Final analysis of the UKLG LY02 trial comparing 6-8 cycles of CHOP with 3 cycles of CHOP followed by a BEAM autograft in patients <65 years with poor prognosis histologically aggressive NHL.

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 (cyclophosphamide, 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.

The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT).

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 MIPI(B) (biological), incorporating Ki-67 expression, identified almost half of the patients as high risk. We suggest that also a simplified MIPI(B) is feasible.

Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma.

PURPOSE: 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). PATIENTS AND MATERIALS: 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. RESULTS: 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. CONCLUSION: 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.

Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.

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.

[Acute lymphoblastic leukaemia in Danish children and young people 10 to 19 years of age. Should young adults with acute lymphoblastic leukaemia be treated in the same way as children?]. / Akut lymfoblastaer leukaemi hos børn og unge på 10-19 år i Danmark. Bor unge voksne med akut lymphoblastaer leukaemi behandles pa samme made som born?

INTRODUCTION: Data seem to indicate that young adults with acute lymphoblastic leukemia (ALL) have a better survival rate when treated with paediatric protocols than with adult ALL protocols. The purpose of this study was to report the clinical characteristics and outcome of all children and young adults 10-19 years of age diagnosed with ALL in Denmark between 1992 and 2001. MATERIALS AND METHODS: The study included 99 patients 10-19 years of age with ALL in Denmark during a 10-year period found in the complete NOPHO (Nordic Society of Pediatric Hematology and Oncology) registry and through the Danish Cancer Registry and local pathology databases. Data were retrieved by reviewing patients' medical charts. 61 children (10-14 years) were treated on paediatric protocols, and 38 young adults (15-19 years) were diagnosed with ALL. Data were reported as of 1 January 2005. RESULTS: There were no differences between the two groups with respect to the distribution of T-ALL, CNS leukemia, total WBC and high-risk chromosomal abnormalities. There was a statistically significant lower event-free survival rate (EFS) (p < 0.01) and lower overall survival rate (p < 0.01) in young adults than in 10-14-year-old children (0.38 vs. 0.60 and 0.47 vs. 0.67). There were more transplant-related deaths in the young adults. The higher treatment intensity in children may be an explanatory factor. Children were given more prednisone, vincristine and high-dose methotrexate than were the young adults. CONCLUSION: Young adult patients with ALL might benefit from therapy with paediatric NOPHO ALL protocols.

Position emission tomography with or without computed tomography in the primary staging of Hodgkin's lymphoma.

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-[18F]fluoro-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.

FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma.

Risk-adapted lymphoma treatment requires early and accurate assessment of prognosis. This investigation prospectively assessed the value of positron emission tomography with 2-[18F]fluoro-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.