Diagnostic and prognostic studies in Hodgkin's lymphoma with special reference to the elderly

Detta är en avhandling från Stockholm : Karolinska Institutet, Department of Medicine

Sammanfattning: The introduction of modem staging procedures, and developments in both radiotherapy and chemotherapy have significantly contributed to improved response and survival rates in Hodgkin's lymphoma (HL) during the last decades. However, still a substantial proportion of patients succumb from tumour progression and/or complications related to diagnostic procedures and/or treatment. The presently identified risk factor profiles do not allow accurate tailoring of treatment, especially in the elderly patient population. The overriding goal of the present study was to improve clinical management of HL patients, particularly in the elderly. Individuals with lymphadenopathy and accessible lymph nodes (n=103) were prospectively studied first by fine-needle aspiration cytology (FNAC) and then by histological examination of a biopsy from the same lymph node site. The diagnoses were concordant in 74%. In 10% a major discordance between FNAC and histopathologic diagnoses was found and in 16% minor discordances without clinical impact were recorded. Since the treatment decisions were based on both clinical and FNAC/histopathology data the discrepancies between FNAC and histopathology had only limited impact on the overall clinical strategy. FNAC is an accurate and safe method in the diagnosis of lymphomas when the cytologic diagnosis is corroborated by immunocytochemistry. In certain risk patients FNAC may well be used as a single method. Concerns about the increasing use of FNAC for primary diagnosis include certain shortcomings in lymphoma classification and loss of archival tissue for complementary analyses, reclassification and research purposes. Freezing of cytospin material or cell pellets may, however, allow certain future analyses. The clinical value of routine bone scintigraphy in untreated HL patients was limited. Bone involvement was a rare finding (7/183; 4%). Only one patient received additional local radiotherapy based on the scintigraphic findings. Bone pain was a good predictor of osseous involvement. Performed follow-up scintigraphies showed regression of the initially observed abnormalities suggesting scintigraphy to be a cost-effective alternative method to assess response to treatment in patients with bone involvement. Based on a vaccination algorithm including repeated 23-valent pneumococcal vaccinations, a significant response was found on three vaccination occasions in splenectomized patients with HL (n=208), autoimmune hemolytic anemia (n= 15), and immune thrombocytopenic purpura (n=60) as well as individuals who underwent splenectomy due to splenic rupture caused by trauma (n=28). The observed case morbidity and fatality rates in the HL cohort were lower as compared to those reported in most studies supporting the value of revaccination and other preventive measures such as education of patients and health care professionals. There is a great heterogeneity in outcome in elderly (>60 years) HL patients. Many factors contribute to a decreased relative dose intensity of chemotherapy which is strongly associated with a dismal prognosis in this patient population. ABVD-based chemotherapy appears superior to MOPP variants. Long-term survival can be achieved even following minimal chemotherapy. There is great lack of apt predictors of prognosis as well as alternative treatment modalities in elderly HL patients. Parental longevity was not associated with improved outcome in an elderly HL cohort. Neither was there a significant difference in the distribution of causes of death with reference to parental lifespan. Serum levels of IL-10 and sCD30 added prognostic information to that achieved by conventional predictors of prognosis, suggesting that these markers should be validated in large prospective trials.

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