Management Of non-Hodgkin Lymphoma Research Articles

Bendamustine in the Management of Non-Hodgkins Lymphoma

Bendamustine is a unique bifunctional cytotoxic agent that includes a nitrogen mustard group with alkylating properties and a benzimidazole ring with potential antimetabolite properties. It shows only partial cross-resistance with other alkylators in vitro and remains highly active in heavily pretreated patients. The history of bendamustine began in the former East German Democratic Republic, where it was developed in the early 1960s. Re-discovered in the 1990s, it demonstrated excellent response rates in several clinical trials with a favorable side-effect profile leading to its approval in 2008 by the U.S. Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia and for the treatment of patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma. Further studies showed efficacy in the first-line treatment of B-cell NHL and in the treatment of patients with multiple myeloma. We review the data on bendamustine published so far and discuss the future role of this promising agent in the treatment of patients with lymphoproliferative malignancies.

Management of non-Hodgkin lymphomas arising at extranodal sites

Primary extranodal lymphomas are relatively rare non-Hodgkin lymphoma presentations with either no or only "minor" nodal involvement along with a clinically "dominant" extranodal component, to which primary treatment must often be directed. Clinical presentations depend largely on the localization and are similar to those of other malignancies affecting that specific organ. In addition to the histological subtype, the primary organ of origin represents the most significant prognostic factor due to differences in natural history and, mainly, in management strategies related to organ-specific problems. In principle, as for primary nodal disease, treatment strategies depends on the patient's clinical conditions, the extent and/or location of the disease, and the histological type. In general, for stage I and II disease with low tumor burden, local therapy is a relevant option both for cure and local control. In advanced stage disease, systemic chemoimmunotherapy is usually required. Localizations with particularly poor survival are the enteropathy-type T-cell lymphoma, the primary testicular diffuse large B-cell lymphoma, and the primary CNS Lymphoma. However, recent studies have shown that site-tailored treatment strategies in testis and brain lymphoma may result in a significant outcome improvement. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the most common indolent subtype. This lymphoma usually arises in mucosal sites where lymphocytes are not normally present and where a lymphoid infiltration is acquired in response to either chronic infectious conditions or autoimmune processes: Helicobacter pylori gastritis, Hashimoto's thyroiditis, Sjögren syndrome. Indeed, a pathogenetic link between gastric MALT lymphoma and H. pylori is strongly suggested by the regression of gastric MALT lymphoma (in approx. 75% of cases) after antibiotic eradication of the microorganism.

Targeted therapy in haematological malignancies.

The recent and rapid development of molecularly targeted therapy is best illustrated by advances in the management of haematological malignancy. In myeloid diseases we have seen dramatic improvements in the overall survival and quality of life for patients with chronic myeloid leukaemia treated with ABL and Src/ABL kinase inhibitors and we are poised to discover whether JAK2 inhibitors may offer similar benefit in myeloproliferative diseases. For acute myeloid leukaemia, the introduction of ATRA and myelotarg have had major impacts on the design of therapy regimens and many novel targeted agents, including farnesyl transferase, FLT3 and histone deacetylase inhibitors, are now in clinical trial. In lymphoid malignancies the highlight has been the introduction of rituximab, with significant improvements in the management of non-Hodgkin lymphoma and chronic lymphocytic leukaemia. The last 10 years has experienced a rapidly expanding interest and acceptance that leukaemic stem cells, including an improved ability to target them, may hold the key to improved response and reduced relapse rates across both myeloid and lymphoid disease. We now eagerly anticipate an era in which a wealth of preclinical discoveries are progressed to the clinic.

New treatment options for the management of non-Hodgkin lymphoma

Although the outcome of patients with non-Hodgkin lymphoma (NHL) has, in general, improved significantly over years, treatment failure due to drug resistance remains a problem. Recently, the focus of drug development has shifted from conventional cytotoxic drugs to agents directed against specific molecular targets and immunotherapy. This has mainly been driven by advances in the understanding of the molecular pathogenesis of NHL. A large number of promising new agents are in preclinical and clinical development. The challenge for clinicians is how best to incorporate them into already existing treatment regimes. This review will highlight some recent clinical trials focussing on targeted small molecules and monoclonal antibodies in NHL.

The Baseline PET SUV Correlates Better with Clinical Outcome Than the Post-Therapy PET Scan in Previously Untreated Patients with Histologically Aggressive Non-Hodgkin Lymphoma (NHL)

The FDG-PET/CT scan has become a standard tool in management of NHL. Failure to achieve an early metabolic CR (mCR) has been previously associated with a poor outcome and is considered as an adverse prognostic feature. Most studies which have supported this finding have used standard CHOP+/−R therapy or included a small or histologically heterogeneous population. As more effective therapies are introduced, some proven prognostic factors will lose relevance. We designed a prospective study to answer the following questions: 1- is the PET scan still capable of predicting outcome with the newer dose dense CHOP−R? 2) Is a very early PET, one week after the first chemotherapy (W1 PET) as good or better as the traditional 3rd course PET scan (C3 PET)? We have entered 55 pts, of which 40 were frontline previously untreated histologically aggressive NHL (35 DLCL, 5 FLCL) and 15 previously treated recurrent NHL (9 DLCL, 3 transformed DLCL, 2 PTCL, 1 high grade NOS). Treatment consisted of CHOP-R in all pts (dose dense in 38/40). A baseline PET was performed and followed by a W1 PET and a C3 PET. Median follow up is 20 mos. IPI was ≥2 in 20/55 (37%). The failure free survival (FFS) at 24 months was 85% for previously untreated pts and 35% for previously treated. For previously untreated pts, median baseline SUVmax= 20.5 (5.6–66.6) and one week after the first course (W1 PET), median SUVmax dropped to 2.6 and by C3 PET the median was 0. We examined the correlation between baseline PET, W1 PET and C3 PET with clinical outcome in previously untreated pts and found that the best correlation was with the baseline PET (figure). [Display omitted] Table 1 shows that the W1 PET as well as the C3 PET failed to correlate with outcome in previously untreated pts. Those who achieved mCR (defined as SUV<4) on the W1 PET or C3 PET didn't have a significantly superior FFS than those who didn't reach mCR. Other cut-off points including SUV<3 and <2 gave similar results. IPI, although showing a trend for correlation with FFS in previously untreated pts, was not significantly associated with outcome: IPI <3 had FFS= 87% vs. ≥3 = 82%, P=0.62. For the 15 cases with recurrent aggressive NHL, the FFS was 100% for those whose W1 PET SUV<4 versus 13% for those with SUV≥4 (P=.013). For those with baseline SUV ≥12 it was 52% vs 0% for SUV <12. For previously treated pts with IPI <3 the 2 yr FFS= 50% vs 0% for those with IPI≥3.Conclusions- for previously untreated pts: a- Striking improvements in PET are seen as early as 1 week after chemotherapy and improved further by C3 PET, but their correlation with the clinical outcome was poor and only the baseline PET SUV correlated well with outcome. b-Those with an SUV below the typical range for DLCL (i.e. <12) were the only ones who relapsed. c- IPI was not significantly associated with outcome. For previously treated pts both the baseline and the W1 PET were predictive of outcome. IPI also correlated with outcome. A possible explanation for these unexpected findings in the frontline group is that traditional prognostic factors might have changed with the introduction of the more effective dose dense CHOP-R regimen. Our FFS of 85% is better than expected for the traditional 21 day CHOP-R. This erosion of traditional prognostic factors might also be reflected by the lack of correlation between the traditional IPI and clinical outcome. For previously treated pts where the impact of treatment is not as prominent, the post treatment PET and IPI still hold as prognostic factors. These findings might not necessarily apply to other histologies or to other treatments.Table 1:W1PET SUVmaxN%FFS 24 mos.P value<4.02483%≥4.01690%0.68C3PET SUV max<4.03583%≥4.03100%0.59

Radio-immunothérapie du lymphome folliculaire : un pas vers la guérison ?

Advanced stage follicular lymphoma is incurable by conventional treatment. Important progress has been observed with the development of new therapies based on monoclonal antibodies and on the use of radioimmunotherapy (RIT) in the treatment of non-Hodgkin lymphomas (NHL). Rituximab in combination with chemotherapy in the upfront setting significantly improved treatment outcome as compared with chemotherapy alone. Different studies also indicate that RIT has an important role in the management of NHL and could be beneficial in combination with chemotherapy. These two new treatment options have clearly distinctive mechanisms of action, rituximab being an exclusively biological treatment and RIT adding targeted systemic radiation therapy. Both RIT and the unlabeled antibody treatments might be further improved by different strategies including repetition of RIT or combination of different antibodies. We present here our experience with RIT using 131I-tositumomab (Bexxar) and discuss different topics regarding RIT, like the use of different antibodies, the best choice of the radioisotope or the place of radio-imaging. From the therapeutic point of view, we argue that the debate should not be as to which one among antibody immunotherapy or RIT should be best added to chemotherapy, but that all three treatments might be optimally combined with the aim to get the highest chance of cure for advanced stage follicular lymphoma.

An update on recent developments in non-Hodgkin's lymphoma

The management of non-Hodgkin's lymphoma (NHL) has changed considerably over the last 15 years with the recognition of independent prognostic factors leading to the development of a predictive model of outcome, the International Non-Hodgkin's Lymphoma Prognostic Factors Index (IPI) and more recently gene array studies. Since then, the therapeutic approaches have tried to improve the outcome of patients with adverse prognostic factors with the building of intensified regimens rather than the classical CHOP regimen. The introduction of monoclonal antibodies (MoAb) into the management of NHL has dramatically improved the response rates and rituximab is now approved for the treatment of diffuse large B-cell lymphoma and follicular lymphoma. Subsequently, MoAb have been conjugated to radioisotopes to target radiotherapy to tumor sites and improve overall survival. The advantages of these radiolabeled antibodies are not only to enhance the therapeutic potency of MoAb by targetting specifically CD20+ tumour cells but also to protect the neighbouring normal organs from cytotoxicity. Finally, the initial staging as well as the evaluation of the response after treatment has been better defined with the introduction of positron emission tomography (PET) into the assessment of NHL. The accuracy of PET imaging in the detection of residual disease and extranodal localizations appears to be the most helpful non-ivasive modality in NHL. The aim of this review is to focus on recent and most significant improvements in the management of lymphomas.

Patterns of mortality after prolonged follow-up of a randomized trial using granulocyte colony-stimulating factor (G-CSF) to maintain chemotherapy dose intensity in non-Hodgkin lymphoma (NHL)

7590 Background: Recombinant G-CSF is commonly used to maintain chemotherapy dose intensity and reduce the incidence of infective complications in the management of NHL. The possible impact of this effect on mortality patterns after prolonged follow-up is worthy of investigation. We investigated the long-term survival and incidence of second malignancies in the first randomized trial utilising recombinant G-CSF in NHL (Pettengell R et al Blood 1992, 80: 1430–1436). Methods: Data on overall survival (OS), progression-free survival (PFS), freedom from progression (FFP) and the incidence of second malignancies were extracted from medical records and cancer registry databases for 80 patients with aggressive subtypes of NHL, who had previously been randomised to receive either VAPEC-B chemotherapy alone (39 patients) or VAPEC-B with G-CSF (41 patients). 10 year survival figures were extracted and Kaplan-Meier survival curves were drawn for the above parameters and compared between treatment groups using the log-rank test. Results: Median follow-up was 11.8 years for surviving patients (range 7.8–13.1 yrs). Patients receiving G-CSF achieved a 12% higher median dose intensity of chemotherapy. No significant differences were found in PFS or OS but 10 year FFP appeared to be better in the G-CSF arm (60.8%) compared with the control arm (45.6%) (log-rank test p=0.12). Eleven deaths from non-NHL causes occurred in the G-CSF arm compared with three in the control arm (log- rank test p=0.06). Five second malignancies were detected on long-term follow-up in the G-CSF arm compared with two in the control arm. Conclusions: The demonstration of different mortality patterns in the two arms may be related to the greater dose intensity of chemotherapy received in the G-CSF arm. Although, our study has insufficient statistical power to draw definite conclusions, this finding warrants further investigation. No significant financial relationships to disclose.

Radioimmunotherapy—A New Approach in the Management of Non-Hodgkin Lymphoma

Radioimmunotherapy—A New Approach in the Management of Non-Hodgkin Lymphoma

Radioimmunotherapy – A New Approach in the Management of Non-Hodgkin Lymphoma

Radioimmunotherapy – A New Approach in the Management of Non-Hodgkin Lymphoma

Optimal Use of Prognostic Factors in Non-Hodgkin Lymphoma

The management of non-Hodgkin lymphoma is complicated by wide heterogeneity within recognized subtypes. Patients with supposedly similar diagnoses can have remarkably varied clinical presentations, molecular profiles and clinical outcomes. Reliable prognostic markers could allow the identification of patient subsets that may benefit from alternate approaches. Historically, a large number of clinical and molecular prognostic factors have been elucidated. However, the recent introduction of new therapies such as monoclonal antibodies has revolutionized treatment practices and greatly improved outcomes. This has called into question the value of previously recognized prognostic factors that need to be revalidated in the era of immunochemotherapy. It would appear that the commonly used clinical indices (IPI and FLIPI) retain predictive capacity, although they may have limited ability to identify a very poor outcome group. Currently there are no molecular markers that have been revalidated and shown to retain significance in the setting of current treatment practices for diffuse large B-cell lymphoma or follicular lymphoma. The biologic insights provided by molecular studies should allow for more targeted therapies to be developed, which will increase treatment choice and the possibility of tailored therapy in the future. It is imperative that future steps forward be made in the context of well-designed clinical trials with prospective correlative studies of clinical and biologic markers. This will allow us to continuously assess outcome predictors in the context of treatment change and to rationally design tailored treatment algorithms.

High-Dose Myeloablative Zevalin Radioimmunotherapy with Tandem Stem-Cell Autografting Has Minimal Toxicity and Full Feasibility in an Outpatient Setting.

Background : High dose chemotherapy has an established, albeit limited role, in the management of non-Hodgkin lymphoma (NHL). In fact, because of its toxicity, in particular mucositis, neutropenia and thrombocytopenia, myeloablative regimens with autologous stem cell support can be safely delivered only to clinically fit and younger pts, require prolonged hospitalization, and have a restricted impact in the therapy of NHL. With the primary aim of widening the applicability of myeloablative regimens, we designed a pilot study using high-dose Zevalin with tandem stem-cell support in a prospective cohort of 13 refractory or relapsed NHL patients, unable to safely undergo a BEAM chemotherapy course.Methods : Prior to Zevalin, all pts received one cycle of high-dose cyclophosphamide plus rituximab, and one cycle of high-dose cytarabine and rituximab, at patient-adapted doses. Hematopoietic stem cells were harvested from the peripheral blood during the post-cyclophosphamide and/or the post-cytarabine recovery phase, and tested for MRD. Zevalin was administered at twice the MTD (0.8 mCi/kg), and followed by tandem autografting of a small amount of CD34+ (0.8–2 x 106/kg) on day +7, and an optimal amount (>=5 x 106 CD34+ cells/kg) on day +14, respectively. The former reinfusion (supportive autografting) was done still in the presence of potentially myelotoxic doses of circulating radioactivity, and its aim was solely to achieve an immediate albeit transient hematopoietic recovery. At the time of the second reinfusion (reconstituting autografting) the calculated radiation dose to the reinfused stem cells was less than 5 cGy, in order to ensure a complete and long lasting hematopoietic reconstitution.Results: From July 2004 through March 2005, 13 overall NHL patients entered into the study (DLBCL 5, follicular 3, mantle cell 2, marginal zone nodal 1, small lymphocytic 1, lymphoplasmacytoid 1). Median age was 60 yrs (29–69). The number of prior chemotherapy regimes was 1 (4 pts), 2 (5 pts), 3 (3 pts) and 4 (1 pt), respectively. Neutropenia grade 1 or higher was documented in all but 1 patient, and lasted a median of 7 days (1–15), while grade 4 neutropenia was observed in 8 pts, in which lasted a median of 3.5 days only (1–10). Grade >=1 thrombocytopenia was observed in all patients (median 16 days, range 7–30), while grade 4 thrombocytopenia occurred in 10 pts for a median duration (in the thrombocytopenic pts) of 6 days (1–13). Eight patients required platelet transfusions (median 2, range 1–6), and 9 pts received 1 RBC transfusion each. No extra-hematologic toxicity was observed, and all but 4 patients were cared for as outpatients. The 4 hospital admissions lasted 2 (2 pts) and 4 days (2 pts) respectively, and were required for FUO that rapidly resolved upon antibiotic administration. After a median follow-up of 6 months (1–11), 11 pts are alive, of which 10 in continuous CR.Conclusions : High-dose Zevalin with tandem stem-cell transplantation was minimally toxic in this heavily pretreated patient population, and fully applicable in an outpatient setting. Its administration at 0.8 mCi/kg (and possibly up to 1.2 mCi/kg) as a final consolidation step, warrants prospective comparison with conventional-dose regimens in a minimally selected NHL patient population.

The role of stem cell transplantation in the management of Non-Hodgkin's lymphoma

The role of stem cell transplantation has markedly improved the clinical outcomes of patients with aggressive and relapsed Non-Hodgkin's lymphoma (NHL), and has now become the treatment of choice. This paper examines the evidence which is resulting in the changing trends in the management of NHL, in the use of stem cell transplantation. Autologous bone marrow transplantation has been much favoured due to the reduced incidence of treatment related complications. Although allogeneic transplants have had equal success, its use has been hampered by the increasing difficulty in finding suitably matched donors. The use of peripheral blood stem cells continues to increase, although further research is required to improve the effects of priming and purging methods used in order to reduce the risk of myelodysplastic syndrome.

Lymphoma: Diagnosis, staging, natural history, and treatment strategies

Non-Hodgkin's lymphoma (NHL) is not a single disease, but a group of closely related B- and T-cell cancers of the lymphatic system. The incidence of NHL is rising, particularly in the countries of the industrialized world. The increased incidence is poorly understood, but several risk factors have been postulated to be associated with NHL, including: exposure to chemicals, viral infections, organ transplantation and blood transfusion, family history, and lifestyle factors. Precise staging of NHL is a prerequisite for the selection of a suitable therapeutic regimen and influences the likelihood of its success. Staging of lymphoma is traditionally conducted using tumor biopsy, imaging (X-ray, computerized tomography [CT], magnetic resonance imaging, lymphangiogram, gallium scan using 67 Ga citrate single photon emission CT [ 67 Ga-SPECT], or positron emission tomography), blood tests, bone marrow examination, and examination of cerebrospinal fluid. CT is the most commonly used imaging technique, but several studies indicate that other techniques, such as 67 Ga-SPECT, are more sensitive and better predictors of response. Low- and high-grade lymphomas differ markedly in prognosis and response to treatment. The management of NHL has been characterized by the increasing recognition that distinct subgroups of NHL respond differently to various therapeutic approaches. In follicular lymphoma (FL), a successful approach has been to combine fludarabine with mitoxantrone (FM), resulting in an overall response rate of 89% (67% complete remission). In an ongoing phase III trial in patients with untreated, advanced, low-grade follicular lymphoma, FM was compared with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) with or without rituximab. Patients previously treated with FM achieved a significantly better complete remission rate (67% v 38%; P = .0013) and a better molecular remission (36% v 20%; P = .049) than patients previously treated with CHOP. Following rituximab treatment, 88% of patients who had received FM achieved clinical and molecular remission compared with 70% who had received CHOP. Strategies using various chemotherapy combinations, including innovative agents such as 90 Y-ibritumomab tiuxetan, show promise in the treatment of NHL, particularly indolent NHL, and hopefully will lead to an improvement in prognosis.

Development of 131I-tositumomab

The median survival for patients with advanced indolent non-Hodgkin's lymphoma (NHL) has remained at 7 to 8 years since the 1960s. Targeted treatment using radioimmunotherapy (RIT), radiolabeled monoclonal antibodies directed against tumor-specific antigens, is an attractive option for this patient population, combining the advantages of an active biologic therapy with low dose-rate irradiation of an inherently radiosensitive tumor. Two anti-CD20 RIT agents have now been approved for the treatment of refractory NHL: 90Y-ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, San Diego, CA, and Schering AG, Berlin, Germany) is approved in both the United States and Europe, and 131I-tositumomab (Bexxar; Corixa Corp, Seattle, WA) is approved only in the United States. This article discusses the development of 131I-tositumomab. Because 131I-labeled antibody clearance varies significantly among patients, prescription of 131I-tositumomab activity must be based on a calculated total-body dose derived from quantitative whole-body imaging. The maximum tolerated total-body dose has been established at 75 cGy in patients with adequate bone marrow reserves and less than 25% bone marrow involvement by lymphoma (65 cGy in patients with mild thrombocytopenia; 45 cGy in patients who have received stem cell transplantation). In a phase III trial, overall response rate (ORR) and complete response (CR) rate were significantly higher following 131I-tositumomab than following the patient's last qualifying chemotherapy (ORR, 65% v 28%; P <.001; CR, 20% v 3%; P <.001). 131I-tositumomab has also been shown to be effective in patients who are refractory to rituximab (ORR, 70%; CR, 32%) and as first-line therapy in patients with NHL (ORR, 97%; CR, 63%). The major side effects of 131I-tositumomab are hematologic. In the phase III study, 20% of patients experienced grade 4 neutropenia and 22% experienced grade 4 thrombocytopenia. Myelodysplastic syndromes or secondary acute myeloid leukemia have been reported in 8.4% of patients with chemotherapy-refractory disease treated with 131I-tositumomab, but have not been observed to date in patients receiving 131I-tositumomab as first-line therapy. Future progress in NHL management is likely to include RIT as part of a multi-modality approach; trials are planned or currently underway to investigate the combination of RIT with chemotherapy regimens.

Radioimmunotherapy – A New Approach in the Management of Non-Hodgkin Lymphoma

Radioimmunotherapy – A New Approach in the Management of Non-Hodgkin Lymphoma

Novel Approaches to the Management of Non-Hodgkin Lymphoma

The rate of increase in the incidence of non-Hodgkin lymphoma (NHL) is outstripping that of other cancers. NHL is increasingly being treated in the context of immune compromise due to age or concomitant disease. Whilst most NHLs fall into the clearly aggressive and indolent categories, it is clear that distinction of less common entities such as Burkitt and mucosa-associated lymphoid tissue (MALT) lymphomas is essential for appropriately targeted treatment. Better diagnostic tools including the WHO histopathological criteria and quality imaging systems for CT, magnetic resonance imaging (MRI), and positron emission tomography (PET) scanning have facilitated accurate disease classification. Prognostic indices have been validated for both aggressive and indolent disease, and multidisciplinary input into diagnosis and management has proved beneficial.

Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas

AbstractDespite the rapid and widespread integration of chimeric CD20 monoclonal antibody (mAb), rituximab, into the management of non-Hodgkin lymphoma, its efficacy remains variable and often modest when used as a single agent. To develop more potent reagents, human immunoglobulin transgenic mice were used to generate a panel of immunoglobulin G1κ (IgG1κ) CD20 mAbs. All reagents bound strongly to CD20+cells and recruited mononuclear cells for the lysis of malignant B cells. However, 2 mAbs, 2F2 and 7D8, were exceptionally active in complement-dependent cytotoxicity (CDC), being able to lyse a range of rituximab-resistant targets, such as CD20-low chronic lymphocytic leukemia (CLL), in the presence of human plasma or unfractionated blood. Further analysis showed that 2F2 and 7D8, like rituximab, redistributed CD20 into Triton X-100-insoluble regions of the plasma membrane, but that they had markedly slower off-rates. To determine whether off-rate influenced CDC, a non-complement activating F(ab′)2antihuman κ reagent was used. This reagent markedly slowed the off-rate of rituximab and increased its CDC activity to that of 2F2 and 7D8. Thus, with increasing evidence that mAb therapeutic activity in vivo depends on complement activation, these new CD20 reagents with their slow off-rates and increased potency in CDC hold considerable promise for improved clinical activity. (Blood. 2004;104:1793-1800)

Durable remissions from fludarabine followed by the iodine I-131 tositumomab Bexxar therapeutic regimen for patients with previously untreated follicular non-Hodgkin's lymphoma (NHL)

6518 Background: The sequential combination of chemotherapy and radioimmunotherapy offers a novel strategy for the initial management of NHL. Tositumomab and iodine I 131 tositumomab (Bexxar) have been demonstrated to have substantial clinical activity in both untreated and relapsed/refractory low-grade NHL. Fludarabine synergizes in vitro with unlabeled and radiolabeled antibodies and can be employed as a “debulking” agent prior to radioimmunotherapy. Methods: Patients with previously untreated, advanced low-grade NHL were treated with IV fludarabine 25 mg/m2/day for 5 days, every 5 wks for 3 cycles followed in 6 to 8 wks by Bexxar therapy. Results: Between August 1998 and June 1999, 38 pts (51% follicular mixed, 49% follicular small cleaved) were enrolled and 97% had stage III/IV disease. Thirty-five subjects received both fludarabine and Bexxar therapy. Three patients came off study before or during fludarabine therapy (one due to cytopenias, 2 unrelated to toxicity or lymphoma progression). Response t...

Management of gastrointestinal lymphoma.

Despite numerous effective chemotherapeutic regimens developed to treat non-Hodgkin’s lymphoma (NHL), it remains the sixth most common cause of cancerassociated deaths in the United States. Estimates from the American Cancer Society project that about 53,000 new cases of NHL will be diagnosed in the United States in 2002 and approximately half of those afflicted will die of their disease. The incidence of NHL has increased greatly since the early 1980s, in large part from increased HIV disease, though ubiquitous environmental and toxic exposures have also been implicated. NHL is more common in men (M/F ratio 1.5/1). The incidence of NHL in younger white men (ages 18 to 45) has stabilized since 1997 but might be increasing in both women and African Americans. Extranodal lymphoma, or lymphoma arising within solid organs, occurs in up to 40% of all cases. The gastrointestinal (GI) tract is the most frequently involved extranodal site, accounting for up to half of all extranodal cases. Lymphomas can involve any part of the GI tract from oral cavity to rectum. Surgical resection can play an important role in the diagnosis and treatment of NHL involving the GI tract. The surgeon should maintain a high index of suspicion for GI lymphomas and appreciate the critical role surgery might play in obtaining an accurate diagnosis and successfully managing these malignancies. This article reviews GI lymphomas with particular emphasis on the role of surgery as part of a multidisciplinary approach to the diagnosis and management of NHL.