Cytotoxic antibody in acute myeloblastic leukaemia during immunotherapy: lack of tumour specificity.

Cytotoxic antibodies to antigens specific for leukaemic myeloblasts have been sought in the serum of patients with acute myeloblastic leukaemia treated by immunotherapy with irradiated allogeneic myeloblasts and BCG. Assays of complement- and K-cell-mediated activity were used. Cytotoxicity to allogeneic myeloblasts was detected in both assays. When sera from 15 patients, taken at various times during immunotherapy, were systematically tested against a panel of 5 myeloblasts, the following patterns emerged: 1. No antibody was cytotoxic against all myeloblasts of the panel in either the K-cell or complement-dependent assay. However, all myeloblasts of the panel were lysed by a number of sera. 2. Cytotoxic antibody was detected as often against a panel of lymphocytes from healthy donors as against the panel of allogeneic myeloblasts. 3. Fresh and cryopreserved myeloblasts were equally susceptible to lysis in both assays. 4. Experiments failed to demonstrate any deterioration of cytotoxic antibody on storage. 5. The number of K-cell-revealed cytotoxic antisera increased with length of immunotherapy. This pattern was not apparent for antibodies revealed by complement. 6. No instance of cytotoxicity in either assay was seen when serum was tested against 12 autologous myeloblasts. It is considered that cytotoxic antibody detected with allogeneic myeloblasts is probably directed against HLA antigens common to immunizing and test target myeloblasts and target lymphocytes

Analysis of treatment of childhood leukaemia. V. Advantage of reduced chemotherapy during and immediately after cranial irradiation.

This paper compares anti-leukaemic efficiency with toxicity to the patient of chemotherapy during and immediately after central nervous system irradiation. The drug regimen consisted of daily mercaptopurine (MP) and weekly methotrexate (MTX) at the maximum tolerated dose. Of 140 patients with acute lymphoblastic leukaemia allocated to receive this drug regimen during and after cranial irradiation, 8 died in complete remission within 6 months of the end of irradiation. Details of the nature of these deaths are given. This result led the Working Party to modify the chemotherapy scheduled for this stage in treatment. The modified chemotherapy consisted of MP at reduced dosage before and during cranial irradiation and omission of MP and MTX for 3 weeks after irradiation, during which time daily prednisolone with 2 doses of vincristine were substituted. Following that, the treatment reverted to the original schedule of daily MP and weekly MTX at maximum tolerated dose. Of 109 patients allocated to this modified regimen only one died in remission within 24 weeks after cranial irradiation. Analysis of the anti-leukaemic effect of the modified regimen showed that up to 600 days it was at least as effective as the original more intensive regimen. We conclude that there is a definite advantage in keeping chemotherapy to a minimum during and immediately following cranial prophylactic irradiation

Analysis of synergy between cyclophosphamide Therapy and Immunity Against a Mouse Tumour

C3H/He and CBA/T6T6 mice which share the H2k haplotype were compared for their capacity to survive challenges with the C3H-derived fibrosarcoma BP8. It was found

Solar Energetic Particle Spectral Breaks

The five large solar particle events during October–November 2003 presented an opportunity to test shock acceleration models with in-situ observations. We use solar particle spectra of H to Fe ions, measured by instruments on ACE, SAMPEX, and GOES-11, to investigate the Q/M-dependence of spectral breaks in the 28 October 2003 event. We find that the break energies scale as (Q/M)^b with b ≈ 1.56 to 1.75, somewhat less than predicted. We also conclude that SEP spectra >100 MeV/nucleon are best fit by a double power-law shape. ©2005 American Institute of Physic