NHL, non-Hodgkin’s lymphoma; NK, natural killer.

^aThe classification of acute lymphoid leukemias will expand on the classification of precursor B-cell and T-cell malignancies, incorporating both immunophenotypic and genetic features.

^bMorphologic and/or clinical variants of these diseases are not listed, for the purpose of clarity and ease of presentation.

             Additional workup after a diagnostic biopsy includes a history and physical examination with documentation of adenopathy, hepatosplenomegaly, performance status, the presence of B symptoms, laboratory evaluations, radiographic studies, and, in most cases, a bone marrow biopsy. Necessary laboratory tests include a CBC, liver-function tests, calcium, creatinine, and lactate dehydrogenase (LDH). Cytopenias usually signify bone marrow involvement or, less commonly, hypersplenism. LDH is an important prognostic factor in the International Prognostics Index (IPI). If the LDH is elevated, a uric acid level should be obtained to evaluate for tumor lysis syndrome. Screening for HIV is indicated for patients with aggressive NHL. The Ann Arbor staging system, initially developed for Hodgkin’s lymphoma, is also used to stage NHL (Table 26-2). Alternative staging systems have been proposed but never adopted. Proper staging requires CT scans of the chest, abdomen, and pelvis, as well as bilateral bone marrow biopsies. Marrow evaluation is not always necessary in asymptomatic, older patients with indolent lymphomas if a CBC is normal, as the findings are unlikely to alter management of the disease. PET/CT scans have improved the accuracy of initial staging and response assessment, and are routinely incorporated in patients with aggressive subtypes of NHL. The role of PET/CT in indolent lymphomas remains controversial, although it can be useful in patients with equivocal CT findings and in patients who appear to have localized disease at presentation, where finding additional sites of involvement could potentially alter management. PET/CT is also helpful in identifying areas of suspected transformation, and although it should not replace the role of biopsy, it assists with directing the most appropriate site to biopsy. Patients with lymphoblastic or Burkitt lymphoma should have a lumbar puncture. If Waldeyer ring is involved, an upper gastrointestinal (GI) or upper endoscopy should be considered, given the increased incidence of gastric involvement in these patients.

      C.  Therapy and prognosis

          1.  Indolent lymphomas. The Follicular Lymphoma International Prognostic Index (FLIPI) includes five independent poor prognostic factors, including age equal to or greater than 60, stage III or IV, greater than four involved nodal areas, elevated serum LDH, and hemoglobin less than 12 gm/dL (Blood 2004;104:1258). The 10-year OS (overall survival) rate for patients with three or more risk factors according to the FLIPI is 35% compared with 70% for patients with none or one high-risk feature. The FLIPI remains prognostic in the rituximab era (Ann Oncol 2013;24:441). Despite the marked improvement in recent outcomes for FL, there is still no plateau in the event-free survival curves with the use of chemoimmunotherapy, and “cures” remain to be achieved.

              a.  Stages I or II. Given the improved sensitivity of staging studies including CT scans, PET/CT scans, and the use of flow cytometry to evaluate bone marrow specimens, the diagnosis of limited-stage indolent lymphoma is uncommon. Observation, involved-field radiotherapy (IFRT), single-agent rituximab, a combination of rituximab and chemotherapy, and combined-modality therapy with rituximab plus or minus chemotherapy with IFRT are all options for patients with this unusual presentation. There are no randomized trials comparing these approaches, and treatment decisions should be based on the site and bulk of disease and patients’ age, with the more aggressive approaches being preferred for younger patients and those with bulky stage I and stage II disease.

                     Gastric and other extranodal MALT lymphomas commonly present with early-stage disease. Gastric MALT lymphomas appear to occur as a direct result of antigenic stimulation from Helicobacter pylori infection. Approximately 80% of patients with gastric MALT lymphoma will have complete regression of disease with appropriate therapy for H. pylori, including antibiotics and proton-pump inhibitors. Long-term studies have demonstrated excellent durability of these remissions, with 80% to 90% of patients remaining in continuous histologic remission (J Clin Oncol 2005;23:8018; Gut 2012;61:507). For the subset of patients with gastric MALT lymphoma who do not respond to or relapse after H. pylori therapy, or are H. pylori negative, results with IFRT are excellent, with one series reporting 10-year freedom from treatment failure and OS of 88% and 70%, respectively (Ann Oncol 2013;24:1344). Other isolated extranodal presentations such as salivary gland, thyroid, breast, conjunctiva, or a unifocal skin site are also effectively treated with low-dose IFRT (30 Gy). Transformation of MALT lymphomas to aggressive, large cell lymphomas occurs in a minority of patients, but can be resistant to therapy.

              b.  Stage III or IV disease. Despite many effective, but to date “noncurative” therapies, there has never been any objective evidence that early intervention versus “watchful waiting” improves OS in asymptomatic patients (Lancet Oncol 2014;15:424). A subset of patients with indolent lymphomas will have no indications for therapy more than 15 years after diagnosis. Asymptomatic, older patients with low-volume disease may still be best served by close observation until progression. The current standard of care for patients with indolent lymphomas requiring therapy is a combination of rituximab and chemotherapy. The treatment approach has changed recently, following the publication of a randomized trial showing a significant improvement in remission duration and toxicity profile with bendamustine and rituximab (BR) compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) (Lancet 2013;381:1203). The newly published BRIGHT trial comparing BR to R-CHOP and R-CVP (rituximab, cyclophosphamide, vincristine, prednisone) demonstrated noninferiority of the BR arm compared with the standard chemotherapy arms (ORR 97% vs. 91%) (Blood 2014;123:2944). Longer follow-up is necessary for progression-free survival (PFS) and OS comparisons.

                     Maintenance rituximab following first-line chemoimmunotherapy is frequently adopted on the basis of data demonstrating improved PFS compared with observation (59% vs. 43% at 6 years); however, an OS benefit has yet to be described (Lancet 2011;377:42). Previous studies utilized a variety of maintenance schedules including one dose every 3 months for 2 years, four weekly doses every 6 months for 2 years, four weekly doses at 3 and 9 months after completion of chemoimmunotherapy, and one dose every 2 months for 8 months, although these were tested in the relapsed setting. For upfront treatment, the maintenance schedule with the most data is with rituximab administered once every two months for a duration of two years. No convincing data is available to recommend maintenance rituximab beyond 2 years. The toxicities of rituximab are mild and are limited primarily to infusion-related reactions such as fevers, chills, myalgias, transient hypotension, and, rarely, bronchospasm.

Related posts:

Testicular Cancer and Germ Cell Tumors Endocrine Malignancies Uterine, Cervical, Vulvar, and Vaginal Cancers Growth Factor Support in Oncology Palliative Care in Oncology Pain Management

Stay updated, free articles. Join our Telegram channel

Join