High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma - results of a comprehensive meta-analysis

BACKGROUND: Randomized controlled trials (RCTs) reported conflicting results on the impact of high-dose chemotherapy (HDCT) and autologous stem cell transplantation in the first-line treatment of patients with aggressive non-Hodgkin lymphoma (NHL). METHODS: We performed a systematic meta-analysis to assess the efficacy HDCT compared to conventional chemotherapy in aggressive NHL patients with regard to complete response (CR), overall survival (OS), event-free survival (EFS), toxicity, and impact of the age-adjusted International Prognostic Index (aaIPI) risk factors. We searched the Cochrane Library, MEDLINE and other databases (1/1990 to 1/2005). Hazard ratio (HR), relative risks (RR) and 95% confidence intervals (CIs) were calculated using the fixed effect model. RESULTS: Fifteen RCTs including 2728 patients were identified. HDCT improved CR when compared to conventional chemotherapy (RR 1.11, CI 1.04-1.18). Overall, there was no evidence for HDCT to improve OS (HR 1.05, 95% CI 0.92-1.19) or EFS (HR 0.92, 95% CI 0.80-1.05) when compared with conventional chemotherapy. However, subgroup analysis indicated OS differences (p=0.032) between good (HR 1.46, 95% CI 1.02-2.09) and poor risk (HR 0.95, 95% CI 0.81-1.11) patients. Conflicting results were reported for poor risk patients, where some studies reported improved and others reduced OS and EFS after HDCT. CONCLUSION: There was no evidence that HDCT improved OS and EFS in good risk NHL patients. The evidence for poor risk patients is inconclusive. HDCT should not be further investigated in good risk patients with aggressive NHL but high quality studies in poor risk patients are warranted.     

Single institute experience of chemotherapy and adjuvant radiotherapy for localized aggressive non-Hodgkin's lymphoma: retrospective analysis of the clinical efficacy of radiation therapy

We retrospectively analyzed the clinical outcome of localized aggressive lymphoma treated with chemotherapy and adjuvant radiotherapy. Between 1982 and 1998, 77 patients who were diagnosed as having aggressive lymphoma stage I-II were treated with chemotherapy followed by radiation therapy. The median radiation dose was 44.4 Gy (range, 30-64 Gy). Some patients who achieved complete response after chemotherapy received limited-field radiation to reduce toxicity. Several prognostic factors were analyzed in the overall (OAS) and relapse-free survival (RFS) by both uni- and multivariate analysis. The 5-year rates of OAS and RFS were 74.6% and 70.8%, respectively. Patient age (p = 0.016), radiation dose (p = 0.043), and prognostic score proposed by the Japan Lymphoma Radiation Therapy Group (JLRTG; p = 0.0073) were significant predictive factors for OAS. As for RFS, predictive factors were patient age (p = 0.042), elevated level of serum lactic dehydrogenase (p = 0.046), and JLRTG score (p = 0.05). At the multivariate level, only patient age greater than 60 years was a significantly adverse variable for both OAS (p = 0.0079) and RFS (p = 0.0198). Our treatment strategy was thought to be acceptable with satisfactory outcomes. Limited-field radiation may have possible advantages in toxicity if it does not lead to worsening of the outcome, although a conclusive result could not be obtained by the current analysis.     

Treatment of Relapsed or Refractory Aggressive Non-Hodgkin Lymphoma with Two Ifosfamide-Based Regimens,IMVP and ICE

Abstract

We report the outcomes of 45 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) treated with a combination of ifosfamide, carboplatinum and etoposide (ICE) and 28 patients treated with a combination of ifosfamide, methotrexate and etoposide (IMVP) during two 5-year periods. The response rate (RR) to ICE was 47%, 2-year overall survival (OS) 31% and 2-year event-free survival (EFS) 22%. These results were similar to those obtained with IMVP (RR 39%, 2-year OS 23%, 2-year EFS 13%; p=0.355 for RR, 0.275 for OS, 0.668 for EFS). Higher IPI scores and refractoriness to treatment were negative prognostic factors, immunophenotype (B vs. T) had no influence on prognosis. Changing from IMVP to ICE does not substantially improve the outcome of patients with relapsed or refractory aggressive NHL. Patients with relapsed/refractory aggressive B-NHL do not have a superior out-come in comparison to those with T-NHL if treated with chemotherapy alone.     

Survival improvement of young patients, aged 16-23, with Hodgkin lymphoma (HL) during the last three decades

The prognostic factors, treatments and outcomes of 55 young adults (16-23 years old) with Hodgkin lymphoma (HL) treated in the Second Department of Internal Medicine Propaedeutic, Medical Oncology Unit, Athens University, over the past 25 years, are reviewed. Patients were treated with the chemotherapy regimens available at each time period which were MOPP (Group A; 1978-1987), MOPP/ABVD (Group B; 1988-1993) and BEACOPP or ABVD (Group C; 1994-2003). The eligible patients, received radiotherapy (RT) according to treatment consensus. Additionally, the patients were retrospectively divided according to risk factors (abnormal erythrocyte sedimentation rate (ESR), bulky mediastinal disease, > 3 involved nodes and extranodal involvement) into low [stage I/II; five patients (9%)], intermediate [stage III with adverse prognostic factors; 18 patients (33%)] and high risk categories [stages IIB bulky and III/IV; 32 patients (58%)]. A total of 21 (38%) patients experienced relapse (three intermediate and 19 high risk). The 5-year survival and the 5-year event free survival (EFS) figures were Group A: 65% and 53%, Group B: 80% and 65%, Group C: 100% and 88.5%, respectively, the improvements between Group B and C were statistically significant (p = 0.04 and p = 0.005, respectively) among the three time periods. The overall survival (OS) and EFS differed significantly between intermediate and high risk categories (OS: p = 0.04, EFS: p = 0.005). The sequential use of RT did not influence OS and EFS but there was a trend of improvement with RT in the later periods. Survival of young patients with HL is significantly improving most probably due to improved chemotherapy treatment and understanding of the risk factors. Current controversial issues surrounding this disease, including the role of radiotherapy, positron emission tomography (PET), bone marrow biopsy and stem cell transplantation are discussed.     

Non-Hodgkin's lymphoma arising in bone in children and adolescents is associated with an excellent outcome: a Children's Cancer Group report.

PURPOSE: Non-Hodgkin's lymphoma (NHL) arising in bone is a heterogeneous histologic type of NHL that includes large-cell lymphoma, lymphoblastic lymphoma, and small noncleaved-cell lymphoma. NHL arising in bone is well recognized in adults but is less well characterized and infrequent in children and adolescents. PATIENTS AND METHODS: We performed a retrospective review of Children's Cancer Group (CCG) studies treating children and adolescents with NHL over a 20-year period (CCG-551, CCG-501, CCG-502, CCG-503, CCG-552, CCG-5911, and CCG-5941) and determined the response and event-free survival (EFS) rates in 31 patients with NHL arising in bone. RESULTS: The patients ranged in age from 3 to 17 years (median, 11 years; mean, 11 years), and 64.5% were male. All 31 (100%) patients achieved complete response. For 31 patients with NHL arising in bone, the product-limit estimated 5-year EFS was 83.8% +/- 6.7%. EFS in 17 patients with localized disease (Murphy stages I and II) was 94.1% +/- 5.7%, and EFS in 14 patients with disseminated disease (Murphy stage III) was 70.7% +/- 12.4% (log-rank P =.10). EFS in 17 patients treated with chemotherapy and radiation was 70.1% +/- 11.2%, and EFS in 14 patients treated with chemotherapy without radiation was 100% (P =.03). EFS in 26 patients with histology-directed treatment (LSA2-L2 or ADCOMP for lymphoblastic, other therapy for nonlymphoblastic) was 92.2% +/- 5.3%, and in five patients with nonhistology-directed treatment it was 40.0% +/- 21.9% (P <.001). CONCLUSION: NHL arising in bone is a heterogeneous type of NHL that makes up approximately 2.0% of NHL in children and adolescents on CCG studies. Response and survival in this young age group seem superb, with histology-directed treatment protocols without radiation in both localized and disseminated disease.     

Stages I and II non-Hodgkin's lymphomas of Waldeyer's ring and the neck

In a previous communication we reported our results for patients with localized extranodal presentations of non-Hodgkin's lymphomas of the head and neck who were admitted between 1961-1969. This review describes our larger experience from 1947-1982 in treating 137 Stages I and II Waldeyer's ring patients whose slides were available for reclassification according to the modified Rappaport System. All of these patients were treated definitively as follows: radiotherapy only, 113 patients; radiotherapy and combination chemotherapy, 17 patients; chemotherapy only, seven patients. The overall 5-year survival was 50%. Significant differences were determined for specific subgroups. For patients staged after lymphangiography, the 5-year survival was 67% as compared with 32% for non-lymphangiogram staged patients (p = 0.002). Stage (Ann Arbor) also influenced results. The 5-year survival figure for Stage I was 70% as compared with 42% for Stage II (p = 0.002). The combination of extent of disease in Waldeyer's ring and the status of the neck had a major impact on survival. When the disease was staged according to the TNMAJCC System, the 5-year survivals were: 75% for T1-T2-TX N0; 53% for T1-T2-TX N+; 54% for T3-T4 N0; and 36% for T3-T4 N+. Also, results for tonsil (52%) and base of tongue (66%) disease were better than for disease involving the nasopharynx (39%) or multiple sites (25%). Treatment also influenced survivals and disease-free survivals. The best results were obtained in patients who were treated with radiotherapy and combination chemotherapy. The 5-year survival and disease-free survival figures were 78% and 69%, respectively.     

Radiotherapy for primary localized (stage I and II) non-Hodgkin's lymphoma of the oral cavity

PURPOSE: To assess the role of radiation therapy in the treatment of primary localized (Stage I: 24 cases and Stage II: 13 cases) non-Hodgkin's Lymphoma (NHL) of the oral cavity. METHODS AND MATERIALS: In total, 37 patients (27 male, 10 female) with primary localized NHL of the oral cavity have been treated with radiotherapy alone (23 cases) or radiation with chemotherapy (14 cases). The age range was 29 to 86 years (median: 65). Clinical and treatment variables with potential prognostic significance for survival were evaluated by univariate and multivariate analysis. Of the 37 patients, 31 (84%) had intermediate-grade lymphomas and six (14%) had high-grade lymphomas. Four patients showed necrotic ulcer in the central portion of the hard palate. RESULTS: The 5-year actuarial survival rate for all cases was 73%. The 5-year survival rates for intermediate-grade and high-grade lymphoma were 85% and 14%, respectively. Significant prognostic factors identified by the multivariate analysis were histologic grade of malignancy (p = 0.02) and central necrotic ulcer in the tumor (p = 0.02). Chemotherapy did not improve survival (p = 0.41). CONCLUSIONS: Our analysis suggests that radiotherapy alone may be approved as the treatment for localized oral NHL with no ulceration and intermediate histology. However, patients with high-grade lymphoma and/or necrotic ulcer are difficult to cure with radiation alone and aggressive treatment should be advocated to improve survival.     

Prognostic factors in localized aggressive non-Hodgkin's lymphoma

To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL), a retrospective study including 118 patients with clinical stage I and II NHL treated at the Institute of oncology, Istanbul University between 1989 and 1998 was conducted. Patients were treated either with radiotherapy alone, radiotherapy and adjuvant chemotherapy, or chemotherapy (with or without adjuvant radiotherapy). The 5-year disease-free survival (DFS) and overall survival rates were calculated, and univariate and multivariate analyses were performed to identify the significance of various prognostic factors such as gender, age, performance status, stage (I versus II), B symptoms, extranodal involvement, gastrointestinal tract disease, erythrocyte sedimentation rate, bulky disease, histologic grade, serum lactate dehydrogenase level, serum beta2-microglobulin level, serum albumin level, treatment regimen, remission status, and the International Prognostic Index risk groups, which may have an influence on the outcome of patients with NHL. The overall 5-year survival rate was 52% with a median follow-up of 30 months. The complete response rate was 68%, and the 5-year DFS of complete responders was 70%. Cox multivariate regression analysis showed that incomplete response, low serum albumin, bulky disease (>10 cm), and high grade histology were the pretreatment factors associated with shorter survival. When remission status was included in the model, the attainment of a complete response was the major determinant of long-term survival; however, low albumin level was still a significant adverse predictor for survival in multivariate analysis. These factors need to be evaluated for analyzing the outcome of treatment and to identify better therapeutic strategies.     

Prognostic Factors in Non-Hodgkin Lymphoma Stage I Treated with Radiotherapy

The results of treatment in 175 consecutive patients with non-Hodgkin lymphoma (NHL) clinical stage I treated between 1969 and 1984 were analysed according to different pretreatment prognostic variables. Treatment consisted of radiotherapy in 166 of the 175 patients. The estimated 5 and 10-year disease-free survival rates (DFS) were 63 % and 60% and the survival rates at 5 and 10 years 82% and 76% respectively. Lymphomas arising from gut-associated lymphoid tissue, i.e. Waldeyer's ring, the thyroid and the gastrointestinal tract had a more favourable clinical course (10-year projected DFS 83%) than nodal (50%) and other extranodal lymphomas. Although the number of patients with other extranodal sites was small, sites such as testis, nasal cavity, paranasal sinus and extradural space seemed to have a high relapse rate. Unfavourable clinical courses were also observed among nodal high-grade NHL if the lymph nodes were larger than 5 cm in diameter. Chemotherapy before radiotherapy may be recommended in NHL subgroups with a high relapse rate and which today are potentially curable with chemotherapy, i.e. high-grade NHL. This study indicates that large nodal lymphomas and some extranodal sites belong to this group.     

Primary gastrointestinal non-Hodgkin's lymphoma: a clinicopathologic study of 128 cases in Greece. A Hellenic Cooperative Oncology Group study (HeCOG)

The aim of this retrospective study was to illustrate the clinicopathologic data and the treatment results in patients with primary gastrointestinal tract non-Hodgkin's lymphoma (GI NHL). Among 810 patients with NHL, 128 cases (15.8%) were diagnosed as primary GI tract NHL. There were 79 males and 49 females with median age of 62 years. The most common primary site was the stomach (68%). Overall, 67.2% of the patients were in stages I - II, and 32.8% in stages III - IV. Simultaneous involvement of the GI tract and other extranodal sites was observed in 26 patients (20%). Extranodal marginal zone B-cell lymphoma (MZBL) (i.e., low-grade lymphoma of mucosa-associated lymphoid tissue type) accounted for 48.4% of lymphomas. Aggressive lymphomas (diffuse large B-cell lymphoma [DLBL]) accounted for 44.5%. Eighty-three patients (67.5%) achieved complete response (CR), either by surgery (43/43 patients, 17 with DLBL and 25 with MZBL) or by primary chemotherapy (40/64 patients, 22 with DLBL and 17 with MZBL). Sixty-two patients remain in CR; 33/43 after surgical resection (13/17 with DLBL and 20/25 patients with MZBL), and 29/40 after only chemotherapy (18/22 with DLBL and 10/17 with MZBL). The major prognostic factor for outcome in the present study was the stage of the disease. Patients with localized lymphoma (stage I and II) had significantly longer DFS and OS (DFS and OS at 3-year: 83% and 87%, respectively) than patients with extended disease (stage III and IV) (DFS and OS at 3-year: 46% and 60%, respectively) (P < 0.0001). The International Prognostic Index (IPI) for patients with aggressive lymphomas was prognostic only for DFS (79% for low-risk patients [IPI score 0 - 1] vs 49% for higher risk groups [IPI score >1] at 3-year, P = 0.0131).     

Prospective randomized study comparing MEMID with a chop-like regimen in elderly patients with aggressive non-Hodgkin's lymphoma

OBJECTIVE: This multicenter phase III study compared the MEMID regimen (mitoxantrone, VP16, methylglyoxal, ifosfamide and dexamethasone) with CEOP, a CHOP-like regimen (cyclophosphamide, epirubicin, vincristine and prednisone), in elderly patients (> or =65 years) with aggressive non-Hodgkin's lymphoma (NHL). Methods: One hundred and forty-nine patients were eligible, 72 in the MEMID arm and 77 in the CEOP arm. The primary endpoint was to compare overall survival (OS) between groups, and secondary endpoints were event-free survival (EFS), response rate and toxicity. RESULTS: Neutropenia (p < 10(-5)), anemia (p < 10(-5)) and thrombocytopenia (p = 0.0006) were significantly more frequent in patients who received MEMID. We observed an objective response rate of 55.5% in the MEMID arm and 64.9% in the CEOP arm (p = 0.24). The median OS and EFS were 15.4 and 8.5 months in the MEMID arm, and 20.3 and 10.5 months in the CEOP arm (p = 0.59 and 0.47), respectively. The median EFS was 15.4 months in the MEMID arm and 20.3 months in the CEOP arm (p = 0.59). CONCLUSION: The increased toxicity without survival benefit confirms the superiority of CHOP and CHOP-like regimens for elderly patient with aggressive NHL.     

200例非霍奇金淋巴瘤预后分析

目的探讨中高度非霍奇金淋巴瘤预后改善。方法对２００例经化学治疗的患者进行预后因素分析。应用多因素Ｃｏｘ模型分析年龄、性别、临床分期、Ｂ症状、淋巴结外病灶、骨髓侵犯、巨大肿块、体力状况和病理恶性度等因素。结果体力状况、结外病灶、病理恶性度和巨大肿块对预后具有显著意义。按预后指数（ＰＩ）将患者分为低危组（ＰＩ为－２．４３～－１．３０）、中危组（ＰＩ为－１．２９～１．０）和高危组（ＰＩ＞１．０）,其５年生存率分别为７６．０％、２１．６％及７．４％。结论预后分组可用于指导治疗,据此,高危组可考虑采用更强烈化疗及自体造血干细胞移植,中危组及低危组可采用标准化疗方案。这将有助于改善患者的预后。     

青少年或儿童原发系统性间变大细胞淋巴瘤CHOP为主化疗±放疗的远期疗效

目的 分析青少年儿童原发系统性间变大细胞淋巴瘤(ALCL)患者接受CHOP方案化疗 ±受累野放疗的疗效。方法 回顾分析本院1998—2010年收治的 28例青少年、儿童ALCL患者资料。Ⅰ、Ⅱ期 12例中单纯化疗 2例、综合治疗 10例,Ⅲ、Ⅳ期 16例中单纯化疗 14例、综合治疗 2例。CHOP方案 15例、CHOP联合其他高强度化疗 13例。化疗周期数 3~17个(中位数6个)。放疗多为受累野照射,剂量 39.6~50.0 Gy (中位数45 Gy)。结果 全组患者首程疗后达CR者 25例(89%),3例病变进展。中位随访时间45.3个月。全组 5年无事件生存率为80%,5年OS为93%。疗终达CR者 5年OS为100%,而未达CR者无 5年OS (P=0.000)。≥2个结外器官受侵者 5年无事件生存率为38%,而<2个结外器官受侵者的为85%(P=0.010)。结论 青少年、儿童原发系统性ALCL按成人方案治疗效果满意,但还需要长期随访。     

Primary Extranodal Non-Hodgkin's Lymphoma in Adults: Clinicopathological and Survival Characteristics

Among 318 cases of non-Hodgkin's lymphoma (NHL) treated in our unit, 145 (45.6%) had primary extranodal NHL (PE-NHL). The stomach was the most common site (42.1 %), followed by the PE-NHL of the head and neck region. Histologically aggressive histologies (65.5% intermediate and 20.7% high grade) predominated. 89.6% of the cases were localized (stage Ie, 51% and stage II, 38.6%) but 28% had B symptoms. CR was achieved in 82.1 % of the cases. 5-years disease free survival and overall survival were both 65%. Factors that influence prognosis were stage and high grade histology. Among various primary sites the Waldeyer's ring, small intestine and testes had the worse prognosis. Compared to nodal NHL, the PE-NHL were more frequently localized, belonged more often to aggressive histologies and had more often distal extranodal relapses. CR rates and disease free and overall survival were significantly better for PE-NHL. The survival rates, however, listed according to stage and histology for nodal and PE-NHL were not different.

We conclude that although PE-NHL differed from nodal NHL in several respects, prognosis is mainly a factor of stage and histology rather than of the primary localization per se.     

Localized aggressive non-Hodgkin’s lymphoma of the nasal cavity: a survey by the Japan Lymphoma Radiation Therapy Group

Purpose: To clarify the role of radiotherapy and chemotherapy in the treatment of patients with localized aggressive non-Hodgkin’s lymphomas (NHL) originating in the nasal cavity.

Methods and Materials: The survey, administered at 25 Japanese institutes in 1998, enabled us to collect the clinical data for 787 patients with localized aggressive NHL who were treated between 1988 and 1992.

Results: There were 42 patients (5%) with nasal lymphomas. Twelve of these patients received radiotherapy alone, and 30 were treated with a combination of radiotherapy and chemotherapy. The median radiation dose was 47 Gy (22–66). Twelve patients were reviewed histopathologically according to REAL (Revised European-American Classification of Lymphoid neoplasms) classification. T-cell or natural killer (NK) cell lymphomas were detected in 9 patients (75%), and diffuse large B-cell lymphomas in 3 (25%). The 5-year overall and disease-free survival (DFS) rates of all patients were 57% and 59%, respectively. The 5-year DFS rate for the 30 patients treated with the combined therapy was 64% and that for the 12 patients treated with radiotherapy alone was 46% (p = 0.021). For the 34 patients with stage-modified International Prognostic Index (m-IPI) 0–1, the 5-year DFS rates of those treated with the combined therapy and radiotherapy alone were 68% and 45%, respectively (p = 0.020), but there was no difference in DFS rate among the two groups of patients with m-IPI 2–3. The 5-year local control rates of the patients who received >46 Gy (n = 22) and ≤46 Gy (n = 20) were 95% and 76% (p = 0.087), respectively. There was no significant difference among the 5-year DFS rates (62% vs. 67%) and local control rates (87% vs. 100%) of the patients with T-cell or NK-cell lymphoma and diffuse large B-cell lymphoma.

Conclusions: Patients with nasal lymphomas (m-IPI 0–1) should be treated with combined therapy. For the patients with high risk (m-IPI 2–3), the effectiveness of combined therapy was not clarified because of the small number of the patients. A high radiation dose >46 Gy may need to be used to achieve good local control.     

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.     

Rituximab and escalated chemotherapy in elderly patients with aggressive diffuse large-cell lymphoma: a controlled clinical trial

The treatment of elderly patients with aggressive malignant lymphoma has not been defined. The addition of rituximab to conventional chemotherapy has been reported to improve the outcome, but most patients have good prognostic factors (performance status < 2, no severe associated diseases, low or low-intermediate clinical risk). Thus, we developed a combined regimen, including escalated doses of anthracycline and rituximab. The endpoint was to improve event-free survival (EFS) and overall survival. Two hundred and four (204) patients were randomly assigned to receive an escalated chemotherapy regimen (CEOP) with escalated dose of epirubicin, compared to the same regimen and addition of rituximab. All patients had poor prognostic factors: high- or high-intermediate clinical risk, poor performance status, bulky disease, and more than 2 with extranodal involvement. In an intent-to-treat analysis, all patients were evaluable for efficacy and toxicity. The complete response rates were similar in both arms: 74% in chemotherapy and 78% in the rituximab + chemotherapy program. EFS and overall survival were similar: 77% and 84%, respectively, in combined chemotherapy and 75% and 81% in the rituximab-chemotherapy regimen. Toxicity was mild and well tolerated. In elderly patients with diffuse large-cell lymphoma and poor prognostic factors, rituximab did not improve their outcome.     

T-cell/histiocyte-rich large B-cell lymphomas and classical diffuse large B-cell lymphomas have similar outcome after chemotherapy: a matched-control analysis.

PURPOSE: Because it is unclear whether T-cell/histiocyte-rich large B-cell lymphomas (H/TCRBCL) should be considered as a true clinicopathologic entity, we conducted a matched-control analysis comparing patients with H/TCRBCL and patients with diffuse large-B cell lymphoma (B-DLCL). PATIENTS AND METHODS: More than 4,500 patients were enrolled onto non-Hodgkin's lymphoma trials conducted by the Groupe d'Etude des Lymphomes de l'Adulte. After histologic review, 50 patients were subclassified as H/TCRBCL. They were matched to 150 patients with B-DLCL for each of the factors of the International Prognostic Index (IPI). RESULTS: Clinical characteristics of H/TCRBCL patients showed a male predominance and a median age of 47 years. Performance status was normal in 89% of patients, whereas lactate dehydrogenase level was increased in 60% of patients. The disease was disseminated in 81% of patients, and 48% had two or more involved extranodal sites. The IPI score was >or= 2 in 53% of patients. The complete response rate to chemotherapy was 63%, and 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- SD) were 58% +/- 18% and 53% +/- 16%, respectively. The matched-control analysis showed a trend toward a better response to chemotherapy for patients with B-DLCL (P =.06), whereas no difference was observed in OS (P =.9) and EFS (P =.8). CONCLUSION: H/TCRBCL is an aggressive disease that often presents with adverse prognostic factors. However, when treatment is adapted to the disease risk, outcome is equivalent to that observed in patients with B-DLCL. Thus H/TCRBCL should be considered a pathologic variant that belongs to the B-DLCL category.     

Early or up-front radiotherapy improved survival of localized extranodal NK/T-cell lymphoma, nasal-type in the upper aerodigestive tract

PURPOSE: To investigate the role of early or up-front radiotherapy (RT), the optimal RT dose required to achieve appropriate treatment outcome and prognostic factors for patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. METHODS AND MATERIALS: Eighty-two patients were reviewed. Eight patients were treated with chemotherapy (CT) alone, 9 patients received RT alone, and 65 patients were given combined modality treatment of CT and RT (CMT). Of those 74 patients receiving RT, 31 patients were given up-front RT, whereas CT was the initial therapy for 43 patients and 41 of those 43 patients received early RT. RESULTS: Five-year overall survival (OS) and disease-free survival (DFS) were 52.3% and 39.2%, respectively. RT was the only independent prognostic factor for both OS and DFS at both the univariate and multivariate level. The 5-year OS and DFS were better in patients receiving >or=54 Gy of RT as compared with that of <54 Gy (5-year OS 75.5% vs. 46.1%, p = 0.019; 5-year DFS 60.3% vs. 33.4%, p = 0.004). Up-front RT presented better survival in Stage I patients when compared with that of initial CT followed by early RT (5-year OS 90.0% vs. 48.9%, p = 0.012; 5-year DFS 78.7% vs. 39.9%, p = 0.021). CONCLUSION: Early or up-front RT had an essential role in improved OS and DFS in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. The recommended tumor dose was at least 54 Gy. Up-front RT may yield more benefits on survival in patients with Stage I disease.     

Chemotherapy for osteosarcoma without high-dose methotrexate: a 12-year follow-up on 53 patients

BACKGROUND: The clinical relevance of polychemotherapy in osteosarcoma is undisputed and well proven. In this retrospective study we report the results of chemotherapy treatment without high-dose methotrexate (HDMTX) for osteosarcoma. PATIENTS AND METHODS: Between 1986 and 1992, 53 patients with stage IIB extremity osteosarcoma received multimodal therapy (age: 6-36 years, median 17 years). All patients received neoadjuvant and adjuvant chemotherapy with adriamycin, cisplatin, cyclophosphamide, and vincristine without HDMTX. In 60.4%, tumor volume was < or =150 ml and in 39.6% >150 ml. Surgical modalities were distributed as follows: 71.7% of patients received limb-sparing surgery, 20.8% ablative surgery, and 7.5% rotationplasty. 35.8% of patients developed pulmonary metastases. RESULTS: Overall survival (OAS) was 71.7% after 5 years and 67.2% after 10 years. Ten-year OAS was not observed with local recurrences; without local recurrence 10-year OAS was 74.2% (p = 0.002). Five-year OAS was 31.6% in patients who developed pulmonary metastases. Ten-year OAS was 71.1% and 61.1% when tumor volume was < or =150 ml and >150 ml, respectively (p = 0.445). Ten-year OAS was 73.5% in responders to preoperative chemotherapy; in poor responders 62.1% (p = 0.353). Event-free 10-year survival was 70.8% in responders and 48.3% in poor responders (p = 0.099). CONCLUSION: Compared to treatment protocols including HDMTX similar survival rates were achieved.