Silvia Trappolini

Tailored therapy in an unselected population of 91 elderly patients with DLBCL prospectively evaluated using a simplified CGA.

BACKGROUND Elderly patients with diffuse large B-cell lymphoma (DLBCL) are a heterogeneous population; clinical trials have evaluated a minority of these patients. PATIENTS AND METHODS Ninety-one elderly patients with DLBCL received tailored treatment based on a comprehensive geriatric assessment (CGA). Three groups were identified: I, fit patients; II, patients with comorbidities; III, frail patients. Group I received 21-day cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-21), group II received R-CHOP-21 with liposomal doxorubicin, and group III received 21-day cycles of reduced-dose CHOP. Fifty-four patients (59%) were allocated to group I, 22 (25%) were allocated to group II, and 15 (16%) were allocated to group III. RESULTS The complete response (CR) rates were 81.5% in group I, 64% in group II, and 60% in group III. With a median follow-up of 57 months, 42 patients are alive, with 41 in continuous CR: 31 patients (57%) in group I, seven patients (32%) in group II, and four patients (20%) in group III. The 5-year overall survival, event-free survival, and disease-free survival rates in all patients were 46%, 31%, and 41%, respectively. Multivariate analysis selected group I assignment as the main significant prognostic factor for outcome. CONCLUSIONS This approach in an unselected population of elderly DLBCL patients shows that treatment tailored according to a CGA allows the evaluation of elderly patients who are currently excluded from clinical trials.

Gene expression profile of cytokines in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with reduced conditioning.

There are no reliable markers useful to predict the onset or the evolution of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT), although several candidate biomarkers have been identified from limited hypothesis-driven studies. In this study we evaluated 14 patients who received a reduced intensity conditioning HSCT. Seven patients had cGVHD, whereas 7 never developed cGVHD during the period of observation. The expression of 114 cytokines in immunoselected cell populations was explored by microarray analysis and 11 cytokines were selected for further evaluation by real-time PCR. Differential gene expression measurements showed a significant up-regulation for INFγ (interferon, gamma) in CD8+ and for TNFSF3 (tumor necrosis factor superfamily, member 3) and for TNFSF10 (tumor necrosis factor superfamily, member 10) in CD14+ cell population when comparing cGVHD with control samples. The expression levels were significantly decreased for TNFSF10 in CD8+ cell population and for TNFSF12 (tumor necrosis factor superfamily, member 12) and for PDGFβ (platelet-derived growth factor, beta) in CD4+. Our data seem to suggest that different immune populations can play a role in cGVHD pathogenesis and the early detection of gene expression profile in these patients could be useful in the monitoring of GVHD. We hypothesized that PDGFβ down-regulation could represent a negative feedback to compensate for enhanced expression of its receptor recently reported.

Telomere length, c-myc and mad-1 expression could represent prognosis markers of myelodysplastic syndrome

Telomere dysfunction might generate genomic instability leading to the progression of myelodysplastic syndromes (MDS) into acute myeloid leukemia (AML). We investigated telomere length (TL), telomerase activity (TA) and hTERT, c-myc, mad1, and p53 expression in the bone marrow of patients with MDS (n=109), AML (n=47) and in controls (n=24). TL was lower in MDS patients than in controls (p<0.001) and higher in L-MDS (low, intermediate-1 IPSS, p<0.01) respect H-MDS (high, intermediate-2 IPSS, p<0.01) patients. Mad-1 expression was higher in MDS patients than in controls (p<0.01), c-myc expression was highest in AML and in H-MDS patients. Our results show that the telomere dynamics might be useful for stratifying patients according to a risk scoring system.

Prognostic role of immunohistochemical analysis of 5 mc in myelodysplastic syndromes.

Aberrant DNA methylation at CpG islands within promoters is increasingly recognised as a common event in human cancers and has been associated with the silencing of important tumour suppressor genes. Epigenetic therapy using hypomethylating agents has demonstrated clinical effectiveness; the drugs azacitidine and decitabine have been approved for the treatment of MDS.

Low-dose Gemtuzumab-Ozogamicin as post-consolidation therapy in elderly patients with acute myeloid leukaemia: a pilot study

T., Heldmann, K., Carmi, R., Parvari, R., Beit-Or, H., Goldman, B., Peleg, L., Levy-Lahad, E., Renbaum, P., Legum, S., Shomrat, R., Yeger, H., Benbenisti, D., Navon, R., Dror, V., Shohat, M., Magal, N., Navot, N. & Eyal, N. (1998) Prevalence of glucocerebrosidase mutations in the Israeli Askenazi Jewish poulation. Human Mutations, 12, 240–244. Pocovi, M., Cenarro, A., Civeira, F., Torralba, M.A., Perez-Calvo, J.I., Mozas, P., Giraldo, P., Girait, M., Myers, R.H., Cupples, L.A. & Ordovas, J.M. (1998) Beta –glucocerebrosidase gene locus as a link for Gaucher’s disease and familial hypo-alfa-lipoproteinaemia. Lancet, 351, 1919–1923.

Fatal Necrotizing Angiotropic Epstein–barr Virus-negative Large B-cell Lymphoma: A Case Report with Unusual Clinicopathological Features In-between Lymphomatoid Granulomatosis and T-cell/histiocyte-rich Large B-cell Lymphoma

AbstractIn the spectrum of diffuse large B-cell lymphomas (DLBCL), both T-cell/histiocyte-rich large B-cell lymphoma (TCHRBCL) and most lymphomatoid granulomatosis (LG) cases are characterized by the relative rarity of the neoplastic B-cell population, with respect to the overwhelming non-neoplastic counterpart of T cells or histiocytes. Here we report a case of aggressive B-cell lymphoma with unusual clinicopathological features partially overlapping these two entities.The patient was a previously healthy 55-year-old male, presenting with a computed tomography finding of a pelvic mass, inguinal lymphadenopathies, and pulmonary nodules. Two excisional lymph node biopsies resulted inconclusive for lymphoproliferative disease. Because of a colonic perforation, the patient underwent an urgent laparotomy, which disclosed a large pelvic abscess. The pathological examination of the surgical specimen could not discriminate between a primary aggressive B-cell lymphoproliferative disorder and an abnormal inflammatory hyper-reaction. The patient developed a septic state, not resolving until death, which occurred because of an abdominal hemorrhage. A second perimortem surgical specimen consisting of a nodal mass revealed a diagnosis of an Epstein–Barr virus-negative high-grade large B-cell lymphoma with massive necrosis, angiocentric pattern of growth, and prominent T-cell infiltrate.The unique clinicopathological features did not allow to classify this tumor within any of the recognized WHO entities, potentially representing a new clinicopathological variant of DLBCL in-between TCHRBCL and LG.