Effect of conditioning regimen intensity on CMV infection in allogeneic hematopoietic cell transplantation.

Nonmyeloablative conditioning is less toxic and results in initial establishment of mixed hematopoietic T cell chimerism for up to half a year with prolonged presence of host T cell immunity. In this study, we examined whether this translates into differences in the risks and/or severity of cytomegalovirus (CMV) infection and disease. We analyzed data from 537 nonmyeloablative (NM-HCT) and contemporaneous 2489 myeloablative hematopoietic cell transplant (M-HCT) recipients. In CMV seropositive recipients, no difference in the overall hazards of CMV infection at any level (adjusted hazard ratio [adj. HR] 0.9, 95% confidence interval [95% CI]: 0.7-1.0, P = .14) was noted; however, NM-HCT was associated with a lower risk of high-grade CMV infection (adj. HR 0.7, 95% CI: 0.5-0.9, P = .02). CMV disease rates were similar between the groups during the first 100 days after HCT, but NM-HCT recipients had an increased risk of late CMV disease (adj. HR 2.0, 95% CI 1.2-3.4). The increased risk of late CMV disease after NM-HCT was pronounced during the earlier years of the study period, but not detectable in more recent years. Contrary to earlier reports, survival following CMV disease was not reduced after NM-HCT when compared to M-HCT recipients. These results suggest that residual host cells after NM-HCT reduce progression to higher CMV viral load in NM-HCT recipients; however, this effect does not appear to protect against serious complications of CMV. Therefore, CMV prevention strategies in NM-HCT recipients should be similar to those used in M-HCT recipients

Myelomatosis with type III hyperlipoproteinemia - clinical and metabolic studies

We investigated the metabolism of intermediate-density lipoproteins (IDL [1.006 to 1.019 g per milliliter]) and low-density lipoproteins (LDL [1.019 to 1.063 g per milliliter]) in two men with Type III hyperlipoproteinemia associated with myelomatosis. In vivo kinetic studies using Radio-labeled autologous lipoproteins demonstrated a greatly reduced fractional catabolic rate of IDL, relative to control values (patients vs. normal, 0.006 and 0.025 per hour vs. 0.20±0.08 per hour [mean ±S.E.M.]) and a greatly prolonged IDL-to-LDL conversion time (45 and 17 hours vs. 5.4±1.6 hours). In studies in vitro, LDL from both patients failed to bind to the LDL receptor of normal blood lymphocytes, whereas LDL from subjects with familial Type III hyperlipoproteinemia bound normally to the receptor. In one patient immunoglobulin was shown to be associated with IDL and LDL. Thus, hyperlipoproteinemia reflected an impaired metabolism of IDL, probably secondary to the binding of immunoglobulin to the lipoproteins. A similar impairment of receptor-mediated LDL catabolism did not elevate the plasma LDL concentration because of the low IDL-to-LDL conversion rate