Cost of illness of malignant lymphoma in Germany

Cancer causes a high economic burden. The purpose of this study is to determine and compare the direct, indirect and societal costs of illness for Hodgkin's Disease (HD), Non-Hodgkin's Lymphoma (NHL), Plasmocytoma and Chronic Lymphatic Lymphoma (CLL). We used a database of 1.9 million individuals enrolled in a statutory sickness fund in Germany to identify 4,172 patients treated for malignant lymphoma in 2000. Direct, indirect and societal costs were calculated using a case-control design and the human capital approach. Direct cost (in Euro) for patients with HD was 3604, for NHL patients 6,149, for Plasmocytoma 8,400, and for CLL patients 3,226. Total indirect cost for HD was 69 million, for NHL patients 404 million, for Plasmocytoma 144 million, and for CLL patients 52 million. Totalling 1.7 billion Euro in economic cost for Germany in 2000, with 44,000 productive years lost, malignant lymphomas are a relatively costly disease group. As life expectancy increases, costs for malignant lymphoma are likely to rise due to the high prevalence among the elderly. Further research employing disaggregated, incidence-based cost is needed.     

Serum soluble interleukin-2 receptor levels are associated with clinical disease status and histopathological grade in non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

Serum soluble Interleukin-2 receptor levels (sIL-2R) were measured in 121 patients (pts) with non-Hodgkin's lymphoma (NHL) and in 30 patients with Chronic lymphocytic leukemia (CLL). Sera collected from 32 normal volunteers and 18 patients with infection or a variety of non malignant hematological disorders served as controls. A small number of patients with Hairy cell leukemia (HCL) and Hodgkin's disease (HD) were also studied. NHL patients were classified according to their clinical status as "active" (82 pts) or "non-active" (39 pts) and CLL according to the stage of their disease. NHL patients were also further classified as low (55 pts), intermediate (38 pts) and high grade malignancy (28 pts), according to the Working formulation scheme. A significant difference was found between the high levels of sIL-2R in patients with "active" disease and the lower levels in patients with quiescent or responsive disease. Significantly different high levels were found in patients with aggressive (intermediate and high grade) lymphoma as opposed to low grade lymphoma and CLL. In CLL itself higher levels of sIL-2R were seen in more advanced disease than in early disease. Thirteen patients with active Hodgkin's disease (HD) had moderately elevated sIL-2R levels, similar to those recorded for patients with infections and some non-malignant hematological disorders while another 13 HD patients in remission, had normal levels comparable to those recorded in normal controls. Extremely high levels of sIL-2R were seen in 2 patients with HD with severe viral infections and levels approaching those seen in HCL, were noted (20-30,000 u/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mime Combination Chemotherapy in Recurrent or Refractory Lymphoproliferative Malignancies: A Phase II Study

Seventy-two patients with recurrent or refractory malignant lymphoproliferative diseases were treated with MIME combination chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide) and concurrent mesna to prevent urothelial toxicity; 41 patients had high/intermediate-grade non-Hodgkin's lymphoma (NHL), 18 low-grade NHL/chronic lymphocytic leukemia (CLL), and 13 Hodgkin's disease (HD). The overall response rates were 56% in high/intermediate-grade NHL, 11% in low-grade NHL/ CLL, and 69% in HD respectively. Median survival in the same 3 groups was 7, 2 and 10 months respectively. Neither previous type of response to chemotherapy nor previous amount of treatment predicted the outcome of MIME chemotherapy. Toxicity was modest, hemorrhagic cystitis did not occur, and only one therapy-related death occurred. Although MIME appears to be a safe treatment with considerable activity in recurrent or refractory lymphoproliferative disease very few patients become long-term survivors. However, MIME is well suited for remission induction in patients intended for subsequent autologous bone-marrow transplantation.     

The influence of parental age and gender on anticipation in familial B-Cell malignancies

Anticipation occurs when a disease manifests at an earlier age and/or with an increased clinical severity in the next generation. Its relationship with parental age and gender is relevant to the patterns of genetic transmission of familial B-cell neoplasms. One hundred and sixty pairs [44 non-Hodgkin's lymphoma (NHL), 38 Hodgkin's disease (HD), 48 HD/NHL, and 30 CLL] were analyzed retrospectively for presence of anticipation in paternal (PT), maternal (MT), and overall transmission. Overall mean anticipation measured -23.0 yr, and varied between -18.93 and -26.46 yr with no significant difference among different diseases, except between CLL and mixed HD/NHL (mean difference -7.68 yr, p = 0.03). A significant Pearson correlation (PC) between the parental age at conception and anticipation was found for all malignancies (PC = -0.339, p < 0.0001), with the exception of mixed HD/NHL pairs of MT. Higher PCs were observed with PT than MT for all diseases. Anticipation manifests in all familial B-cell malignancies analyzed and it correlates with the parental age at conception. Although less prominent than with neurological disease, this phenomenon indicates a possible germline inheritance of B-cell malignancies and a common genetic basis for HD and NHL.     

Interleukin-8 and granulocyte-macrophage colony-stimulating factor secretion in hematologic malignancies

Interleukin-8 (LL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are cytokines/hematopoietic growth factor and are important mediators of inflammation and immune resoponse producing pathophysiological changes in human disease. Levels of IL-8 and GM-CSF in circulation of various hematologic diseases are unknown. To demonstrate their importance in lymphoproliferative disorders, we have measured the circulating levels of these two cytokines from patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). IL-8 and GM-CSF levels were determined by highly specific enzyme-linked immunosorbent assays. IL-8 levels were elevated in most patients with B-cell malignancies, B-cell CLL (B-CLL) and B-cell NHL (B-NHL) as well as in patients with HD. However, GM-CSF levels were higher in most patients with NHL (T-NHL and B-NHL) and HD. IL-8 was undetectable in T-cell malignancies (T-CLL and T-NHL), whereas GMCSF was undetectable from CLL (T-CLL and B-CLL). Of interest, IL-8 levels were correlated with white blood cell counts (WBC) in B-cell malignancies (B-CLL and B-NHL) but not in HD. These results suggest that both IL-8 and GMCSF may play an important role in pathophysiological changes in B-NHL and HD. IL-8 may be related with recruitment and activation of neutrophils, whereas, GM-CSF in proliferation and differentiation of hematopoietic progenitor cells and immune response in these malignancies. The clinical status of B-CLL patients in regards to WBC counts appeared to be associated with the serum levels of IL-8.     

Hodgkin's Disease in Patients Infected with Human Immunodeficiency Virus: Frequency, Presentation and Clinical Outcome

We report the frequency, presenting characteristics, progression-free survival, event-free survival, overall survival and AIDS-free survival of patients with previously untreated Hodgkin's disease (HD) in the setting of infection by human immunodeficiency virus (HIV). To accomplish this we retrospectively reviewed all untreated patients presenting to the University of Texas M.D. Anderson Cancer Center between July 1985 and August 1999 with HD and HIV infection. All available records were reviewed to determine presentation, clinical characteristics, treatment outcome, progression-free survival and overall survival. We identified 887 patients with HD and 3,500 with Non-Hodgkin's Lymphoma (NHL). The ratio of NHL to HD in HIV-negative versus HIV-positive patients was 3.9 versus 6.9, respectively. There were 14 HIV-positive patients with HD and 97 with NHL. The median age of the HIV-positive HD patients was 33 years, and 13 were male. Three patients had Acquired Immune Deficiency syndrome (AIDS) at the time of HD diagnosis, and seven had B-symptoms. Ann Arbor stage was I in one, II in three, III in four and IV in six patients. Mixed cellularity histology was seen in eight, bone marrow involvement in five and extranodal disease in seven patients. Four patients had elevated serum lactate dehydrogenase, three low serum albumin, and nine elevated serum β2-microglobulin, The median CD4 count was 160/μl. Eleven patients received ABVD or equivalent regimens, followed by radiotherapy in five. One patient was treated with COPP and radiotherapy, one with NOVP and radiotherapy and one only with radiotherapy. All patients received some antiretroviral therapy, but it was variable over the years. With a median follow-up of 64 months for survivors, the projected 5-year progression-free survival was 64%, event-free survival 45%, overall survival 54% and AIDS-free survival 45%. Six patients died of complications arising from HIV infection, including one patient who had preexisting AIDS at HD presentation. Two patients died of HD, without developing other conditions diagnostic of AIDS. We conclude that in our referral patient population HIV infection is associated with preferential development of NHL rather than HD, which appears curable with standard treatment regimens. Since HIV-related deaths exceed those caused by HD, future investigation should focus on integration of chemotherapy and highly active antiretroviral therapy.     

Hodgkin's disease in patients infected with human immunodeficiency virus: frequency, presentation and clinical outcome

We report the frequency, presenting characteristics, progression-free survival, event-free survival, overall survival and AIDS-free survival of patients with previously untreated Hodgkin's disease (HD) in the setting of infection by human immunodeficiency virus (HIV). To accomplish this we retrospectively reviewed all untreated patients presenting to the University of Texas M.D. Anderson Cancer Center between July 1985 and August 1999 with HD and HIV infection. All available records were reviewed to determine presentation, clinical characteristics, treatment outcome, progression-free survival and overall survival. We identified 887 patients with HD and 3,500 with Non-Hodgkin's Lymphoma (NHL). The ratio of NHL to HD in HIV-negative versus HIV-positive patients was 3.9 versus 6.9, respectively. There were 14 HIV-positive patients with HD and 97 with NHL. The median age of the HIV-positive HD patients was 33 years, and 13 were male. Three patients had Acquired Immune Deficiency syndrome (AIDS) at the time of HD diagnosis, and seven had B-symptoms. Ann Arbor stage was I in one, II in three, III in four and IV in six patients. Mixed cellularity histology was seen in eight, bone marrow involvement in five and extranodal disease in seven patients. Four patients had elevated serum lactate dehydrogenase, three low serum albumin, and nine elevated serum beta2-microglobulin, The median CD4 count was 160/microl. Eleven patients received ABVD or equivalent regimens, followed by radiotherapy in five. One patient was treated with COPP and radiotherapy, one with NOVP and radiotherapy and one only with radiotherapy. All patients received some antiretroviral therapy, but it was variable over the years. With a median follow-up of 64 months for survivors, the projected 5-year progression-free survival was 64%, event-free survival 45%, overall survival 54% and AIDS-free survival 45%. Six patients died of complications arising from HIV infection, including one patient who had preexisting AIDS at HD presentation. Two patients died of HD, without developing other conditions diagnostic of AIDS. We conclude that in our referral patient population HIV infection is associated with preferential development of NHL rather than HD, which appears curable with standard treatment regimens. Since HIV-related deaths exceed those caused by HD, future investigation should focus on integration of chemotherapy and highly active antiretroviral therapy.     

Yorkshire Case Control Study of Leukaemias and Lymphomas Parallel Multivariate Analyses of Seven Disease Categories

Between 1980 and 1986 a case control study of leukaemias aid lymphomas in Yorkshire conducted face to face interviews on 1362 cases and 2442 age and sex matched hospital controls. Case diagnoses were histopathologically confirmed and grouped into non-Hodgkin's lymphomma (NHL), Hodgkin's Disease (HD), malignant lymphocytic lymphoma (MLL.), chronic lymphocytic leukaemia (CLL), acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL). Multivariate analyses were completed on each separate disease to evaluate risk factors relating to past medical history, occupation, environmental exposures and social contact variables. The results show a significant association (with OR adjusted for other risk factors) between a family history of leukaemia/lymphoma and HD (OR = 4.29), NHL (OR = 1.98) and AML (OR = 6.36). For HD other cancers in the family also conveyed a significant risk (OR = 1.61). Use of heart drugs l(and heart disease) was linked to the chronic leukaemias (CML, CLL). A previous cancer and NHL, CLL and AML were associated even after adjustment for radiotherapy. A complex set of risk factors including prior skin lesions and steroid use showed significant links with HD, NHL and CLL., Increasing risk of NHL was linked to small family size. A significant excess of NHL cases reported exposure to glues and similarly ALL cases with agricultural chemical exposure. There present data provide both confirmatory and novel results. Overall they concur with the hypothesis of a multifactoral aetiology encompassing both genetic and immunological components.     

Expression of leucocyte-common antigen and large sialoglycoprotein on leukemic cells in B-cell chronic lymphocytic leukemia and non-Hodgkin's lymphoma

Patterns of leucocyte-common antigen (L-CA) and large sialoglycoprotein (LSGP) expression on leukemic peripheral blood lymphocytes of 13 patients with chronic lymphocytic leukemia (CLL), 17 with non-Hodgkin's lymphoma (NHL) in leukemic phase and one with hairy cell leukemia (HCL) have been examined by means of surface labelling and electrophoresis in 5% polyacrylamide gels. The 13 CLL, 10 of the 11 diffuse NHL and the six nodular poorly differentiated lymphocytic lymphoma (PDLL) patients fell into three groups according to expression of 210, 198 and 185k forms of L-CA. Group 1 (210 less than 198 less than 185k L-CA) included eight CLL and one diffuse NHL; Group 2 (210 greater than or equal to 198 and 185k L-CA) included four CLL, three diffuse NHL and four nodular PDLL; Group 3 (mainly 210k L-CA) included one CLL, six diffuse NHL and two nodular PDLL. A patient with diffuse large cell lymphoma and the HCL patient both had patterns of multiple, diffuse, very high Mr labelled glycoproteins. LSGP on these cells varied from nil to very high and levels were not related to L-CA patterns. Lymph node cells from five patients were also studied and were found to express larger numbers of L-CA forms and less LSGP than corresponding peripheral blood lymphocytes. Possible relationships of L-CA forms and LSGP to lymphocyte function and disease patterns are discussed.     

Clinical experience of bendamustine treatment for non-Hodgkin lymphoma and chronic lymphocytic leukemia in Spain

Bendamustine is a alkylating agent with a purine-like benzamidazole ring currently approved in Europe for indolent non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma. Our aim was to analyze retrospectively the efficacy and toxicity of bendamustine in NHL and CLL in Spain in the bendamustine Compassionate Use Program. Patients with relapsed/refractory NHL or CLL were eligible. Any regimen containing bendamustine was eligible. 109 patients were included from 22 institutions. Forty-nine patients had indolent NHL, 18 aggressive NHL and 42 CLL, being 44 patients (40%) refractory to previous treatment. 63% of patients had adverse events grade 3-4, mainly hematological. Overall response rate (ORR) was 66%, complete responses 30%. ORR observed in refractory patients was 45%. The median progression-free survival (PFS) was 13 months. Outcome was influenced by histology, number of previous treatments, resistance to previous chemotherapy and type of response achieved with bendamustine. Alone or in combination, bendamustine shows a meaningful clinical antitumor activity in patients with relapsed or refractory NHL or CLL, with an acceptable toxicity profile.     

Familial cancers associated with subtypes of leukemia and non-Hodgkin's lymphoma

To investigate whether a history of hematolymphoproliferative cancers (HLP) and other cancers among a parent or sibling is a risk factor for specific subtypes of leukemia and non-Hodgkin's lymphoma (NHL), data from a population-based case-control study, in Iowa and Minnesota, of 578 leukemia cases, 622 NHL cases and 1245 controls were evaluated. Having at least one sibling with HLP significantly increased the risk for all leukemias combined (odds ratio (OR) = 2.3) and for NHL (OR = 2.7). In particular, chronic lymphocytic leukemia (CLL) was significantly increased among those reporting a sibling with leukemia (OR = 3.0) or lymphoma (OR = 4.3). Elevated risks of small lymphocytic NHL (SML) (OR = 7.3) and diffuse NHL (DIF) (OR = 5.4) were also observed among subjects who had a sibling with lymphoma (primarily Hodgkin's disease). A significantly increased risk of follicular NHL was noted among those with a sibling history of pancreatic cancer (OR = 4.8) and colorectal cancer (OR = 2.7). Parental history of HLP was not associated with any type of leukemia or NHL. A history of stomach cancer among parents was associated with a 2-fold elevation of CLL and DIF compared to controls. Increased risks of CLL and DIF were also linked to breast cancer among sisters and mothers, respectively. Prostate cancer among fathers increased the risk 2-fold for CLL and 3-fold for SML. This study confirms some familial cancer associations previously reported for leukemia and NHL, and provides new information regarding the various subtypes of leukemia and NHL.     

Non-Hodgkin's lymphoma of the brain after Hodgkin's disease. An immunohistochemical study

Non-Hodgkin's lymphoma (NHL) of the central nervous system (CNS) is a rarely reported complication of Hodgkin's disease (HD). Two patients with NHL of the brain after HD were studied by histologic and immunohistochemical methods. Both patients were in the second decade, had been treated with radiation and chemotherapy, had experienced a relapse of HD before development of NHL, had no evidence of HD at the time of diagnosis of NHL, and died within 1 year of diagnosis. Both brain neoplasms were large cell immunoblastic lymphomas of B-cell lineage. Patients with HD appear to be at increased risk for NHL of the CNS, which may have a poor prognosis.     

Hodgkin's disease after treatment of non-Hodgkin's lymphoma

A review of the clinical data base of the Hematology/Lymphoma Service at Memorial Hospital was carried out to determine the incidence of Hodgkin's disease (HD) after treatment of non-Hodgkin's lymphoma (NHL). Five patients (four men, one woman) developed HD after treatment for NHL, with an interval ranging from 60 months to 23 years (median, 7.6 years). All but one had no evidence of NHL, when HD was diagnosed. Three patients in whom the diagnosis of HD was made soon after or concomitantly with the diagnosis of NHL also are reported. Supervening HD was more frequently of nodular sclerosis type. The patients were older (median, 63 years) than patients with HD as the first cancer (median, 32 years). The occurrence of HD after NHL has been observed so infrequently that it is unlikely that it may be related to the treatment of the first neoplasia.     

Detection of simian virus 40 DNA sequences in Egyptian patients with different hematological malignancies

SV40 DNA sequences have been detected in non-Hodgkin's lymphoma patients. A link between SV40 and NHL is biologically plausible since SV40 causes hematological malignancies in laboratory rodents. We investigated 266 Egyptian cases of hematological malignancies (158 NHL, 54 HD, 26 ALL, 13 AML, 8 CLL, 7 CML) and 34 subjects as a control for detection of SV40 DNA using nested PCR. SV40 DNA sequences were found in (53.8%) of NHL, (29.6%) of HD and in (40.7%) of different types of leukemia cases. Frequency of SV40 DNA sequences was higher in NHL patients compared with those with the other tumors and control group (p < 0.05). The highest frequency was in Burkitt's lymphoma followed by diffuse large B-cell lymphoma. The present study suggests that SV40 is significantly associated with non-Hodgkin's lymphoma and most probably acts as a cofactor in the pathogenesis of these tumors. This could lead to new diagnostic, therapeutic, and preventive approaches.     

Hodgkin's Disease Variant of Richter's Syndrome: Experience at a Single Institution

Patients developing Hodgkin's disease (HD) after a diagnosis of chronic lymphocytic leukemia (CLL), are frequently included in a series of patients with Richter's syndrome (RS). We sought to determine the natural history of the association of CLL and HD. Over a 21 year period, 1374 patients with CLL have been registered in our computer data base. Seven cases of CLL and HD have been documented and confirmed. The median age of these patients was 71 years (range 44-77) and clinical features included male gender (86%), B symptomatology (86%), rapidly progressive lymphadenopathy (71%), prior CLL therapy (71%), advanced Ann Arbor stage (86%), marrow involvement with HD (43%), and autoimmune hemolytic anemia (29%). HD was documented by excisional lymph node biopsy in six cases and splenectomy in one. Mixed cellularity HD was shown in six and nodular sclerosis in one. Five of the biopsies revealed intervening areas consistent with small lymphocytic lymphoma. The Sternberg-Reed (SR) cells were CD15+ in 6/7 cases, and Ki-1+ in the 6 patients tested. CD45 and CD20 staining of the SR cells was nonreactive. The median time to development of HD was 45 months (range 0 to 96). The overall responses to different chemotherapy regimens was approximately 25% with only one CR. Six patients have died at 3,9,10,13,15 and 36 months and one patient is alive with progressive disease at 11 months. Our data suggests that CLL patients have a heightened risk for HD, features of advanced HD on presentation, and a poor response rate with short survival.     

Increased incidence of IgA antibodies to the Epstein-Barr virus-associated viral capsid antigen and early antigens in patients with chronic lymphocytic leukemia

Antibody titers to Epstein-Barr virus (EBV)-associated early antigens (EA) and the viral capsid antigen (VCA) were determined by ELISA on 263 sera obtained from healthy donors, patients with Hodgkin's disease (HD), non-Hodgkin lymphomas (NHL), infectious mononucleosis (IM), Burkitt's lymphoma (BL), and nasopharyngeal carcinoma (NPC). As expected, most lymphoma patients showed markedly elevated anti-VCA IgG and anti-EA IgG antibody titers. Only one patient in the NHL group (n = 56) consisting of patients with lymphomas other than chronic lymphocytic leukemia (CLL) and hairy-cell leukemia (HCL), and 3 patients with HCL (n = 19) had high antibody titers of the IgA class to VCA and EA. Seventeen out of 48 patients (36%) with CLL had high IgA anti-VCA titers and 10 of these sera (21%) also contained IgA anti-EA. The geometric mean titer (GMT) of IgA anti-VCA was 2,510, the GMT of IgA anti-EA was 780. These antibody titers were about 10 times lower than the corresponding GMT of the NPC patients investigated in this study. The elevated IgG and IgA antibody titers to VCA and EA in CLL and HCL patients seem to reflect an immunodeficiency secondary to the malignant disease leading to reactivation of latent EBV infection. The possibility that at least some of these B-cell lymphomas are associated with EBV cannot be excluded.     

Evidence for an association between cutaneous malignant melanoma and lymphoid malignancy: a population-based retrospective cohort study in Scotland

We analysed the risk of cutaneous malignant melanoma (CM) occurring in patients following a diagnosis of non-Hodgkin's lymphoma (NHL) or chronic lymphatic leukaemia (CLL), and of NHL or CLL subsequently developing in CM survivors. Cohorts of patients with CM, NHL or CLL (index cancer) diagnosed between 1975 and 1997 were identified from the Scottish national cancer registry and followed through the registry for subsequent CM, NHL or CLL. The standardised incidence ratio (SIR) for each cancer was calculated and overall risk, risk in relation to gender and age at diagnosis of the index cancers and time from diagnosis of the index cancer to the diagnosis of the second malignancy were measured. There were 9385 CM patients, 4016 CLL patients and 13 857 NHL patients identified with an index cancer with 56 195, 14 450 and 44 999 person-years of follow-up, respectively. There was an increased risk of both CLL and NHL following a diagnosis of CM (SIR 2.3 and 1.5, respectively) and of CM following a diagnosis of CLL and NHL (SIR 2.3 and 2.1, respectively). The risk was statistically significantly increased for CLL developing in CM patients and for CM occurring in NHL survivors (P<0.05). This study supports an association between CM, CLL and NHL developing in the same patient. Immunosuppression, exposure to ultraviolet radiation and genetic factors may lead to a host environment that is conducive to the development of these malignancies.     

淋巴细胞恶性增生性疾病患者肝炎病毒感染状况的分析

目的研究淋巴细胞恶性增生性疾病（MLPD）患者乙型（HBV）、丙型（HCV）肝炎病毒感染情况.方法回顾性分析67例初诊MLPD和170例正常体检人群血清乙型肝炎病毒标记物和抗HCV.结果 67例MLPD中HBV阳性10例（14 93%）.其中33例淋巴瘤（NHL/HD）中6例阳性,16例MM中2例阳性,18例淋巴细胞白血病（ALL/CLL）中2例阳性,170例体检人员中8例阳性（4.71%）,MLPD患者群体内HBV感染的阳性率高于正常人群的HBV感染的阳性率（P＜0.01）;67例MLpD中抗HCV阳性5例（7.46%）,其中33例淋巴瘤中2例阳性,16例MM中2例阳性,18例淋巴细胞白血病中1例阳性,170例体检人员中2例阳性（1.18%）.MLPD患者群体内抗HCV的阳性率高于正常人群抗HCV的阳性率（P＜0.05）.结论 MLPD患者有较高的HBV和HCV感染率.     

The incidence of lymphoma in first-degree relatives of patients with Hodgkin disease and non-Hodgkin lymphoma: results and limitations of a registry-linked study

BACKGROUND: The precise incidence of familial Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) in first-degree relatives is unknown. Through record linkage using two population-based sources, the authors estimated the risk of HD and NHL in family members of lymphoma probands. METHODS: The authors identified 8,037 first-degree relatives of 2,606 lymphoma cases (28.5% HD, 71.5% NHL) treated between 1970 and 1993 in 3 hospitals in Israel via the family file of the Population Registry. The authors linked this file with the Israel Cancer Registry, then calculated the standardized incidence ratio (SIR) by dividing the observed number of cases with the expected, adjusting for age, gender, calendar year, and continent of origin. RESULTS: The family file yielded incomplete ascertainment of relatives (for 771 probands, no relatives were identified). Twenty cases of lymphoma--6 HD and 14 NHL--were identified among relatives of lymphoma patients. The SIR for HD was 1.15 (95% confidence interval [CI]: 0.42-2.51) and for NHL 1.71 (95% CI: 0.93-2.87), considering the entire population of first-degree relatives. SIRs among siblings of lymphoma probands were 3.12 (95% CI: 1.01-7.29) for HD, 2.16 (95% CI: 0.45-6.31) for NHL, and 2.68 (95% CI: 1.15-5.27) for all lymphomas. There were 4 HD/HD, 1 NHL/NHL, and 3 NHL/HD sibling pairs. For HD/HD and NHL/NHL sibling pairs, the interval between lymphoma occurrence in proband and sibling was 1-4 years, whereas for HD/NHL pairs this ranged from 16 to 21 years. CONCLUSIONS: The risk of lymphoma among siblings of lymphoma probands was over 2.5-fold that of the general population and lower among other family members. The temporal proximity of HD/HD and NHL/NHL sibling pairs argues for environmental as well as genetic etiology. This method was hampered by incomplete data.     

Association of Thyroid Carcinoma with Malignant Lymphoma

Radiation-associated thyroid carcinoma is of clinical importancein modern radiation therapy of both Hodgkin's disease (HD) andnon-Hodgkin's lymphoma (NHL), because anatomically the thyroidis often in the radiation field. We have reviewed the recordsof HD and NHL patients seen at Roswell Park Memorial Institute(RPMI) between 1910 and 1960 to determine associated occurrenceof thyroid cancer. Radiation therapy was the major therapeuticmodality with the occasional use of single agent chemotherapywith nitrogen mustard, triethylene melamine (TEM), chlorambuciland prednisone. There were 519 patients with HD and 863 withNHL. The thyroid glands of 439 (84%) HD and 544 (63%) NHL patientswere included in the field of radiation. The mean age of patientswith HD was 39 yr while for those with NHL, it was 53 yr. Themean survival in HD was 4.2 yr and in NHL 3.8 yr. There werethree cases of thyroid cancer among the HD patients occurring31, 44 and 48 yr, respectively, after radiation therapy. Whencompared with the number of thyroid cancers expected to develop,the incidence was significantly greater (p < 0.005). In contrast,three NHL patients were found to have thyroid cancer at thetime of surgery or postmortem examination. This number is againgreater than expected in such a population (p < 0.005); however,in only two cases could the cancer be considered as a sequelato NHL treatment. In all three cases the cancer turned out tobe subclinical thyroid carcinoma, incidentally found at surgeryor autopsy. One of the patients is still alive without evidenceof either disease. The reason for this difference between patientswith HD and NHL treated with a similar principle is unclear.Some of the factors contributing to this difference may include:the younger age of HD patients at diagnosis; the longer survivalof patients with HD as compared with those with NHL; differencesin the sites of radiation and type of treatment given; and possibledifferences in immunological status between the two groups. ²Present addresses: 211 Owen Drive, Fayetteville, North Carolina,28304, U.S.A. ⁴Present addresses: 212 West 18th Street, Hopkinsville, Kentucky,42240, U.S.A. ⁵Present addresses: St. Francis Hospital, Park Avenue, Memphis,Tennessee, 38119, U.S.A ⁷Present addresses: Vassar Brothers Hospital, Poughkeepsie,NewYork, 12601, U.S.A.