Risk-adapted lymphoma treatment requires early and accurate assessment of prognosis. This investigation prospectively assessed the value of positron emission tomography with ...2-18Ffluoro-2-deoxy-D-glucose (FDG-PET) after two cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS) in Hodgkin lymphoma (HL). Seventy-seven consecutive, newly diagnosed patients underwent FDG-PET at staging, after two and four cycles of chemotherapy, and after completion of chemotherapy. Median follow-up was 23 months. After two cycles of chemotherapy, 61 patients had negative FDG-PET scans and 16 patients had positive scans. Eleven of 16 FDG-PET–positive patients progressed and 2 died. Three of 61 FDG-PET–negative patients progressed; all were alive at latest follow-up. Survival analyses showed strong associations between early FDG-PET after two cycles and PFS (P < .001) and OS (P < .01). For prediction of PFS, interim FDG-PET was as accurate after two cycles as later during treatment and superior to computerized tomography (CT) at all times. In regression analyses, early interim FDG-PET was stronger than established prognostic factors. Other significant prognostic factors were stage and extranodal disease. Early interim FDG-PET is a strong and independent predictor of PFS in HL. A positive early interim FDG-PET is highly predictive of progression in patients with advanced-stage or extranodal disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mantle cell lymphoma (MCL) has a heterogeneous clinical course. The recently proposed Mantle Cell Lymphoma International Prognostic Index (MIPI) predicted the survival of MCL better than the ...International Prognostic Index in MCL patients treated with conventional chemotherapy, but its validity in MCL treated with more intensive immunochemotherapy has been questioned. Applied here to 158 patients of the Nordic MCL2 trial of first-line intensive immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation, the MIPI and the simplified MIPI (s-MIPI) predicted survival significantly better (P < .001) than the International Prognostic Index (P > .004). Both the MIPI and the s-MIPI mainly identified 2 risk groups, low and intermediate versus high risk, with the more easily applied s-MIPI being just as powerful as the MIPI. The MIPIB (biological), incorporating Ki-67 expression, identified almost half of the patients as high risk. We suggest that also a simplified MIPIB is feasible. This trial was registered at www.isrctn.org as #ISRCTN 87866680.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. hutchings@dadlnet.dk
BACKGROUND AND OBJECTIVES: In order to receive the ...most appropriate therapy, patients with Hodgkin's lymphoma (HL) must be accurately stratified into different prognostic staging groups. Computed tomography (CT) plays a pivotal role in the conventional staging. The aim of the present study was to investigate the value of positron emission tomography using 2-18Ffluoro-2-deoxy-D-glucose (FDG-PET) and combined FDG-PET/CT for the staging of HL patients, and the impact on the choice of treatment. DESIGN AND METHODS: Ninety-nine consecutive, prospectively included patients had FDG-PET and CT in their staging work-up. Sixty-one of the 99 patients had combined FDG-PET/CT. A standard of reference for each nodal region and organ was determined using all available information including scan results, histology and a minimum of one year's clinical follow-up data. The lack of a satisfactory diagnostic gold standard limits the reliability of accuracy calculations. RESULTS: FDG-PET would have upstaged 19% of patients and downstaged 5% of patients, leading to a different treatment in 9% of patients. For FDG-PET/CT, the corresponding figures are 17%, 5%, and 7%. In nodal regions, the sensitivity of FDG-PET and FDG-PET/CT seemed higher than that of CT (92% and 92% vs. 83%). FDG-PET identified more false positive nodal sites than did CT and FDG-PET/CT (1.6% vs 0.7% and 0.5%). FDG-PET and FDG-PET/CT were highly sensitive for evaluating organs (86% and 73%) while CT detected 37% of involved organs. INTERPRETATION AND CONCLUSIONS: FDG-PET and FDG-PET/CT have a substantial potential impact on staging and choice of treatment and the methods tend to upstage rather than downstage patients. FDG-PET and FDG-PET/CT seem to have a higher diagnostic accuracy than CT in the staging of HL. However, care should be taken so patients with an excellent prognosis and at risk of over-treatment do not receive more intensive treatment because of these staging methods.
Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive ...treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT).
MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks.
Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR.
Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.
Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 ...consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The promise of prolonged survival after psychosocial interventions has long been studied, but not convincingly demonstrated. This study aims to investigate whether a psychosocial group intervention ...improved long-term survival in women with early-stage breast cancer and investigate differences in baseline characteristics and survival between study participants and non-participants.
A total of 201 patients were randomized to two six-hour psychoeducation sessions and eight weekly sessions of group psychotherapy or care as usual. Additionally, 151 eligible patients declined to participate. Eligible patients were diagnosed and treated at Herlev Hospital, Denmark, and followed for vital status up to 18 years after their primary surgical treatment. Cox's proportional hazard regressions were used to estimate hazard ratios (HRs) for survival.
The intervention did not significantly improve survival in the intervention group compared with the control group (HR, 0.68; 95% confidence interval (CI), 0.41-1.14). Participants and non-participants differed significantly in age, cancer stage, adjuvant chemotherapy, and crude survival. When adjusted, no significant survival difference between participants and non-participants remained (HR, 0.77; 95% CI, 0.53-1.11).
We could not show improved long-term survival after the psychosocial intervention. Participants survived longer than nonparticipants, but clinical and demographic characteristics, rather than study participation, seem accountable for this difference.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
This trial involved 457 patients and sought to assess the value of early intensification with autologous transplantation in patients with poor prognosis histologically aggressive non‐Hodgkin ...lymphoma (NHL) showing a response to initial CHOP (cyclosphosphamide, doxorubicin, vincristine, prednisolone) chemotherapy. Randomization was made at the time of diagnosis with 223 assigned to continuing CHOP and 234 to 3 cycles of CHOP followed by a BEAM (carmustine, etoposide, cytarabine, melphalan) autograft. Analysis was on an intention to treat basis. After the initial three cycles of CHOP 19% of the whole group were in complete response (CR) and 53% in partial remission (PR). At the end of treatment 86% of patients in the CHOP arm had responded with 58% in CR. In the high‐dose therapy arm the overall response rate was 83% with 64% in CR (difference between arms not significant). The progression‐free survival (PFS) and overall survival at 5 years for the continuing CHOP arm were 38% and 50% respectively, and for the autograft arm were 44% and 50% (differences not significant). Of the patients who attained CR and subsequently relapsed, there were no long‐term survivors in the autograft recipients compared to 46% of the continuing CHOP recipients (P = 0·0008). In conclusion, no survival benefit was demonstrated for an early autograft in first response.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background: The addition of rituximab (R) to bi-weekly CHOP (CHOP-14) in the RICOVER-60 trial resulted in improved time to treatment failure in 828 elderly (61–80 years) DLBCL patients (Blood 106:9a, ...2005). We investigated the addition of LTBI in a dose of 1,6 Gy given as adjuvant therapy in high-risk elderly patients with DLBCL treated according to the best performing arm of the RICOVER-60 trial (R-CHOP-14 x 6 + 2xR).
Methods: A phase II trial including pts >60 yrs with stage II-IV, CD20-positive DLBCL was performed between 2003 and 2007. Pts received 6x R-CHOP-14 and 2 x R alone followed by LTBI given as 2 courses of 4 daily fractions of 0,2 Gy separated by 2 weeks of rest.
Results: We report the results of the first 36 patients. The median age was 69 years; 56% had ≥ 1 extranodal lesion; 67% had stage III or IV; 48% had B symptoms and 37% had Bulky (> 7.5 cm) disease; 54% had ECOG score ≥ 1; 75% had elevated LDH and 63% had IPI of >2, while 73% stained positive for BCL2 in pre-therapeutic histological samples. One patient got off study because of the discovery of breast cancer and one patient refused to get LTBI. Twenty one pts achieved a CR or CRu at the end of chemotherapy (58%), 10 (27%) were in PR while only one patient progressed under chemotherapy. All 10 PR pts achieved CR in the first follow up after LTBI. Four pts relapsed within 12 months after achieving CR. All treatment failures occurred in patients with IPI 3&4. Of the administered R-CHOP-14, Rituximab and LTBI cycles, 95%, 100% and 96%, respectively, were given in full dose and on time. CTC Gr 3–4 neutropenia occurred following 50 of 250 R-CHOP-14 cycles (20%). There were 3 toxic deaths (7.8%) due to sepsis occurring during chemotherapy. CTC Gr. 3–4 thrombocytopenia was seen in 8 pts following the last LTBI cycle (22%) and could be prolonged. The 2-Y Overall survival (OS) was found to be 79% (SE ± 8%) while the 2-Y disease free survival (DFS) was 74% (SE ± 10%).
Conclusion: In a selected DLBCL group of elderly patients with high-risk prognostic profile, R-CHOP-14 followed by LTBI, although sometimes associated with severe infections and thrombocytopenia, seems to achieve high response rates and provide correspondingly high OS and DFS values.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
By fluorescence microscopy (FM), flow cytometry (FCM) and immunoelectron microscopy (IEM) we have shown that B1 and B2 monoclonal antibodies (MoAbs) were able to induce modulation of CD20 and CD21 in ...RAJI and JOK-1 cell lines. Redistribution and internalization of both antigens (Ags) after binding with MoAbs was readily demonstrated by FM, and by IEM CD20 and CD21 were found to be processed by the pathway of receptor-mediated endocytosis. The rate of intracellular transport varied: CD21 > CD20 and RAJI > JOK-1. Approximately 65 and 55% of CD20 and 60 and 45% of CD21 were cleared from the surface of RAJI and JOK-1 cells, respectively (FCM and IEM). These values, however, clearly exceeded those corresponding to internalization (11, 9, 24 and 16%) indicating shedding of Ag-MoAb complexes. No evidence of recycling was found. The present data support the hypothesis that the kinetics of modulation vary from one Ag to another and probably also reflect the stage of differentiation of the malignant B-cells. The results are discussed in the context of the possible usefulness of B1 and B2 MoAbs in the therapy of B-cell malignancies.
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