non-Hodgkin's lymphoma
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Classification
- B-cell lymphoma (85%), T-cell lymphoma (13%), NK-cell lymphoma (2%)
- aggressive lymphomas
- rapidly progressive systemic disease
- diffuse large B-cell lymphoma
- high-grade Burkitt's lymphoma, Burkitt's-like lymphoma
- lymphoblastic lymphoma
- indolent lymphomas
- slowly progressive lymphocytosis or lymphadenopathy, often asymptomatic
- follicular lymphoma
- chronic lymphocytic leukemia/small lymphocytic lymphoma
Etiology
predisposing factors
- majority of cases have no predisposing factors
- immune suppression
- AIDS
- autoimmune disease
- inherited immunodeficiency states
- viruses
- Helicobacter pylori
- toxins
- radiation
- herbicides, organochlorides used in farming
- prior chemotherapy
- pharmacologic agents
Epidemiology
- approximately 40,000 cases/year
- average age of presentation early 40's
- majority of patients present with advanced disease
- 10-20% present with disease outside of lymph nodes & spleen
- more common in men[5]
Pathology
- diverse group of lymphomas histologically & pathologically
- tends to spread hematogenously
- T- & B-cell dysfunction
- CD5(+):
- CD10(+): follicular lymphoma
- CD20(+):
- CD23(+):
Genetics
- t(14;18)(q32;q21) translocations
- 85% of follicular lymphomas
- 28% of higher-grade lymphomas
- BCL-2 juxtaposition with heavy-chain region of immunoglobulin region
- t(1;1)(p36.3;q21.1-2) involving FCRL4
- t(10;14)(q24;q32) involving NFKB2 with IGHA1
- t(2;5)(p23;q35.1) involving ALK with NPM1
- t(3;4)(q27;p11) involving RhoH with BCL6
- t(11;14) bcl-1 with Ig heavy chain, mantle cell lymphoma
- t(1;18) API2, MALT lymphoma
- t(1;14) MALT1 with bcl-10, MALT lymphoma
- trisomy 12
- overexpression of RGS1
- other implicated genes hemogen, LETMD1, CASP10, MCTS1, BRAF
Clinical manifestations
- general
- fatigue
- localized pain
- pruritus may be a presenting symptom[9]
- does not produce ulcerations[10]
- lymphadenopathy
- 75% of patients present with palpable lymphadenopathy
- any lymph node > 1 cm in diameter present for > 4 weeks not associated with infection should be biopsied
- B-symptoms present in 20% of patients
- fever
- night sweats
- weight loss (> 10% of body weight)
- mediastinal adenopathy (20%)
- persistent cough
- abnormal chest X-ray
- retroperitoneal, mesenteric & pelvic adenopathy common
- generally asymptomatic
- obstruction may occur with massive disease
- hepatosplenomegaly, hepatic infiltration (25-50%)
- primary gastrointestinal lymphoma (<5%)
- pain
- obstruction
- hemorrhage
- abdominal fullness
- early satiety
- primary bone lymphoma (<5%)
- pain
- lytic lesions on X-ray
- generally diffuse large B-cell lymphoma
- primary CNS lymphoma
- primary cutaneous lymphoma
- renal infiltration (rare)
- prostate infiltration (rare)
- testis infiltration (rare)
- ovary infiltration (rare)
Laboratory
- considered essential*
- surgical excisional lymph node biopsy to examine lymph node architecture (most important test)
- physical examination
- documentation of B symptoms
- laboratory evaluation
- complete blood count (CBC)
- liver function tests (including LDH)
- LDH correlates with tumor bulk
- renal function tests (BUN & creatinine)
- uric acid
- serum Ca+2
- serum protein electrophoresis
- serum beta-2 microglobulin
- associated with poor prognosis
- bone marrow biopsy
- tests which may be indicated*
- tests which may be useful
- cell surface marker phenotype analysis
- cytogenetic analysis
- gene rearrangement analysis
- polymerase chain reaction (PCR)
- flow cytometry for DNA analysis
- liver biopsy
Diagnostic procedures
- tests which may be indicated*
- endoscopic examination
- echocardiogram
Radiology
- considered essential*
- tests which may be indicated*
- tests which may be useful
* essential for clinical staging
Staging
- Clinical staging of non-Hodgkin's lymphoma (see lymphoma)
Complications
- spinal cord compression
- pericardial tamponade
- hypercalcemia
- superior vena cava syndrome, inferior vena cava syndrome
- hyperuricemia, tumor lysis syndrome
- autoimmune hemolytic anemia
- immune thrombocytopenic purpura
- infection with Pneumocystis carinii[4]
- steroid chemotherapy
- T- & B-cell dysfunction
Management
- rituximab (monoclonal antibody against CD20) for routine treatment of B-cell lymphoma
- used for induction & maintenance
- rituximab alone
- rituximab combination chemotherapy for stage 3 & 4 regardless of age
- cyclophosphamide, vincristine & prednisone (R-CVP)
- cyclophosphamide, doxorubicine, vincristine & prednisone (R-CHOP)
- rituximab + bendamustine
- pixantrone may be appropriate in patients who fail rituximab
- also see more specific lymphomas
- recommendations prior to the introduction of rituximab
- based on histopathology, extent of disease, performance status
- stage IA or IIA:
- radiation, 3500-5000 cGy adjuvant to combination chemotherapy
- low-grade lymphoma:
- small lymphocytic lymphomas & follicular small cleaved cell lymphomas are not treated until they produce symptoms
- long term remissions are not usual
- overall survival is not favorably influenced
- transformation to a higher-grade lymphoma is common
- median survival is about 7 years
- radiation therapy, local or extended field[3]
- chemotherapy: single alkylating agent
- combination chemotherapy
- three purine analogs have shown activity in low-grade non-Hodgkin's lymphoma
- fludarabine
- 2-Chlorodeoxyadenosine (2-CDA)
- 2-deoxyformycin (adenosine deaminase inhibitor)
- intermediate-grade-lymphoma:
- intermediate-grade-lymphomas are treated similarly
- diffuse large-cell lymphoma
- follicular mixed cell lymphoma
- follicular large-cell lymphoma
- diffuse small cleaved lymphoma
- treatment of large-cell lymphomas is one of the major success stories of chemotherapy
- combination chemotherapy
- C-MOPP (cyclophosphamide, vincristine, prednisone, & procarbazine) first regimen, 40% remissions
- CHOP (cyclophosphamide, vincristine, prednisone, & doxorubicin), 35% long-term disease-free survival
- BACOD (CHOP plus one or more of *)
- M-BACOD (CHOP plus one or more of *)
- m-BACOD (CHOP plus one or more of *)
- Pro-MACE-MOPP (CHOP plus one or more of *)
- COP-BLAM (CHOP plus one or more of *)
- COMLA (CHOP plus one or more of *)
- MACOP-B (CHOP plus one or more of *)
- ProMACE/CytaBOM (CHOP plus one or more of *)
- MACOB-B (CHOP plus one or more of *)
- intermediate-grade-lymphomas are treated similarly
* bleomycin, methotrexate, procarbazine, nitrogen mustard, cytosine arabinoside, etoposide.
- duration of treatments may be as long as 12 months
- complete remission rates 80%
- however, toxicities have increased:
- infections
- pulmonary & cardiac complications
- high-grade lymphoma:
- extremely poor prognosis
- aggressive treatment indicated
- 56% disease-free survival at 3 years has been reported in patients treated with CHOP & high-dose methotrexate, L-asparaginase & intrathecal methotrexate
- AIDS-related lymphomas:
- most a high-grade immunoblastic or non-cleaved cell types
- some intermediate-grade large cell lymphomas are observed
- combination chemotherapy, intrathecal methotrexate, & GM-CSF produce remissions in 1/3 of patients with high incidence of CNS-relapse & fatal opportunistic infections
- cutaneous T-cell lymphoma:
- topical chemotherapeutic agents such as nitrogen mustard can produce remissions in up to 90% of patients
- local radiation also produces high rates; however, most patients relapse within 3 years
- 8-methoxypsoralen followed by UV light (PUVA) also produces similar remissions
- systemic therapy in combination with topical therapy results in few long-term remissions
- prognosis:
- histology is most important factor
- markers associated with poor prognosis
- CD71 (transferrin receptor) present on proliferating cells
- CD44 (homing receptor)
- serum beta-2 microglobulin
- extranodal involvement (multiple lymph nodes involved) is associated with poor prognosis
- serum LDH correlates with tumor bulk
- increased age is associated with a poorer prognosis
- better physical condition or performance status is associated with better prognosis
- sex is not a factor
- 89% 5 year survival if no poor prognostic factors; 56% 5 year survival with 5 poor prognostic factors
- salvage chemotherapy for patients who fail to achieve remission on conventional chemotherapy:
- cytosine arabinoside, cisplatin, etoposide, ifosamide may produce remission in 20-30% of patients; however long term survival is minimal.
- stem cell transplantation:
- very high dose chemotherapy can induce complete remission in patients with relapses after conventional therapy
- however, prolonged myelosuppression occurs
- bone marrow transplantation, usually autologous from harvested circulating hematopoietic stem cells benefits a subset of patients who have previously responded favorably to conventional therapy.[3][8]
- non-myeloablative allogeneic hematopoietic stem-cell transplantation may be useful for relapses, refractory, & transformed indolent non-Hodgkin's lymphoma[7]
- GM-CSF & G-CSF appear to be useful adjuncts for hastening recovery from chemotherapy
More general terms
More specific terms
- B-cell lymphoid neoplasm (B-cell lymphoma)
- body cavity-based lymphoma
- cutaneous lymphoma
- lymphoblastic lymphoma
- lymphoma by size & distribution
- lymphomatous meningitis
- primary central nervous system (CNS) lymphoma (PCNSL)
- primary thyroid lymphoma
- stem cell leukemia lymphoma syndrome (SCLL)
- T-cell lymphoid neoplasm (T-cell leukemia, T-cell lymphoma)
Additional terms
- bcl-2 proto-oncogene
- chromosomal translocation t8q24.1:14q32 (B-cell leukemia, Burkitt's lymphoma)
- classification of non-Hodgkin's lymphoma
References
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1782, 1786
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 426-28
- ↑ 3.0 3.1 3.2 3.3 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012
- ↑ 4.0 4.1 Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 539
- ↑ 5.0 5.1 5.2 Schiller G, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ Ferri's Clinical Advisor, Instant Diagnosis and Treatment, Ferri FF (ed), Mosby, Philadelphia, 2003
- ↑ 7.0 7.1 Resvani AR et al, Nonmyeloablative allogeneic hematopoietic cell transplantation in relapses, refractory, and transformed indolent non-Hodgkin's lymphoma. J Clin Oncol 2008, 26:211 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18056679
- ↑ 8.0 8.1 Philip T, Guglielmi C, Hagenbeek A et al Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7477169
- ↑ 9.0 9.1 Deng J et al. Risk of hematologic cancer in patient with undifferentiated pruritis. JAMA Dermatol 2022 Jul; 158:791. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35612839 PMCID: PMC9134041 (available on 2023-05-25) https://jamanetwork.com/journals/jamadermatology/fullarticle/2792454
- ↑ 10.0 10.1 10.2 NEJM Knowledge+ Otolaryngology
Patient information
non Hodgkin's lymphoma patient information