Lymphocytic toxicity in patients after peptide-receptor radionuclide therapy (PRRT) with 177lu-DOTATATE and 90Y-DOTATOC

Purpose: Peptide-receptor radionuclide therapy (PRRT) with somatostatin analogs is an efficient new tool in patients with neuroendocrine tumors, with low risk of toxicity. Since lymphocytes express somatostatin receptors, the aim of this study was to evaluate lymphocytic toxicity after PRRT. Methods: From May 2005 to May 2007, 16 patients affected by neuroendocrine tumors received PRRT with 90Y-DOTATOC (9), 177Lu-DOTATATE (5), or both (2). Absolute count, percentage of leukocytes and lymphocytes, and lymphoid subsets (B, T, and NK) were tested at baseline and until 90 days after treatment. Results: A significant lymphoid toxicity (G2-3), mainly affecting B-cells, was observed. It was particularly evident after 90Y-DOTATOC. Toxicity resulted in being transient and resolved completely at the end of the follow-up (90 days). Conclusion: Lymphocyte toxicity in PRRT is mainly due to the selective targeting on B-cells. The relative sparing of T-lymphocytes could explain the absence of clinical side-effects in these patients, such as increased risk of infections. These findings open interesting perspectives in the treatment of B-cell lymphoproliferative disorders. © 2009 Mary Ann Liebert, Inc

If it is in the marrow, is it also in the blood? An analysis of 1,000 paired samples from patients with B-cell non-Hodgkin lymphoma

<p>Abstract</p> <p>Background</p> <p>Staging of B-cell non Hodgkin's lymphoma (NHL) routinely involves bone marrow (BM) examination by trephine biopsy (BM-TB). The evidence of disease in the BM-TB results in a clinical stage IV classification affecting therapeutic strategies for NHL patients. BM immunophenotyping by flow cytometry (FC) is also used, although its clinical value is still under debate.</p> <p>Methods</p> <p>Using FC we analyzed 1,000 paired BM aspirates and peripheral blood (PB) samples from 591 NHL patients to investigate the concordance between BM and PB. B-lymphocytes were defined monoclonal when a ratio of 0.3 < κ/l > 3 was observed. Aberrant immunophenotypes present in the B-cell subpopulation were also investigated. BM-TB was also performed in 84.1% of samples (841/1000), and concordance between BM-TB and BM-FC was evaluated. Concordance was defined as the presence of a positive (in terms of disease detection) or negative result in both BM-FC and PB-FC or BM-TB and BM-FC.</p> <p>Results</p> <p>Using FC, the overall concordance between BM and PB was 95%. Among the discordant cases (ie presence of neoplastic B-lymphocyte in the BM but under the sensibility of the technique in the PB) the most frequent diagnosis was Waldenstrom's macroglobulinemia (WM, accounting for 20.8% of all discordant cases). The expression of CXCR4, a receptor involved in B-cell trafficking and homing, was found to be down regulated in WM compared to other NHL types, thus suggesting a possible role of CXCR4 in WM cell homing in the BM. WM excluded, FC investigation of BM and PB in NHL patients gives overlapping information.</p> <p>BM involvement was observed by FC in 38% of samples, and concordance between BM-FC and BM-TB was 85%.</p> <p>Conclusions</p> <p>The finding that FC data from BM and PB samples overlap in NHL might have major implications for the design of future clinical studies and for patients' follow-up.</p

Patients characteristics.

<p>Patients characteristics.</p

Expression of Ulex Europeaus Lectin.on CD109+CECs and CD146+CECs+ (4A–B1).

<p>Epcam staining (4C–C1) confirmed that Epithelial Cells even if present in the DNA+CD45− cell compartment, are negative for the expression of CD31 present only on endothelial cells.</p