The lymphocyte to monocyte ratio improves the IPI-risk definition of diffuse large B-cell lymphoma when rituximab is added to chemotherapy.

The peripheral blood lymphocyte to monocyte ratio (LMR) at diagnosis can be clinically relevant in patients with diffuse large B-cell lymphoma (DLBCL). We reviewed the outcome of 1,057 DLBCL patients followed from 1984 to 2012 at four centers. LMR was analyzed as a clinical biomarker by receiver-operating characteristic (ROC) analysis and Harrell's C-statistics. Patients were characterized by a median age of 61 years, International Prognostic Index (IPI) score of >2 in 39%, and were treated with a rituximab-containing chemotherapy in 66%. LMR proved strongly predictive for survival in patients treated with rituximab-based programs, but not in those receiving chemotherapy alone. Additionally, an LMR value of ≤2.6 (as determined by ROC analysis) was associated with a worst performance status, a higher lactate dehydrogenase (LDH) level, an advanced clinical stage, and a higher IPI score (P = 0.000). In patients treated with rituximab-supplemented chemotherapy programs, an LMR value of <2.6 was found in most of the primary refractory patients (75%) which proved as the best cutoff to predict both response and survival (P = 0.018). Finally, multivariate analysis and Harrell's C-statistics confirmed the IPI-independent role of LMR on survival (P = 0.0000). In conclusion, LMR is a potent predictor of clinical response and survival in DLBCL treated with rituximab-containing chemotherapy.

Primary duodenal follicular lymphoma: 6-years complete remission after combined radio-immunotherapy.

Primary gastrointestinal lymphoma (PGL) is known to account for 40% of all extranodal non-Hodgkin's lymphomas (NHLs) and between 4% to 12% of all NHLs. The small intestine is the site of presentation in 20-30% of cases, with the terminal ileum usually involved. Duodenal localizations have always been thought to be rare, but are presently growing in incidence. We herein report on a case of Stage IV primary duodenal FCL, located to the second portion of the duodenum with concomitant minimal bone marrow involvement. The patient was frontline approached with a conservative combined modality treatment consisting of 4 weekly infusions of the chimeric human-murine IgG1 mono-clonal antibody against the B-cell surface antigen CD-20, Rituximab (375 mg/m2) and consolidation 3D conformal external beam radiotherapy up to a total dose of 36 Gy given into 20 fractions to the involved duodenal portion. Six years after treatment has been completed, the patient is free from disease with no treatment-related toxicity.

High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: a multicenter study of the intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence.

BACKGROUND: The objective of the current study was to evaluate in a multicenter setting the feasibility and efficacy of a high-dose sequential (HDS) chemotherapy regimen that combined intensive debulking and high-dose therapy (HDT) with peripheral blood progenitor cell (PBPC) autografting in patients with refractory or recurrent Hodgkin lymphoma (HL). METHODS: Data were collected from 102 patients with HL who were treated with the HDS regimen at 14 centers associated with the Intergruppo Italiano Linfomi. Twenty-four patients had primary refractory HL, 59 patients had their first recurrence of HL (within 1 year in 32 patients and > 1 year in 27 patients), and 19 patients had multiple disease recurrences. The HDS regimen included the sequential delivery of high-dose (hd) cyclophosphamide with PBPC harvesting, methotrexate, etoposide, then HDT (usually hd mitoxantrone plus L-phenylalanine mustard) with PBPC autografting. In addition, radiotherapy was delivered to 36 patients at sites of bulky or persistent disease. RESULTS: Ninety-two patients (90%) completed the HDS program. There were five toxic deaths (treatment-related mortality rate, 4.9%) and six secondary malignan cies (five patients developed myelodysplastic syndrome/acute myelogenous leukemia, and one patient developed colorectal carcinoma). At a median follow-up of 5 years, the 5-year overall survival (OS) and event-free survival (EFS) projections were 64% (95% confidence interval [95% CI], 54-74%) and 53% (95% CI, 43-63%), respectively. Patients with their first recurrence had the most favorable outcome, with 5-year OS and EFS projections of 77% (95% CI, 66-88%) and 63% (95% CI, 50-76%), respectively. There were no significant differences between patients with early first recurrence and late first recurrence. The poorest outcome was observed in patients with refractory HL, with 5-year OS and EFS projections of 36% (95% CI, 16-55%) and 33% (95% CI, 14-52%), respectively. Patients who received HDS chemotherapy after multiple recurrences had an intermediate outcome. Multivariate analysis showed that refractory disease and systemic symptoms at the time of initial presentation were associated significantly associated with poor OS and EFS. CONCLUSIONS: The use of HDS chemotherapy for patients with refractory and/or recurrent HL is feasible at the multicenter level. The combination of intensive debulking and HDT with PBPC autografting offers a good chance of prolonged disease free survival for patients with their first recurrence of HL.

High rate of clinical and molecular remissions in follicular lymphoma patients receiving high-dose sequential chemotherapy and autografting at diagnosis: a multicenter, prospective study by the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Single-center experiences have shown that intensified treatments with autologous transplantation are a promising therapeutic strategy for patients with high-risk follicle-center lymphoma (FCL) at diagnosis, whereas data from prospective multicenter trials are still lacking. This paper describes the results of a prospective multicenter study of an intensified purging-free high-dose sequential (i-HDS) chemotherapy schedule with peripheral blood progenitor cell (PBPC) autografting. The main feature of this program is harvesting stem cells after intensified chemotherapeutic debulking, with no ex vivo manipulation of PBPCs. Ninety-two previously untreated patients aged 60 or younger with advanced-stage FCL were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis. i-HDS proved feasible with limited toxicity (87% patients completed the planned treatment schedule). i-HDS led to a complete remission rate of 88%. The projected overall survival and disease-free survival (DFS) were, respectively, 84% and 67% at 4 years. Centralized molecular analysis showed that polymerase chain reaction-negative harvests could be collected in 47% of cases. Following autograft, 65% of molecularly evaluable patients achieved clinical and molecular remission. The projected DFS at 4 years of this subgroup is 85%. This result emphasizes the importance of achieving maximal tumor reduction in these patients. In conclusion, our data show that highly effective intensified treatments can now be routinely offered to young patients with poor-risk FCL even at small institutions, with no need for sophisticated and expensive cell manipulation procedures.