Hypertriglyceridemia resulting from amplified triglyceride production is another indirect effect of impaired gluconeogenesis, amplified by chronically low insulin levels. During fasting, the normal conversion of triglycerides to free fatty acids, ketones, and ultimately acetyl-CoA is impaired. Triglyceride levels in GSD I can reach several times normal and serve as a clinical index of "metabolic control". Hyperuricemia results from a combination of increased generation and decreased excretion of uric acid, which is generated when increased amounts of G6P are metabolized via the pentose phosphate pathway. It is also a byproduct of purine degradation. Uric acid competes with lactic acid and other organic acids for renal excretion in the urine. In GSD I increased availability of G6P for the pentose phosphate pathway, increased rates of catabolism, and diminished urinary excretion due to high levels of lactic acid all combine to produce uric acid levels several times normal. Although hyperuricemia is asymptomatic for years, kidney and joint damage gradually accrue. Elevated lactate and lactic acidosis
High levels of lactic acid in the blood are observed in all people with GSD I, due to impaired gluconeogenesis. Baseline elevations generally range from 4 to 10 mol/mL, which will not cause any clinical impact. However, during and after an episode of low blood sugar, lactate levels will abruptly rise to exceed 15 mol/mL, the threshold for lactic acidosis. Symptoms of lactic acidosis include vomiting and hyperpnea, both of which can exacerbate hypoglycemia in the setting of GSD I.
In DLBCL, NOS variants which trend to spread or to the central nervous system, methotrexate has been recommended to be added to regimens not containing it for use as prophylaxis to reduce the incidence of this complication. The role of Autologous stem-cell transplantation as an addition to first-line therapy in the treatment of DLBCL, NOS, including cases with a poor prognosis, is unclear.A phase I clinical research trial found that the addition of lenalidomide to the R-CHOP regimen produce an ~80% complete response rate in GBC as well as non- GBC DLBCL, NOS variants. Two phase III clinical research trials are underway to confirm these results and determine if the R-CHOP + lenalidomide regimen is superior to R-CHOP in the up-front treatment of GBC and/or non-GBC variants. Treatment of recurrent and refractory DLBCL, NOS
Patients with DLBCL, NOS who relapse or progress following first-line therapy have been treated with "salvage regimens" consisting of high-dose (also termed high-intensity) chemotherapy conditioning drugs followed by autologous stem cell transplantation. This regimen has attained 3-year progression-free survival rates of 21–37%. Relapse following this treatment carries a very poor prognosis with median overall survival times of ~10 months. Patients who have failed or because of health issues are ineligible for autologous stem cell transplantation have been treated with low-dose (i.e. low-intensity) chemotherapy conditioning regimens followed by allogeneic stem cell transplantation. This regimen has achieved 3 year progression-free and overall survival rates of 41% and 52%, respectively. Further studies are underway to determine the best treatment regimens for these cases.