Incidence and risk factors for central nervous system relapse in patients with primary mediastinal large B-cell lymphoma in the rituximab era.

Central nervous system (CNS) involvement is rare in primary mediastinal large B-cell lymphoma (PMLBCL). We aimed to evaluate the incidence of CNS relapse as first treatment failure event and the effect of the induction chemotherapy regimen, central nervous system - international prognostic index (CNS-IPI) and other clinical and laboratory variables on the risk of CNS relapse in 564 PMLBCL patients treated with immunochemotherapy. Only 17 patients (3.0%) received CNS prophylaxis. During a 55-month median follow-up only 8 patients experienced CNS relapse as first event, always isolated. The 2-year cumulative incidence of CNS relapse (CI-CNSR) was 1.47% and remained unchanged thereafter. The CI-CNSR was not affected by the chemotherapy regimen (R-CHOP or R-da-EPOCH). None of the established International Prognostic Index factors for aggressive lymphomas predicted CNS relapse in PMLBCL. The 2-year CI-CNSR in patients with versus without kidney involvement was 13.3% versus 0.96% (p < 0.001); 14.3% versus 1.13% with versus without adrenal involvement (p < 0.001); and 10.2% versus 0.97% with versus without either kidney or adrenal involvement. CNS-IPI was also predictive (2-year CI-CNSR in high-risk vs. intermediate/low-risk: 10.37% vs. 0.84%, p < 0.001). However, this association may be driven mainly by kidney and/or adrenal involvement. In conclusion, in PMLBCL, CNS relapse is rare and appears to be strongly associated with kidney and/or adrenal involvement.

Identification of Very Low-Risk Subgroups of Patients with Primary Mediastinal Large B-Cell Lymphoma Treated with R-CHOP.

BACKGROUND: R-CHOP can cure approximately 75% of patients with primary mediastinal large B-cell lymphoma (PMLBCL), but prognostic factors have not been sufficiently evaluated yet. R-da- EPOCH is potentially more effective but also more toxic than R-CHOP. Reliable prognostic classification is needed to guide treatment decisions. MATERIALS AND METHODS: We analyzed the impact of clinical prognostic factors on the outcome of 332 PMLBCL patients ≤65 years treated with R-CHOP ± radiotherapy in a multicenter setting in Greece and Cyprus. RESULTS: With a median follow-up of 69 months, 5-year freedom from progression (FFP) was 78% and 5-year lymphoma specific survival (LSS) was 89%. On multivariate analysis, extranodal involvement (E/IV) and lactate dehydrogenase (LDH) ≥2 times upper limit of normal (model A) were significantly associated with FFP; E/IV and bulky disease (model B) were associated with LSS. Both models performed better than the International Prognostic Index (IPI) and the age-adjusted IPI by Harrel's C rank parameter and Akaike information criterion. Both models A and B defined high-risk subgroups (13%-27% of patients [pts]) with approximately 19%-23% lymphoma-related mortality. They also defined subgroups composing approximately one-fourth or one-half of the patients, with 11% risk of failure and only 1% or 4% 5-year lymphoma-related mortality. CONCLUSION: The combination of E/IV with either bulky disease or LDH ≥2 times upper limit of normal defined high-risk but not very-high-risk subgroups. More importantly, their absence defined subgroups comprising approximately one-fourth or one-half of the pts, with 11% risk of failure and minimal lymphoma-related mortality, who may not need more intensive treatment such as R-da-EPOCH. IMPLICATIONS FOR PRACTICE: By analyzing the impact of baseline clinical characteristics on outcomes of a large cohort of patients with primary mediastinal large B-cell lymphoma homogeneously treated with R-CHOP with or without radiotherapy, we developed novel prognostic indices which can aid in deciding which patients can be adequately treated with R-CHOP and do not need more intensive regimens such as R-da-EPOCH. The new indices consist of objectively determined characteristics (extranodal disease or stage IV, bulky disease, and markedly elevated serum lactate dehydrogenase), which are readily available from standard initial staging procedures and offer better discrimination compared with established risk scores (International Prognostic Index [IPI] and age-adjusted IPI).

Positron emission tomography after response to rituximab-CHOP in primary mediastinal large B-cell lymphoma: impact on outcomes and radiotherapy strategies.

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

Serum ferritin levels in previously untreated classical Hodgkin lymphoma: correlations and prognostic significance.

Serum ferritin (SF) is frequently elevated in classical Hodgkin lymphoma (cHL). We report on its prognostic significance in an unselected series of 529 cHL patients treated with state-of-the-art therapy. Higher baseline levels correlated with markers of advanced/aggressive disease. SF levels were significantly higher in male and older patients, those with high body mass index and mixed cellularity histology. The strongest correlation was recorded between SF and complement reactive protein (CRP) levels. Gender-specific SF cutoffs which provided the best discrimination in terms of freedom from progression (FFP) were identified. In multivariate analysis elevated SF levels, advanced stage and high lactate dehydrogenase (LDH) were independent prognostic factors of inferior FFP. SF also appears to retain independent prognostic significance for progression-free survival (PFS) but not for overall survival (OS). In conclusion, SF levels in cHL reflect disease activity and are associated with adverse patient outcomes.

Chronic myelomonocytic leukemia treated with 5-azacytidine - results from the Hellenic 5-Azacytidine Registry: proposal of a new risk stratification system.

Hypomethylating agents are widely used in chronic myelomonocytic leukemia (CMML). We analyzed the characteristics of 88 patients with CMML homogeneously treated with 5-azacytidine (Hellenic 5-Azacytidine Registry). The overall response rate was 48.9% and the median overall survival (OS) 29.7 months. Out of the seven most widely used prognostic scoring systems for CMML, the Dusseldorf score (DUSS) showed the best prognostic capability (HR, 2.27; p < .001). Forty-one (48.8%) patients progressed to acute myeloid leukemia (AML) after a median time of 15.2 months following treatment initiation. High serum ferritin levels at diagnosis were independently correlated with low OS (HR, 2.84; p = .022), as were circulating blasts (HR, 3.47; p = .014), while a platelet count <100 × 109/L was marginally predictive of lower OS (HR, 1.45; p = .06). We selected these three factors to create a new risk stratification system for CMML with three risk groups. Finally, we highlighted for the first time the prognostic significance of serum ferritin levels in CMML.