630 Objectives We evaluated long-term efficacy and toxicity of tailored 177Lu-dotatate (177Lu-PRRT) therapy in 65 consecutive patients with G1-G2 pancreatic neuroendocrine tumors (P-NENs).The role of 18F-FDG PET-CT as an independent prognostic factor was also investigated. Methods From March 2008 to September 2011, 65 consecutive P-NEN patients were enrolled in a prospective study and followed-up until March 2015. Patients were treated with two different total activities (18.5GBq or 27.8 GBq) and underwent 5 cycles of 177Lu-PRRT depending on the kidney and bone marrow status. Fifty-nine patients underwent 18F-FDG PET-CT before 177Lu-PRRT. Results Median follow-up was 59 months (7-82). Thirty patients received a mean full activity (FA) of 25.5 GBq (20.7-27.8) and 35 a mean reduced activity (RA) of 17.8 GBq (11.1-19.9). The disease control rate (DCR) in the FA group was 87% and 85% in the RA group (p=0.83). Median progression-free survival (PFS) was 53.4 months (21.2-68.7) in the FA arm and 24.4 months (19.5-59.2) in the RA arm (p= 0.42). Median overall survival (OS) was not reached in FA patients and was 63.8 months in the RA group (p= 0.013). No cases of grade 3 or 4 hematological toxicity were registered. One (3%) RA patient showed grade 2 renal toxicity and another (3%), grade 3 renal toxicity. Median PFS in the PET-CT-positive group was 21.2 months (18.9-28.7) compared to 68.7 months in PET-CT-negative patients (53.4-nr) (p Conclusions Personalized 177Lu-PRRT showed effective antitumor activity and mild toxicity in advanced P-NEN patients, and was feasible in patients with severe comorbidities. 18F-FDG PET-CT was confirmed as a valid independent prognostic factor in these patients.
Folic acid binding protein (FABP) has been measured in the supernatant of leukocytes of 12 patients affected with chronic granulocytic leukaemia (CGL). The folate binding capacity ranged from 1.37 to 697.52 pg/mg protein, showing a considerable heterogeneity. When the supernatant was preincubated with methotrexate (MTX), the inhibition of folic acid binding was complete in some cases whereas in others it was negligible: these findings have been confirmed by studying the 3H-MTX binding capacity by the same supernatants. In this case the range of bound 3H-MTX varied from 0.00 to 927 pg/mg protein. The presence of a binder in the cytoplasm of leukocytes might represent a new step in the regulation of endogenous folate metabolism. The MTX, widely used as an antifolate drug, may also be bound by FABP of CGL leukocytes, although in different amounts from case to case: this finding suggests a new point of interference of MTX in the folate metabolism. It has also been demonstrated that FABP, which is present in serum, may reduce the uptake of folate by leukocytes opening a new field of investigation on the megaloblastic transformation.
S ummary . In three cases of acute myeloid leukaemia marked increases in expression of the nuclear enzyme, terminal deoxynucleotidyl transferase (TdT), were observed during disease relapse. The first case was heterogeneous at diagnosis, consisting of subpopulations of large TdT − myeloblasts and small TdT + blasts; however, at relapse there was complete replacement by TdT + lymphoblasts. The other cases at diagnosis were both typical acute myeloid leukaemia, TdT − ; at relapse, one showed a mixture of TdT − myeloblasts and TdT + lymphoblasts, while in the other, TdT was demonstrated on a subpopulation of myeloblasts. No chromosomal abnormalities were found. It is suggested that in the first two cases these phenomena may have been due to leukaemic involvement of a pluripotential stem cell, or that sub‐clones with different properties may have coexisted. In the third case at relapse, TdT was expressed aberrantly by malignant myeloid cells.
