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The aggressive type of NHL has a shorter natural history, but a significant number of these patients can be cured with intensive combination chemotherapy regimens.In general, with modern treatment of patients with NHL, overall survival at 5 years is over 60%.

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Patients who present with or convert to aggressive forms of NHL may have sustained complete remissions with combination chemotherapy regimens or aggressive consolidation with marrow or stem cell support.[5,6] Late effects of treatment for non-Hodgkin lymphoma (NHL) have been observed.

Pelvic radiation therapy and large cumulative doses of cyclophosphamide have been associated with a high risk of permanent sterility.[1] For as many as three decades after diagnosis, patients are at a significantly elevated risk for second primary cancers, especially the following:[1-3] Left ventricular dysfunction was a significant late effect in long-term survivors of high-grade NHL who received more than 200 mg/m² of doxorubicin.[4,5] Myelodysplastic syndrome and acute myelogenous leukemia are late complications of myeloablative therapy with autologous bone marrow or peripheral blood stem cell support, as well as conventional chemotherapy-containing alkylating agents.[1,6-13] Most of these patients show clonal hematopoiesis even before the transplantation, suggesting that the hematologic injury usually occurs during induction or reinduction chemotherapy.[8,14,15] With a median 10-year follow-up after autologous bone marrow transplantation (BMT) with conditioning using cyclophosphamide and total-body radiation therapy, in a series of 605 patients, the incidence of a second malignancy was 21%, and 10% of those were solid tumors.[16] Successful pregnancies with children born free of congenital abnormalities have been reported in young women after autologous BMT.[17] Some patients have osteopenia or osteoporosis at the start of therapy; bone density may worsen after therapy for lymphoma.[18] A pathologist should be consulted before a biopsy because some studies require special preparation of tissue (e.g., frozen tissue).

In 1982, results of a consensus study were published as the Working Formulation.[3] The Working Formulation combined results from six major classification systems into one classification.

This allowed comparison of studies from different institutions and countries.

On a comparative basis, it is difficult to prove benefit when relapsing disease is followed with watchful waiting, or when the median survival is more than 10 years.

Follicular lymphoma and primary follicular lymphoma of the duodenum are particularly indolent variants that rarely progress and rarely require therapy.[20,21] A so-called pediatric-type nodal follicular lymphoma has indolent behavior and rarely recurs; adult patients with this histologic variant are characterized by a lack of rearrangement in conjunction with a Ki-67 proliferation index greater than 30% and a localized stage I presentation.[22] Patients with indolent lymphoma may experience a relapse with a more aggressive histology.

Indolent NHL types have a relatively good prognosis with a median survival as long as 20 years, but they usually are not curable in advanced clinical stages.[3] Early-stage (stage I and stage II) indolent NHL can be effectively treated with radiation therapy alone.

Most of the indolent types are nodular (or follicular) in morphology.

Rearrangement of the Despite the advanced stage, the median survival ranges from 8 to 15 years, leading to the designation of being indolent.[5-7] Patients with advanced-stage follicular lymphoma are not cured with current therapeutic options.

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