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

Continuous mush disaggregation during the long-lasting Laki fissure eruption, Iceland

Plagioclase textures were investigated in the products of the voluminous AD 1783–1784 Laki eruption from the Eastern Volcanic Zone (EVZ) of Iceland to establish whether mush disaggregation occurred solely at the onset of the eight-month eruption or throughout its whole duration. Phase proportions and plagioclase size distributions were determined using standard optical and manual techniques as well as automated approaches based on Quantitative Evaluation of Minerals by SCANing electron microscopy (QEMSCAN). Based on optical microscopy and the explicit combination of textural and compositional information in QEMSCAN images, plagioclase crystals were divided into two populations: small ( 4) microcrysts with low-anorthite (0.5 mm long), low-aspect ratio(length/width = 2–3) macrocrysts with high-anorthite (An₈₄–An₉₂) cores. Small microcrysts grew from their carrier liquid during the final phase of pre-eruptive crystallization while large macrocrysts, which are out of geochemical equilibrium with their carrier liquids, were entrained from crystal mushes. Changes in phase proportions and plagioclase size distributions between eruptive episodes demonstrate that macrocryst entrainment efficiency varied substantially during the eruption; material erupted in later episodes contain proportionally more mush-derived material. Using stereologically corrected plagioclase size distributions, we estimate that the pre-eruptive residence times of microcrysts in the Laki carrier liquid were probably of the order of 2–20 days. Because microcryst crystallization was concurrent with macrocryst rim growth, these day-to-week residence times also indicate that macrocryst entrainment occurred on much shorter timescales than the eruption’s eight- month duration. In line with constraints from independent geochronometers, macrocryst entrainment and mush disaggregation thus appears to have continued throughout the eruption. Magmas were assembled on an episode by episode basis, and the volume of eruptible magma in the plumbing system at any given time was probably closer to 1–2 km³ than the final erupted volume of 15.1 km³.This work was supported by NERC grants NER/S/A/2004/12727, NE/1528277/1 and NE/I012508/1. DAN acknowledges support from the Alexander von Humboldt Foundation

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