Radiotherapy versus radiotherapy plus chemotherapy in stages I and II non-Hodgkin's lymphoma of the upper digestive and respiratory tract

From 1975 through 1985 88 patients with a primary manifestation of non-Hodgkin's lymphoma in the upper digestive and respiratory tract were referred to our hospital. Fifty-seven of them were in Stage I or II. The results of therapy in 48 evaluable patients are the subject of this retrospective study. Low, intermediate, and high grade malignant histologic features were encountered in 6, 27, and 15, respectively. The authors compared retrospectively the patients treated with radiotherapy (RT) with those who received additionally chemotherapy (RT + CT). Patients have been followed for a minimum of 1 year. Four of 29 patients with intermediate-grade or high-grade malignant lymphoma treated with CT and RT relapsed whereas eight of 13 patients treated with RT alone relapsed. Actuarial survival curves differed significantly in favour of the CT and RT group. These figures were also significant when the high-grade lymphomas plus centroblastic lymphomas were considered. It is recommended to add CT to RT in both Stage I and II NHL of high-grade and intermediate-grade malignancy.     

Primary non-Hodgkin lymphoma of the breast: The Mayo Clinic Experience

BACKGROUND AND OBJECTIVES: To retrospectively evaluate the characteristics, natural history, results of treatment, and prognostic factors for patients diagnosed with primary breast lymphoma. METHODS: Between 1973 and 1998, 25 women and 1 man with the diagnosis of primary breast non-Hodgkin lymphoma (PNHLB) were seen at Mayo Clinic Rochester and Mayo Clinic Scottsdale. Patient characteristics, treatment methods, and outcome were analyzed. RESULTS: The median follow-up for surviving patients was 6.6 years (range: 1.8-22.1 years). There were 11 low-grade NHL, 13 intermediate-grade NHL, and 2 high-grade NHL. Three patients underwent mastectomy while 23 had local excision. The Ann Arbor stage of disease included: Stage I-21 patients, Stage II-5 patients. Sixteen patients received radiation after surgery (15 after biopsy, 1 after mastectomy). Chemotherapy was given to 10 patients as part of the initial treatment. Four patients with low-grade disease were treated with excision only. The 5-year overall survival rate was 70% and relapse-free survival rate 42%, while local control rate was 75% and distant control rate 51%. Five-year survival and relapse-free survival rates for patients with low-grade disease were 91 and 61%, respectively. Three of four patients with low-grade disease treated with excision alone were free of local recurrence. For intermediate- and high-grade PNHLB, 5-year survival rate was 61% for those treated with chemotherapy, compared to 31% for those without chemotherapy (P = 0.35), and the 5-year relapse-free survival rates were 49%, compared to 0%, respectively (P = 0.0017). Three patients with intermediate- or high-grade disease developed central nervous system (CNS) dissemination. On univariate analysis, Ann Arbor stage was the only significant prognostic factor for survival (P = 0.0021). CONCLUSIONS: The management of PNHLB should be based on histologic grade. Patients with low-grade disease may be managed with local therapy alone. The role of chemotherapy in this group is unclear. Patients with intermediate- or high-grade disease have better outcome if chemotherapy is included. An unusual site of distant dissemination for these patients is the CNS. The only significant prognostic factor for survival is Ann Arbor stage.     

Tumor bulk as a prognostic factor for the management of localized aggressive non-Hodgkin's lymphoma: a survey of the Japan Lymphoma Radiation Therapy Group

PURPOSE: To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL). METHODS AND MATERIALS: The survey was carried out at 25 radiation oncology institutions in Japan in 1998. The 5-year event-free (EFS) and overall survival rates (OAS) were calculated, and univariate and multivariate analyses were done to identify which of the following factors, namely, gender, age, performance status (PS), serum lactate dehydrogenase (LDH) level, Stage (I vs. II), tumor bulk (maximum diameter), and treatment, were significant from the viewpoint of prognosis. RESULTS: A total of 1141 patients with Stage I and II NHL were treated by the Japanese Lymphoma Radiation Therapy Group between 1988 and 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate- and high-grade lymphomas in working formulation, constituted the core of this study. Primary tumors arose mainly from extranodal organs (71%) in the head and neck (Waldeyer's ring: 36% and sinonasal cavities: 9%). The factors associated with poorer prognosis were age over 60 years old (p < 0. 0001), radiation therapy alone (p < 0.0001), PS = 2-4 (p = 0.0011), (sex male, p = 0.0078), a bulky tumor more than 6 cm in maximum diameter (p = 0.0088), elevated LDH (p = 0.0117), and stage II (p = 0.0642). A median dose of 42 Gy was delivered mainly to the involved fields. Short-course chemotherapy was provided in 549 (70%) patients. The 5-year OAS and EFS rates for all patients were 71% and 67%, respectively. According to the stage-modified International Prognostic Index, the 5-year EFS of the patients with risk factors from 0 to 1 was 76%, 61% for patients with two risk factors, and 26% for patients with three or more risk factors. CONCLUSION: Extranodal presentation, especially Waldeyer's ring and sinonasal cavities, is encountered more frequently in Japan than in Western countries. Tumor bulk is an important prognostic factor in patients with localized aggressive extranodal NHL. Short course chemotherapy followed by radiation therapy was associated with prolonged survival in patients with localized aggressive NHLs of extranodal origin and 0-1 risk factor.     

Head-and-neck stages I and II extranodal non-Hodgkin's lymphomas: real classification and selection for treatment modality

PURPOSE: We re-evaluated histopathological specimens of head and neck early-stage extranodal non-Hodgkin's lymphoma (NHL) using the revised European and American lymphoma (REAL) classification, and also investigated the relationship between the clinical characteristics and histopathological classification in an attempt to evaluate the usefulness of this new classification system in selecting treatment modalities. MATERIALS AND METHODS: Between 1979 and 1995, 117 patients with histologically confirmed stages I and II NHL of head-and-neck extranodal regions were treated. Of these patients, 110 specimens were available for re-evaluation. Sixty-four patients had Stage I, and 46 had Stage II diseases. All but 3 had received radiation therapy, and 59 patients were also treated with intensive combination chemotherapy. RESULTS: There were 32 extranodal marginal-zone B-cell lymphomas, 57 diffuse large B-cell lymphomas, 11 peripheral T/NK-cell lymphomas, and 10 others. The 5- and 10-year cause-specific survival rates for all patients were 72% and 62%, respectively. Patients with extranodal marginal-zone B-cell lymphoma or other low-grade B-cell lymphomas demonstrated higher survival rates than patients with other lymphomas. Patients with peripheral T/NK lymphomas showed the lowest survival rate. CONCLUSION: The REAL classification accurately indicated the prognosis of patients with NHL. These results suggest that appropriate treatment modalities can be selected using this classification.     

Changing incidence and survival in patients with aids-related non-Hodgkin's lymphomas in the era of highly active antiretroviral therapy (HAART)

To determine role of highly active antiretroviral therapy (HAART) and additional factors in incidence and outcome of patients with AIDS-related non-Hodgkin's lymphomas (NHL) we retrospectively analyzed 257 cases of AIDS-related NHL (24 low-grade, 168 high-grade B-cell, 6 high-grade T-cell, and 59 primary CNS lymphomas (PCNSL) among 2004 patients with HIV-infection treated at the University Hospital of Frankfurt, Germany from January 1983 to May 1999. Data were evaluated by univariate and multivariate analyses, using overall survival as end point. Patients received CHOP-like therapy as standard treatment. Until May 1999 incidence of all diagnosed cases of NHL was decreasing (1991-94: 14.2% versus 1995-5/99: 12.8%). Mainly, the incidence of low-grade NHL and PCNSL clearly decreased whereas the incidence of high-grade B-cell NHL increased compared to all diagnosed cases of NHL (1983-86: 53.3% versus 1995-5/99: 78.6%). One-year survival probability of all screened patients with AIDS related NHL was 54%, while 5-year survival rate remained 5%. We found age <25 years, development of NHL in the years before 1990, IVDU, CD4 counts <150/microl, PCNSL as well as NHL as the AIDS index disease, to be highly significant independent predictors of poor survival, including increased hazard ratios. In the era of HAART incidence of NHL is decreasing, mainly the incidence of low-grade NHL and PCNSL. Overall survival of patients has been prolonged with HAART. This development is mainly due to improvement of antiretroviral therapy, rather than to any fundamental changes in the chemotherapeutic treatment of NHL. Therefore, new treatment approaches for AIDS-related NHL should focus on more efficient antiretroviral therapy in association with combination chemotherapy.     

Treatment and prognosis of orbital non-Hodgkin's lymphomas.

Twenty patients with orbital lymphomas were treated and followed over a 14-year period. Ten of these patients had well-differentiated lymphocytic lymphoma (WDL), and all of them were clinical stage IE. Five patients had nodular poorly differentiated lymphocytic lymphomas (NPDL), three patients had diffuse histiocytic lymphomas (DHL), one had nodular mixed-cell lymphoma, and one had diffused mixed-cell lymphoma. The patients with WDL received local radiation therapy, and all of them entered completed remissions. The projected survival at 10 years was 100% for these patients. The patients with low-grade lymphomas with advanced disease were treated with chlorambucil and prednisone or cytoxan and vincristine. The patients with high-grade lymphomas received treatment with methotrexate, cyclophosphamide, doxorubicin, vincristine, bleomycin, dexamethasone (mBACOD) or cyclophosphamide, vincristine, methotrexate, cytosine arabinoside, leucovorin (COMLA). The overall survival estimate for all patients was 63% at 10 years. The disease-free survival was 49% at 10 years. The patients with high-grade lymphomas had a poor prognosis, with no survivors after 4 years. This study suggests that patients with WDL usually present with localized disease to the involved orbit, and have an excellent prognosis with radiation therapy alone. Patients with high-grade orbital non-Hodgkin's lymphomas have a poor outcome despite use of aggressive combination chemotherapy regimens.     

Radiotherapy and chemotherapy in stages I and II non-Hodgkin's lymphomas of Waldeyer's ring

Sixty-four patients with stages I and II non-Hodgkin's lymphomas (NHL) involving Waldeyer's ring treated between 1970 and 1987 were reviewed. Patients with stage II NHL were subdivided into stage II 1 (limited type) and stage II2 (advanced type) from the state of neck nodes. Stage II1 was defined as involvement of unilateral cervical nodes less than 4 cm in diameter as well as Waldeyer's ring involvement. Other stage II cases were classified as stage II2. All 17 patients with stage I NHL were treated with radiation therapy alone. Their diseases were well controlled, and none of them died of causes related to the lymphoma. Among 14 patients with stage II1 NHL, the 5-year survival rate for the 9 patients treated with radiation therapy alone was 87.5%. Until 1982, 19 of 21 patients with stage II2 NHL treated with radiation therapy alone or radiation therapy and adjuvant chemotherapy (VEMP or COPP) died within 5 years mainly of disseminated diseases. Since 1983, CHOP has been used as the main treatment as well as radiotherapy for the 12 stage II2 NHL patients. So far, only 3 of them relapsed and 2 of them died of causes related to the lymphoma. Only 1 of these 12 patients was T-cell lymphoma compared to 7 of 9 stage II2 patients before 1982. This suggests that patients with stage I and those with limited stage II can be safely treated with radiotherapy. Also aggressive chemotherapy as well as radiotherapy should be used for patients with advanced stage II NHL involving Waldeyer's ring.     

Characteristics of indolent non-Hodgkin lymphoma in patients with type 1 human immunodeficiency virus infection

BACKGROUND: There is recent evidence that the incidence of indolent non-Hodgkin lymphoma (NHL) appears to be increased in persons with the acquired immunodeficiency syndrome (AIDS). The current study was conducted to describe the clinical, immunologic, and pathologic characteristics of indolent B-cell lymphoma in patients infected with the human immunodeficiency virus (HIV). METHODS: The current report was a retrospective study of 10 cases of indolent NHL identified from the AIDS-Lymphoma Registry at the University of Southern California School of Medicine. These patients were compared with 336 consecutive patients with systemic intermediate/high-grade AIDS-related NHL who were diagnosed and treated at a single institution. RESULTS: The pathology of the indolent cases included follicular lymphoma (five patients), small lymphocytic lymphoma (two patients), and one case each of mucosa-associated lymphoid tissue (MALT), monocytoid B-cell, and marginal zone lymphoma. When comparing the indolent lymphomas with the intermediate/high-grade AIDS-NHL cases, no differences were observed with regard to demographic characteristics or history of prior opportunistic infection. HIV patients with indolent lymphomas were found to have a significantly higher median CD4+ lymphocyte count compared with patients with intermediate/high-grade NHL (531 /mm3 vs. 90 /mm3) (P < 0.0001). Bone marrow involvement was significantly more common in indolent NHL cases (50%) versus intermediate/high-grade NHL cases (17%) (P = 0.02). The median survival for patients with indolent NHL was significantly longer compared with patients with intermediate/high-grade NHL (66.8 months vs. 7.1 months) (P = 0.007). CONCLUSIONS: Indolent lymphomas occurring in patients infected with HIV appear to differ from intermediate/high-grade lymphomas with regard to immune status and propensity for bone marrow involvement and prolonged survival. The median survival in the group of HIV-seropositive patients with indolent NHL examined in the current study was found to be comparable to that reported in HIV-negative individuals.     

Incidence and prognostic significance of blood lymphocyte clonal excess in localized non-Hodgkin's lymphoma.

Despite elaborate staging procedures, a substantial number of patients with localized NHL experience dissemination after local therapy, indicating that current routine methods are insufficient to detect tumour spread. We have used flow cytometric clonal excess (CE) analysis of peripheral blood in conjunction with routine staging procedures to study the occurrence of occult leukaemic spread in patients with localized NHL stages I, IE and IIE. CE in peripheral blood was a rare finding, identified in only 11% (14/130), and slightly more frequent in low-grade NHL, 20% compared to high-grade NHL, 7%. There was no correlation to any of the other major prognostic factors studied. Occult tumour spread would suggest an increased risk of relapse and possibly a decreased survival after local therapy. Among 93 patients given only local treatment there was an increased risk of relapse in those with low-grade malignant lymphomas and CE, which was not found in patients with high-grade malignant lymphomas and CE. CE in peripheral blood had no influence on survival in either of the histologic groups. A tentative explanation is that circulating lymphoma cells represent indolent populations irrespective of the histology of the primary tumour. The malignant nature of such a lymphoma spread might not be obvious during this rather limited follow-up of a median 34 months. The clinical interpretation is that the existence of CE in peripheral blood in patients with localized high-grade NHL should have no influence on the choice of therapy. In localized low-grade lymphoma the same therapeutic attitude which applies to widespread disease might be considered.     

造血干细胞移植治疗中高度恶性非霍奇金淋巴瘤5例

造血干细胞移植治疗非霍奇淋巴瘤５例,包括４例第 完全缓中,高度恶性ＮＨＬ;１例高度恶性ＮＨＬ合并淋巴瘤白血病。其中自体骨髓移植４例,异基因外周血干细胞移植１例。所有病例的移植成功。４例ＡＢＭＴ患者已无病生存５０,４８,３９和３个月,１例ａｌｌｏ－ＰＢＳＣＴ发生慢性移植物抗宿主病,移植后１２人月死于白血病复发。结果显示ＡＢＭＴ是治疗中,高度恶性ＮＨＬ有效手段。     

Bone marrow involvement by non-Hodgkin's lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group.

Bone marrow specimens from 317 patients with non-Hodgkin's lymphoma (NHL) obtained at initial staging were evaluated for the presence of lymphoma or benign lymphoid aggregates. Thirty-two percent (102 patients) had lymphoma in their bone marrow, and 9% had benign lymphoid aggregates. Bone marrow lymphoma was present in 39% of low-grade, 36% of intermediate-grade, and 18% of high-grade lymphomas. The bone marrow was involved in 25% of patients with diffuse large-cell or immunoblastic NHL (ie, diffuse histiocytic lymphoma of Rappaport). Bone marrow involvement did not affect survival of patients with low-grade NHL, but survival was significantly shorter (P = .03) for patients with intermediate- and high-grade NHL with bone marrow involvement. Bone marrow involvement was equally common in B-cell and T-cell NHL (31% v 32%). However, patients with T-cell NHL and bone marrow involvement had shorter survival than B-cell NHL with marrow involvement (P = .02) or T-cell NHL without marrow involvement (P = .05). A high incidence of morphologic discordance between lymph node and bone marrow was observed (ie, 40%), always with a more aggressive subtype in the lymph node than in the bone marrow. Presence of large-cell lymphoma in the bone marrow predicted for short survival. Survival for patients with small-cell lymphoma in their bone marrow did not differ significantly from patients with negative bone marrows. We conclude that bone marrow involvement in large-cell NHL, especially in those of T-cell origin, portends a poor prognosis. However, the subgroup of patients with an aggressive histologic subtype of NHL in a lymph node biopsy and small-cell NHL in the bone marrow do not have a poorer outlook than those without bone marrow involvement.     

External beam radiation therapy in the treatment of patients with extranodal stage IA non-Hodgkin's lymphoma

The purpose of this report was to study the results of external beam radiotherapy for patients with extranodal stage IA non-Hodgkin's lymphoma (NHL). A retrospective review was carried out on 27 patients seen between 1984 and 1998 with stage IA NHL of extranodal sites, and followed up for a minimum of 1 year. Sites involved included eye/orbit (seven), parotid (five), breast (four), Waldeyer ring (four), thyroid (three), other head and neck (two), stomach (one), and prostate (one). All patients had biopsy-proven disease and underwent staging workup to rule out other sites of disease. Histologic analysis revealed 16 patients with low-grade NHL, 9 with intermediate-grade, and 2 with high-grade. Ten patients received chemotherapy before radiation therapy, and eight of them had a complete response. The remaining 17 patients were treated with external beam radiation therapy alone. Radiation was directed to the involved field at 1.8 Gy to 2.0 Gy per fraction to a median dose of 40 Gy (range: 20-50.4 Gy). The median patient age was 71 years (range: 39-85 years); 55% were female, and 45% were male. A complete response was attained in all 27 patients after radiation therapy. There were five failures (all in uninvolved distant sites), and two deaths during the follow-up. Median disease free survival (DFS) and overall survival (OS) have not been reached. The 5-year DFS and OS are 85% and 94%, respectively. Older age at presentation showed a trend toward worse outcome (p = 0.07), but because of the relatively few events, other factors (radiation dose, grade of disease, sex, or the use of chemotherapy) showed no statistical differences among the patients. External beam radiation therapy is a highly effective treatment for stage IA NHL found in extranodal sites.     

Primary non-Hodgkin's lymphomas of the female breast.

The charts of 35 women with primary malignant non-Hodgkin's lymphomas (NHL) of the breast were retrieved from the files of the Istituto Nazionale Tumori, Milan, over a 30-year period (1957 to 1986). These cases represented 0.1% of the more than 25,000 primary malignant tumors of the breast treated during the same period. The median age of these patients was 57 years (range, 28 to 81 years). In most cases, the clinical diagnosis was carcinoma. The tumors were either Stage IE(48%) or IIE(52%) at presentation, and only two patients had B symptoms. The right breast was involved in 17 patients, the left breast in 14, and both breasts in two. According to the updated Kiel classification and the Working Formulation (WF) for Clinical Usage, three cases were lymphoplasmacytoid (immunocytoma) NHL (WF, A); three, centroblastic-centrocytic, follicular NHL (WF, B); four, centroblastic-centrocytic, diffuse NHL (WF, F); 17 centroblastic NHL (WF, G); three immunoblastic NHL (WF, H); two B-lymphoblastic NHL (WF, I); and one, a Burkitt-like NHL (WF, J). Treatment consisted either of a combination of surgery, radiation therapy, and chemotherapy or radiation therapy and chemotherapy. The follow-up period for 32 patients ranged from 6 to 161 months (mean, 45 months); 17 patients died of their disease. The prognosis appeared to be related to the histologic type and stage of the disease. Median survival periods were 63, 52, 42, and 47 months for centroblastic-centrocytic follicular, centroblastic-centrocytic diffuse, centroblastic, and immunoblastic NHL, respectively. The overall 5-year survival rate was 43%; the 5-year survival rate and the probability of freedom from progression at 5 years were, respectively, 61% and 50% for Stage I and 27% and 26% for Stage II disease.     

A therapeutic approach to primary adenocarcinoma of the cervix

Retrospective study of 97 patients with primary adenocarcinoma of the uterine cervix was undertaken to evaluate the efficacy of two treatment methods, radiation alone and radiation plus surgery. Of 31 Stage I patients, 16 were treated with radiation alone and 15 with combined radiation plus surgery. There was no difference in 5-year disease-free survival of Stage I patients treated by either method. Of 44 Stage II patients, 30 were treated with radiation alone with 54% survival rate; while 14 were treated with a combined approach, with 86% survival rate. It is apparent from the results of this study that surgery in conjunction with radiation showed a significant improved survival rate from 54% to 86% in Stage II disease. Factors influencing the prognosis appear to be tumor volume, uterine size, and tumor grade. Furthermore, these data suggest that early primary adenocarcinoma of the cervix (Stage I, lesion smaller than 4 cm) can be treated effectively by radiation alone or radical hysterectomy with comparable results. Tumors larger than 4 cm, Stage II or beyond disease, uterine enlargement, a high-grade tumor or barrel-shaped lesion, would necessitate a combined therapy to improve the cure rate.     

Primary lymphoma of the central nervous system. An unresolved therapeutic problem

From January 1979 to December 1987, 35 cases of primary central nervous system lymphoma (CNS-L) were treated. We recently reviewed these cases focusing on treatment results, treatment modalities, and radiotherapy (RT) or chemotherapy-radiotherapy (CT-RT). Variables such as age, risk factors, presenting symptoms, and histologic condition (all were high-grade or intermediate-grade non-Hodgkin's lymphomas [NHL]) and radiologic data were similar to those of series reported previously. The median survival time was 36 months (+/- 0.2 months) and the disease-free survival (DFS) time was 16 months (+/- 0.12 months). Twelve of 32 patients evaluable for treatment results experienced a recurrence (all but one occurred in the CNS). The DFS rate was 70% for the CT-RT group and 50% for the RT group (median follow-up time, 24 months). Therapeutic results in CNS-L are discussed with special emphasis on a putative role of CT in the management of this rare type of tumor.     

Stage I and II aggressive B-cell lymphomas of the head and neck: radiotherapy alone as a treatment option and the usefulness of the new prognostic index B-ALPS

PURPOSE: To evaluate the outcome according to treatment modality and prognostic factors in clinical Stage I and II intermediate- or high-grade B-cell lymphomas of the head and neck. METHODS AND MATERIALS: We analyzed 155 patients treated between 1983 and 1997, excluding those with the Working Formulation low-grade lymphomas. Of these patients, 88 had Stage I and 67 had Stage II disease. Forty-one patients were treated with radiotherapy (RT) alone, and 114 patients were treated with a combination of RT and chemotherapy. Most of the chemotherapy regimens included anthracycline derivatives. More patients with Stage I disease and more patients with poor performance status were treated with RT alone. The treatment results were evaluated according to the new prognostic index B-ALPS, consisting of tumor bulk, age, lactate dehydrogenase level, performance status, and stage. RESULTS: The 5-year overall and failure-free survival rate was 71.5% and 68.3%, respectively, for all 155 patients. The 5-year survival rate was 67% for those treated with RT alone and 73% for those treated with radiochemotherapy (p = 0.13). Among the various potential prognostic factors, age >60 years, World Health Organization performance status 2-4, and tumor size >or=6 cm were associated with poorer survival. The 5-year survival rate was 82% for those with no or one B-ALPS factor, 66% for those with two factors, and 49% for those with three or more factors (p <0.0001). The B-ALPS index appeared to predict the prognosis of these patients better than did the International Prognostic Index. No single prognostic factor was useful to identify patient groups more suitable to treatment with RT alone, but in patients with two B-ALPS risk factors, those treated with radiochemotherapy had a better survival rate and tended to have a better failure-free survival rate than those treated with RT alone. CONCLUSION: A proportion of patients with clinical Stage I or II head-and-neck B-cell lymphoma may be successfully treated with RT alone. B-ALPS is a useful prognostic index in this disease.     

Treatment results of radiotherapy for malignant lymphoma of the orbit and histopathologic review according to the WHO classification

PURPOSE: To analyze the results of radiotherapy (RT) for malignant lymphoma of the orbit and to evaluate them compared with the World Health Organization (WHO) classification published in 2001. METHODS AND MATERIALS: The data from 29 patients with malignant lymphoma of the orbit treated with RT at Gunma University Hospital between 1978 and 2001 were retrospectively analyzed. Pathologic slides from 23 cases were available and were reviewed by a hematopathologist according to the WHO classification. The original and reviewed diagnoses, patient characteristics, treatment results, and complications were analyzed. In principle, patients with low-grade or indolent lymphoma were treated with RT alone, using 30 Gy as the tumor dose. Survival data were calculated using the Kaplan-Meier method. RESULTS: One case that proved to be a pseudotumor was excluded from evaluation. Of the 28 cases, 25 were Stage IAE, 1 was Stage IIAE, and 2 were Stage IVAE. The median follow-up was 71 months. According to the original classification and the Working Formulation, the 5- and 10-year overall survival rate of patients with low-grade lymphoma was 94% and 73%, respectively. The corresponding rates for those with intermediate-grade lymphoma were 67% and 67% (p = 0.15). In contrast, the WHO classification showed a significant difference in the survival curves. The 5- and 10-year overall survival rate of patients with mucosa-associated lymphoid tissue (MALT) lymphoma was 100% and 88%, respectively; for diffuse large B-cell patients, the rates were both 0% (p < 0.001). In patients with MALT lymphoma, one local and four distant relapses developed; two of them >10 years after initial treatment. All of the relapsed MALT lymphomas were controlled by salvage therapy. CONCLUSION: Excellent local control and survival can be achieved for patients with orbital MALT lymphoma using RT alone. A precise histopathologic diagnosis using the WHO classification and long-term follow-up for >10 years is recommended.     

Changes in acquired immunodeficiency syndrome-related non-Hodgkin lymphoma in the era of highly active antiretroviral therapy: incidence, presentation, treatment, and survival

BACKGROUND: The authors sought to determine whether the availability of highly active antiretroviral therapy (HAART) coincided with changes in the epidemiology of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). METHODS: Cancer registry data from 1988-2000 were linked with AIDS registry data from 1981 to July 2003 for San Diego County to identify 537 AIDS-NHL patients. By using the total number of patients with AIDS who were alive as of July 1 annually as the AIDS population denominator, the average annual incidence of NHL was estimated among patients with AIDS for the pre-HAART period (1988-1995) and post-HAART period (1996-2000). The chi-square test was used to compare proportions, and a Cox proportional hazards model was used to compare survival between the pre-HAART and post-HAART periods. RESULTS: The incidence of NHL decreased from 29.6 per 1000 person-years pre-HAART to 6.5 per 1000 person-years post-HAART. The proportion of patients who had NHL of central nervous system (CNS) origin decreased from 28% pre-HAART to 17% post-HAART. Among patients with systemic NHL, 54% received chemotherapy pre-HAART, and 72% received chemotherapy post-HAART. The percentage of intermediate-grade NHL increased from 33% pre-HAART to 49% post-HAART, and the percentage of high-grade NHL decreased from 38% to 19%, respectively. A diagnosis of human immunodeficiency virus infection preceding the NHL diagnosis and Stage IV NHL were associated with worse survival, whereas a diagnosis of NHL in the post-HAART period and chemotherapy were associated with better survival. The median survival was 4 months pre-HAART and 9 months post-HAART. CONCLUSIONS: Since the introduction of HAART, there has been a decrease in the incidence of systemic and CNS NHL among patients with AIDS. Among patients with systemic, AIDS-related NHL, there has been decreased high-grade histology, increased use of chemotherapy, and improved survival.     

Expression of the activation antigen, 4F2, by non-Hodgkin's lymphomas of B-cell phenotype.

The monoclonal antibody, 4F2, which reacts with an antigen expressed by activated and proliferating cells, was applied to frozen sections of nine reactive lymphoid lesions, 146 B-cell non-Hodgkin's lymphomas (NHL), and six plasmacytic neoplasms. In reactive cases, the 4F2 antigen was expressed by germinal center cells and interfollicular immunoblasts, the activated or proliferating lymphoid cells, and histiocytes. In the malignant cases, the 4F2 antigen was expressed by 94 (64%) B-cell NHL and all six plasma cell tumors. The incidence of positivity and intensity of expression loosely correlated with the three morphologic grades of NHL identified in the Working Formulation. Approximately one half of all low-grade lymphomas, two thirds of intermediate-grade lymphomas, and all high-grade lymphomas were 4F2 positive. Similarly, the mean intensity of 4F2 antigen expression increased with higher grade. However, for certain histologic subtypes, 4F2 antigen expression did not correlate with morphologic grade. For example, in the intermediate-grade category less than one half of diffuse small cleaved cell lymphomas were 4F2 positive, and expression was weak, similar to that of low-grade lymphomas. In contrast, all other histologic subtypes of lymphoma in the intermediate-grade category were strongly 4F2 positive. Expression of 4F2 antigen also correlated with plasmacytoid differentiation. Seventy-three percent of plasmacytoid small lymphocytic lymphomas (compared with 31% of cases of non-plasmacytoid small lymphocytic lymphoma/chronic lymphocytic leukemia) and all plasma cell neoplasms expressed the 4F2 antigen, the latter cases strongly.     

Biologic progression in non-Hodgkin's lymphoma. A flow cytometric study

The nuclear DNA content of 37 primary non-Hodgkin's lymphomas both at presentation and at relapse was determined by flow cytometric analysis from paraffin-embedded tissue to investigate changes in DNA ploidy and S-phase fraction (SPF) during the course of the disease, and their association with survival. The repeat biopsies were done from 5 months to 15 years after the diagnosis. Four low-grade lymphomas according to the Working Formulation transformed into intermediate-grade lymphomas (four of 11, 36%), and four intermediate-grade lymphomas into high-grade lymphomas during the follow-up (four of 16, 25%), and five of these eight transformed lymphomas were fatal within 18 months after relapse. The SPF correlated strongly with poor prognosis if measured either from the primary biopsy (P = 0.008), the first (P = 0.009), or the latest repeat biopsy (P = 0.006). If SPF was greater than or equal to 6% larger in a repeat biopsy than at presentation prognosis was poor; six of nine such patients died from lymphoma within 11 months from recurrence. An increase of greater than or equal to 6% in the SPF was more common in high-grade (four of nine, 44%) and intermediate-grade (four of 16, 25%) lymphomas than in low-grade lymphomas (one of 11, 9%), and it was occasionally (three of nine) associated with a morphologic change. In a few cases a repeat biopsy was diploid despite DNA aneuploidy at presentation. In conclusion, the study provides evidence that not only may low-grade lymphomas transform into higher grade lymphomas, but high-grade lymphomas may also frequently transform into more malignant forms during the course of the disease. The SPF is useful in monitoring the biological behavior of non-Hodgkin's lymphoma, and it appears to give information not obtained by histologic study alone.