Second Malignancy Risks After Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia: Differences by Lymphoma Subtype

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD 20892, USA.
Journal of Clinical Oncology (Impact Factor: 17.88). 10/2010; 28(33):4935-44. DOI: 10.1200/JCO.2010.29.1112
Source: PubMed

ABSTRACT Previous studies have shown increased risks of second malignancies after non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL); however, no earlier investigation has quantified differences in risk of new malignancy by lymphoma subtype.
We evaluated second cancer and leukemia risks among 43,145 1-year survivors of CLL/small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL) from 11 Surveillance, Epidemiology, and End Results (SEER) population-based registries during 1992 to 2006.
Among patients without HIV/AIDS-related lymphoma, lung cancer risks were significantly elevated after CLL/SLL and FL but not after DLBCL (standardized incidence ratio [SIR], CLL/SLL = 1.42, FL = 1.28, DLBCL = 1.00; Poisson regression P for difference among subtypes, P(Diff) = .001). A similar pattern was observed for risk of cutaneous melanoma (SIR: CLL/SLL = 1.92, FL = 1.60, DLBCL = 1.06; P(Diff) = .004). Acute nonlymphocytic leukemia risks were significantly elevated after FL and DLBCL, particularly among patients receiving initial chemotherapy, but not after CLL/SLL (SIR: CLL/SLL = 1.13, FL = 5.96, DLBCL = 4.96; P(Diff) < .001). Patients with HIV/AIDS-related lymphoma (n = 932) were predominantly diagnosed with DLBCL and had significantly and substantially elevated risks for second anal cancer (SIR = 120.50) and Kaposi's sarcoma (SIR = 138.90).
Our findings suggest that differing immunologic alterations, treatments (eg, alkylating agent chemotherapy), genetic susceptibilities, and other risk factors (eg, viral infections, tobacco use) among lymphoma subtypes contribute to the patterns of second malignancy risk. Elucidating these patterns may provide etiologic clues to lymphoma as well as to the second malignancies.


Available from: Neil Caporaso, Aug 21, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cure of Helicobacter pylori infection induces remission in most patients with gastric mucosa-associated lymphoid tissue lymphoma (GML) that is associated with these bacteria. We determined the long-term outcomes of these patients in a prospective multicenter trial and investigated whether they developed second cancers or had histologic residual disease. We followed 120 patients with stage EI1 GML for a median of 122 months after H pylori eradication (range, 1-171 months). Remission was determined by histology analysis and development of second cancers was documented. Of the patients, 80% (96 of 120) achieved complete remission from GML, and 80% of those (77 of 96) remained disease free. Estimated mean survival time in the Kaplan-Meier analysis was 147 months (95% confidence interval: 138-156 months). Of the patients that achieved complete remission, 17% (16 of 96) had histologic residual disease after a median of 32 months (range, 3-68 months). Disease did not progress in any of these patients, and all but 1 achieved a second complete remission (median duration, 46 months). Standardized morbidity ratios revealed a significantly higher incidence of gastric cancer (8.567; 95% confidence interval, 3.566-20.582) or non-Hodgkin lymphoma (18.621; 95% confidence interval: 8.365-41.448) in the 96 patients that achieved a complete remission, compared with the general German population. Cure of H pylori infection leads to continuous complete remission in most patients with H pylori-associated GML. Patients are at risk for development of secondary cancers (ie, gastric cancer and non-Hodgkin lymphoma).
    Gastroenterology 06/2012; 143(4):936-42. DOI:10.1053/j.gastro.2012.06.035 · 13.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Malignant cells in chronic lymphocytic leukemia (CLL) and related diseases are heterogeneous and consist primarily of long-lived resting cells in the periphery and a minor subset of dividing cells in proliferating centers. Both cell populations have different molecular signatures that play a major role in determining their sensitivity to therapy. Contemporary approaches to treating CLL are heavily reliant on cytotoxic chemotherapeutics. However, none of the current treatment regimens can be considered curative. Pharmacological CDK inhibitors have extended the repertoire of potential drugs for CLL. Multi-targeted CDK inhibitors affect CDKs involved in regulating both cell cycle progression and transcription. Their interference with transcriptional elongation represses anti-apoptotic proteins and, thus, promotes the induction of apoptosis. Importantly, there is evidence that treatment with CDK inhibitors can overcome resistance to therapy. The pharmacological CDK inhibitors have great potential for use in combination with other therapeutics and represent promising tools for the development of new curative treatments for CLL.
    Future medicinal chemistry 03/2012; 4(4):395-424. DOI:10.4155/fmc.12.12 · 4.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dysphonia is frequently an expression of laryngitis, especially when it comes in the evolution of an immunosuppressed patient, as happens in chronic lymphoproliferation. But other causes of dysphonia should also not be forgotten, including the possibility of new malignancies, especially due to the fact that these patients have genomic instability that predisposes to appearance of a second or even a third cancer. We present the case of a patient who developed dysphonia during chronic lymphocytic leukemia evolution. Its etiology was a mediastinal compression through lymph nodes, not linked to leukemia, but produced by metastases of a bronchopulmonary cancer, appeared recently. Dysphonia condition due to vocal cord dysfunction must include diseases of the mediastinum, the neck and the brain stem. The rapid and correct diagnosis and the prompt start of an appropriate treatment are of paramount importance for clinician who manage their care and for patient survival.
    Pakistan Journal of Medical Sciences Online 01/2015; 31(1):223-5. DOI:10.12669/pjms.311.6091 · 0.10 Impact Factor