(P9) Clinical presentation, treatment, and outcome of HIV-associated hematologic malignancies in people living with HIV

Författare/Medförfattare

Oscar Kieri [1], Gaetano Marrone [1], Anders Sönnerborg [1, 2], Piotr Nowak [1,2,3]

Affiliates

[1] Department of Infectious Diseases, Karolinska University Hospital/Division of Infectious diseases, Department of Medicine Huddinge, Karolinska Institute; [2] Division of Clinical Microbiology, Department of Laboratory Medicine ANA Futura Laboratory, Karolinska Institute; [3] The Laboratory for Molecular Infection Medicine Sweden MIMS, Umeå University.

Abstract

Background
People living with HIV (PLHIV) have an increased risk of developing hematologic malignancies, in particularly non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Despite a decline observed since the introduction of effective combined antiretroviral therapy (ART), which allows HIV control and preserved CD4+ cell counts, the risk is still increased. HIV and the development of hematologic malignancies in the era of ART in Sweden needs therefore further characterization.

Methods
We performed a retrospective study of PLHIV receiving care at the Department of Infectious Diseases, Karolinska University Hospital, between January 1, 2004 and December 31, 2018. PLHIV diagnosed with hematologic malignancies were identified and data was collected linking the InfCareHIV database with the medical records (TakeCare).

Results
During the observation period, 3,484 patients received HIV care for a total of 22,903 person-years. Hematologic malignancies were identified in 43 patients (31 males, 12 females) consisting of 30 cases of NHL (70%), nine cases of HL (21%), two cases of multicentric Castleman’s disease (MCD) and one case each of myeloma and myelodysplastic syndrome (MDS). The NHL cases consisted of 12 diffuse large b-cell lymphoma (DLBCL), 12 unspecified NHL, 4 Burkitt’s lymphoma (BL) and 2 Primary CNS-lymphoma (PCNSL). The incidence rate of lymphoma was 172 per 100 000 person-years. In the early period, 2004 – 2010, the incidence rate was significantly higher compared to the late period, 2011 – 2018 (284 versus 113 per 100 000 person-years; p=0.006).
The patients were followed for a median of 7,6 years (IQR 3,1 – 9,3). Median time from HIV diagnosis to malignancy was 2,8 years (IQR 0,1 – 12,9) and was significantly shorter in patients developing NHL compared to HL (1,2 vs 8,9 years; p=0.01). As many as 14 patients with hematologic malignancies (33%) were diagnosed within 6 months of HIV diagnosis and 12 of these had presented with symptoms leading to malignancy diagnosis prior to HIV diagnosis.
Nineteen patients (44%), were on effective ART (180 d prior to malignancy) with undetectable viral load, significantly more often in the HL group compared to NHL (89% vs 30%; p=0.005). Median CD4+ cell count at malignancy was 190 cells/l and a majority (86%) had a nadir CD4+ cell count <200 cell/l.
Majority of patients (79%) received chemotherapy. The overall survival was 58% (25 / 43) and 18 patients died during the study time. Median time from malignancy to death was 0,4 years (IQR 0-1,4). The five year-survival rate of lymphoma was 55% (16 / 29). Autologous hematopoietic stem-cell transplantation was conducted in three patients, resulting in complete remission in two cases.

Conclusion
The incidence rate of lymphoma in the era of combined ART is still elevated in PLHIV as compared to the general population in Sweden (incidence rate of lymphoma in Sweden, 2004 – 2017, 21 per 100 000 person-years, Socialstyrelsen). Moreover, the lymphoma five-year survival rate was poorer as compared to survival rate of the general population in Sweden (74% five-year survival rate in Sweden, 2007 – 2016, Socialstyrelsen; p=0,03). As a great proportion of hematologic malignancies was found close to HIV diagnosis and associated with low nadir CD4 counts, efforts for earlier identification of HIV infected individuals is likely to affect the incidence. However, even patients with effective ART have an increased risk of developing hematologic malignancies e.g. Hodgkin’s lymphoma as found in our study.

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