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Non-Hodgkin lymphoma — Clinical Guidelines

Overview

Non-Hodgkin lymphoma (NHL) encompasses a diverse group of lymphoid malignancies characterized by the uncontrolled proliferation of lymphocytes. Treatment strategies vary based on histology, stage, and patient-specific factors. 1 2 6 16 26

Diagnosis

Imaging: CT, PET-CT for staging and assessing extent.

Bone Marrow Evaluation: Histopathology and flow cytometry to assess involvement. 5 13 26

Biopsy: Essential for definitive diagnosis and subtype classification.

Immunophenotyping: Essential for distinguishing between B-cell and T-cell NHL.

Genetic Testing: Consider for prognostic assessment and guiding therapy (e.g., FISH for specific translocations). 9 18

Management

First-Line Treatment:

- Chemotherapy: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for many B-cell NHLs. 1 26 - Targeted Therapy: Rituximab subcutaneously or intravenously for B-cell NHLs. 1 - CAR T-Cell Therapy: Axicabtagene ciloleucel for relapsed/refractory indolent NHL, including follicular lymphoma. 6

Adjunctive Treatments:

- Radioimmunotherapy: (90)Y-ibritumomab tiuxetan and (131)I-tositumomab for specific B-cell NHL subtypes. 16 19 - Supportive Care: Management of side effects, including renal protection and infection prophylaxis.

Special Populations

Elderly Patients: Tailored chemotherapy dosing; consider less intensive regimens like R-CVP (rituximab, cyclophosphamide, vincristine, prednisone) in septuagenarians and octogenarians. 15

Pediatrics: Challenges include advanced disease at presentation and supportive care limitations; outcomes vary widely. 7

Comorbidities: Special considerations for patients with renal impairment (e.g., dose adjustments for renally cleared drugs). 3 15

Key Recommendations

Use R-CHOP as a first-line therapy for most B-cell NHLs due to robust evidence from clinical trials and meta-analyses. (Evidence: Strong) 1 26

Consider subcutaneous rituximab as an effective alternative to intravenous administration for maintenance therapy in NHL, supported by systematic reviews and meta-analyses. (Evidence: Moderate) 1

Evaluate elderly patients individually for chemotherapy tolerance, potentially opting for less intensive regimens like R-CVP to balance efficacy and toxicity. (Evidence: Moderate) 15

Incorporate CAR T-cell therapy for patients with relapsed/refractory indolent NHL, given high response rates and durable clinical benefit observed in clinical trials. (Evidence: Moderate) 6

Tailor supportive care measures, including renal protection strategies, for patients undergoing chemotherapy, especially those with pre-existing renal conditions. (Evidence: Expert opinion) 3 15

References

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Blood reviews 2021. link 6 . CAR T-Cell Therapy Shows Durable Responses in Indolent NHL. The oncologist 2020. link 7 Peña-Hernandez A, Ortiz R, Garrido C, Gomez-Garcia W, Fuentes-Alabi S, Martinez R et al.. Outcome of pediatric non-Hodgkin lymphoma in Central America: A report of the Association of Pediatric Hematology Oncology of Central America (AHOPCA). Pediatric blood & cancer 2019. link 8 Conte C, Bourrel R, Despas F, Lapeyre-Mestre M. Is there overuse of proton pump inhibitors in B-cell non-Hodgkin lymphomas? A cohort study based on the French health insurance database in the Midi-Pyrénées region. Fundamental & clinical pharmacology 2019. link 9 Zhang S, Sun J, Fang Y, Nassiri M, Liu L, Zhou J et al.. Signet-ring cell lymphoma: clinicopathologic, immunohistochemical, and fluorescence in situ hybridization studies of 7 cases. Annals of diagnostic pathology 2017. link 10 Weaver MS. Room to roar: eliciting the perspectives of adolescent oncology patients. The oncologist 2014. link 11 Maio P, Bento D, Vieira R, Afonso A, Sachse F, Kutzner H. Non Hodgkin T cell lymphoma: an atypical clinical presentation. Anais brasileiros de dermatologia 2013. link 12 Deepak P, Sifuentes H, Sherid M, Stobaugh D, Sadozai Y, Ehrenpreis ED. T-cell non-Hodgkin's lymphomas reported to the FDA AERS with tumor necrosis factor-alpha (TNF-α) inhibitors: results of the REFURBISH study. The American journal of gastroenterology 2013. link 13 Chen T, McDonald A, Shadbolt B, Talaulikar D. Precision of histological bone marrow staging in follicular lymphoma and diffuse large B-cell lymphoma. Clinical and investigative medicine. Medecine clinique et experimentale 2012. link 14 Cabrera ME, Martinez V, Nathwani BN, Muller-Hermelink HK, Diebold J, Maclennan KA et al.. Non-Hodgkin lymphoma in Chile: a review of 207 consecutive adult cases by a panel of five expert hematopathologists. Leukemia & lymphoma 2012. link 15 Huntington SF, Talbott MS, Greer JP, Morgan DS, Reddy N. Toxicities and outcomes among septuagenarians and octogenarians with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy. Leukemia & lymphoma 2012. link 16 Schaefer NG, Huang P, Buchanan JW, Wahl RL. Radioimmunotherapy in non-Hodgkin lymphoma: opinions of nuclear medicine physicians and radiation oncologists. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2011. link 17 Panicharoen C, Hirunwiwatkul P. Current pattern treatment of hordeolum by ophthalmologists in Thailand. Journal of the Medical Association of Thailand = Chotmaihet thangphaet 2011. link 18 Drakos E, Leventaki V, Atsaves V, Schlette EJ, Lin P, Vega F et al.. Expression of serine 194-phosphorylated Fas-associated death domain protein correlates with proliferation in B-cell non-Hodgkin lymphomas. Human pathology 2011. link 19 Schaefer NG, Ma J, Huang P, Buchanan J, Wahl RL. Radioimmunotherapy in non-Hodgkin lymphoma: opinions of U.S. medical oncologists and hematologists. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2010. link 20 Herold MA, Kühne R, Vosberg M, Ostheeren-Michaelis S, Vogt P, Karrer U. Disseminated toxoplasmosis in a patient with non-Hodgkin lymphoma. Infection 2009. link 21 Gurol Y, Kipritci Z, Selcuk NA, Koc Y, Kocagoz S. Bacillus circulans paracardiac infection in non-hodgkin lymphoma--a case report. Prague medical report 2008. link 22 Koutros S, Zhang Y, Zhu Y, Mayne ST, Zahm SH, Holford TR et al.. Nutrients contributing to one-carbon metabolism and risk of non-Hodgkin lymphoma subtypes. American journal of epidemiology 2008. link 23 Kromhout H, Vermeulen R. Non-Hodgkin lymphoma and occupational exposures: multiple exposures not = multiple papers. Occupational and environmental medicine 2007. link 24 Polesel J, Dal Maso L, La Vecchia C, Montella M, Spina M, Crispo A et al.. Dietary folate, alcohol consumption, and risk of non-Hodgkin lymphoma. Nutrition and cancer 2007. link 25 Coroi M, Roşca E, Muţiu G, Burtă L, Todor V, Coroi T et al.. Non-Hodgkin Malignant Lymphoma Study--admitted cases during 1990-2005 in Ophthalmologic Clinical Department, Oradea. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 2006. link 26 Barosi G, Carella A, Lazzarino M, Marchetti M, Martelli M, Rambaldi A et al.. Management of nodal indolent (non marginal-zone) non-Hodgkin's lymphomas: practice guidelines from the Italian Society of Hematology, Italian Society of Experimental Hematology and Italian Group for Bone Marrow Transplantation. Haematologica 2005. link 27 Naresh KN, Agarwal B, Nathwani BN, Diebold J, McLennan KA, Muller-Hermelink KH et al.. Use of the World Health Organization (WHO) classification of non-Hodgkin's lymphoma in Mumbai, India: a review of 200 consecutive cases by a panel of five expert hematopathologists. 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Non-Hodgkin lymphoma