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Breast implants linked to NHL lymphoma

A systematic review has highlighted an association between breast implants and anaplastic large-cell lymphoma (ALCL), a rare and indolent form of Non-Hodgkin Lymphoma (NHL). A second paper reviewing evidence is expected within a few weeks.

Anaplastic large cell lymphoma and breast implants: a systematic review. Kim B, Roth C, Chung KC et al. Plastic Reconstruct Surg. Advance on-line publication (doi: 10.1097/PRS.0b013e3182172418.

The review was undertaken following growing concerns about a possible link between NHL and breast implants. In January 2011, a review conducted by the US Food and Drug Administration indicated a possible association with ALCL. Although this form of lymphoma is extremely rare, the FDA concluded that women with breast implants may have a very small but increased risk of developing this disease in the scar capsule adjacent to the implant. However, there remains uncertainty about the true cause of ALCL in women with breast implants.1

The current review identified 36 cases of NHL in patients with implants, of which 29 (86%) were ALCL. Typically, these cases were characterised by the presence of a seroma in the fibrous capsule that forms around the implant. However, many cases lacked detailed information. The authors concluded, on the basis of available data that there may be an association which warrants further evaluation.

Haematology Now comment

Historically, ALCL appears to comprise two subtypes: 1) systemic disease with lymphadenopathy and extranodal involvement and 2) primary cutaneous disease limited to the skin. The two subtypes also differ histologically. While this report suggests a possible association between this rare form of NHL and breast implants, there remain unanswered questions about which subtype of disease is indicated. In addition, the study is limited by possible inconsistencies in the interpretation of pathology findings and reporting of the condition.

Reference 1. U.S. Food and Drug Administration. Anaplastic Large Cell Lymphoma (ALCL) In Women with Breast Implants: Preliminary FDA Findings and Analyses. January 2011. Available from: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/BreastImplants/ucm239996.htm Accessed 16 March 2011.

Survivorship care plan improves compliance and awareness in Hodgkin lymphoma survivors

A personalized survivorship care plan mailed to survivors of Hodgkin lymphoma (HL) is effective in communicating risk and increasing patients’ compliance with medical surveillance.

Despite survivors of Hodgkin lymphoma having increased rates of breast cancer and cardiovascular disease, they and their physicians are often unaware of the risks and surveillance recommendations.

A prospective one-arm study was conducted among a random sample of 72 HL survivors (aged 27-55 years) in the Childhood Cancer Survivor Study (CCSS) who were at increased risk for breast cancer and/or cardiomyopathy and had not had a screening mammogram or echocardiogram within the prior 2 years. A 1-page survivorship care plan with recommendations for surveillance was mailed to participants. In addition, survivors' primary physicians were contacted and provided patient-specific information and a web-based Virtual Information Centre was made available for both survivors and physicians. Outcomes were assessed by telephone 6 months after the intervention.

The survivor participation (62/72; 86%) and 6-month retention (56/61; 92%) rates were high. Tension and anxiety, measured by the Profile of Mood States, did not increase following risk notification; 91% of survivors described their reactions to receiving the information in positive terms. At 6 months, 41% of survivors reported having completed the recommended mammogram; 20% reported having an echocardiogram (females 30%, males 10%). Only 29% of survivors visited the website. Nine physicians enrolled, and none used the study resources.

Haematology Now comment

A simple mailed care plan, rather than telephone-based or web-based strategies, appears to motivate patients to fulfill recommended surveillance requirements. Further studies are required to assess the effectiveness of different tools in improving compliance.

Reference Oeffinger K et al. Pediatr Blood Cancer 2011;56(5):818-24.

Hodgkin’s lymphoma: BEACOPP vs. ABVD?

In a recent trial in advanced Hodgkin’s lymphoma, BEACOPP (an intensified regimen of bleomycin, etoposide, doxorubicin,cyclophosphamide, vincristine, procarbazine, and prednisone) resulted in better initial tumour control compared with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). However, as long-term clinical outcome did not differ significantly between the two regimens, ongoing debate continues as to which regimen is preferable.

Viviani S, Zinzani PL, Rambaldi A. ABVD versus BEACOPP for Hodgkin’s Lymphoma when high-dose salvage Is planned. N Engl J Med 2011;365:203-12.

Investigators from the Michelangelo Foundation, the Gruppo Italiano di Terapie Innovative nei Linfomi and the Intergruppo Italiano Linfomi randomized 331 patients with previously untreated and unfavourable Hodgkin’s lymphoma (stage IIB, III, or IV, or an international prognostic score of ≥3) to treatment with either 6 (if complete response after 4 cycles) or 8 cycles of ABVD (n=168) or 8 cycles of BEACOPP (n= 163), followed by local radiotherapy if indicated. Patients with residual or progressive disease after the initial therapy were treated according to a state of the-art high-dose salvage program. The primary end point was the rate of freedom from first progression and secondary endpoints were the rates of freedom from second progression, event-free survival after the initial therapy, and overall survival.

The estimated 7-year rate of freedom from first progression (ITT population) was 85% in the BEACOPP group and 73% in the ABVD group (p = 0.004). There was no difference between the groups in the 7-year rate of event-free survival (78% vs. 71%, p = 0.15). In total, 65 patients (20 in the BEACOPP group, and 45 in the ABVD group) went on to receive salvage therapy. After completion of the overall planned treatment including salvage therapy, there was no difference between the groups for 7-year rate of freedom from a second progression (88% vs.82%, p=0.12) or the 7-year rate of overall survival (89% vs. 84%, p = 0.39).

Severe adverse events occurred more frequently in the BEACOPP group than in the ABVD group (81% vs. 43%, <0.001 for haematological toxicity and 19% vs. 7% for nonhaematological toxicity, p=0.001). In particular, treatment with BEACOPP was associated with an increase in acute hematologic adverse events, severe infections, and mucositis.

Haematology Now comment

Clinicians and patients need to weigh up the risks and benefits of these two regimens. With BEACOPP, this study showed an excess risk of severe toxic effects in the absence of a significant survival benefit whereas with ABVD, one in eight patients required subsequent salvage that was associated with severe early and late toxic effects similar to those of BEACOPP.

New insight into why some patients do not respond to rituximab

Rituximab plays a key role in the treatment of Non-Hodgkin’s lymphoma. Its mode of action is via ‘tagging’ the surface of the tumour cells so they can be sought out and destroyed by the patient’s own immune system. However, resistance remains a problem, affecting up to 30% of patients.

Lim SH, Vaughan AT, Ashton-Key M et al. Fc gamma Receptor IIb on target B cells promotes rituximab internalization and reduces clinical efficacy. Blood 2011; published ahead of print July 18, 2011, doi:10.1182/blood-2011-01-330357.

Researchers at the University Of Southampton Faculty Of Medicine investigated the reasons for this. They previously showed that in some lymphoma patients, rituximab is rapidly internalised after binding to the surface of the lymphoma cells, therefore limiting the involvement of natural effectors in this process. In this report, they showed that the presence of the inhibitory FcγRIIb on target B cells promotes this process. When FcγRIIb is present at high levels, this reduced the ability of macrophages cells to destroy tumour cells. In a preliminary analysis, patients with high levels of FcγRIIb on lymphoma cells were less likely to be treated successfully. These data suggest that FcγRIIb is a potential biomarker of response to rituximab.

Haematology Now comment

Non-Hodgkin’s lymphoma is the sixth most common cancer, responsible for around 4,500 deaths each year in the UK. Treatment for non-Hodgkin’s lymphoma has made rapid progress. Despite this, a substantial proportion of patients do not respond to rituximab, currently regarded as the treatment of choice. This research not only helps in understanding why these patients do not respond, but potentially will help clinicians to identify these non-responsive patients with a view to offering alternative, more effective treatments at a much earlier stage. These promising data also suggest that FcγRllb may be a potential therapeutic target in lymphoma.

Rituximab +CHOP-like regimen benefits younger patients with diffuse large-B-cell lymphoma

Rituximab added to 6 cycles of CHOP-like chemotherapy improves long-term outcomes in young patients with good-prognosis diffuse large-B-cell lymphoma.

Pfreundschuh M, Kuhnt E, Trumper L et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diff use large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol 2011, published online, DOI:10.1016/S1470-2045(11)70235-2.

The original MabThera International Trial (MInT) was the first to show improved 3-year outcomes (event-free, progression-free and overall survival) with the addition of rituximab to a CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like regimen in young patients with good prognosis diffuse large-B-cell lymphoma. A total of 824 patients were enrolled at 172 participating centres in 18 countries. This new follow-up study provides 6-year results.

The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab. After a median follow-up of 72 months (range 0•03–119), 6-year event-free survival was 55•8% (95% CI 50•4–60•9) in patients assigned to chemotherapy alone and 74•3% (69•3–78•6) in those assigned to chemotherapy plus rituximab (difference between groups 18•5%, 11•5–25•4, log-rank p<0•0001).

Multivariable analyses showed that event-free survival was affected by treatment group, the presence of bulky disease, and age-adjusted International Prognostic Index (IPI) and that overall survival was affected by treatment group and presence of bulky disease only.

After chemotherapy and rituximab, a favourable subgroup (IPI=0, no bulk) could be defined from a less favourable subgroup (IPI=1 or bulk, or both; event-free survival 84•3% [95% CI 74•2–90•7] vs 71•0% [65•1–76•1], log-rank p=0•005). A total of 18 (4•4%, 95% CI 2•6–6•9) second malignancies occurred in the chemotherapy-alone group and 16 (3•9%,2•2–6•2) in the chemotherapy and rituximab group (Fisher’s exact p=0•730).

Haematology Now comment

This study confirms that the outcome benefits reported in the 3-year trial are also maintained after 6 years with improvements in event-free, progression-free and overall survival without increased toxicity or at the cost of secondary malignancies. Bulky disease and age-adjusted IPI are predictive of positive outcomes and allow for a more refined therapeutic approach in young patients with low risk diffuse B-cell lymphoma.

More Articles...

  • Prophylactic strategies in large B-cell lymphoma prevent CNS relapse
  • Dose intensification of R-CHOP provides no additional benefit in treating B-cell lymphoma
  • New epidemiological data on primary CNS lymphoma highlights low survival rates
  • Current smoking increases risk of Hodgkin’s lymphoma by 35%

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Unless otherwise indicated, opinions expressed in Haematology Now are those of the contributors.  Although every effort is made to ensure accuracy and avoid mistakes, no liability on the part of the sponsor, publisher, editors or the editorial board is accepted for the consequences of any misleading or inaccurate information.

© 2014 . All rights reserved. 'Viewpoints' photo courtesy of the American Society of Hematology.



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