Infectious Complications and Mortality after Autologous Stem Cell Transplantation for Lymphomas: A Comparison Between HIV-Infected and HIV-Negative Patients
Authors: Churruca Juan , Bastos-Oreiro Mariana , Suárez González Julia , Martinez-Laperche Carolina , Balsalobre Pascual , Miralles Pilar , Berenguer Juan , Serrano David , Kwon Mi , Gayoso Jorge , Diez-Martin Jose Luis 
Published: October 2019

Abstract

Introduction: Lymphomas continue to be a leading cause of death in HIV-positive patients (HIV+ pts) in the cART era. The aim of this study was to review our 15-year single institution experience in performing Autologous Stem Cell Transplantation (ASCT) for HIV-infected and non-HIV patients with high-risk or relapsed lymphomas, focusing on infectious complications.
Patients and Methods: We retrospectively evaluated our cohort of 28 HIV+ pts who underwent an ASCT between 2000-2015, and compared it with a well-matched control group of 39 HIV-negative pts.
Patient and ASCT characteristics are described in Table 1. All HIV+ pts were on cART. Chemomobilization was used in 60% of the HIV cohort and 84% of the controls. BEAM conditioning regimen was the most common. All transplants were performed in the same tertiary hospital JACIE-accredited SCT unit.
The primary end points were first-year cumulative incidence (CI) of infection, total infectious episodes and infection-related mortality. For the analysis, we defined 3 different time frames: 1st Pre-engraftment; 2nd from engraftment to day +100 and 3rd from day +100 until 1 year after SCT. Events occurring during the first 2 periods were considered early infections as compared to late.
Results:
All patients received antiviral and anti-PJP prophylaxis, but a significantly higher proportion of HIV+ pts were given antibacterial and antifungal prophylaxis (2/3 vs 1/3 approximately, Table 1). G-CSF support was initiated in all HIV recipients and 66% of controls, and the median days of use was longer for the HIV group (7 vs 4 days, p= 0.04). Median time to neutrophil engraftment was similar in both groups (13 vs 11 days, p=0.55); 93% of HIV pts and all control pts reached ANC > 500c/uL by day +30.
Infectious episodes (IE) are described in Table 2, divided by pathogen subtype and time frame. Globally, all infection subtypes were more common in the HIV-infected cohort at some point.
The most significant findings from the analysis are as follows. CI of early global infections: HIV 75% vs non-HIV 25% (p= 0.04), Figure 1. Median number of global infectious events: HIV 65 vs non-HIV 39 (p= 0.002; OR 1.8 [1.2-2.8]). Bacteria: CI of pre-engraftment and early bacterial infections were not different among groups (42% vs 28%, p= 0.47), but the median number of bacterial episodes was clearly different: HIV 17 vs non-HIV 12 (p= 0.08; OR 2.16 [0.96-4.8]). Fungi: CI of early fungal infections: HIV 10.7% vs non-HIV 0% (p= 0.03); minor infections were not considered. Viruses: CI of early viral infections: HIV 46% vs non-HIV 15% (p= 0.004). Median nº of early viral IE: HIV 19 vs non-HIV 6 (p= 0.007; OR 4.16 [1.43-12]). CI of late viral infections: HIV 30% vs non-HIV 11.7% (p= 0.04). CMV reactivations were by far more common in the HIV cohort (p=0,01). HIV viral load bleeps were documented in 35% of the HIV patients (most commonly in the day +30 control) and one post-transplant virological failure was diagnosed, forcing HAART substitution.
Of note, 1st year CI of infection-related mortality was 14% in the HIV group vs 0% in the non-HIV group (p= 0.01), Figure 2. Three HIV+ pts suffered early fulminant septic episodes (1 E. coli + Enterococcus, 1 Rothiamucilaginosa, 1 non-clarified - possible Stenotrophomonasmaltophilia) and a 29-year old woman in CR after a 1st line for a stage IVsB Burkitt-like lymphoma died due to a severe influenza A pneumonia. Length of admission was also significantly longer for the HIV+ pts (median days 34 vs 28, p=0.041).
Regarding long-term outcome, median follow up as of July 2016 is 82 months for the HIV+ group and 70 months for the control group: 57% and 61% of the pts in each cohort are still alive, respectively. One HIV-infected pt and 3 controls have been lost to follow-up. EFS: 1 year 71.4% vs 81.9% (ns); 5 years: 63.9% vs 66.5% (ns). Overall Survival: 1 year 75% vs 84% (ns); 5 years 66.3% vs 74.6% (ns).
Conclusion: Autologous stem cell transplantation has been proven to be feasible and effective in HIV-related lymphomas, but in our experience and despite great advances in cART and virological control, HIV+ patients are at high risk of infection and this might influence post-ASCT short-term survival. It is mandatory to focus on prophylactic and supportive measures and to choose carefully the optimal timing for transplantation.
Table 2 Table 2.

Disclosures
No relevant conflicts of interest to declare.