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Bouthaina S Dabaja,
Jack Phan,
Osama Mawlawi,
L Jeffrey Medeiros,
Carol Etzel,
Fu-Wen Liang,
Donald Podoloff,
Yasuhiro Oki,
Fredrick B Hagemeister,
Hubert Chuang,
Luis E Fayad,
Jason Robert Westin,
Ferial Shihadeh,
Pamela K Allen,
Christine F Wogan, Maria A Rodriguez
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ABSTRACT: ABSTRACT Response to primary treatment in diffuse large B cell lymphoma (DLBCL) is highly predictive of long-term outcome. We evaluated the value of computed tomography (CT) findings relative to positron emission tomography (PET) findings, after the completion of chemotherapy; we retrospectively reviewed records from 491 patients with DLBCL at MD Anderson in 2001-2007; 22 patients were excluded for uncertain pathology and 169 for having received consolidative radiation, leaving 300 patients for the current analysis (median age, 61 years; 53% men, 47% women; 27% stage I-II, 73% stage III-IV; 73% completed 6-8 cycles of doxorubicin-based therapy). Factors associated with outcome on univariate analysis were response according to PET/CT and CT (P<0.0001 for OS, DSS, and PFS); number of chemotherapy cycles received (P<0.0001 OS, P<0.0001 DSS, P<0.002 PFS); the combined presence of Ki-67 >50%, PET SUV ≥13, and bulky (>5 cm) disease (P=0.005 OS, P=0.001 DSS, P=0.001 PFS); and International Prognostic Index (IPI) score (P=0.003 OS, P=0.005 DSS, P=0.003 PFS). On multivariate analysis, PET/CT-negative, CT residual mass (>2 cm) significantly influenced OS, DSS and PFS (P<0.0001). The presence of a residual mass >2 cm on CT, coupled with negative findings on PET/CT, has prognostic value in DLBCL.
Leukemia & lymphoma 03/2013; · 2.40 Impact Factor
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Anas Younes,
Yasuhiro Oki,
Peter McLaughlin,
Amanda R Copeland,
Andre Goy,
Barbara Pro,
Lei Feng,
Ying Yuan,
Hubert H Chuang,
Homer A Macapinlac,
Fredrick Hagemeister,
Jorge Romaguera,
Felipe Samaniego,
Michelle A Fanale,
Bouthaina Shbib Dabaja, Maria A Rodriguez,
Nam Dang,
Larry W Kwak,
Sattva S Neelapu,
Luis E Fayad
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ABSTRACT: In the present study, we evaluated the efficacy and safety of rituximab in combination with standard doxorubicin, bleomycin, vinblastine, and dacarbazine (RABVD) in patients with classical Hodgkin lymphoma (cHL). In this phase 2 study, patients with chemotherapy-naive, advanced-stage cHL were treated with rituximab 375 mg/m(2) weekly for 6 weeks and standard ABVD for 6 cycles. The primary outcome was event-free survival (EFS) at 5 years. Eighty-five patients were enrolled, of whom 78 were eligible. With a median follow-up duration of 68 months (range, 26-110), and based on an intent-to-treat analysis, the 5-year EFS and overall survival rates were 83% and 96%, respectively. The 5-year EFS for patients with stage III/IV cHL was 82%. Furthermore, the 5-year EFS for patients with an International Prognostic Score of 0-2 was 88% and for those with a score of > 2, it was 73%. The most frequent treatment-related grade 3 or 4 adverse events were neutropenia (23%), fatigue (9%), and nausea (8%). Our results demonstrate that the addition of rituximab to ABVD is safe and has a promising clinical activity in patients with advanced-stage cHL. These data are currently being confirmed in a multicenter randomized trial.
Blood 02/2012; 119(18):4123-8. · 9.90 Impact Factor
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ABSTRACT: Previous studies have shown that interferon-α (IFN-α) and chemotherapy is an effective treatment for patients with newly diagnosed follicular lymphoma. Therefore, we performed a phase II trial to determine the safety and effectiveness of IFN-α and standard doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy (IABVD) in these patients. Patients with newly diagnosed advanced stage classic Hodgkin lymphoma (HL) were enrolled between July 1997 and March 2000 on IABVD as initial therapy. This consisted of six cycles of ABVD with concurrent IFN-α followed by radiation therapy if indicated. IFN-α 6 million IU/m(2) was administered subcutaneously daily for 3 days and on day 4 patients received IFN-α with ABVD. Courses were repeated every 2 weeks for a maximum of 12 courses. IFN-α dose reduction was allowed for cytopenia. Outcome and baseline characteristics were reported. Thirty patients (median age, 30 years [range, 18-62 years]) were evaluable. Patients had Ann Arbor stage II (7%), III (30%) or IV (63%) disease, and 47% were at intermediate or high risk, as defined by the International Prognostic Score (≤ 2 vs. > 2). The 3-year event-free survival rate was 71% (95% confidence interval [CI], 56-90%), and the 3-year overall survival rate was 96% (95% CI, 89-100%). Treatment was well tolerated, with only three patients requiring IFN-α dose reduction or discontinuation because of cytopenia. IABVD is an effective regimen against advanced HL and is well tolerated. However, because of the emergence of effective new biologic agents, further development of this regimen is not warranted.
Leukemia & lymphoma 01/2012; 53(5):801-6. · 2.40 Impact Factor
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Nina Shah,
Fernando Cabanillas,
Bradley McIntyre,
Lei Feng,
Peter McLaughlin, Maria A Rodriguez,
Jorge Romaguera,
Anas Younes,
Fredrick B Hagemeister,
Larry Kwak,
Luis Fayad
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ABSTRACT: Elevated serum CD44, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been linked to poor prognosis in aggressive lymphomas, but their utility in low grade lymphomas remains undefined. We evaluated serum CD44, VCAM-1 and ICAM-1 levels in 100 patients with newly diagnosed indolent NHL. The median pre-treatment values of the markers were as follows: CD44 540 ng/mL (range 156-1201), ICAM-1 311 ng/mL (range 102-1222) and VCAM-1 1165 ng/mL (range 248-4779). On univariate analysis, elevated sCD44, sICAM-1 and sVCAM-1 were significantly associated with worse overall (OS) and progression-free survival (PFS). In a subset analysis of patients with stage IV disease, the effects of sCD44 and sICAM-1 on OS persisted (p<0.05), as did the effect of sCD44 on PFS (p<0.01). In a multivariate analysis that included conventional prognostic factors and the Follicular Lymphoma International Prognostic Index (FLIPI) model, sICAM-1 demonstrated prognostic value for OS and PFS. We conclude that serum CD44, ICAM-1 and VCAM-1 can potentially be prognostic in patients with indolent NHL. Though the FLIPI model remains the gold standard for prognosis, these quantitative serologic markers may be useful as adjunct tools in assessing disease risk.
Leukemia & lymphoma 09/2011; 53(1):50-6. · 2.40 Impact Factor
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ABSTRACT: In 2007, the US Food and Drug Administration (FDA) issued regulatory alerts for use of erythropoiesis-stimulating agents (ESAs) in cancer patients with anemia after clinical trials and meta-analysis data found that high ESA doses were associated with adverse outcomes in patients. In response to these findings, specific patient management tools for anemia (consisting in an algorithm and prescribing order set) were developed by a multidisciplinary team at The University of Texas MD Anderson Cancer Center.
A retrospective study consisted of 7117 patients aged 18 years and older with cancer malignancies who had received an ESA between January 2006 and December 2008 at MD Anderson. Changes in utilization of ESAs and packed red blood cells (PRBCs) were evaluated.
The number of ESA doses dispensed each month decreased by 83% from January 2006 to December 2008 (P < .01), and the number of patients who received ESAs decreased by 80% (P < .01). The number of dispensed ESA doses for hemoglobin (Hb) levels ≥ 12 g/dL decreased significantly from 4% to 0% (P < .01), and the number for ≥ 10 g/dL decreased from 44% to 12% (P < .01). The PRBC transfusion rate remained stable in solid tumor patients (P > .05) but increased from 7% to 9% (P < .05) in patients with hematologic malignancies.
The authors summarized their experience with use of ESAs in a tertiary oncology center. The implementation of their patient management tools for anemia might have facilitated the observed change at MD Anderson Cancer Center.
Cancer 01/2011; 117(14):3268-75. · 4.77 Impact Factor
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ABSTRACT: We conducted a retrospective cohort study examining the influence of obesity on treatment outcome and survival among 712 patients with intermediate-grade B-cell NHL receiving frontline therapy between 1988 and 2001. Baseline adiposity was approximated by body mass index categorized according to the World Health Organization schema. Logistic and Cox proportional hazards regression modeling was used to adjust for baseline patient demographic, disease, and treatment variables. Approximately 37% of cohort patients were overweight (BMI 25 to <30 kg/m(2)) and more than 23% were obese (BMI >or= 30 kg/m(2)). Risk factors were similar across groups and treatment intensity did not vary by BMI. Median follow-up was 45.7 and 62.8 months for PFS and OS, respectively. After adjustment for other significant prognostic factors, BMI in the overweight range was associated with significantly reduced hazard for both PFS (OR 0.72, p = 0.011) and OS (OR 0.74, p = 0.030). Increased BMI is associated with significantly improved survival among patients with treatment-naive, intermediate-grade B-cell NHL. Prospective confirmation of these results is warranted given the increasing prevalence of both NHL and obesity.
Leukemia & lymphoma 09/2010; 51(9):1649-57. · 2.40 Impact Factor
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Anas Younes, Maria A. Rodriguez,
Peter McLaughlin,
Luceil North,
Andreas H. Sarris,
Odeal Pate,
Fredrick B. Hagemeister,
Jorge Romaguera,
Alejandro Preti,
Carlos Bachier,
Fernando Cabanillas
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ABSTRACT: We conducted a phase I clinical trial of a new combination of fludarabine and paclitaxel in which 19 patients with histologically confirmed recurrent low-grade non-Hodgkin's lymphoma (NHL) were treated at five dose levels. Fludarabine was administered intravenously by bolus for 5 days and paclitaxel was given by intravenous (IV) continuous infusion for 96 or 72 hours starting day 1. Courses were repeated every 4 weeks. Patients whose disease responded received a maximum of six courses. All 19 patients received at least one course and could be evaluated for toxic effects, and 18 patients could be evaluated for response. The maximum tolerated dose (MTD) was 20 mg/m2/day IV bolus for 5 days of fludarabine plus 60 mg/m2/day IV of paclitaxel given as a continuous infusion over 72 hours. The limiting toxic effect was neutropenic fever, which was observed in five of the seven patients treated at the highest dose level. Grade 3 non-hematologic toxic effects of stomatitis (14%), neuropathy (14%), and hypotension (14%) were also observed at the highest dose level. No grade 4 non-hematologic toxic effects or treatment-related deaths occurred. One patient had herpes zoster infection of the skin 1 year after the completion of therapy. The overall response rate was 50%, with the two patients whose disease completely responded remaining disease free at 22 and 17 months. Patients with no prior exposure to either paclitaxel or fludarabine had 62% response rate. We conclude that the combination of fludarabine and paclitaxel appears to have promising activity for the treatment of recurrent low-grade NHL.
08/2009; 26(1-2):77-82.
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ABSTRACT: Relapsed or refractory mantle cell lymphoma has a very poor prognosis. The authors evaluated the response rates and survival times of patients treated with an intense regimen known to be effective against untreated aggressive mantle cell lymphoma: rituximab plus hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with rituximab plus methotrexate-cytarabine.
In this prospective, open-label, phase 2 study, patients received this combination for 6 to 8 cycles. Twenty-nine patients were evaluable for response.
The median number of cycles received was 5 (range, 1-7 cycles), and the overall response rate was 93% (45% complete response [CR] or CR unconfirmed [CRu] and 48% partial response [PR]). All 5 patients previously resistant to treatment had a response (1 CR, 4 PR), and both patients whose disease did not change in response to prior therapy had PRs. Toxic events occurring in response to the 104 cycles given included neutropenic fever (11%), grade 3 or 4 neutropenia (74%), and grade 3 or 4 thrombocytopenia (63%). There were no deaths from toxicity. At a median follow-up of 40 months (range, 5-48 months), the median failure-free survival time was 11 months with no plateau in the survival curve.
This combination chemotherapy was effective for refractory/relapsed mantle cell lymphoma.
Cancer 12/2008; 113(10):2734-41. · 4.77 Impact Factor
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ABSTRACT: Based on the single-agent activity of both paclitaxel and cyclophosphamide in the treatment of non-Hodgkin's lymphoma (NHL), we conducted a phase II study to evaluate the efficacy of the combination of the two drugs in patients with refractory and relapsed aggressive NHL. All patients received 900 mg/m2 bolus of cyclophosphamide intravenously daily for 3 consecutive days with a concurrent infusion of 150 mg/m2 of paclitaxel over 72 h (50 mg/m2/d). 24 h after the completion of chemotherapy, patients received subcutaneous injections of 5 μg/kg of granulocyte-colony stimulating factor (G-CSF) daily until white cell count recovery. Treatment was repeated every 3 weeks. Patients who had at least a partial response (PR) after two courses continued to receive a maximum of four courses. Patients with responding disease were allowed to undergo high-dose chemotherapy followed by stem-cell/bone marrow transplantation if they were eligible. Of the 77 patients who were eligible for the study, 74 (96%) were evaluable for toxicity and treatment response. The overall response rate was 45% (95% CI 33–57%). Patients who received treatment after their disease relapsed from a complete response (CR) had an 81% response rate (38% CRs), whereas those with primary refractory disease had a 22% response rate. Toxicities of >grade 2 included alopecia (100%) and stomatitis (25%). Neutropenic fever of grade >2 occurred after 18% of the courses, and platelet count of 20 × 109/l developed after 20% of the courses. Thus, the combination of paclitaxel plus high-dose cyclophosphamide is an effective new regimen in the treatment of refractory and relapsed NHL.
British Journal of Haematology 10/2008; 103(3):678 - 683. · 4.94 Impact Factor
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Nam H Dang,
Luis Fayad,
Peter McLaughlin,
Jorge E Romaguara,
Fredrick Hagemeister,
Andre Goy,
Sattva Neelapu,
Felipe Samaniego,
Pamela L Walker,
Michael Wang, Maria A Rodriguez,
Ann T Tong,
Barbara Pro
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ABSTRACT: Denileukin diftitox plus rituximab was evaluated in relapsed/refractory B-cell non-Hodgkin lymphoma patients. Of the 38 evaluable patients, 30 (80%) were rituximab-refractory. The overall response rate (ORR) was 32%, with six complete responses (CR) and six partial responses (PR). The median time to progression for responders was 8 months (range: 2-36+); two patients with rituximab-refractory follicular lymphoma were in CR at 25 and 36+ months. The ORR was 55% (4 CRs, 2 PRs) in 11/14 patients with rituximab-refractory follicular lymphoma, and 100% in the three patients with rituximab-sensitive tumour. Most toxicities were low grade and transient, and myelotoxicity was uncommon.
British Journal of Haematology 09/2007; 138(4):502-5. · 4.94 Impact Factor
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ABSTRACT: We report the first case of a primary adrenal natural killer (NK)/T-cell nasal type lymphoma in adults. The patient presented with an enlarging left adrenal mass and the initial concern was for adrenocortical carcinoma. Surgical resection revealed NK/T-cell lymphoma. Rapid recurrence in the contralateral adrenal gland was treated with a single cycle of chemotherapy before he died due to infectious complications and progressive disease. This case demonstrates the aggressive presentation of a novel subset of primary adrenal lymphoma that should be considered in the differential diagnosis of a rapidly enlarging adrenal mass.
American Journal of Hematology 05/2007; 82(4):299-303. · 4.67 Impact Factor
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Nam H Dang,
Barbara Pro,
Fredrick B Hagemeister,
Felipe Samaniego,
Dan Jones,
Barry I Samuels, Maria A Rodriguez,
Andre Goy,
Jorge E Romaguera,
Peter McLaughlin,
Ann T Tong,
Francesco Turturro,
Pamela L Walker,
Luis Fayad
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ABSTRACT: This phase II study evaluated the safety and efficacy of denileukin diftitox, an interleukin-2-diphtheria toxin fusion protein, in relapsed/refractory T-cell non-Hodgkin lymphoma (T-NHL), excluding cutaneous T-cell lymphoma. Eligible patients received denileukin diftitox 18 microg/kg/d x 5 d every 3 weeks for up to eight cycles. Tumour staging was performed every two cycles and the primary endpoint was the objective response rate [complete response (CR) + partial response (PR)]. For 27 patients enrolled, median age: 55 years (range 26-80 years), 70.4% male, and mean prior therapies: 2.5 (range 1-6). Objective responses (six CRs, seven PRs) were achieved in 13 patients (48.1%), stable disease in eight (29.6%) and six (22.2%) had progressive disease. An objective response was achieved in eight of 13 patients (61.5%) with CD25(+) tumours (four CR/four PR) and five of 11 patients (45.5%) with CD25(-) tumours (two CR/three PR). Median progression-free survival was 6 months (range, 1-38+ months). Most adverse reactions were grade 1/2 and transient. No grade 4-5 toxicities were reported. Denileukin diftitox had significant activity and was well tolerated in relapsed/refractory T-NHL, with responses observed in both CD25(+) and CD25(-) tumours. Further studies of denileukin diftitox in combination with other agents are warranted in previously untreated and relapsed/refractory T-NHL.
British Journal of Haematology 03/2007; 136(3):439-47. · 4.94 Impact Factor
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ABSTRACT: Although numerous options are available for patients with recurrent low-grade non-Hodgkin's lymphoma (NHL), responses are rarely durable. We previously conducted a phase I trial of fludarabine and paclitaxel in the treatment of recurrent low-grade lymphoma. The present phase II study was performed to determine the activity of fludarabine and paclitaxel in patients with recurrent low-grade NHL. Patients with histologically confirmed recurrent low-grade NHL were treated with fludarabine 20 mg/m2/day intravenously (i.v.) on days 1-5 plus paclitaxel 50 mg/m2 given by i.v. continuous infusion over 72 h starting on day 1. Treatment was repeated at 4-week intervals for a maximum of six courses. Twenty-eight evaluable patients were entered into this phase II trial. The median age was 53 years and the median performance status (Zubrod) was 1. Twenty-two (78%) patients had grade 1 or 2 follicular lymphoma, and six patients (21%) had small lymphocytic lymphoma. The median number of prior chemotherapy regimens was 1 (range, 1-3). Objective responses occurred in 16 patients (57%); nine patients (32%) achieved a complete remission with a median duration of 32 months (range 4-84+ months), and seven patients (25%) had a partial remission. Grade 3 and 4 toxicities included neutropenia (72%), neutropenic fever (34%), infection (13%), mucositis (7%), and neuropathy (3%). The combination of fludarabine and paclitaxel has clinical activity in patients with recurrent low-grade NHL.
Leukemia and Lymphoma 10/2006; 47(9):1818-21. · 2.58 Impact Factor
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ABSTRACT: Pegfilgrastim is a pegylated form of a granulocyte colony-stimulating factor with a long half-life allowing for a single administration per chemotherapy cycle. The efficacy of a single dose of pegfilgrastim in supporting severely myelosuppressive regimens in previously treated cancer patients is unknown. Patients included in the present study had recurrent or refractory aggressive non-Hodgkin's lymphoma (NHL), had received two to three prior treatment regimens, and had good performance status and marrow reserve. Patients received intravenous paclitaxel 200 mg/m(2) on day 1 and topotecan 1 mg/m(2) daily for 5 days, repeated every 21 days for at least two cycles. On day 6, patients were given a single fixed dose of pegfilgrastim (6 mg) subcutaneously. Twenty patients were evaluable for analysis. After the first course of therapy, grade 4 neutropenia developed in all 20 patients. The median time to the neutrophil nadir was 9 days. The mean +/- SD duration of grade 4 neutropenia was 3.8 +/- 1.7 days. Nineteen (95%) patients received cycle 2 on time, on day 22. Five patients developed neutropenic fever (25%), which was associated with infection in one patient. In these previously treated patients with NHL, a single dose of pegfilgrastim was effective in promoting neutrophil count recovery after paclitaxel and topotecan, and allowed patients to receive the next planned dose on time.
Leukemia and Lymphoma 04/2006; 47(3):481-5. · 2.58 Impact Factor
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ABSTRACT: Outcomes with salvage therapy for patients with recurrent or refractory acute lymphocytic leukemia (ALL) are poor, with complete response (CR) rates reported to be 20-30% and a median survival ranging from 2-6 months. New agents are needed to reduce the recurrence rate after frontline chemotherapy. Vincristine is an important component of ALL therapy. In animal models, the encapsulation of vincristine into sphingomyelin liposomes or "sphingosomes" for injection (SV) has improved efficacy compared with conventional vincristine.
A Phase II clinical trial of single-agent SV given at a dose of 2.0 mg/m2 every 2 weeks was conducted in patients with recurrent or refractory ALL. Approximately half of the 16 patients who received SV had a first CR duration of less than 1 year, 19% had failed standard induction chemotherapy, and 50% had Philadelphia chromosome-positive disease. SV was the first salvage attempt in 69% of the patients.
The overall response rate in the 14 evaluable patients was 14% (1 CR and 1 partial response). Five patients (36%) had transient reductions in bone marrow leukemia infiltrate with subsequent regrowth of the leukemia between SV infusions. Toxicity with limited treatment (median number of doses was two; range, one to five doses) was minimal with expected peripheral neuropathy.
Further study of SV in patients with ALL is warranted. A Phase I-II clinical trial of weekly SV with pulse dexamethasone currently is ongoing.
Cancer 02/2006; 106(1):120-7. · 4.77 Impact Factor
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Jorge E Romaguera,
Luis Fayad, Maria A Rodriguez,
Kristine R Broglio,
Frederick B Hagemeister,
Barbara Pro,
Peter McLaughlin,
Anas Younes,
Felipe Samaniego,
Andre Goy,
Andreas H Sarris,
Nam H Dang,
Michael Wang,
Virginia Beasley,
L Jeffrey Medeiros,
Ruth L Katz,
Harish Gagneja,
Barry I Samuels,
Terry L Smith,
Fernando F Cabanillas
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ABSTRACT: 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).
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.
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.
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.
Journal of Clinical Oncology 11/2005; 23(28):7013-23. · 18.37 Impact Factor
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ABSTRACT: This study was undertaken to compare the molecular response (MR) rates of 2 regimens, central lymphatic irradiation (CLI) and alternating triple therapy (ATT), in the treatment of Stage I-III follicular lymphoma. MR was defined as disappearance of t(14;18) (q32;q21) amplified by polymerase chain reaction (PCR).
Sixty-five patients with Stage I to III follicular lymphoma were randomized. CLI consisted of the mantle, abdomen, and pelvic radiation fields. ATT alternated among CHOD-Bleo, ESHAP, and NOPP for 12 courses. Bone marrow (BM) and peripheral blood (PB) samples were obtained before treatment for PCR analysis. PCR-positive patients were followed by PCR analysis. The random-effects logistic model was fitted to the data from the posttreatment PCRs. The factors included in the model were treatment arm, type of PCR (BM vs. PB), and time to PCR sample procurement from the date of registration.
At a median follow-up of 71 months, the 5-year relapse-free survival (RFS) rates were 45% and 54% for CLI and ATT, respectively (p = 0.42). The probability of attaining an MR increased with time after registration (p = 0.007), was lower for BM compared with PB (p = 0.012), and was higher for ATT than for CLI (p = 0.020).
ATT regimen achieved a higher MR than CLI, although both arms had similar 5-year RFS.
International Journal of Radiation OncologyBiologyPhysics 10/2005; 63(1):188-93. · 4.11 Impact Factor
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ABSTRACT: Myelosuppression and immunosuppression occur with purine analogs. The objective of the current study was to investigate the effects of combined fludarabine, mitoxantrone, and dexamethasone (FND) followed by interferon/dexamethasone on myelosuppression (absolute neutrophil counts), immunosuppression (CD4 and CD8 counts), and infectious complications in patients with previously untreated, Stage IV indolent lymphoma.
Seventy-three patients were treated. All patients received Pneumocystis carinii pneumonia (PCP) prophylaxis. CD4 and CD8 counts, serum immunoglobulin (Ig) levels, and neutrophil counts were correlated with infectious complications.
The median follow-up was 6.1 years. Sixty of 73 patients had CD4, CD8, or Ig measurements. The median baseline CD4 count was 764/microL. This CD4 level decreased to 238/microL at 1 year and to 264/microL at 2 years; and it rose to 431/microL by 3 years and to 650/microL at 4 years. CD8 counts did not change significantly. The median baseline serum IgG level was 989 mg/d, decreased to 536 mg/dL at 1 year and to 693 mg/dL at 2 years, and it rose to 949 mg/dL at 3 years and to 1080 mg/dL at 4 years. Fourteen patients (19%) developed Grade 3-4 infections, the majority during FND therapy with neutropenia and/or accompanied by CD4 counts < 200/microL. CD4, CD8, and neutrophil counts did not differ between patients who developed Grade 3-4 infections, Grade 1-2 infections, or no infections.
Most infections with FND occurred during FND, in the setting of neutropenia, often with concurrent low CD4 counts. The overall safety profile for FND was good. However, patients should be monitored for opportunistic infections, and prophylactic antibiotics are recommended, particularly against PCP.
Cancer 07/2005; 104(2):345-53. · 4.77 Impact Factor
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Nam H Dang,
Fredrick B Hagemeister,
Barbara Pro,
Peter McLaughlin,
Jorge E Romaguera,
Dan Jones,
Barry Samuels,
Felipe Samaniego,
Anas Younes,
Michael Wang,
Andre Goy, Maria A Rodriguez,
Pamela L Walker,
Yolanda Arredondo,
Ann T Tong,
Luis Fayad
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ABSTRACT: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL.
Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles.
Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient.
Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.
Journal of Clinical Oncology 11/2004; 22(20):4095-102. · 18.37 Impact Factor
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Barbara Pro,
Anas Younes,
Maher Albitar,
Nam H Dang,
Felipe Samaniego,
Jorge Romaguera,
Peter McLaughlin,
Fredrick B Hagemeister, Maria A Rodriguez,
Marilyn Clemons,
Fernando Cabanillas
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ABSTRACT: 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.
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.
One patient (5%) with evidence of recurrent gastric mucosa-associated lymphoid tissue lymphoma achieved a complete response, and 3 patients (16%) achieved stable disease.
The current study suggests that thalidomide has limited single-agent activity in heavily pretreated patients with recurrent or refractory lymphoma.
Cancer 04/2004; 100(6):1186-9. · 4.77 Impact Factor
