Elevated plasma prostaglandin E2 levels found in 14 patients undergoing autologous bone marrow or stem cell transplantation.

In the present study, plasma prostaglandin E2 (PGE2) levels were quantitated serially in 14 patients during the period preceding and following autologous bone marrow transplantation (ABMT) or autologous stem cell transplantation (ABSCT). In eight ABMT recipients, the pre-transplant conditioning regimen consisted of combined supralethal doses of chemo- and radiotherapy which was followed by ABMT using autografts purged in vitro either with mafosfamide or monoclonal antibodies (moAbs) plus immunomagnetic beads (IB). A further two ABMT recipients received only high-dose chemotherapy without irradiation as conditioning, followed by unpurged autologous BM. The four ABSCT recipients were also treated solely with chemotherapy followed by untreated autologous stem cell reinfusion. Elevation of plasma PGE2 levels occurred in all 14 patients, despite the difference in the pre-transplant conditioning. The peak levels of PGE2 ranged from about three times the mean value obtained with ten control individuals (29.8 +/- 3.7 pg/ml) to ten times this level. In all cases plasma PGE2 normalised with recovery of the peripheral leucocyte count.

Elevated post-stimulatory intracellular adenosine 3,5-cyclic monophosphate (cAMP) levels are found in peripheral blood cells after ABMT.

Intracellular cyclic adenosine monophosphate (cAMP) levels were measured in the peripheral mononuclear cells of 25 recipients of ABMT after stimulation with forskolin (10(-4) M), cholera toxin (1 microgram/ml) and prostaglandin E2 (PGE2, 10(-6) M). Significantly increased post-stimulatory cAMP levels were found in cells derived from patients' cells less than 30 days after ABMT (after forskolin stimulation: mean 89.7 +/- 45.4 pmol per 5 x 10(6) cells, p < 0.001; after cholera toxin stimulation: mean 78.6 +/- 37.9 pmol per 5 x 10(6) cells, p = 0.003; after PGE2 stimulation: mean 93.6 +/- 36.6 pmol per 5 x 10(6) cells, p < 0.001). However, at a later time after ABMT (7-60 months), cAMP levels had returned to normal and no significant differences in intracellular cAMP content between cells from patients and normal individuals could be detected. In addition, in six patients cAMP levels after PGE2 stimulation were measured serially pre- or peri-transplantation up to a time when haematologic recovery had occurred: the significantly elevated inducible cAMP levels found early post-ABMT returned to normal with peripheral blood reconstitution. This observation could be of interest in the post-transplantation period, because cAMP, as a 'second messenger', is a modulator of the immune system.