The Prognostic Significance of Serum β2 Microglobulin Levels in Acute Myeloid Leukemia and Prognostic Scores Predicting Survival: Analysis of 1,180 Pa

Purpose:
Serum β2 microglobulin (β2M) is prognostic in other hematologic malignancies; therefore, we evaluated its prognostic significance in acute myeloid leukemia (AML).

Experimental Design:
Multivariate analyses were used to examine the effect of pretreatment serum β2M levels on clinical outcomes in patients with AML. β2 microglobulin (β2M) was associated with poorer survival in older but not younger patients. We thus fit separate Cox survival models in patients above and below age 60 years treated with remission induction therapy containing high-dose cytarabine (n = 1,280). In each age group, 50% of the patients were used to develop the model, which was tested in the other 50%. Resampling methods were also used to validate the independent prognostic significance of covariates.

Results:
In patients 60 years or older (n = 591), poorer risk cytogenetics; poorer performance status; and higher levels of β2 microglobulin (β2M), uric acid, and lactate dehydrogenase were each found to independently predict shorter survival and formed the basis of a scoring system. A similar approach was used in patients younger than 60 years (n = 589), with poorer risk cytogenetics, poorer performance status, older age, higher hemoglobin level, and higher leukocyte count predicting a shorter survival and forming the basis of the scoring system. Higher β2M levels were an adverse independent factor for response, survival, relapse-free survival, and event-free survival in older but not in younger patients.

Conclusions:
Serum β2 microglobulin (β2M) levels can help predict outcome in patients 60 years with untreated AML, and their use is strongly encouraged.

Molecular differences b/t divergent responses of ovalbuminspecific CD4 T cells to alumprecipitated ovalbumin compared toovalbumin expressed Salmonella

CD4 T helper (Th) cell differentiation defined by in vitro cytokine-directed culture systems leaves major gaps in our knowledge of the mechanisms driving divergent Th differentiation. This is evident from our analysis of the response of mouse ovalbumin-specific CD4 T cells to different forms of ovalbumin that induce markedly distinct responses in vivo. We show that live attenuated ovalbumin-expressing Salmonella (SalOVA) induce Th1-associated T-bet and IFN-γ. Conversely, alum-precipitated ovalbumin (alumOVA) induces the Th2-associated GATA-3 and IL-4. The early diversity occurring within these CD4 T cells isolated 3 days after immunization was assessed using real-time RT-PCR microfluidic cards designed with 384 selected genes. The technique was validated both at the population and single cell levels at different stages of the responses, showing β2-microglobulin to be a more stably expressed reference mRNA than either β-actin or 18S RNA. SalOVA was then shown selectively to induce the OVA-specific CD4 T cells to produce many chemokines and pro-inflammatory cytokines, contrasting with alumOVA-induced cells that only produced a few Th2-associated cytokines. Several cytokines and features associated with follicular helper functions were induced in the OVA-specific CD4 T cells by both antigens. Finally, IL-17RB is strongly associated with OVA-specific CD4 T cells responding to alumOVA, suggesting that alum may promote Th2 immune response through a role for the IL-25/IL-17RB pathway.

ARTICLE

Reduction in β2-Microglobulin With Super-flux Versus High-flux Dialysis Membranes: Results of a 6-Week, Randomized, Double-blind, Crossover Trial

Background
Uremic toxicity is a major concern in the dialysis population. There is keen interest in techniques that increase the removal of larger uremic molecules. We examined the short-term impact of a new, more porous, super-flux Helixone membrane (FX-E) versus the conventional high-flux Helixone membrane (FX-60) on β2-microglobulin (Beta 2 Microglobulin) reduction and nutritional and inflammatory parameters.

Study Design
Randomized, double blind, crossover, pilot trial.

Setting & Participants
A single freestanding dialysis center. 30 stable hemodialysis patients.

Intervention
Patients were treated with FX-60 and FX-E membranes for a treatment period of 6 weeks each, with a 2-week washout period in between.

Outcome & Measurements
Primary outcome was change in β2-microglobulin (Beta 2 Microglobulin) concentrations from baseline to end of treatment. Serum samples were obtained predialysis and postdialysis at 0, 2, and 6 weeks, and dialysate albumin samples were collected continuously throughout dialysis sessions.

Results
Mean postdialysis β2M concentrations at the end of 6 weeks of treatment were 6.73 mg/L for FX-E versus 8.22 mg/L for FX-60, which was significantly lower overall by 0.69 mg/L (95% confidence interval [CI], −1.09 to −0.29; P = 0.001). β2M reduction ratios were greater overall with FX-E by 4.83% (95% CI, 2.78 to 6.89; P < 0.001), with mean values of 57% for FX-60 versus 66% for FX-E at the end of treatment. Median dialysate albumin loss with FX-E was 1.23 g (range, 0.22 to 4.83 g) compared with 0.17 g (range, 0.0017 to 2.69 g) with FX-60, which was greater by 1.52 g (95% CI, 1.11 to 1.93; P < 0.001). Serum albumin concentrations were slightly lower with FX-E by 0.1 g/dL (0.55 g/L; 95% CI, −1.04 to −0.07; P = 0.03), but prealbumin concentrations were not significantly different at 8.53 mg/L (95% CI, −23.76 to 6.71; P = 0.3). There were no differences in inflammatory cytokine concentrations or small-solute removal.

Limitations
Short-term pilot study.

Conclusion
In this stable dialysis population, removal of β2-microglobulin (Beta 2 Microglobulin) was more efficient with the Helixone super-flux FX-E membrane, with only a small decrease in albumin concentrations despite increased albumin loss. Large trials with longer treatment periods are required to evaluate the impact of the FX-E membrane on clinical outcomes.

ARTICLE