR, patients received two additional cycles as consolidation therapy. After the second restaging, patients were randomized to observation v additional radiotherapy. Of 191 patients, 148 have passed first restaging with 51% in CR; 85 went through the second restaging with 61% in CR. Of 32 patients who only reached PR after the first restaging, 15 (47%) achieved CR with IMV. For primary treatment of HD, the German Hodgkin Study Group added a third non-cross-resistant regimen, IMEP (ifosfamide, methotrexate, etoposide, prednisone), to supplement COPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABV in the primary treatment of HD. In a pilot study, 87% of 63 evaluable patients reached CR. The current phase-III protocol is comparing COPP/ABVD with fast alternating cycles of COPP/ABV/IMEP.