Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma

Leah Shepherd; Lene Ryom; Matthew Law; Camilla Ingrid Hatleberg; Stephane de Wit; Antonella d'Arminio Monforte; Manuel Battegay; Andrew Phillips; Fabrice Bonnet; Peter Reiss; Christian Pradier; Andrew Grulich; Caroline Sabin; Jens Lundgren; Amanda Mocroft

doi:10.1093/jnci/djx249

Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma

Leah Shepherd, Lene Ryom, Matthew Law, Camilla Ingrid Hatleberg, Stephane de Wit, Antonella d'Arminio Monforte, Manuel Battegay, Andrew Phillips, Fabrice Bonnet, Peter Reiss, Christian Pradier, Andrew Grulich, Caroline Sabin, Jens Lundgren, Amanda Mocroft

Department of Clinical Medicine

5 Citations (Scopus)

Abstract

Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Methods: Data from the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different associations with NHL and HL were identified using marginal Cox models. All statistical tests were two-sided. Results: Among 41 420 people followed for 337 020 person-years, 392 developed NHL (incidence rate ¼ 1.17/1000 person-years of follow-up [PYFU], 95% confidence interval [CI] ¼ 1.06 to 1.30) and 149 developed HL (incidence rate ¼ 0.44/1000 PYFU, 95% CI ¼ 0.38 to 0.52). Higher risk of both NHL and HL was associated with lower current CD4 cell count (adjusted HR [aHR] of NHL for CD4 <100 vs > 599 cells/mm³ ¼ 8.08, 95% CI ¼ 5.63 to 11.61; HL ¼ 4.58, 95% CI ¼ 2.22 to 9.45), whereas higher current HIV viral load (aHR of NHL for HIV-VL >1000 vs < 50 copies/mL ¼ 1.97, 95% CI ¼ 1.50 to 2.59) and higher AUC of HIV-VL (aHR of NHL for highest vs lowest quintile ¼ 2.91, 95% CI ¼ 1.92 to 4.41) were associated with NHL only. Both current and AUC of HIV-VL were factors that had different associations with NHL and HL, where the hazard ratio for NHL was progressively higher than for HL with increasing HIV-VL category. Lower current CD4 cell count had a strong but similar association with both NHL and HL. Conclusions: CD4 depletion increased risk of both types of lymphomas while current and accumulated HIV-VL was associated with NHL only. This suggests that NHL development is related to both CD4 cell depletion and added immune dysfunction derived from ongoing HIV replication. This latter factor was not associated with HL risk.

Original language	English
Journal	Journal of the National Cancer Institute
Volume	110
Issue number	6
Pages (from-to)	598-607
ISSN	0027-8874
DOIs	https://doi.org/10.1093/jnci/djx249
Publication status	Published - 1 Jun 2018

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Shepherd, L., Ryom, L., Law, M., Hatleberg, C. I., de Wit, S., Monforte, A. DA., Battegay, M., Phillips, A., Bonnet, F., Reiss, P., Pradier, C., Grulich, A., Sabin, C., Lundgren, J., & Mocroft, A. (2018). Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma. Journal of the National Cancer Institute, 110(6), 598-607. https://doi.org/10.1093/jnci/djx249

Shepherd, L, Ryom, L, Law, M, Hatleberg, CI, de Wit, S, Monforte, ADA, Battegay, M, Phillips, A, Bonnet, F, Reiss, P, Pradier, C, Grulich, A, Sabin, C, Lundgren, J & Mocroft, A 2018, 'Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma', Journal of the National Cancer Institute, vol. 110, no. 6, pp. 598-607. https://doi.org/10.1093/jnci/djx249

@article{cded294b4f3d46ff9023930329d21794,

title = "Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma",

abstract = "Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Methods: Data from the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different associations with NHL and HL were identified using marginal Cox models. All statistical tests were two-sided. Results: Among 41 420 people followed for 337 020 person-years, 392 developed NHL (incidence rate ¼ 1.17/1000 person-years of follow-up [PYFU], 95% confidence interval [CI] ¼ 1.06 to 1.30) and 149 developed HL (incidence rate ¼ 0.44/1000 PYFU, 95% CI ¼ 0.38 to 0.52). Higher risk of both NHL and HL was associated with lower current CD4 cell count (adjusted HR [aHR] of NHL for CD4 <100 vs > 599 cells/mm3 ¼ 8.08, 95% CI ¼ 5.63 to 11.61; HL ¼ 4.58, 95% CI ¼ 2.22 to 9.45), whereas higher current HIV viral load (aHR of NHL for HIV-VL >1000 vs < 50 copies/mL ¼ 1.97, 95% CI ¼ 1.50 to 2.59) and higher AUC of HIV-VL (aHR of NHL for highest vs lowest quintile ¼ 2.91, 95% CI ¼ 1.92 to 4.41) were associated with NHL only. Both current and AUC of HIV-VL were factors that had different associations with NHL and HL, where the hazard ratio for NHL was progressively higher than for HL with increasing HIV-VL category. Lower current CD4 cell count had a strong but similar association with both NHL and HL. Conclusions: CD4 depletion increased risk of both types of lymphomas while current and accumulated HIV-VL was associated with NHL only. This suggests that NHL development is related to both CD4 cell depletion and added immune dysfunction derived from ongoing HIV replication. This latter factor was not associated with HL risk.",

author = "Leah Shepherd and Lene Ryom and Matthew Law and Hatleberg, {Camilla Ingrid} and {de Wit}, Stephane and Monforte, {Antonella d'Arminio} and Manuel Battegay and Andrew Phillips and Fabrice Bonnet and Peter Reiss and Christian Pradier and Andrew Grulich and Caroline Sabin and Jens Lundgren and Amanda Mocroft",

year = "2018",

month = jun,

day = "1",

doi = "10.1093/jnci/djx249",

language = "English",

volume = "110",

pages = "598--607",

journal = "National Cancer Institute. Journal (Print)",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "6",

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TY - JOUR

T1 - Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma

AU - Shepherd, Leah

AU - Ryom, Lene

AU - Law, Matthew

AU - Hatleberg, Camilla Ingrid

AU - de Wit, Stephane

AU - Monforte, Antonella d'Arminio

AU - Battegay, Manuel

AU - Phillips, Andrew

AU - Bonnet, Fabrice

AU - Reiss, Peter

AU - Pradier, Christian

AU - Grulich, Andrew

AU - Sabin, Caroline

AU - Lundgren, Jens

AU - Mocroft, Amanda

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Methods: Data from the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different associations with NHL and HL were identified using marginal Cox models. All statistical tests were two-sided. Results: Among 41 420 people followed for 337 020 person-years, 392 developed NHL (incidence rate ¼ 1.17/1000 person-years of follow-up [PYFU], 95% confidence interval [CI] ¼ 1.06 to 1.30) and 149 developed HL (incidence rate ¼ 0.44/1000 PYFU, 95% CI ¼ 0.38 to 0.52). Higher risk of both NHL and HL was associated with lower current CD4 cell count (adjusted HR [aHR] of NHL for CD4 <100 vs > 599 cells/mm3 ¼ 8.08, 95% CI ¼ 5.63 to 11.61; HL ¼ 4.58, 95% CI ¼ 2.22 to 9.45), whereas higher current HIV viral load (aHR of NHL for HIV-VL >1000 vs < 50 copies/mL ¼ 1.97, 95% CI ¼ 1.50 to 2.59) and higher AUC of HIV-VL (aHR of NHL for highest vs lowest quintile ¼ 2.91, 95% CI ¼ 1.92 to 4.41) were associated with NHL only. Both current and AUC of HIV-VL were factors that had different associations with NHL and HL, where the hazard ratio for NHL was progressively higher than for HL with increasing HIV-VL category. Lower current CD4 cell count had a strong but similar association with both NHL and HL. Conclusions: CD4 depletion increased risk of both types of lymphomas while current and accumulated HIV-VL was associated with NHL only. This suggests that NHL development is related to both CD4 cell depletion and added immune dysfunction derived from ongoing HIV replication. This latter factor was not associated with HL risk.

AB - Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Methods: Data from the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different associations with NHL and HL were identified using marginal Cox models. All statistical tests were two-sided. Results: Among 41 420 people followed for 337 020 person-years, 392 developed NHL (incidence rate ¼ 1.17/1000 person-years of follow-up [PYFU], 95% confidence interval [CI] ¼ 1.06 to 1.30) and 149 developed HL (incidence rate ¼ 0.44/1000 PYFU, 95% CI ¼ 0.38 to 0.52). Higher risk of both NHL and HL was associated with lower current CD4 cell count (adjusted HR [aHR] of NHL for CD4 <100 vs > 599 cells/mm3 ¼ 8.08, 95% CI ¼ 5.63 to 11.61; HL ¼ 4.58, 95% CI ¼ 2.22 to 9.45), whereas higher current HIV viral load (aHR of NHL for HIV-VL >1000 vs < 50 copies/mL ¼ 1.97, 95% CI ¼ 1.50 to 2.59) and higher AUC of HIV-VL (aHR of NHL for highest vs lowest quintile ¼ 2.91, 95% CI ¼ 1.92 to 4.41) were associated with NHL only. Both current and AUC of HIV-VL were factors that had different associations with NHL and HL, where the hazard ratio for NHL was progressively higher than for HL with increasing HIV-VL category. Lower current CD4 cell count had a strong but similar association with both NHL and HL. Conclusions: CD4 depletion increased risk of both types of lymphomas while current and accumulated HIV-VL was associated with NHL only. This suggests that NHL development is related to both CD4 cell depletion and added immune dysfunction derived from ongoing HIV replication. This latter factor was not associated with HL risk.

U2 - 10.1093/jnci/djx249

DO - 10.1093/jnci/djx249

M3 - Journal article

C2 - 29267895

SN - 0027-8874

VL - 110

SP - 598

EP - 607

JO - National Cancer Institute. Journal (Print)

JF - National Cancer Institute. Journal (Print)

IS - 6

ER -

Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma

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