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We explored the safety and efficacy of rituximab plus alemtuzumab in patients with relapsed or refractory lymphoid malignancies. Forty-eight patients were treated and were assessable for response (32 with chronic lymphocytic leukemia [CLL], 9 with CLL/prolymphocytic leukemia [PLL], 1 with PLL, 4 with mantle cell leukemia/lymphoma, 2 with Richter transformation). The overall response rate was 52% (complete remission, 8%; nodular partial response, 4%; partial response, 40%). With a median follow-up of 6.5 months (range, 1-20 months), the median time to progression was 6 months (range, 1-20 months); median survival, 11 months (11+ months for responders vs 6 months for nonresponders). Most toxicities were grade 2 or lower and infusion-related. Infections occurred in 52% of the patients. Cytomegalovirus (CMV) antigenemia assays were positive in 27% of the patients, but only 15% were symptomatic and required therapy. The combination of rituximab and alemtuzumab is feasible, has an acceptable safety profile, and has clinical activity with a short course in a group of patients with poor prognoses.

Background: The reported frequency of gastrointestinal (GI) tract involvement in patients with mantle cell lymphoma (MCL) is 15-30%. However, this figure most likely is an underestimate because most patients with MCL involving the GI tract previously reported were examined endoscopically only if they had GI tract symptoms. The impact of endoscopic assessment on the management of MCL patients is unknown., Methods: From March 1998 to May 2001 baseline upper and lower endoscopy of the GI tract was performed in consecutive untreated patients with MCL as part of a prospective therapeutic trial. Biopsies were performed on abnormal as well as macroscopically normal mucosa. Endoscopy was repeated during treatment and as part of follow-up evaluations., Results: Only 26% of patients presented with GI symptoms at the time of diagnosis. MCL was present histologically in the lower GI tract of 53 of 60 patient (88%) and in the upper GI tract of 28 of 58 patients (43%). Microscopic evidence of MCL was found in 84% of patients with normal visual (macroscopic) findings by lower endoscopy and in 45% of patients with macroscopically normal findings by upper endoscopy. Despite this high frequency of GI tract involvement, the use of upper and lower endoscopy with biopsies in this group of patients resulted in changes in clinical management in only three (4%) patients., Conclusions: Gastrointestinal tract involvement was found to be present in most patients with MCL, usually at a microscopic level involving macroscopically normal mucosa. The use of aggressive staging evaluation of the GI tract was found to have little impact on patient management decisions in the current study., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11096)

There is little information in the literature on outcomes using doxorubicin-based chemotherapy with or without radiotherapy for early-stage peripheral T-cell lymphomas. The purpose of this study was to analyze The University of Texas M.D. Anderson Cancer Center results in such patients. From 1985 to 1998, 39 patients with Stage I or II World Health Organization classification anaplastic large cell lymphoma (ALCL; n = 20), peripheral T-cell lymphoma, unspecified (PTCLu; n = 11), or nasal-type NK/T-cell lymphoma (NKTCL; n = 8) were treated using doxorubicin-based chemotherapy (median, 6 cycles) with (n = 24) or without (n = 15) radiotherapy (median dose, 40 Gy). Median age was 41 years. Median follow-up of surviving patients was 85 months. Even though patients who presented with bulky disease or who achieved less than a complete response to chemotherapy were the ones typically treated with combined modality therapy rather than chemotherapy alone, there was no significant difference in local control (5-year rates: 60 vs. 70%, p = 0.49), progression-free survival (5-year rates: 65 vs. 60%, p = 0.62), or overall survival (5-year rates: 74 vs. 67%, p = 0.47) between the groups treated with combined modality therapy and chemotherapy alone. Fifteen (38%) patients relapsed. Twelve relapses were limited to the initial site of disease; two involved the initial site and new sites, and one involved only new sites. Based on the significant risk of relapse at the initial site of disease, different approaches, including chemotherapy with concomitant radiotherapy to doses > or = 45 Gy, warrant investigation.

Because irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a broad spectrum of antitumor clinical activity, we investigated its activity in relapsed or refractory non-Hodgkin's lymphomas (NHLs). Irinotecan at 300 mg/m2 i.v. was administered every 21 days with intensive loperamide management of diarrhea. Responders received up to six treatment cycles. Of 44 registered patients, 32 are evaluable for response. Seventeen patients had received one previous regimen, and 15 patients had received two. Disease was refractory to the regimen preceding irinotecan in 12 patients. At baseline, serum lactate dehydrogenase levels were high in 47% (14/30), and beta-2-microglobulin levels were higher than 3.0 mg/L in 29% (8/28) of patients. Responses were seen in 12 of 32 (38%) patients (95% confidence interval [CI] = 21%-56%). Response rates were 43% for seven indolent (95% CI = 10%-82%), 0% for three mantle cell (95% CI = 0%-71%), 44% for 18 relapsed aggressive (95% CI = 22%-69%), and 20% for five refractory aggressive NHLs (95% CI = 1%-72%). Grade 3/4 toxicities included myelosuppression, neutropenic fever, and diarrhea. Irinotecan appears active and relatively well tolerated in patients with relapsed aggressive or indolent NHL. Accrual to this study is continuing for better determination of response rates in all histologic subtypes of NHL.

Background: We present the results of doxorubicin-based chemotherapy with or without involved-field radiotherapy for patients with diffuse large B-cell lymphoma (DLBCL) according to the international prognostic index (IPI)., Methods: From September 1988 through December 1996, 294 patients with Stage I-IV Working Formulation large B-cell or T-cell lymphomas were treated prospectively on two protocols at our center. Diagnoses were reclassified subsequently according to the new World Health Organization classification. Two-hundred and twenty-four patients had DLBCL, including 24 patients with primary mediastinal large B-cell lymphoma. Treatment consisted of a median of six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy with or without involved-field radiotherapy (median dose, 39.6 Gy)., Results/conclusions: The median length of follow-up among surviving patients was 5.0 years. Patient subgroups differed from each other in terms of progression-free (P = 0.003), cause-specific (P = 0.003), and overall (P = 0.001) survival rates when analyzed by IPI. Five-year progression-free, cause-specific, and overall survival rates for 212 patients with an IPI of 0-2 were 73%, 84%, and 82%, respectively, versus only 37%, 33%, and 32% for 12 patients with an IPI of 3-4. To improve our results, we are conducting clinical trials with young DLBCL patients and with patients who are older than 60 years. The young DLBCL patients, who have more than two adverse prognostic features, are receiving high-dose chemotherapy and autologous stem cell rescue. The patients who are older than 60 years, regardless of IPI, are receiving rituximab immunotherapy and liposomal CHOP chemotherapy with or without involved-field radiotherapy., (Copyright 2002 American Cancer Society.)

Irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a broad spectrum of antitumor clinical activity. Various schedules and doses have been studied, and major complications were delayed diarrhea and myelosuppression. We explored the activity of irinotecan in patients with relapsed or refractory non-Hodgkin's lymphoma, using a 3-week schedule of administration. Eligible patients had histologically proven relapse, had received no more than two previous regimens, were > or = 15 years and < or = 75 years old, had normal renal function, neutrophil count > 1,500/microL, platelet count > 100,000/microL, and no human immunodeficiency virus infection or central nervous system involvement. Patients were treated with irinotecan 300 mg/m2 i.v. every 21 days with intensive loperamide management of diarrhea. Responders received up to six treatment cycles. Of 25 patients registered so far, 22 are evaluable for response. The median age was 67 years (range: 25 to 74 years) and 11 were male. The median number of previous regimens was 2 (range: 1 to 4 regimens), and 16 patients had disease that was refractory to their last regimen. Serum lactate dehydrogenase level was high in 75%, and beta2-microglobulin was > 3.0 mg/L in 26% of patients. Responses were seen in 8 of 22 (36%) patients with non-Hodgkin's lymphoma. Response rates were 40% for indolent, 0% for mantle cell, 45% for relapsed aggressive, and 33% for refractory aggressive lymphomas. Grade 3/4 toxicities included myelosuppression, neutropenic fever, and delayed diarrhea. Irinotecan appears active and relatively well tolerated in patients with relapsed aggressive non-Hodgkin's lymphoma. Accrual to this study is continuing for better determination of the response rate in all histologic subtypes of non-Hodgkin's lymphoma.

Background: In the current study, the authors analyzed prognostic factors in patients with aggressive lymphoma treated with a chemotherapy regimen comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without radiotherapy., Methods: Between September 1988 and December 1996, 294 patients with newly diagnosed, clinical Ann Arbor Stage I-IV, aggressive lymphoma were enrolled on 2 protocols at The University of Texas M. D. Anderson Cancer Center. Patients on these studies had a relatively favorable prognosis; 100% had M. D. Anderson tumor scores 1 extranodal site of disease (P < 0.001), bulky disease (>or= 7 cm) (P = 0.005), and an at least 10% elevation in the serum lactate dehydrogenase (LDH) level (P = 0.007). Patient age > 60 years (P = 0.001), bulky disease (P = 0.016), and an at least 10% elevation in the serum LDH level (P = 0.040) also were found to be independent prognostic factors for overall survival., Conclusions: The independent prognostic factors in the current study suggest that either the M. D. Anderson tumor score system or the IPI can be used to select which aggressive lymphoma patients are at high risk for disease recurrence based on their having more than two adverse factors and who consequently are candidates for more intensive frontline therapy. Involved-field radiotherapy should be considered in those patients with bulky lymphomas., (Copyright 2001 American Cancer Society.)

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

Purpose: Severe diarrhea can represent a dose-limiting toxicity with the use of CPT-11. Conventional therapy is ineffective in some patients and is also limited by patient compliance. We report our observation on the effectiveness of octreotide acetate in the treatment of CPT-11-induced diarrhea refractory to opioids., Patients and Methods: We describe 4 patients with metastatic gastrointestinal tumors who developed severe diarrhea following treatment with CPT-11 (65-125 mg/m2/weekly for 4 weeks every 6 weeks). Diarrhea was refractory to treatment with loperamide and diphenoxylate and was treated with octreotide acetate., Results: Complete resolution of diarrhea was observed within 2-4 days of octreotide acetate treatment. Three patients responded to SC octreotide given every 8 hours and the 4th patient to octreotide given by continuous s.c. infusion., Conclusions: Our preliminary observation suggests value of octreotide in the control of CPT-11 induced refractory diarrhea. Prospective studies are warranted.