The clinical course of B-cell chronic lymphocytic leukemia (B-CLL) is variable, and novel biologic parameters need to be added to the clinical staging systems to predict an indolent or aggressive outcome. We investigated the 70-kDa zetaassociated protein (ZAP-70), CD38, soluble CD23 (sCD23), and cytogenetics in 289 patients with B-CLL. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70 ؉ (P < .001), in CD38 ؉ (P < .001) and in sCD23 ؉ patients (P < .001 and P ‫؍‬ .013, respectively). ZAP-70 ؉ CD38 ؉ or ZAP-70 ؉ patients with an unmutated IgV H status showed both a shorter PFS (P < .001) and OS (P < .001 and P < .001, respectively) as compared with ZAP-70 ؊ /CD38 ؊ or ZAP-70 ؊ patients with mutated IgV H genes. Discordant patients showed an intermediate outcome. Note, ZAP-70 ؉ patients even if CD38 ؊ or mutated showed a shorter PFS, whereas ZAP-70 ؊ patients even if CD38 ؉ or unmutated had a longer PFS. Furthermore, ZAP-70 positivity was associated with a shorter PFS both within normal karyotype (P < .001) and within the poor-risk cytogenetic subset (P ‫؍‬ .02).

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

SummaryInterim 2-[18F]Fluoro-2-deoxy-D-glucose Positron Emission Tomography performed after two chemotherapy cycles (PET-2) is the most reliable predictor of treatment outcome in ABVD-treated Hodgkin Lymphoma (HL) patients. We retrospectively analysed the treatment outcome of a therapeutic strategy based on PET-2 results: positive patients switched to BEACOPP, while negative patients continued with ABVD. Between January 2006 and December 2007, 219 newly diagnosed HL patients admitted to nine centres were enrolled; 54 patients, unfit to receive this treatment were excluded from the analysis. PET-2 scans were reviewed by a central panel of nuclear medicine experts, according to the Deauville score (Meignan, 2009). After a median follow up of 34 months (12-52) the 2-year failure free survival (FFS) and overall survival for the entire cohort of 165 patients were 88% and 98%; the FFS was 65% for PET-2 positive and 92% for PET-2 negative patients. For 154 patients in which treatment was correctly given according to PET-2 review, the 2-year FFS was 91%: 62% for PET-2 positive and 95% for PET-2 negative patients. Conclusions: this strategy, with BEACOPP intensification only in PET-2 positive patients, showed better results than ABVD-treated historic controls, sparing BEACOPP toxicity to the majority of patients (Clinical Trials.gov Identifier NCT00877747).

IntroductionCNS dissemination in patients with aggressive non-Hodgkin lymphoma (NHL) is a relatively rare but often fatal complication that occurs in the different subtypes of NHL with a frequency of 5% (ie, diffuse large B-cell lymphoma [DLBCL]) to 30% 1 (ie, Burkitt lymphoma [BL] and B-cell lymphoblastic lymphoma [B-LL]). Many CNS events occur early after diagnosis (4.7-9 months), during therapy, or shortly after completion of treatment, suggesting that initial CNS involvement could have been undetected in most cases. Prophylactic treatment likely reduces the incidence of CNS relapse, but may increase the toxicity of systemic chemotherapy; furthermore, the incidence of CNS dissemination is not high enough to suggest the use of prophylaxis treatment in all patients affected by aggressive NHL. Therefore, CNS prophylaxis is usually incorporated into protocols for the treatment of B-LL and BL, but it is not systematically warranted in patients with DLBCL. Therefore, the identification of patient subgroups for which CNS prophylaxis may be useful is important, especially for DLBCL patients who have no well-defined risk factors for CNS relapse. Risk models for DLBCL have been developed, but are mainly derived from analyses of retrospective studies. [2][3][4][5] An increased risk of CNS dissemination is associated with involvement of the BM and certain extranodal sites such as testis, paranasal sinuses, orbits, and paravertebral masses. Moreover, patients with a high to intermediate or high risk according to the International Prognostic Index (IPI), particularly those with high serum levels of lactate dehydrogenase (LDH) and involvement of more than 1 extranodal organ, are much more prone to develop CNS involvement than others and should receive CNS prophylaxis. 6 Nevertheless, CNS risk predictors and related prognostic scores have been identified in retrospective and heterogeneous series, including different lymphoma categories; however, resulting scores show a low sensitivity in predicting CNS involvement.The diagnosis of CNS dissemination is frequently suspected by the presence of related signs or symptoms and confirmed by examination of cerebrospinal fluid (CSF) and neuroimaging techniques. The diagnostic standard conventional cytology (CC) examination of CSF is considered as having low sensitivity and low specificity, with reported falsenegative rates of 20%-60%. 7 This has been ascribed to the paucity of neoplastic cells in the CSF of patients with minimal disease and to the presence of confounding reactive lymphocytes. Therefore, patients with low tumor burden in the CSF, who are more likely to benefit from CNS treatment, are actually more commonly exposed to false-negative [8][9][10][11][12][13][14] However, it is still unknown whether detecting occult leptomeningeal involvement and consequently changing treatment may improve outcome in these patients.In the present study, we compared prospectively FCM analysis versus CC examination of baseline samples of CSF to detect occult leptomeningeal disease in patie...

The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.