We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of ...rituximab to chemotherapy and interferon.
The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42-58%) and 72% (95%CI 64-78%), respectively.
The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41-62%) versus 40% (95%CI 24-55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78-97%) versus 63% (95%CI 51-72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival.
Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients.
Summary
Despite a high curability rate, some patients with Hodgkin lymphoma (HL) fail to respond to, or relapse after, primary conventional treatment. This review aims to identify prognostic factors ...at relapse and guidelines for treatment in relapsed HL. Patients with relapsed HL should be identified according to their prognostic factors at relapse (duration of remission and extranodal disease or stage). This enables relapsing patients to be separated in to three different prognostic groups; primary refractory patients should be included in the unfavourable group because of their poor prognosis. All relapsed HL should receive second‐line chemotherapy and the response to this chemotherapy is crucial for the outcome. Benefit of autologous stem‐cell transplantation (ASCT) has been shown in a large randomized study and, although is often proposed in relapsed HL, it may be not necessary in the rare group of patients with stage I/II and late relapse who can receive additional radiotherapy after response to chemotherapy. Patients with intermediate and unfavourable relapse should receive high‐dose chemotherapy and ASCT when chemosensitive; the first goal is to achieve this chemosensitivity. For patients in the unfavourable group, including refractory patients, the role of tandem HDT or allogeneic SCT will be discussed and should be proposed for patients not in complete remission at the time of HDT.
Purpose
We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over ...doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials.
Patients and methods
Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression‐free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT).
Results
About 1227 patients were included. The 7‐year OS was 84.3% (95% CI 80.8‐87.2) for ABVD vs 87.7% (95% CI 84.5‐90.2) for BEACOPP. Two follow‐up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09‐2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7‐year PFS was 71.1% (95% CI 67.1‐74.6) for ABVD vs 81.1% (95% CI 77.5‐84.2) for BEACOPP (P < .001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP.
Conclusions
This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT.
Advanced Hodgkin lymphoma (HL) are treated with two different chemotherapy regimens (doxorubicin Adriamycin, bleomycin, vinblastine, and dacarbazine ABVD or bleomycin, etoposide, doxorubicin Adriamycin, cyclophosphamide, vincristine Oncovin, procarbazine, and prednisone BEACOPP) that have two different toxicity profiles. In this pooled analysis of four randomized trials comparing these two regimens, and with a median follow‐up of 7 years, progression‐free survival is significantly superior with the BEACOPP regimen. The 7 years overall survival was 84.3% for ABVD and 87.7% for BEACOPP. The main cause of death after ABVD is HL, but second malignancy including 10 myeloid malignancies after BEACOPP.
Summary Detection of MUM1+ cells in follicular lymphoma (FL) tissues was previously found to be associated with poor prognosis in a single report, whereas the usefulness of Ki-67 immunostaining ...remains debated. Our goal was to establish whether these markers have predictive value for patients with FL. We analyzed MUM1 and Ki-67 expression using immunohistochemistry in biopsy samples from 434 patients from the PRIMA randomized trial. The MUM1 prognostic value was then validated in a cohort of 138 patients from the FL2000 randomized trial, using the optimal cutoff value obtained from the PRIMA cohort. The surface of positive staining was quantified using computerized image analysis. In the PRIMA cohort, both high levels of MUM1 positivity (cutoff value of 0.80%) and high levels of Ki-67 positivity (cutoff value of 10.25%) were significantly associated with a shorter progression-free survival (PFS) ( P = .004 and P = .007 for MUM1 and Ki-67, respectively). In a multivariate Cox proportional hazards regression model, only MUM1 retained a statistical significance (hazards ratio 1.56; 95% confidence interval, 1.02-2.37; P = .038) after adjustment for the maintenance arm of treatment and the follicular lymphoma international prognostic index score. In the FL2000 cohort, high levels of MUM1 positivity were significantly associated to a shorter PFS ( P = .004) and to a trend toward a shorter overall survival ( P = .043). This remained significant using a multivariate Cox regression model after adjustment for the follicular lymphoma international prognostic index and the treatment arm for PFS ( P = .016). These results show that MUM1 is a strong and robust predictive immunohistochemical marker in patients with FL.
PURPOSE First-line treatment for patients with newly diagnosed follicular lymphoma (FL) still remains debated, even in the rituximab-based combination therapy era. Few studies have addressed the ...question whether complete remission (CR) translates into better survival. The aim of this study was to assess the long-term follow-up of prospectively treated patients with FL and the potential correlation between response quality to first-line treatment and overall survival (OS). PATIENTS AND METHODS Data from 536 patients with FL with low (n = 193) or high (n = 343) tumor burden enrolled from October 1986 to May 1995 in the French and Belgian GELF86 studies were analyzed. Data from these trials have been previously reported for low-tumor burden and high-tumor burden patients. Results Median follow-up was 14.9 years, and median OS was 9.8 years. Treated patients who achieved a complete response (CR; n = 194; 45%) had a significant longer OS than those only reaching a partial response (PR; n = 168; 39%) throughout treatment (hazard ratio HR, 0.55; 95% CI, 0.42 to 0.72; P < .001) in an univariate time-dependent Cox model. Similar findings were found when response to treatment (CR v PR) was adjusted for potentially confounding factors in a multivariate model (HR, 0.53; 95% CI, 0.38 to 0.73; P < .001). CONCLUSION These data provide a long follow-up of these patients' cohorts and indicate that a better response to first-line treatment translates into an improved survival for patients with FL. Therefore, response-adapted therapy aiming to achieve a CR should be considered as first-line treatment.
Background
Hypersensitivity reactions (HSR) to pegylated liposomal doxorubicin (PLD; Caelyx
®
) have been reported, and symptoms usually resolve with drug withdrawal. However, the risk of relapse of ...severe HSR and prevention remain poorly described.
Objectives
To report the management and outcome in four patients with HSR due to PLD.
Materials & Methods
Patient characteristics, premedication regimen, rate of infusion, time between onset and HSR, clinical manifestations, and management were documented.
Results
A first cycle of PLD was received for cutaneous T-cell lymphoma (
n
= 3) and Kaposi sarcoma (
n
= 1). The drug was diluted in 250 mL 5% glucose and administered over one hour (4.17 mL dilution/min, i.e. 0.6 mg PLD/min for 1.8m
2
body surface area BSA). Grade 3 HSR occurred in the first minutes in the four patients. Because of the absence of alternative treatment for the underlying disease, PLD was resumed. Premedication was reinforced with 300 mg oral ranitidine and 50 mg hydroxyzine the night before and the morning of infusion. The rate of infusion was 1 mL dilution/min (0.14 mg PLD/min for 1.8 m
2
BSA) for the first 15 minutes. No HSR occurred in three patients. In contrast, severe symptoms appeared in the first seconds of resumption in one patient.
Conclusion
To minimise HSR to PLD, an initial reduced rate of infusion of 0.1-0.2 mg of PLD/min is warranted. In the event of HSR, alternative therapy must be privileged, and if necessary, careful re-challenge with PLD may be attempted, however relapse of HSR may occur.
Conventional lymphography has long been the method of choice for imaging the lymphatic system. However, the number of lymphographic studies performed in oncology centers has declined markedly since ...the introduction of cross-sectional imaging techniques, especially computed tomography (CT). Therefore, levels of expertise in both performing lymphography and interpreting lymphograms are falling. The unique ability of lymphography to demonstrate derangements of the internal architecture of normal-sized lymph nodes can be valuable and makes it more accurate than CT in evaluation of some lymphomas (especially Hodgkin disease) and genitourinary malignancies. In fact, lymphography and CT are complementary rather than mutually exclusive techniques for the staging of some lymphomas and genitourinary malignancies. In addition, lymphography opacifies the lymphatic channels and therefore may be a valuable tool for detection of lymphatic fistulas or lymphatic leakage. Finally, lymphography helps guide subsequent therapy in patients with lymphomas, genitourinary malignancies, or disorders of lymphatic flow.
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