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Primary refractory diffuse large B cell lymphoma (DLBCL) following R-CHOP chemotherapy is a major concern. We identified 1126 patients with DLBCL treated with R-CHOP from 2000 to 2009, of whom 166 (15 %) had primary refractory disease. Of the 75/166 (45 %) who were age <70 years and had been planned for stage-directed curative therapy, 43 (57 %) were primary nonresponders and 32 (43 %) relapsed within 3 months of completing R-CHOP. Thirty of 75 (40 %) patients had serious comorbidity and organ dysfunction precluding intensive treatment and had palliative treatment only. Twelve of 45 (27 %) patients responded to second-line treatment and underwent ASCT. The median overall survival for the 75 patients was 10 months with only seven patients alive without evidence of disease at follow-up ranging from 14 to 106 months. Primary refractory DLBCL after R-CHOP has a very poor outcome with only anecdotal survivors independent of the intended treatment approach.

Splenic marginal zone lymphoma (SMZL) accounts for less than 2% of all non-Hodgkin lymphomas. We identified 107 cases diagnosed with SMZL between 1985 and 2012 from the British Columbia Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Patient characteristics were: median age 67 years (range 30-88), male 40%, stage IV 98%, splenomegaly 93%, bone marrow involvement 96%, peripheral blood involvement 87%. As initial treatment, 52 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 chemoimmunotherapy containing rituximab, 1 rituximab alone), two antivirals for hepatitis C, and 15 were only observed. The 10-year overall survival for first-line splenectomy versus chemotherapy was 61% and 42%, respectively [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·26-0·88, P = 0·017]. The 10-year failure-free survival (FFS) after first-line splenectomy vs chemotherapy was 39% and 14%, respectively (HR 0·48, 95% CI 0·28-0·80, P = 0·004). Among the 38 patients who received first-line chemotherapy, FFS was similar between those receiving rituximab (n = 22) and those who did not (n = 16) (HR 0·64, 95% CI 0·31-1·34, P = 0·238). Fifteen patients transformed to aggressive lymphoma with median time to transformation of 3·5 years (range 6 months to 12 years) and the 10-year transformation rate was 18%. In conclusion, splenectomy remains a reasonable treatment for patients with SMZL., (© 2015 John Wiley & Sons Ltd.)

Background: We examined the relationship between location of residence at the time of diagnosis of diffuse large B-cell lymphoma (DLBCL) and health outcomes in a geographically large Canadian province with publicly funded, universally available medical care., Patients and Methods: The British Columbia Cancer Registry was used to identify all patients 18-80 years of age diagnosed with DLBCL between January 2003 and December 2008. Home and treatment center postal codes were used to determine urban versus rural status and driving distance to access treatment., Results: We identified 1,357 patients. The median age was 64 years (range: 18-80 years), 59% were male, 50% were stage III/IV, 84% received chemotherapy with curative intent, and 32% received radiotherapy. There were 186 (14%) who resided in rural areas, 141 (10%) in small urban areas, 183 (14%) in medium urban areas, and 847 (62%) in large urban areas. Patient and treatment characteristics were similar regardless of location. Five-year overall survival (OS) was 62% for patients in rural areas, 44% in small urban areas, 53% in medium urban areas, and 60% in large urban areas (p = .018). In multivariate analysis, there was no difference in OS between rural and large urban area patients (hazard ratio [HR]: 1.0; 95% confidence interval [CI]: 0.7-1.4), although patients in small urban areas (HR: 1.4; 95% CI: 1.0-2.0) and medium urban areas (HR: 1.4; 95% CI: 1.0-1.9) had worse OS than those in large urban areas., Conclusion: Place of residence at diagnosis is associated with survival of patients with DLBCL in British Columbia, Canada. Rural patients have similar survival to those in large urban areas, whereas patients living in small and medium urban areas experience worse outcomes.

Background: Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinico-pathological subtype of diffuse large B-cell lymphoma (DLBCL). The optimal treatment is unknown, with some studies suggesting a superior outcome with dose-intensive chemotherapy regimens, and the role of radiotherapy remains ill-defined., Patients and Methods: The British Columbia Cancer Agency lymphoma database was searched and records reviewed to identify those patients presenting with a prominent mediastinal mass and considered to be PMBCL based on the current REAL/WHO classifications. Patients were treated based on era-specific BCCA guidelines (1980-1992 MACOPB/VACOPB; 1992-2001 CHOP-type; 2001-present CHOP-R). Beginning in January 1998 involved-field radiotherapy was recommended to be routinely administered following chemotherapy. Prior to this, use of radiotherapy was individualized in advanced disease., Results: In total, 153 patients with newly diagnosed PMBCL were identified between 28 July 1980 and 30 June 2003. The median age was 37 years (range 13-82) and the majority had stage I/II (74%), bulky mediastinal disease (75%). Overall (OS) and progression-free (PFS) survival at 5 years for the entire cohort were 75% and 69%, respectively. In direct comparison with a cohort of patients with DLBCL (n = 1273), OS (P = 10(-4)) and PFS (P = 0.0001) favored PMBCL. The age-adjusted International Prognostic Index (aaIPI) was not predictive of survival (P = 0.18). Five-year OS in patients < 65 years old treated with MACOPB/VACOPB, CHOP-R and CHOP-type was 87%, 81% and 71% respectively (P = 0.048). In pair-wise survival comparisons, only MACOPB/VACOPB and CHOP-type treated patients were significantly different (P = 0.016). In Cox multiple regression analysis, poor performance status remained the only predictor of survival, with treatment received demonstrating a trend to worse outcome for patients treated with CHOP-type regimens (P = 0.09). In an intention-to-treat analysis comparing the era before radiotherapy was routinely administered with after, there was no significant difference in 5-year PFS (74% versus 62%; P = 0.09) or OS (78% versus 69%; P = 0.14)., Conclusions: In this single institution, population-based retrospective study, we found that PMBCL patients have excellent survival rates and a distinct plateau is observed in PFS, in striking comparison to DLBCL. The aaIPI was not predictive of survival in this population, suggesting that other prognostic models may be better suited for risk stratification. Dose-intensified chemotherapy with MACOPB or VACOPB demonstrated a trend to superior outcome over CHOP-type chemotherapy. However, further randomized studies are needed and the impact of rituximab on these comparisons must be considered. Finally, the routine addition of radiotherapy does not improve survival.

Purpose: For more than two decades, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the standard therapy for diffuse large B-cell lymphoma (DLBCL). The addition of rituximab to CHOP has been shown to improve outcome in elderly patients with DLBCL. We conducted a population-based analysis to assess the impact of this combination therapy on adult patients with DLBCL in the province of British Columbia (BC)., Methods: We compared outcomes during a 3-year period; 18 months before (prerituximab) and 18 months after (postrituximab) institution of a policy recommending the combination of CHOP and rituximab for all patients with newly diagnosed advanced-stage (stage III or IV or stage I or II with "B" symptoms or bulky [> 10 cm] disease) DLBCL., Results: A total of 292 patients were evaluated; 140 in the prerituximab group (median follow-up, 42 months) and 152 in the postrituximab group (median follow-up, 24 months). Both progression-free survival (risk ratio, 0.56; 95% CI, 0.39 to 0.81; P = .002) and overall survival (risk ratio, 0.40; 95% CI, 0.27 to 0.61, P < .0001) were significantly improved in the postrituximab group. After controlling for age and International Prognostic Index score, era of treatment remained a strong independent predictor of progression-free survival (risk ratio, 0.59; 95% CI, 0.41 to 0.85; P = .005) and overall survival (risk ratio, 0.43; 95% CI, 0.29 to 0.66; P < .001). The benefit of treatment in the postrituximab era was present regardless of age., Conclusion: The addition of rituximab to CHOP chemotherapy has resulted in a dramatic improvement in outcome for DLBCL patients of all ages in the province of BC.

The incidence and spectrum of non-Hodgkin lymphoma (NHL) differ between the Chinese and Caucasian populations. Using population-based registries, we studied the pattern of NHL in Chinese migrants to British Columbia (BC). The records of all NHL cases of Chinese descent diagnosed between 1980 and 1997 were retrieved. Age-standardized incidences were calculated by 5-year intervals in terms of age and calendar years and the relative rates were compared between the migrant, Hong Kong and BC populations. The histological distribution of NHL was compared with 4500 consecutive NHL cases diagnosed in the two populations. A total of 211 cases of migrant NHL were identified, with an age-standardized incidence rate of 7.11 per 100 000 per year, compared with the Hong Kong and BC rates of 7.91 [standardized incidence ratio (SIR) = 0.86, P = 0.01] and 11.88 (SIR = 0.56, P < 0.01). The standardized rates of follicular lymphoma remained low, but the incidence of gastric and nasal natural killer/T lymphomas in migrants were lower than expected. Genetic factors appeared to be stronger than environmental factors in governing the overall incidence of NHL in Chinese. However, certain subtypes of lymphoma may show decreased rates in migrants because of environmental factors.

Background: Compared with the West, Hodgkin's lymphoma in Oriental countries is characterized by a lower incidence rate and a higher proportion of mixed cellularity histology. Both environmental and genetic factors may be involved., Patients and Methods: The incidence and pattern of pathology of Hodgkin's lymphoma in the migrant Chinese population (0.4 million) in British Columbia (population 3.2 million) were studied. From a computerized database, all Hodgkin's lymphoma cases diagnosed in British Columbia from 1970 to 1997 were identified. Chinese descent was determined using patient surname by standard methodology and verified from the treatment record or by patient interview. The corresponding figures from the Chinese population in Hong Kong were used for comparison. For incidence rates, the age-specific incidence of Hodgkin's lymphoma in Hong Kong was obtained from the government cancer registry. For comparison of histology subtypes, 200 Hodgkin's lymphoma records from a Hong Kong regional referral center for the same time period were reviewed. Crude and age-standardized incidence rates were calculated by 5-year intervals in terms of age and calendar year, and relative rates were compared between the three populations., Results: From 1970 to 1997, Hodgkin's lymphoma was diagnosed in 34 Chinese patients in BC, with 24 cases diagnosed from 1970 to 1994. Thus, the crude and age-adjusted incidence rates from 1970 to 1994 were 0.91 and 1.14 per 100,000 per year in the British Columbia Chinese migrant population. Within the same period, 1862 cases of Hodgkin's lymphoma were diagnosed in British Columbia, giving a provincial background crude and age-adjusted incidence rates of 5.2 and 4.87 per 100,000 per year. The number of cases in the Hong Kong Chinese population (1970-1994) was 404, giving crude and age-adjusted incidence rates of 0.32 and 0.31 per 100,000 per year, respectively. Corrected for age and calendar year trends, the observed 25-year incidence of Hodgkin's lymphoma in British Columbia Chinese was significantly lower than expected from the British Columbia background population [24 observed versus 71 expected cases; standardized incidence ratio (SIR) = 0.34; 90% confidence interval (CI) 0.24-0.48; P <0.0001]. On the other hand, it is higher than that expected by extrapolating from the Hong Kong Chinese population (24 observed versus 8.5 expected cases; SIR = 2.81; 90% CI 1.94-3.95; P <0.0001). The difference is mainly accounted for by young patients with nodular sclerosis type disease in the migrant population., Conclusions: Although any conclusion about the impact of migration on Hodgkin's lymphoma incidence and types in the Chinese population must be considered tentative due to the small number of observed cases and confounding variables such as age, changing diagnostic standards and secular trends in Hodgkin's lymphoma rates, our data demonstrate a tendency for the Chinese population of British Columbia to take on a Western pattern of Hodgkin's lymphoma. This observation provides additional evidence that both genetic and environmental influences play a role in the pathogenesis of this lymphoma, and that environmental factors can exert their influence over a relatively short period of time.

Purpose: To evaluate clinical outcome of patients with limited-stage diffuse large-cell lymphoma (DLCL) treated with three cycles of chemotherapy followed by involved-region irradiation (IRRT)., Patients and Methods: Adults with limited-stage DLCL were treated with brief doxorubicin-containing chemotherapy regimens between 1980 and 1998. IRRT was administered 3 to 4 weeks after the third chemotherapy treatment in a dose equivalent to 30 Gy in 10 fractions., Results: Three hundred and eight patients (median age, 64 years) were included, and 299 experienced complete remission. After a median follow-up of 86 months, 64 patients developed progressive disease, and 104 patients died (43 from lymphoma, three from toxicity, and 58 from other causes). Actuarial overall and progression-free survival (PFS) rates were, respectively, 80% and 81% at 5 years and 63% and 74% at 10 years. For subgroups identified using the Miller modification of the International Prognostic Index (IPI), the overall survival rates at 5 and 10 years were, respectively, 97% and 89% (no factors), 77% and 56% (one or two factors), and 58% and 48% (three or four factors), and the 5-year and 10-year PFS rates were, respectively, 94% and 89% (no factors), 79% and 73% (one or two factors), and 60% and 50% (three or four factors). Men with testicular presentation, had a definitely inferior outcome., Conclusion: Long-term outcome with three cycles of doxorubicin-based chemotherapy and IRRT confirms that this is a successful approach for the majority of patients with limited-stage DLCL. Subgroups with worse prognoses can be identified, and these patients should be offered alternative treatment approaches.

Background: Lymphomas of mucosa associated lymphoid tissue (MALT) are a special type of extranodal lymphoma, possibly related to chronic antigenic stimulation. Increased cancer susceptibility may also contribute to the development of MALT lymphoma (MALToma). It has been suggested that patients with MALToma have an increased incidence of other malignancies., Patients and Methods: We retrospectively reviewed the histology and clinical records of 147 patients with MALToma, including 51 cases of gastric MALToma. The incidence of any second malignancy was confirmed with a provincial registry. The relative rates of cancer, excluding MALToma, were calculated relative to the background population of the same age group and secular year., Results: A total of 41 tumors occurred in 32 patients (21%), including 22 solid tumors. The incidence of solid tumors in the gastric MALToma group was 15%. Seven patients had two or more second malignancies. Cancer occurred before diagnosis of MALToma in 29 cases, concurrent with MALToma in three, and after MALToma in nine. Follow-up of the surviving patients is short (median 17.6 months). The relative rate from birth of a second malignancy was 0.86 in the whole group (90% confidence interval (CI): 0.62-1.16) and 0.95 (90% CI: 0.55-1.54) in the gastric MALToma group. The rates were roughly the same if skin cancers were excluded., Conclusions: The incidence of second cancers in this series is similar to previous reports. However, when compared to an age-matched population followed for the same period of time, MALToma patients do not appear to have a statistically significant increased rate of cancers.

The purpose of this study was to compare the relative risk of second malignancies in a cohort of patients with hairy cell leukemia (HCL) against the normal population. Potential effects of type of treatment and duration of follow-up and the site distribution of cancer were also examined. Between 1976 and 1996, 117 patients were diagnosed with HCL in British Columbia who were referred to the British Columbia Cancer Agency (BCCA) for treatment. All additional malignancies were traced using a provincial population-based cancer registry and follow-up records from the BCCA. There were 90 men and 27 women. Median age at diagnosis was 53 years. The median follow-up time was 68 months. Twenty-three patients underwent primary splenectomy, 65 received interferon alpha, 24 deoxycoformycin, and 67 cladribine (2-chlorodeoxyadenosine). Thirty-six patients had an additional malignancy (30.7%) with a total of 44 tumors. Six patients (5.1%) had two or more malignancies. Twenty-five patients had malignancies diagnosed after HCL (21.3%), three concurrent with HCL (2.6%), and 12 preceding HCL (10.2%). Second tumors (n = 28 tumors) occurred at a median of 40 months after HCL (range, 3 to 167). The relative rate (RR) of second malignancy among men and women was 2.91 (P < .001) and 1.65 (P = .23), respectively, compared with age and secular trend-matched controls. There were eight prostate cancers, nine nonmelanoma skin cancers, two lung cancers, and four gastrointestinal adenocarcinomas. The RR (90% confidence interval [CI]) in the various treatment groups were: splenectomy (RR = 0.21 to 3.81), purine analogues (RR = 0.60 to 5.69), interferon then purine analogues (RR = 1.60 to 4.31), interferon alone (RR = 1. 57 to 8.40). Cancer risk peaked at 2 years after HCL (RR = 4.13) and fell steadily afterwards, reaching a RR of 1.82 at 6 years. Twenty patients died, six due to HCL, 10 due to second malignancies, and four of unrelated causes. HCL patients appear to be inherently prone to malignancies. This appears to be more related to HCL tumor burden than to genetic predisposition or treatment effect. RR tends to fall with time after effective treatment. However, close monitoring for and vigorous prevention of cancer in HCL patients is advisable., (Copyright 1998 by The American Society of Hematology.)