Biomedical subjects

Barbara Pro

Publications and source records attributed to Barbara Pro.

29 records · Page 2Linked to original sources

PubMed2004

Thalidomide for patients with recurrent lymphoma.

BACKGROUND: Thalidomide has significant clinical activity in patients with multiple myeloma. However, its activity against other lymphoid tumors is unknown. The authors reported their experience with thalidomide in patients with recurrent/refractory non-Hodgkin lymphoma and in patients with Hodgkin disease. METHODS: Nineteen patients (median age, 62 years) who had undergone a median of 5 previous treatment regimens were treated with escalating doses of thalidomide (200-800 mg per day) until disease progression or prohibitive toxicity was observed. The authors measured serum levels of angiogenesis factors before and after treatment. RESULTS: One patient (5%) with evidence of recurrent gastric mucosa-associated lymphoid tissue lymphoma achieved a complete response, and 3 patients (16%) achieved stable disease. CONCLUSIONS: The current study suggests that thalidomide has limited single-agent activity in heavily pretreated patients with recurrent or refractory lymphoma.

Adult↗

PubMed2004

New molecular targets for treatment of lymphoma.

In recent years, several molecular mechanisms involved in promoting cancer cell survival and growth have been identified. These discoveries helped in designing and testing novel drugs that target specific cellular pathways. In this review, we focus on new molecular targets that are being explored for the treatment of non-Hodgkin's lymphoma and Hodgkin's disease.

Antineoplastic Agents↗

PubMed2003

Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma.

PURPOSE: Patients with relapsed mantle-cell lymphoma have poor prognosis and short survival. Our aim was to determine the efficacy of nonablative allogeneic stem-cell transplantation in patients with relapsed mantle-cell lymphoma. PATIENTS AND METHODS: Eighteen patients were treated in one of two consecutive trials. Thirteen patients underwent a conditioning regimen of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days), and high-dose rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m2 daily for 4 days), fludarabine (30 mg/m2 daily for 2 days), and cytarabine (1,000 mg/m2 daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. RESULTS: The median age was 56.5 years. Patients underwent a median of three prior chemotherapy regimens. Prior autologous transplantation failed in five (28%) patients and 16 (89%) had chemosensitive disease. Donor cell engraftment occurred in all patients. Eight patients (44%) required no platelet or RBC transfusion, and acute graft-versus-host disease of greater than grade 2 did not develop in any patient. The day-100 mortality was 0%. Complete remission (CR) occurred in 17 patients. Three patients progressed, and one was reinduced into continuous CR with donor lymphocyte infusion. With a median follow-up period of 26 months, the actuarial probability of current-event-free-survival at 3 years was 82% (95% CI, 65% to 99%). CONCLUSION: Our data suggest that nonablative allogeneic transplantation is a safe and potentially effective strategy for patients with relapsed and chemosensitive mantle-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Primary central nervous system lymphoma: Phase I evaluation of infusional bromodeoxyuridine with whole brain accelerated fractionation radiation therapy after chemotherapy.

BACKGROUND: The current study was performed to determine the maximum tolerated dose (MTD), toxicity, and outcome of infusional 5 bromo-2'-deoxyuridine (bromodeoxyuridine; BUdR) given with accelerated fractionation whole brain radiation therapy (WBRT) after chemotherapy for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: Twelve patients with untreated and histologically confirmed PCNSL were entered on the study between 1994 and 1996. Chemotherapy was comprised of one course of IDHAP plus high-dose methotrexate (HD-MTX). IDHAP is comprised of idarubicin at a dose of 1.5 mg/m(2)/day x 4 days intravenously by continuous infusion (i.v. CI), dexamethasone at a dose of 40 mg i.v. on Days 1-5, cytosine arabinoside at a dose of 2000 mg/ m(2) i.v. on Day 5 after cisplatin, and cisplatin at a dose of 25 mg/m(2)/day x 4 days i.v. CI. HD-MTX was given at a dose of 3.5 g/m(2) i.v. between Day 10 and Day 14 after IDHAP. BUdR was given as an i.v. CI over 48 hours, 2-3 days prior to WBRT and then weekly during WBRT. Dose escalation started at 1.5 g/m(2)/day for Cohort 1 with subsequent increments of 0.3 g/m(2)/day. The WBRT dose was 45 grays (Gy) at a dose of 1.5 Gy twice a day, 5 days per week. Neurocognitive testing was performed before, during, and after treatment. RESULTS: Nine of 12 patients entered on the study received BUdR. One of 3 patients in Cohort 1 developed leukoencephalopathy (LEP), a dose-limiting toxicity (DLT), within 2 months of the completion of therapy. Therefore, the next cohort received the same dose level. Because no toxicity was observed in Cohort 2, the third cohort received a BUdR dose of 1.8 g /m(2)/day. Shortly after completing enrollment in Cohort 3, 3 more patients developed LEP, including 2 from Cohort 1 who had received a dose of 1.5 g/m(2)/day. Thus, DLT occurred at a dose of 1.5 g/m(2)/day, the starting level in the current study. As a result, the trial was stopped. Eight of 12 patients achieved a complete response, 3 achieved a partial response, and 1 patient died before response assessment. CONCLUSIONS: Hyperfractionated WBRT with concurrent BUdR after chemotherapy was found to result in modest disease control but has unacceptable neurotoxicity.

Adult↗

PubMed2003

Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent non-Hodgkin's lymphoma.

PURPOSE: Standard therapy for patients with stage I-II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients. PATIENTS AND METHODS: A total of 102 eligible patients with stage I-II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT. RESULTS: The patients' median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease (>/= 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P =.02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta2-microglobulin was associated with shorter survival (P <.0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields. CONCLUSION: With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.

Adult↗

PubMed2003

Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma.

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.

Adult↗

PubMed2003

Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies.

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.

Adult↗

PubMed2002

International prognostic index-based outcomes for diffuse large B-cell lymphomas.

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.

Adolescent↗

PubMed2002

Outcomes using doxorubicin-based chemotherapy with or without radiotherapy for early-stage peripheral T-cell lymphomas.

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.

Adult↗

PubMedDate not supplied

Importance of esophagogastroduodenoscopy in the evaluation of non-gastrointestinal mucosa-associated lymphoid tissue lymphoma.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal low-grade B-cell lymphoma that most commonly presents in the gastrointestinal (GI) tract. However, it can present in non-GI primary sites. This study was conducted to determine the incidence of gastric involvement in non-GI presentation of MALT lymphoma. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 36 consecutive patients who presented with non-GI MALT lymphoma and had EGD as a part of the initial staging work-up between 1992 and 2001. RESULTS: The median age was 62 years (range, 27-82); 27 were female patients. The frequency of the primary site was; salivary gland/parotid gland (N = 14), ocular adnexa (N = 7), lung (N = 3), oral cavity (N = 3), skin (N = 3), thyroid (N = 2), nasopharynx (N = 2), larynx (N = 1), breast (N = 1). Twelve patients were found to have gastric involvement; 2 additional patients progressed in the stomach 5 and 6 months later, respectively. DISCUSSION: Routine evaluation of the stomach should be a part of the initial staging work-up of non-GI MALT lymphoma.

Adult↗

PubMedDate not supplied

Pentostatin in T-non-Hodgkin's lymphomas: efficacy and effect on CD26+ T lymphocytes.

Pentostatin is an adenosine deaminase (ADA) inhibitor with antineoplastic activity. CD26 is a surface glycoprotein with a key role in T cell function as the ADA binding protein. We conducted a phase II study to evaluate pentostatin efficacy in relapsed T-non-Hodgkin's lymphoma (T-NHL) and to correlate response with tumor CD26 expression. We also examined the lymphopenic effect of pentostatin on CD26+ T lymphocytes. Eighteen patients were registered for the study. Pentostatin was administered as intravenous bolus daily over 3 days at an initial dose of 5 mg/m(2)/day, repeated every 4 weeks. CD26 surface expression on tumor cells and T lymphocytes was determined by flow cytometry. Out of 14 patients evaluable for response, there was 1 (7%) complete response (CR) and 6 (43%) partial responses (PR). Median progression-free survival for responders was 6 months (range: 2-15 months); median number of courses was 4 (range: 1-6). Responders included 1 of 2 CD26+ and 5 of 9 CD26- cases. Pentostatin also specifically depleted CD26+ rather than CD26- T lymphocytes, potentially associated with immunosuppression. We therefore conclude that while pentostatin is a safe and active agent for T-NHL regardless of CD26 expression, it may selectively deplete CD26+ T lymphocytes, with potentially significant clinical implications.

Adult↗