Incidence, Predictors, and Significance of Severe Toxicity in Patients with HIV-Associated Hodgkin Lymphoma
Bibliographic record
Abstract
Abstract Hodgkin lymphoma (HL) occurs in HIV-infected individuals more frequently than in the HIV-negative population and the incidence is rising. Patients (pts) with non-Hodgkin’s lymphoma in HIV appear to have improved outcomes if they receive HAART with chemotherapy (CT). ABVD is standard CT for HL and is frequently administered with HAART in pts with HIV-HL. However, some components of the ABVD regimen may interact with antiretroviral (ARV) medications to alter metabolism and increase toxicity. In particular, vinblastine (VBL) is metabolized by CYP3A4 and protease inhibitors, particularly ritonavir (RTV), appear to inhibit this cytochrome potentially leading to higher VBL exposure. Little definitive information is available regarding how interactions might affect clinical outcome. We conducted a retrospective review of 36 pts with HIV-related HL to identify the frequency of neurotoxicity (NT), hematologic toxicity (HT), and lung toxicity (LT), to identify risk factors for severe (grade III–IV) toxicity, and to determine its clinical significance. Clinical data were collected from the CFE database and by chart review from 3 centers. The median age at HL diagnosis (dx) was 41 (range 29–66) years and 34 (94%) were male. HL was advanced stage in 28 (78%). Hasenclever score could be calculated in 23 pts and was 0–4 and ≥5 in 15 and 8 pts respectively. ECOG PS was 0–1 in 13 and ≥2 in 8 (n=21). HIV risk factor was: sexual, n=21 and other, n=5 (n=26). Median CD4 count at HL dx was 210 (2–660) cells/ul (n=31). Median HIV viral load (VL) was undetectable (<50; range <50->500,000) copies/ml (n=25). Hepatitis B and C coinfection was present in 8 and 7 pts respectively (n=29). Prior AIDS was present in 23, all opportunistic infections. Twenty-four pts received HAART with CT. Primary HL CT was: ABVD, n=29 (81%); MOPP/ABV, n=4 (11%); palliative, n=3 (8%). G-CSF was used in 22 pts. All pts received prophylaxis for PCP and 3 for HSV/VZV. HAART included 17 Arts in numerous combinations. Infectious complications were: bacterial infection, n=6; febrile neutropenia, n=4; HSV, n=3; PCP, n=1. HT occurred in 21 (75%) of 28 assessable pts and was grade 3–4 in 18 (64%; 18 and 15 were on HAART, respectively). NT occurred in 14 (50%) pts and was grade 3–4 in 6 (21%; 13 and 5 on HAART respectively, n=28). Of 6 cases of severe NT, 3 were autonomic neuropathy with pseudobowel obstruction that in 1 pt resulted in perforation. Bleomycin LT occurred in 3 pts (n=26). CT dose reduction (DR) of ≥25% in ≥1 agent was required in 9 pts (n=26). Factors associated with grade 3–4 HT were: receiving RTV, p=0.04, HR 2.9 (95% CI 1.1–7.4); and receiving lopinovir (LPV), p=0.02, HR 7.0 (2.3–21.3) and for any HT were: RTV, p=0.004, HR 3.1 (1.3–7.3); emtricitabine, p=0.01, HR 4.8 (1.4–11.6); and LPV, p=0.04, HR 4.4 (1.6–12.1). Factors for grade 3–4 NT were: LPV, p=0.05, HR 10.8 (2.0–59.5) and for any NT was: RTV, p=0.01, HR 4.0 (1.3–12.1). Fourteen pts received RTV and of 8 receiving LPV, 7 received LPV with RTV (p=0.007). At a median follow-up of 15.3 (0.1–154.8) months (mo) 25 pts (69%) are alive. The median overall survival (OS) for all pts was 44.5 (2–154.8) mo and there was no difference in OS by baseline features or the occurrence of HT or NT. However, CT dose reduction was associated with inferior OS (p=0.04, HR 3.9 [1.0–15.7]); although only 1 of 9 deaths was from HL progression; others were: infectious, n=6; and unrelated, n=2. In conclusion, pts with HIV-HL appear to experience a significantly increased incidence of NT compared to rates reported in non-HIV HL pts. In contrast, rates of HT and LT appear to be similar to those in non-HIV HL. The use of RTV or LPV during CT appeared to be associated with an increased risk of NT, suggesting a clinically significant interaction between these ARV agents and CT, particularly VBL. Prospective studies to devise a rational dosing strategy using measurements of ARV and/or CT levels are warranted.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".