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Background: A retrospective review and analysis of 275 patients with marginal zone lymphoma (MZL) was performed to determine prognostic factors. An effort was also made to establish a specific prognostic score for patients with extranodal MZL., Methods: Patients were divided into 3 groups according to the type of MZL: extranodal, nodal, and splenic. Factors analyzed included age; gender; presence of B symptoms; Zubrod performance score; clinical stage; serum β(2)-microglobulin, lactate dehydrogenase, albumin, and hemoglobin levels; and presence of autoimmune disorder., Results: The 5-year overall survival rates of patients with extranodal, nodal, and splenic MZL were 87%, 89%, and 93%, respectively (P = .95). On multivariate analysis, splenic MZL patients had the best prognosis (hazard ratio, 0.18; P = .018). An elevated serum β(2)-microglobulin level (P = .010), B symptoms (P = .021), and male gender (P = .036) were found to be correlated with decreased recurrence-free survival (RFS) on multivariate analysis. Using these 3 variables, a 3-tier prognostic scoring system was created for patients with extranodal MZL: low-risk with no adverse factors, intermediate-risk with 1 adverse factor, and high-risk with ≥ 2 adverse factors. The 5-year RFS rates for the low-risk, intermediate-risk, and high-risk groups were 80%, 71%, and 44%, respectively (P = .01)., Conclusions: Patients with extranodal and nodal MZL have a similar prognosis, whereas patients with splenic MZL have a better prognosis despite the increased prevalence of negative prognostic indicators. With the use of 3 readily available factors, a prognostic scoring system was identified for patients with extranodal MZL., (© 2010 American Cancer Society.)

Purpose: To determine the response, failure-free survival (FFS), and overall survival rates and toxicity of rituximab plus an intense chemotherapy regimen in patients with previously untreated aggressive mantle-cell lymphoma (MCL)., Patients and Methods: This was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of six to eight cycles., Results: Of 97 assessable patients, 97% responded, and 87% achieved a complete response (CR) or unconfirmed CR. With a median follow-up time of 40 months, the 3-year FFS and overall survival rates were 64% and 82%, respectively, without a plateau in the curves. For the subgroup of patients < or = 65 years of age, the 3-year FFS rate was 73%. The principal toxicity was hematologic. Five patients died from acute toxicity. Four patients developed treatment-related myelodysplasia/acute myelogenous leukemia, and three patients died while in remission from MCL. A total of eight treatment-related deaths (8%) occurred., Conclusion: Rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine is effective in untreated aggressive MCL. Toxicity is significant but expected. Because of the shorter FFS concurrent with significant toxicity in patients more than 65 years of age, this regimen is not recommended as standard therapy for this age subgroup. Larger prospective randomized studies are needed to define the role of this regimen in the treatment of MCL patients compared with existing and new treatment modalities.

Purpose: The purpose of this study was to evaluate the clinical activity and toxicity of recombinant human Interleukin (IL)-12 in patients with relapsed and refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD)., Experimental Design: Forty-two previously treated patients (32 patients with NHL and 10 patients with HD) were enrolled on the study. Patients were treated with either intravenous (n = 11) or subcutaneous (n = 31) administration of IL-12. The patients had received a median of three prior treatment regimens, and 16 patients had undergone prior autologous stem cell transplantation., Results: All patients were assessable for toxicity, and 39 of 42 (93%) patients were assessable for response. Six of 29 (21%) patients with NHL had a partial or complete response, whereas none of the 10 patients with HD responded. Furthermore, 15 patients had stable disease that lasted for up to 54 months. Progression-free survival in patients with indolent NHL, aggressive NHL, and HD was 6, 2, and 2.5 months, respectively. Treatment was well tolerated, and the most common toxicity was flu-like symptoms. Reversible grade 3 hepatic toxicity was observed in three patients requiring dose reduction. IL-12 therapy increased the median number of peripheral blood CD8 T lymphocytes from 423/microl to 576/microl (P = 0.0019). Furthermore, IL-12 therapy decreased serum vascular endothelial growth factor and basic fibroblast growth factor concentrations in 37% of the patients., Conclusions: The ability of recombinant human IL-12 therapy to increase the number of circulating CD8+ cells and induce clinical remissions in patients with relapsed NHL warrants further investigation of the drug.

This study investigated the use of a nonablative conditioning regimen to decrease toxicity and achieve engraftment of an allogeneic blood stem cell transplant, allowing a graft-versus-malignancy effect to occur. All patients had follicular or small cell lymphocytic lymphoma after relapse from a prior response to conventional chemotherapy. Patients received a preparative regimen of fludarabine (25 mg/m(2) given daily for 5 days or 30 mg/m(2) daily for 3 days) and intravenous cyclophosphamide (1 g/m(2) given daily for 2 days or 750 mg/m(2) daily for 3 days). Nine patients received rituximab in addition to the chemotherapy. Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Twenty patients were studied; their median age was 51 years. Twelve were in complete remission (CR) at transplantation. All patients achieved engraftment of donor cells. The median number of days with severe neutropenia was 6. Only 2 patients required more than one platelet transfusion. The cumulative incidence of acute grade II to IV GVHD was 20%. Only one patient developed acute GVHD of greater than grade II. All patients achieved CR. None have had a relapse of disease, with a median follow-up period of 21 months. The actuarial probability of being alive and in remission at 2 years was 84% (95% confidence interval, 57%-94%). Nonablative chemotherapy with fludarabine/cyclophosphamide followed by allogeneic stem cell transplantation is a promising therapy for indolent lymphoma with minimal toxicity and myelosuppression. Further studies are warranted to compare nonablative allogeneic hematopoietic transplantation with alternative treatment strategies.

Purpose: To evaluate the outcome of high-dose chemotherapy (HDCT) and autologous or allogeneic hematopoietic transplantation in patients with peripheral T-cell lymphoma (PTCL) who experienced disease recurrence after prior conventional chemotherapy., Patients and Methods: We performed a retrospective analysis of 36 PTCL patients from the University of Texas M.D. Anderson Cancer Center treated between 1989 and 1998 with HDCT and autologous or allogeneic hematopoietic transplantation., Results: A total of 36 patients were studied (29 received autologous transplantation, and seven received allogeneic transplantation). The overall survival rate at 3 years was 36% (95% confidence interval [CI], 23% to 59%), and the progression-free survival (PFS) rate was 28% (95% CI, 16% to 49%). The pretransplant serum lactate dehydrogenase level was the most important prognostic factor for both survival and PFS rates (P < .001). A Pretransplant International Prognostic Index score of < or = 1 indicated a superior survival rate (P = .036) but not an improved PFS rate. A median follow-up of 43 months (range, 13 to 126 months) showed 13 patients (36%) were still alive with no evidence of disease., Conclusion: Our results are comparable to the published data on HDCT in B-cell non-Hodgkin's lymphoma (NHL) patients despite the fact that patients with PTCL are known to have a worse outcome compared with B-cell NHL patients. Considering the dismal outcome of conventional chemotherapy in PTCL patients, these data suggest the hypothesis that the poor prognostic implication of T-cell phenotyping in NHL might be overcome by frontline HDCT and transplantation.

Purpose: To analyze the results with involved-field radiotherapy after aggressive lymphomas had decreased in size by 50-99% in response to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy., Methods and Materials: From 1988 through 1996, 294 previously untreated patients with Working Formulation intermediate-grade or large-cell immunoblastic lymphomas underwent CHOP-based chemotherapy on 2 consecutive protocols at the M. D. Anderson Cancer Center. Forty-four (15%) of these patients achieved, based on international working group guidelines, a partial (50-75%) response (n = 25), or unconfirmed complete (76-99%) response (n = 19) to a median of 6 cycles of chemotherapy. These patients were treated with salvage involved-field radiotherapy (n = 32) or chemotherapy (n = 12), e.g., MINE-ESHAP, without autologous stem-cell rescue (ASCR)., Results: Median follow-up was 43 months. Partial responders experienced similar outcomes to unconfirmed complete responders. Local control (4-year rates: 86% vs. 53%, p = 0.009) and progression-free survival (4-year rates: 67% vs. 8%, p < 0.0001), but not overall survival (4-year rates: 70% vs. 50%, p = 0.067) were significantly better in those who received salvage radiotherapy, which was well tolerated., Conclusion: Progression-free and overall survival in aggressive lymphoma patients who underwent salvage radiotherapy were similar to results reported for high-dose chemotherapy with ASCR. The role of salvage radiotherapy in partial and unconfirmed complete responders to CHOP chemotherapy justifies examination in a large, cooperative group trial.

Background and Purpose: The present study examines outcomes in patients with primary orbital lymphomas who underwent complete staging., Materials and Methods: From 1978 to 1997, 21 adult patients at the M.D. Anderson Cancer Center had stage IEA-IIEA orbital non-Hodgkin's lymphomas based on staging that included computed tomography scans. Sixteen (76%) patients had working formulation low-grade lymphomas, and five (24%) had aggressive lymphomas. Fourteen of 16 (88%) patients with low-grade lymphomas were treated with radiotherapy alone, and four of five (80%) patients with aggressive lymphomas were treated using combination chemotherapy with or without radiotherapy. Total radiotherapy doses ranged from 30.0 to 40.0 Gy using daily 1.5-2.0 Gy fractions., Results: The median follow-up was 84 months. For the low-grade lymphomas, the 5-year local control, progression-free survival, and overall survival rates were 100, 100, and 92%, respectively. For the seven low-grade lymphomas treated with radiotherapy alone to 30.0 Gy in 20 fractions, the 5-year local control, progression-free, and overall survival rates were 100, 100, and 75%, respectively. The 5-year incidence of complications, which were typically mild, in eyes irradiated to 30 Gy in 20 fractions versus higher biologically effective doses were 25 and 38%, respectively (P = 0.62). Of the five patients with aggressive lymphomas, none of the four who underwent chemotherapy with or without radiotherapy relapsed (all four remain alive), whereas the one treated with radiotherapy alone for stage IEA disease experienced a distant relapse., Conclusions: In patients with low-grade lymphomas, a good therapeutic ratio was obtained with low-dose radiotherapy alone. In patients with aggressive lymphomas, chemotherapy with or without radiotherapy resulted in excellent local control, progression-free survival, and overall survival; however, the statistical power was limited.

Purpose: To test the hypothesis that prechemotherapy tumor size affects the dose of radiation that should be delivered to intermediate-grade and large-cell immunoblastic lymphomas that have completely responded to cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-based induction chemotherapy., Methods and Materials: From September 1988 through December 1996, 294 patients with newly diagnosed, Stage I-IV, intermediate-grade or large-cell immunoblastic lymphomas were enrolled on 2 prospective protocols at the M. D. Anderson Cancer Center. Treatment consisted of CHOP-based chemotherapy with or without involved field radiotherapy. One hundred seventy-two patients, with 178 nodal sites and 87 nonbony, extranodal sites of disease achieved a complete response to 2-6 cycles of chemotherapy and underwent involved field radiotherapy. Total radiation doses ranged from 30.0 to 50.4 Gy (mean +/- standard deviation: 39.7 +/- 2.5 Gy) over 22-49 days using a daily fraction size of 1.3-2.3 Gy. Because various fraction sizes were delivered, the linear-quadratic model was used to convert total radiation doses to biologically equivalent doses given at 1.8 Gy per fraction (D1.8). An alpha/beta ratio of 10 Gy was used for the lymphomas, resulting in D1.8 ranging from 29.1 to 50.8 Gy. Regression tree analysis was performed on nodal sites of disease to determine which of the following factors were predictive of local control: age, tumor size, D1.8, total radiation dose, and duration of radiotherapy. Based on the results of the regression tree analysis, Kaplan-Meier analysis was used to determine the probability of local control per site as a function of tumor size and D1.8. Regression tree analysis was also performed on patients with nonbony disease who received D1.8 = 29.1-39.1 Gy to determine if small lymphomas could be locally controlled with relatively low doses of radiation. The log-rank test was used to compare local control curves., Results: The median length of follow-up among survivors was 63 months. Regression tree analysis of nodal sites identified 3 distinct groups: (a) lymphomas < or = 10 cm and D1.8 = 29.1-39.1 Gy; (b) lymphomas < or = 10 cm and D1.8 = 39.2-50.8 Gy; and (c) lymphomas > 10 cm. For nonbony lymphomas that measured < 3.5 cm, low doses of radiation resulted in excellent local control (5-year rates: 96% vs. 97% for D1.8 = 29.1-39.1 Gy vs. D1.8 = 39.2-50.8 Gy; p = 0.610). For 3.5-10.0 cm lymphomas, higher doses of radiation resulted in better local control (5-year rates: 40% versus 98% for D1.8 = 29.1-39.1 Gy versus D1.8 = 39.2-50.8 Gy, p < 0.0001). A narrow dose range (D1.8 = 39.2-40.7 Gy) was delivered to the 8 lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, resulting in a 5-year local control rate of only 70%. There was no difference in local control for nodal versus nonbony, extranodal sites of disease., Conclusion: D1.8 ranging from 29.1 to 39.1 Gy yielded excellent local control for nonbony lymphomas measuring < 3.5 cm that had completely responded to a median of 3 cycles of CHOP-based chemotherapy. D1.8 ranging from 39.2 to 50.8 Gy yielded excellent local control for nonbony lymphomas measuring 3.5-10.0 cm that completely responded to either 3 or 6 cycles of chemotherapy. For nonbony lymphomas measuring > 10 cm that completely responded to 6 cycles of chemotherapy, D1.8 ranging from 39.2 to 40.7 Gy yielded suboptimal local control, suggesting that higher doses of radiation are indicated.

Purpose: To analyze the impact of involved field radiotherapy on local control, freedom from progression, and overall survival in patients with clinical Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based induction chemotherapy., Methods and Materials: From July 1989 through October 1996, 32 patients with clinical Stage III and 27 patients with clinical Stage IV, intermediate grade, or large-cell immunoblastic lymphomas were prospectively enrolled on two protocols at The University of Texas M. D. Anderson Cancer Center. None had previously undergone treatment for lymphoma. The median patient age was 54 years (range: 26-85 years). There were a total of 172 involved sites of disease at presentation. All 59 patients received CHOP-based chemotherapy. At least six cycles of chemotherapy were delivered to 92% of the patients. Involved field radiotherapy (39.6-40.0 Gy in 20-22 fractions in 74% of cases) was administered to 28/59 (47%) patients beginning 3-4 weeks after chemotherapy. Sites were irradiated at the discretion of the treating physician. Irradiated and nonirradiated groups were compared in terms of maximum pre-chemotherapy tumor size and University of Texas M. D. Anderson Cancer Center tumor score. Kaplan-Meier estimates of local control per patient, freedom from progression, and overall survival for the irradiated and nonirradiated groups were calculated in terms of the stage of disease and treatment delivered. The resulting curves were compared using the log-rank test. The Cox proportional hazards model was used to assess the prognostic significance of tumor size, tumor score, treatment delivered, and stage., Results: The median length of follow-up for all patients was 53 months (range: 4-96 months). The median tumor size at the start of chemotherapy in irradiated patients was 4.5 cm (range: 0-15 cm) versus 3 cm (range: 0-7 cm) in nonirradiated patients (p = 0.004). The irradiated and nonirradiated groups were not significantly different in terms of tumor scores. Radiotherapy improved (p = 0.001) local control (5-year rates: 89% versus 52%) for Stages III and IV combined. This benefit was due to the dramatic improvement (p = 0.0009) in local control for patients with lymphomas measuring > or =4 cm at the start of chemotherapy (5-year rates: 89% for irradiated patients versus 33% for nonirradiated patients). Radiotherapy also improved (p = 0.003) freedom from progression (5-year rates: 85% for irradiated patients versus 51% for nonirradiated patients) for Stages III and IV combined. On multivariate analysis, radiotherapy was the most significant factor affecting local control and freedom from progression. Overall survival was not significantly different (p = 0. 620) between irradiated and nonirradiated patients (5-year rates: 87% versus 81%, respectively). When Stages III and IV were analyzed separately, radiotherapy improved local control and freedom from progression but not overall survival. Radiotherapy was tolerated reasonably well, with the main toxicity being moderate myelosuppression. Eleven out of 12 (92%) patients with recurrent disease at the time of their last follow-up visit were treated initially with chemotherapy alone., Conclusion: Involved field radiotherapy improved local control and freedom from progression in patients with > or = 4 cm Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to CHOP-based induction chemotherapy. Involved field radiotherapy was tolerated reasonably well.

We assessed cytologic specimens from 11 mantle cell lymphomas (MCLs) and 32 other B-cell non-Hodgkin lymphomas (NHLs) for 11q13 breakpoints using a 2-color fluorescence in situ hybridization (FISH) assay that uses an 11q13 probe centered on the CCND1 gene and a centromeric chromosome 11 probe (CEP11). The number of nuclei in 200 cells were counted, and results were expressed as an 11q13/CEP11 ratio. All MCLs showed a high percentage of interphase nuclei with 3 or more 11q13 signals (mean, 74.8%; range 57%-90%). In contrast, in other B-cell NHLs the mean percentage of cells with 3 or more 11q13 signals was 9.2%. All MCLs had an elevated 11q13/CEP11 ratio (mean, 1.38). The mean ratio for other B-cell NHLs was 0.99. Two non-MCL cases, 1 large B-cell and 1 B-cell unclassified NHL, had high 11q13/CEP11 ratios of 1.15 and 1.30, respectively. Conventional cytogenetic analysis performed on the former case revealed a t(5;11)(q31;q13). Interphase FISH analysis using 11q13 and CEP11 probes is a convenient ancillary method for assisting in the diagnosis of MCL. This commercially available assay is simple to use on cytology or imprint specimens, and results can be obtained within 24 hours.

We describe the usefulness of a real-time polymerase chain reaction (PCR) assay for detection of the t(11;14)(q13;q32), most commonly present in mantle cell lymphoma (MCL). This assay is based on the 5'-->3' exonuclease activity of Taq polymerase, which cleaves an internal probe labeled with a reporter dye at its 5' end and a quencher dye at its 3' end during PCR. The real-time t(11;14) PCR assay was established using DNA from a case of MCL with the t(11;14), amplifiable using conventional PCR and primers specific for the major translocation cluster (MTC) region of the bcl-1 locus and the immunoglobulin heavy chain joining region gene (JH). The specificity was determined by analyzing DNA from 82 cases: 50 MCL, 27 other types of non-Hodgkin lymphoma (NHL), and 5 reactive lymphoid proliferations. The real-time t(11;14) PCR results were correlated with data obtained by a conventional PCR assay. By using the real-time assay, bcl-1 MTC/JH DNA fusion sequences were detected in 25 of 50 MCLs but not in other NHLs or reactive lymphoid proliferations. Concordance between real-time and conventional PCR methods for MCL was 96% and for all samples was 98%. The results demonstrate that this real-time PCR method to detect bcl-1 MTC/JH DNA fusion sequences is specific and reliable. In addition, the results are available immediately following amplification, without standard post-PCR manipulations.

Purpose: To evaluate response and outcome with a front-line intensive multiagent chemotherapy regimen in adults with Burkitt's-type acute lymphoblastic leukemia (B-ALL)., Patients and Methods: From September 1992 to June 1997, 26 consecutive adults with newly diagnosed untreated B-ALL received hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD). Their median age was 58 years (range, 17 to 79 years), and 46% were > or = 60 years. Patients received Hyper-CVAD alternated with courses of high-dose methotrexate and cytarabine. Granulocyte colony-stimulating factor and prophylactic antibiotics were administered for all eight planned courses. CNS prophylaxis alternated intrathecal methotrexate and cytarabine on days 2 and 7 of each course., Results: Complete remission (CR) was obtained in 21 patients (81%). There were five induction deaths (19%). The median time to CR was 22 days (range, 15 to 89 days); 70% achieved CR within 4 weeks. The 3-year survival rate was 49% (+/- 11%); the 3-year continuous CR rate was 61% (+/- 11%). Twelve CR patients (57%) were in continuous CR at a median follow-up of 3+ years (range, 13+ months to 6.5+ years). Characteristics predicting for worse survival were age > or = 60 years, poor performance status, anemia, thrombocytopenia, peripheral blasts, and increased lactate dehydrogenase level. The 3-year survival rate was 77% for 14 patients younger than 60 years and 17% for 12 patients > or = 60 years (P <.01). Regression analysis identified older age, anemia, and presence of peripheral blasts as independent factors associated with shorter survival. Patients could be stratified according to (1) no or one adverse feature, (2) two adverse features, and (3) all adverse features. The 3-year survival rates were 89%, 47%, and 0%, respectively (P <.01)., Conclusion: Hyper-CVAD is effective in adult B-ALL. Identification of patients with high risk for relapse and improved methods to detect residual disease may result in risk-oriented approaches.

Background: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is related to Helicobacter pylori infection and may depend on this infection for growth., Objective: To determine the response of gastric MALT lymphoma to antibiotic treatment., Design: Prospective, uncontrolled treatment trial., Setting: University hospital referral center and three collaborating university and community hospitals., Patients: 34 patients with stage I or stage II N1 gastric MALT lymphoma., Intervention: Two of three oral antibiotic regimens--1) amoxicillin, 750 mg three times daily, and clarithromycin, 500 mg three times daily; 2)tetracycline, 500 mg four times daily, and clarithromycin, 500 mg three times daily; or 3) tetracycline, 500 mg four times daily, and metronidazole, 500 mg three times daily--were administered sequentially (usually in the order written) for 21 days at baseline and at 8 weeks, along with a proton-pump inhibitor (lansoprazole or omeprazole) and bismuth subsalicylate., Measurements: Complete remission was defined as the absence of histopathologic evidence of lymphoma on endoscopic biopsy. Partial remission was defined as a reduction in endoscopic tumor stage or 50% reduction in the size of large tumors., Results: 34 patients were followed for a mean (+/-SD) of 41 +/- 16 months (range, 18 to 70 months) after antibiotic treatment. Of 28 H. pylori-positive patients, 14 (50% [95% CI, 31% to 69%]) achieved complete remission, 8 (29%) achieved partial remission (treatment eventually failed in 4 of the 8), and 10 (36% [CI, 19% to 56%]) did not respond to treatment. Treatment failed in all 6 (100% [CI, 54% to 100%]) H. pylori-negative patients. Patients with endoscopic appearance of gastritis (stage I T1 disease) were most likely to achieve complete remission within 18 months. Tumors in the distal stomach were associated with more favorable response than tumors in the proximal stomach., Conclusions: A subset of H. pylori-positive gastric MALT lymphomas, including infiltrative tumors, may respond to antibiotics. The likelihood of early complete remission seems to be greatest for superficial and distal tumors.

Purpose: To define the disease course, therapeutic strategies, patterns and rates of relapse and causes of death for patients with Hodgkin's disease with lymphocyte predominance (LPHD) and to assess prognostic factors including nodular and diffuse histologic patterns., Patients and Methods: The records of all previously untreated patients with LPHD who received initial treatment at the University of Texas M. D. Anderson Cancer Center (UTMDACC) from 1960 through 1992 were reviewed. Clinical and histopathologic characteristics, specifically nodular and diffuse LPHD, and treatment groups were assessed by overall and relapse-free survival, patterns of relapse, and causes of death., Results: Of 70 patients, 58 (83%) had nodular LPHD and 12 (17%) had a diffuse pattern: clinical characteristics were similar between the two subtypes. The median age of all patients was 25 years, 79% were male, 96% presented with stage I or II disease and 93% were free of B symptoms. Laparotomy (23 patients) failed to upstage any patient with a negative lymphogram. With a median follow-up of 12.3 years for alive patients, 19 (27%) patients have relapsed. All 3 relapses among the patients with diffuse subtype occurred within 3 years while 9 of 16 relapses occurred after 5 years with nodular subtype. However, we did not detect any statistically significant difference in relapse free survival or survival between the subtypes in our patient population. There was some suggestion that patients aged 40 and older experienced shorter survival; no other pretreatment characteristics were noted to be associated with relapse free survival or survival. Though there were no relapses within the radiation fields, no effect of extent of radiation therapy on relapse rate was observed. Thirteen (19%) patients have died, 6 (8.6%) of whom succumbed to LPHD. Two patients developed diffuse large cell lymphoma., Conclusions: Patients with LPHD usually present with localized and asymptomatic disease. Laparotomy is unnecessary if the lymphogram is negative. Nodular histology occurred in the majority of patients. Though all relapses from diffuse subtype occurred within 3 years in contrast to some late relapses observed for nodular subtype, there was no statistically significant difference in relapse free survival or survival between the subtypes. The extent of irradiation had no effect on relapse free survival or survival. We could not find any evidence that LPHD should be treated any different from the classical Hodgkin's disease at this point despite suggestions that it be classified as a non-Hodgkin's B-cell lymphoma.

Purpose: To review the long-term clinical effects of unilateral kidney irradiation on overall renal function and blood pressure in patients with gastric lymphoma., Methods and Materials: In the study were 27 patients with Stage I or II gastric lymphoma who had undergone irradiation of at least 24 Gy to > or = 1/3 of the left kidney. They include 16 women and 11 men, aged 31 to 77, with a mean age of 57.6 years (median 56). Fifteen patients had Stage I and 12 had Stage II disease. In 13 patients the whole kidney had been irradiated, and 14 had had partial kidney irradiation, at doses ranging between 24 and 40.5 Gy. All patients received combined chemotherapy with various drugs: all patients received corticosteroids, and five received cis-platinum. Their follow-up ranged between 0.7 and 7.8 years (mean 3.4 years). Data on possible effects of the treatment on blood pressure, renal function as assessed by blood urea and creatinine, and kidney shrinkage as seen by serial computed tomography scanning were collected on all patients., Results: Three patients had persistent, mild elevations of urea and creatinine levels, which did not require special treatment. All three also received cis-platinum. Ipsilateral kidney shrinkage was evident in most patients. In 19 patients the craniocaudal measurement of the kidney shrank by > or = 1.6 cm. Shrinkage in other dimensions was also evident. The degree of atrophy was related to the volume of kidney irradiated. Only two patients developed hypertension, both at a low level of 150/90; one patient had had 40 Gy to the whole kidney, the other 40 Gy to half the kidney. Neither patient had elevated urea or creatinine., Conclusions: Notwithstanding the shrinkage to the irradiated part of the kidney, the treatment did not lead to clinically significant hypertension or renal dysfunction. The administration of cis-platinum to patients with gastric lymphoma that requires kidney irradiation should be further evaluated.

Background: The histologic features of primary mediastinal non-Hodgkin's nonlymphoblastic lymphoma (NHL) are well described in the surgical pathology literature. However, the fine-needle aspiration (FNA) cytology of these lesions has not been characterized thoroughly., Methods: FNA material from 12 patients with primary mediastinal NHL was reviewed. The series was comprised of 7 men and 5 women with a mean age of 42 years (age range, 26-65 years). All 12 patients underwent a mediastinal FNA as the initial step in their diagnostic evaluation. In some cases, flow cytometry or immunocytochemical studies were performed on the FNA material to render a definitive diagnosis., Results: On the basis of the cytomorphologic findings and ancillary studies performed on the FNA material, a diagnosis of malignant lymphoma (five cases), consistent with/suspicious for malignant lymphoma (four cases), or nondiagnostic/negative for lymphoma (three cases) was rendered for each case. In general, a definitive diagnosis of malignancy was established when there was cytomorphologic evidence of lymphoma and a monoclonal lymphoid population could be demonstrated by immunocytochemistry. Eleven of the 12 primary mediastinal non-Hodgkin's lymphomas were large cell lymphomas (LCL), and 1 was a composite lymphoma (LCL and Hodgkin's disease). In three of the LCL cases the neoplastic cells exhibited prominent nuclear hyperlobation in association with sclerosis., Conclusions: A diagnosis of primary mediastinal NHL can be established with a high degree of accuracy on the basis of FNA cytology. The FNA cytomorphology of primary mediastinal NHL correlates with the spectrum of morphologic diversity associated with this entity in the surgical pathology literature.

Purpose: Because the effects of mitoxantrone on human male fertility were unknown, we determined prospectively the effects of three courses of mitoxantrone (Novantrone), vincristine (Oncovin), vinblastine, prednisone (NOVP) chemotherapy on the potential for fertility of men with Hodgkin's disease (HD)., Patients and Methods: Semen analyses were performed on 58 patients with stages I-III HD before, during, and after chemotherapy and after the sperm count recovered from the effects of abdominal radiotherapy that was given after chemotherapy., Results: Before the initiation of treatment, 84% of the patients were normospermic. Sperm counts declined significantly within 1 month after the start of NOVP chemotherapy. In the month after chemotherapy, 38% of patients were azoospermic, 52% had counts < 1 million/ mL, and 10% had counts between 1 and 3 million/mL. Between 2.6 and 4.5 months after the completion of chemotherapy, sperm counts recovered rapidly to normospermic levels in 63% of patients. In the remaining patients who were followed up for at least 1 year after standard upper abdominal radiotherapy, counts also recovered to normospermic levels., Conclusion: NOVP chemotherapy, like most other regimens, produced marked temporary effects or spermatogenesis. However, sperm production recovered very rapidly, within 3 to 4 months after the end of NOVP chemotherapy. This pattern was caused by killing differentiating spermatogenic cells, but there was little cytotoxicity or inhibition of stem cells from mitoxantrone or the other drugs. After the combination of NOVP plus abdominal radiotherapy, sperm counts and motility were restored in most patients to pretreatment levels, which were compatible with normal fertility.

Background: Cutaneous T-cell lymphoma (CTCL) may respond to many therapies, but long-term disease-free survival is uncommon. Patients with advanced disease have a median survival of approximately 3 years., Objective: Our purpose was to combine known effective agents sequentially to determine whether we could achieve remission in more patients or for longer duration., Methods: Patients with mycosis fungoides (n = 23) or Sézary syndrome (n = 5) were treated with 4 months of recombinant interferon alfa together with isotretinoin, followed by total skin electron beam therapy alone (for stage I to II disease) or preceded by chemotherapy (for stage III to IV disease). Maintenance therapy consisted of interferon for 1 year and topical nitrogen mustard for 2 years., Results: Twenty-eight patients were treated. The overall response rate (complete and partial remissions) was 82%. Although the median duration of remission was 5 months in patients with stage III to IV disease, two patients remain in complete remission at 39 + and 46 + months. In patients with stage I to II disease the median duration of remission has not been reached at a median follow-up of 18 months. Five patients, all with stage III to IV disease, have died. Overall, the regimen was well tolerated with one treatment-related death from neutropenic sepsis., Conclusion: Combined modality therapy may be effective for the treatment of CTCL with similar response rates to other current therapies.

Purpose: To evaluate outcomes and identify prognostic factors in allogeneic bone marrow transplantation in patients with end-stage lymphoma., Patients and Methods: Data were retrospectively analyzed of 64 patients (42 men and 22 women) 18 to 48 years of age with recurrent or refractory lymphoma who underwent allogeneic bone marrow transplantation from matched sibling donors (or in 1 case from a one antigen-mismatched relative) between May 1981 and July 1994., Results: Twelve patients survived free of disease. They were 8 of 15 with low-grade lymphoma (disease-free survival at 2 years 59% +/- 13%); 3 of 25 with lymphoblastic lymphoma (disease-free survival 17% +/- 8%); and 1 of 10 with diffuse small non-cleaved cell lymphoma (disease-free (10% +/- 9%). Survival and disease-free survival of patients with low-grade lymphoma were significantly superior compared to any other subgroup of patients (P <0.01). Only 2 patients with low-grade lymphoma had disease progression (9% +/- 9% actuarial risk at 2 years) as opposed to 5 of 15 with intermediate-grade lymphoma (39% +/- 14%), 9 of 25 with lymphoblastic lymphoma (28% +/- 9%), and 8 of 10 (80% +/- 13%) with diffuse small non-cleaved lymphoma. The actuarial risk for disease progression was significantly lower for patients with low-grade lymphoma than for any other histologic subgroup (P <0.02). It was significantly higher for those with diffuse small non-cleaved cell lymphoma than for other histologic subgroups (P < or = 0.003)., Conclusions: Allogeneic bone marrow transplantation is an effective procedure in patients with refractory low-grade lymphoma. It results in long-term remissions and should be considered in younger patients with recurrent disease who have a matched sibling donor. The late recurrence in 1 patient indicates the necessity of continued follow-up. A small fraction of patients with end-stage intermediate- and high-grade lymphoma can obtain prolonged disease-free survival, but recurrence and regimen-related toxicity remain major problems. The results could be improved by the development of conditioning regimens with less toxicity and by the use of bone marrow transplantation earlier in the course of the disease.

Background: Primary lymphomas of the uterus or cervix are so rare that treatment series of single institutions consist of very small numbers of patients, making standard treatment difficult to define. The outcome of patients treated with a combination of chemotherapy and radiation therapy was analyzed for all but patients with the most advanced disease., Methods: From 1976 to 1992, 16 patients received definitive treatment. Thirteen patients had intact uteri (group 1) and 3 presented with paracolpal lymphomas after previous hysterectomies (group 2). Twelve of the patients received chemotherapy and external irradiation. The remaining four underwent only chemotherapy. The overall survival and freedom from disease progression were analyzed according to Kaplan-Meier methods. Prognoses were related to the International Index, Ann Arbor stage, and International Federation of Gynecology and Obstetrics stage., Results: Five-year survival and freedom from disease progression were 77% and 67%, respectively, for group 1, and all patients in group 2 were cured. A statistically significant correlation of survival with scores of the International Index was found in group 1. For patients with scores in the low or low-intermediate range (n = 10), 5-year survival was 90%. All patients who scored in the high-intermediate or high range (n = 3) died by 66 months after their diagnosis (P = 0.0153). The Ann Arbor stage had less predictive value, with 5-year survival of 89% for Stage I and II patients (n = 9), compared with 50% survival for the four Stage III and IV patients (P = 0.0701). International Federation of Gynecology and Obstetrics staging did not predict outcome., Conclusions: The combination of chemotherapy and irradiation is the most effective treatment regimen for all uterine and cervical lymphomas. The International Index is most predictive of outcome.

Background: Numerous treatment strategies have been tried with the aim of improving results for patients with intermediate-grade lymphomas (IGL) over those achieved with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and numerous prognostic models have been developed to identify and separate risk groups. This study reports on a new protocol for Ann Arbor Stages II-IV IGL that consists of CHOP-Bleo alternated with a new regimen of cyclophosphamide, methotrexate, etoposide, and dexamethasone (CMED) and radiation therapy and demonstrates the usefulness of prognostic models for identifying risk groups and comparing treatment programs., Methods: One hundred seventy patients with Ann Arbor Stages II-IV IGL were treated with alternating cycles of CHOP-Bleo and CMED for a total of 12 cycles. Involved field radiation therapy was interspersed with courses of chemotherapy for patients with Stage II and Stage III disease. Results were analyzed and compared with those of the authors' previous study of CHOP-Bleo and radiation therapy using the Ann Arbor staging system, their earlier prognostic model, and the recently published International Index., Results: A complete remission occurred in 78% of the patients. The overall 5-year survival rate was 67%. Survival was better for patients with Ann Arbor Stage II disease (80%) than for those with Stage III or Stage IV (67% and 58%, respectively). High tumor burden, above-normal levels of serum lactic dehydrogenase, serum beta 2-microglobulin, and Ann Arbor Stage IV disease were adverse factors. The International Index and the authors' earlier prognostic model separated four prognostic groups. CHOP-Bleo/CMED was generally well tolerated. Neutropenic fever was the major complication that occurred in 25 patients during treatment. Six of these patients died of sepsis., Conclusions: This study demonstrated that CHOP-Bleo/CMED is a well-tolerated regimen that produced better results than those reported for a former study that used CHOP-Bleo alone. Further, results for CHOP-Bleo/CMED compared favorably with those of other second- and third-generation regimens. The study also validated the usefulness of prognostic models and, in particular, the new International Index for identifying risk groups.

Recently, the combination chemotherapy Novantrone, Oncovin, Velban, Prednisone [NOVP] was developed by The University of Texas M. D. Anderson Cancer Center for treatment of Hodgkin's disease [HD]. Preliminary clinical results show that NOVP is as effective as the traditional Mechlorethamine, Oncovin, Procarbazine, Prednisone [MOPP] regimen in achieving remission, but with fewer side-effects. To determine if NOVP is genotoxic, we studied the induction of chromosome breaks and sister chromatid exchanges [SCEs] in lymphocytes of 42 HD patients both before and during NOVP treatment. Furthermore, in vitro bleomycin treatment was used to unmask potential single-stranded DNA breaks inducted by the therapy. Our results showed that NOVP did not cause elevated levels of chromosome or single-stranded DNA breaks, or SCEs. These results together with previous findings that NOVP caused minimal acute and gonadal toxicities suggest that NOVP is less toxic than MOPP. Therefore, this new regimen shows promise as an effective and minimally toxic regimen for treatment of HD.

Background: Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage., Methods: A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors., Results: The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors., Conclusions: Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer.

A total of 220 fine needle aspiration (FNA) specimens from 212 patients with clinically suspected or previously histologically confirmed lymphoma were evaluated by cytology in conjunction with immunophenotyping analysis of the aspirate; the results were compared with the histologic diagnosis made on previous or current accessions of lymph node or extranodal tissue. Smears of the aspirates were stained with the Diff-Quik and Papanicolaou stains while immunoperoxidase staining using antibodies against kappa and lambda immunoglobulin light chains and Leu-4 was routinely performed on Cytospin preparations. Where indicated, additional marker studies (including T-200, Leu-1, Leu-2a, Leu-3a + 3b, Leu-M1, B1, Leu-12, IgM, CALLA and TdT) were performed. For the non-Hodgkin's lymphomas, specimens were classified by the cytologic characteristics of the neoplastic cells according to the International Working Formulation scheme. The combination of cytologic smears and immunoperoxidase studies resulted in a diagnosis of lymphoma in 173 cases (79%). The remaining aspirates were interpreted as suspicious for lymphoma (7%), benign (10%) or inadequate for diagnosis (4%). Of the 15 suspicious aspirates, 5 proved to be Hodgkin's disease and 2 to be T-cell lymphoma by subsequent biopsy. The cause of failure in the nine inadequate aspirates were necrosis (3 cases), sclerosis (2 cases) and faulty technique (4 cases). In the cases that had concurrent tissue biopsies, no false-positive diagnoses were rendered. These results indicate that FNA used in association with immunocytochemistry is a reliable tool for establishing the diagnosis and classification of the majority of cases of lymphoma. Optimal immunoglobulin light-chain ratios for defining monoclonality in FNA specimens of B-cell lymphomas are proposed.

To detect early relapse in the central nervous systems (CNS) of patients with acute leukemia or lymphoma, we measured levels of beta 2-microglobulin (beta 2 m) in serum and cerebrospinal fluid (CSF). CSF levels were significantly higher in patients with leukemia (P < 0.001) or lymphoma (P < 0.02) with clinical evidence of CNS involvement than in those without this complication. When serum and CSF levels were measured simultaneously, the CSF level of beta 2 m was significantly higher than the serum level in patients with acute leukemia and lymphoma with CNS involvement (P = 0.05), but not in patients without CNS involvement. Serial determination of CSF beta 2 m correlated well with the clinical appearance and disappearance of CNS involvement. These data suggest that serial and simultaneous determination of beta 2 m in serum and CSF may be useful in early diagnosis of CNS involvement and in monitoring intrathecal therapy in patients with acute leukemia or lymphoma.

Thirty patients with relapsed Hodgkin's disease were treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) and autologous bone marrow transplantation. The median age of the patients was 28 years, and 18 were male. More than half had extranodal sites of relapse and constitutional symptoms. Most had been heavily pretreated with multiple salvage chemotherapy regimens and radiotherapy. At the time of transplantation, 23 patients were having progressive disease despite salvage chemotherapy. High-dose CBV chemotherapy induced complete responses in 15 patients and partial responses in 10 patients. Eleven patients are still in complete remission, 1 of whom has had an unmaintained remission for more than 44 months. Toxicity was moderate; all patients had severe myelosuppression requiring supportive therapy, and 1 patient failed to reconstitute her bone marrow. High-dose CBV chemotherapy and autologous bone marrow rescue proved to be effective as salvage therapy for a select group of heavily pretreated patients with relapsed Hodgkin's disease.

Sixty-two patients with follicular large cell lymphoma were treated between 1973 and 1981. The overall median survival was 78 months with a five-year survival of 62%. The complete remission rate was 76%, with a median relapse-free interval of 72 months for responders. Complete remission produced a significantly longer survival than partial response and failure. Patients who tolerated therapy with an intensive doxorubicin-containing regimen had a significantly longer relapse-free interval and survival. Patients with stage I-II disease treated with radiation therapy alone had a higher relapse rate than those treated with radiation and combination chemotherapy. The addition of radiation therapy to combination chemotherapy in stage III-IV disease decreased the incidence of relapse at irradiated sites, but did not translate into improved survival. Pretreatment prognostic factors associated with poor response were thrombocytosis and stage III-IV disease; those associated with shortened survival were thrombocytosis, elevated lactic dehydrogenase level, stage III-IV disease, and bulky abdominal disease. Follicular large cell lymphoma is an aggressive lymphoma. Treatment should be curative in intent, and should include intensive combination chemotherapy even in stage I-II disease. Knowledge of important prognostic factors can be useful for analysis of future trials and planning therapeutic strategies.

The sperm production of 25 patients with Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was studied retrospectively. All but two patients also received radiotherapy treatment to pelvic and/or non-pelvic fields. Sperm counts were obtained from patients treated either with three or fewer (MOPP-2 group) or with five or more (MOPP-6 group) chemotherapy cycles. Recovery of spermatogenesis following treatment-induced azoospermia was significantly higher among the MOPP-2 patients (Mann-Whitney rank sum test, p = 0.001). Patients in this group who did not receive pelvic irradiation appeared to have greater recovery rates (p = 0.06). The results suggest that three cycles of MOPP chemotherapy represent a maximum exposure compatible with the recovery of spermatogenesis.

Percutaneous needle biopsy of lymph nodes and abdominal masses was performed in 48 patients with abdominal lymphoma. A correct diagnosis was obtained in 15 of 28 biopsies performed on lymph nodes and in 17 of 25 abdominal masses or organs. The overall success rate was 64%. No false-positive diagnoses were rendered. No complications related to the procedure were encountered. The value of this technique in the management of selected patients with abdominal lymphoma is detailed.

Pentamethylmelamine, an analog of hexamethylmelamine developed for iv use, was administered to 42 patients in a phase I clinical trial. The dose ranged from 0.080 to 2.50 g/m2/day x 5 and was repeated approximately every 3 weeks. The dose-limiting toxic effects included moderate to severe nausea, vomiting, and central nervous system (CNS) toxicity. Myelosuppression was mild and was not dose-limiting. Antineoplastic activity was observed in four patients. Due to unacceptable gastrointestinal and CNS toxic effects from pentamethylmelamine at the active dose levels, we do not recommend disease-specific phase II trials.

To determine whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) can accelerate granulocyte recovery after high-dose combination chemotherapy with autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease, we performed a nonrandomized phase II study using historical controls as a comparison. Eighteen relapsed/refractory Hodgkin's disease patients who received cyclophosphamide at 1.5 g/m2/day (days -6 to -3), carmustine (BCNU) at 300 mg/m2 (day -6), and etoposide (VP-16) at 125 mg/m2 every 12 hours (days -6 to -4), followed by ABMT (day 0) were treated with rhG-CSF at 60 micrograms/kg/day for a maximum of 28 days beginning on day 1. rhG-CSF dosage was gradually diminished and stopped once an adequate granulocyte count was maintained. rhG-CSF significantly accelerated absolute granulocyte count (AGC) compared with historical controls recovery to the 100/microL level (median, 9 days v 13 days; P = .103 x 10(-4), 500/microL level (median, 13 days v 22 days; P = 0.189 x 10(-2), and 1000/microL level (median, 16 days v 30 days levels; P = .125 x 10(-5). Platelet recovery to 50,000/microL was not significantly altered (P = .370). rhG-CSF was well tolerated, bone pain and myalgia being the only side effects noted. rhG-CSF hastens granulocyte recovery after high-dose chemotherapy with ABMT in patients with relapsed/refractory Hodgkin's disease without significant toxicity.

The demonstration by computed tomography (CT) of enlarged nodes and/or masses in lymphoma patients has been interpreted as indicating that active disease is present. Four cases are presented in which either biopsy or laparotomy of a CT-detected mass after therapy revealed fibrous tissue with no evidence of viable neoplasm. These four cases demonstrate the possible pitfall of diagnosing viable lymphoma in masses detected by CT after therapy.