Immunomonitoring of Transplanted Patients Infused With Mesenchymal Stromal Cells (MSC) for Treating Steroid-Refractory GVHD

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Incidence and Outcome of Invasive Fungal Diseases after Allogeneic Stem Cell Transplantation: A Prospective Study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

AbstractEpidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs

Bortezomib plus dexamethasone is highly effective in relapsed and refractory myeloma patients but responses are short-lived.

Objectives Bortezomib has proven to be effective as single agent in myeloma patients. Aim of this study was to evaluate the efficacy and toxicity of bortezomib in combination with dexamethasone in a cohort of MM relapsed/refractory patients treated in a single centre. Patients and Methods In this single center study 70 patients were treated with bortezomib alone (9) or in combination with dexamethasone (61). Results Forty-one patients (59%) achieved at least a partial response (PR), including 7% complete response (CR), 36% very good partial response (VGPR) reaching the best response within 4 cycles. The duration of response (DOR) was significantly longer for patients achieving CR/VGPR than for those achieving PR (7.3 versus 3.8 months, p=0.03). Likewise, time to progression (TTP), time to alternative treatment (TTAT), and treatment free interval (TFI) were significantly better for patients obtaining CR/VGPR (6.8, 9.4, 6.5 months respectively) as compared to PR (4.9, 6.3, 2 months respectively). The only dose-limiting toxicity was peripheral neuropathy (PN), which occurred in 38/70 patients (55%) and was of grade 3-4 in 12 (17%). PN led to a dose reduction or treatment discontinuation in 17 (24%) patients. Complete resolution or improvement of PN occurred in 29/38 (76%) after a median time of 100 days (range: 17-202). Conclusions Bortezomib in combination to dexamethasone is highly effective in relapsed/refractory MM producing an impressive rate of CR/VGPR, but responses are short-lived

Epidemiology of invasive fungal diseases in haematopoietic stem cell transplant recipients: preliminary analysis of a multicentre, prospective, observational study from Italy

Objectives: The purpose of our study was to describe the cur- rent epidemiology, incidence, risk factors and current diagnos- tic strategies for invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplant (HSCT). Methods: This prospective, observational, multicenter study involved 30 HSCT Centers from Italy, started in January 2008 and is ongoing. Each Center reported data on consecutive patients who underwent HSCT and data were collected until 1 year from transplant. The data collection is ongoing and pre- liminary data are now reported. Results: To date, the baseline characteristics are available for 691 patients. Of them, 71 patients (10.3%) had experienced a proven/probable IFD before HSCT. They were 53 (74.6%) inva- sive aspergillosis (IA), 12 invasive candidosis (IC) and 6 IFDs by other fungi. Out of 515 patients evaluable at 100 days from HSCT, 53 (10.3%) developed a proven/probable IFD (IA, 46 cases; IC 5 cases; other IFDs, 2 cases). Out of 348 patients evaluable for the follow-up from 100 to 180 days from HSCT, 15 (4.3%) devel- oped an IFD. Finally, 5 IFDs (2.6%) were documented among 190 patients evaluable for the follow-up from 180 to 365 days. Overall, according to these preliminary data, the incidence of IFDs at 1 year from HSCT seems higher than 15%. According to the data until now available at least 15% of patients with an IA diagnosed before HSCT experienced an infection recurrence within 100 days after transplant. Out of 58 cases of proven/prob- able IA documented after HSCT serum detection of Aspergillus galactomannan antigen contributed to the diagnosis in 45 cases (77.6%). At a preliminary analysis, the 3 months mortality rate for HSCT recipients with an IFD was lower than 30%. Conclusion: This is a prospective study on the “real life” epide- miology of IFDs in allogeneic HSCT population. The available data show that IA remains the most commonly identified IFD and rates of survival appear to have improved, compared with historical literature data

An insidious presentation of splenic marginal zone lymphoma

Herein, we report on a patient with splenic marginal zone lymphoma who initially presented without splenomegaly and bone marrow (BM) or peripheral blood involvement. At first, the patient showed moderate leukothrombocytopenia; she was completely asymptomatic, and BM examination excluded a hematologic disease. After 7 months, spleen enlargement was detected without determining any symptoms or worsening of the bilinear cytopenia. Bone marrow histologic, immunohistochemic, cytologic, and immunophenotypic examinations were normal. Splenectomy was performed, and a diagnosis of splenic marginal zone B-cell lymphoma was established. A monoclonal IgVH gene rearrangement was identified in the spleen tissue (VH3 gene family) and subsequently detected in the BM mononuclear cells. Because of the large surgical debulking and the absence of histologic, cytologic, and immunophenotypic BM involvement, no further treatment was proposed. After the splenectomy, the blood cell count normalized, and neither BM nor peripheral blood involvement appeared after 12 months of follow-up