Mantle-cell lymphoma is an uncommon aggressive subtype of NHL accounting for <10% of all lymphomas, and has characteristic features of poor OS and FFS, with a median survival of approximately three years (71). Mantle-cell lymphoma has been reported to involve the GI tract in 15% to 30% of cases in the historical literature, typically in a diffuse polypoid pattern of colonic involvement termed MLP (99,100) as is demonstrated in Figure 2. Individual case reports of non-MLP forms of GI tract involvement (101) and polypoid involvement of the stomach (102) have also been reported. Intussusception is a rare complication (103).
Romaguera et al. (104) detected a significantly increased incidence of GI tract involvement when complete endoscopic assessment was performed in a series of 60 patients with mantle-cell lymphoma. While only a quarter of these patients presented with GI symptoms, 88% of patients harbored microscopic disease in the lower GI tract and 43% displayed abnormalities in the upper tract. Aggressive endoscopic staging did not result in treatment changes despite the higher frequencies of GI-tract involvement. PET scans may now be utilized to assess the GI tract (105).
Few series (106,107) have evaluated treatment of MLP as a separate entity. The largest series of MLP has been reported by the GELD. In 31 patients, anthracycline-based chemotherapy with AVmCP (doxorubicin, teniposide, cyclophosphamide, prednisolone) resulted in superior
ORR compared to cyclophosphamide, vincristine, prednisolone (COP ) (80% vs. 30%) with a projected five-year survival of 59% in the anthracycline-containing chemotherapy arm. Highdose therapy was an effective regimen for relapsing or partially responding patients (106).
The clinical series of MLP parallel results of standard and dose-intensified combination chemotherapy for mantle-cell lymphoma in general. The addition of rituximab to CHOP chemotherapy has been evaluated in two series, which resulted in improved ORR but did not impact PFS (108,109). Dose-intense chemotherapy without stem-cell rescue (110,111) has been evaluated to improve results achieved with conventional CHOP chemotherapy. The hyper-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone) regimen alternating with high-dose methotrexate and cytarabine (MA) without autologous stem-cell transplantation (ASCT) was originally reported in elderly patients and yielded an ORR of 92% (CR 68%) and median FFS of 15 months (110). Preliminary results of a prospective phase II trial of hyper-CVAD alternating with MA without ASCT in all age groups demonstrate a CR rate of 87% after six cycles with a three-year FFS of 67% and OS of 81% at 40 month's median follow up. Complete endoscopic assessment was performed in all patients with 70% harboring GI tract involvement (111).
Superior treatment results have also been demonstrated with high-dose therapy and ASCT in comparison to conventional chemotherapy (112-118). In a matched-pair analysis of patients with advanced-stage mantle-cell lymphoma treated with rituximab and ASCT versus historical controls who received standard chemotherapy, a statistically significant improvement in three-year PFS (89% vs. 29%; p < 0.00001) and a trend toward better OS (88% vs. 65%, p = 0.052) were detected (113). Myeloablative regimens using a radiolabeled anti-CD20 antibody, 131I tositumomab, result in CR rates in excess of 90% and an estimated three-year PFS of 62% (117). Mini-allogeneic transplantation is a promising treatment strategy for relapsed mantle-cell lymphoma (118).
Collectively, these clinical series highlight the role of combination chemotherapy as the standard treatment for mantle-cell lymphoma. The presence of GI-tract involvement does not generally alter treatment, and few adverse GI complications have been reported with systemic therapy, as patients usually present with diffuse polyps rather than ulcerative or hemorrhagic disease. Different forms of dose-intense therapy, either with or without stem-cell transplantation, demonstrate considerable improvements in response rates and intermediate survival endpoints reflecting significant progress in this field.
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