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Background: The achievement of complete response (CR) significantly correlates with a better clinical outcome in multiple myeloma (MM) patients treated with autologous stem cell transplant (ASCT). The depth of response is one of the most relevant factors to predict patient's outcome, however the definition of CR through standard criteria has shown several limitations., Methods: In this study we evaluated the minimal residual disease (MRD) in 50 consecutive MM patients who underwent an up-front tandem ASCT in our center, using a single-tube six-colors flow cytometry assay (FC) based on intra-cytoplasmic immunoglobulin (cy-Ig) light chains ratio evaluated on patient-specific plasma cells (PC) immune profile, in a real-life setting., Results: With a sensitivity up to 10(-5), clonal-PC were documented by FC in 36.4% (12/33) of patients in conventional CR after second transplant. The number of flow MRD-negative patients significantly increased after induction and first ASCT, but not between first and second transplant. The 5-years progression-free survival (5ys-PFS) of flow MRD-negative patients after second transplant was significantly better than patients who remained MRD-positive considering both all patients (5ys-PFS: 70% vs 5%) and patients in CR according to standard criteria (5ys-PFS: 67% vs 0%)., Conclusions: FC remission through cy-Ig light ratio on PC sub-populations is a sensitive, highly informative, low-cost and routinely applicable MRD assay, a powerful tool in treatment response evaluation and a crucial marker of outcome in MM.

Background: Hematopoietic Stem Cell Transplantation (HSCT) is known to induce the inhibitory immune receptor NKG2A on NK cells of donor origin. This occurs in allogeneic recipients, in both the haploidentical and HLA-matched settings., Methods: To gain further insight, not only NKG2A, but also the activating receptors NKG2C and NKG2D were assessed by flow cytometry. Immunophenotyping was carried out not only on CD56(+) but also on CD8(+) lymphocytes from leukemia and lymphoma patients, receiving both HLA-matched (n = 7) and autologous (n = 5) HSCT grafts. Moreover, cognate NKG2 ligands (HLA-E, MICA, ULBP-1, ULBP-2 and ULBP-3) were assessed by immunohistochemistry in diagnostic biopsies from three autotransplanted patients, and at relapse in one case., Results: All the NKG2 receptors were simultaneously up-regulated in all the allotransplanted patients on CD8(+) and/or CD56(+) cells between 30 and 90 days post-transplant, coinciding with, or following, allogeneic engraftment. Up-regulation was of lesser entity and restricted to CD8(+) cells in the autotransplantation setting. The phenotypic expression ratio between activating and inhibitory NKG2 receptors was remarkably similar in all the patients, except two outliers (a long survivor and a short survivor) who surprisingly displayed a similar NKG2 activation immunophenotype. Tumor expression of 2 to 3 out of the 5 tested NKG2 ligands was observed in 3/3 diagnostic biopsies, and 3 ligands were up-regulated post-transplant in a patient., Conclusions: Altogether, these results are consistent with a dual (activation-inhibition) NK cell re-education mode, an innate-like T cell re-tuning, and a ligand:receptor interplay between the tumor and the immune system following HSCT including, most interestingly, the up-regulation of several activating NKG2 ligands. Turning the immune receptor balance toward activation on both T and NK cells of donor origin may complement ex vivo NK cell expansion/activation strategies in unmanipulated patients.

All-trans retinoic acid (ATRA) has made acute promyelocytic leukemia (APL) a very curable disease also in patients aged >60 years; however, there are only few case reports in very elderly APL patients. To address this issue, we reviewed treatment results in 13 patients aged >70 years with newly diagnosed APL followed at our institution from January 1991 to December 2008. According to Sanz score, seven patients were at low risk, five at intermediate risk, and one at high risk. Induction therapy consisted of ATRA + idarubicin in nine patients (3/9 with reduced idarubicin dosage) and ATRA alone in four patients; in this latter group, however, 2/4 needed to add chemotherapy (CHT) due to hyperleukocytosis during ATRA treatment. All patients achieved both morphological and molecular complete remission (CR) after a median time of 51 [interquartile range (IR) 43-55] and 114 (IR 74-155) days, respectively. Infective complications were observed in 10/13 patients, APL differentiation syndrome in 3/13 patients. Twelve patients received consolidation therapy, followed by maintenance treatment in nine patients. Five patients relapsed after 7, 8, 11, 35, and 56 months. At present, seven patients are still alive, five died due to disease progression (four) or senectus while in CR (one), and one was lost to follow-up while in CR. The 5-year event-free survival was 56.1 % (95 % CI, 26.0-86.2); the 5-year overall survival (OS) was 64.5 % (95 % CI, 35.6-93.4). ATRA-based treatment of APL is safe and effective also in very elderly patients, with long-lasting disease-free OS.