Background. Outcome of HIV-associated NHL (HIV-NHL) with adverse prognostic features is not satisfactory with standard therapy. High dose therapy (HDT) and autologous stem cell transplantation (ASCT) has proven safe and active in HIV-NHL in salvage setting.
Aims. To define the role of HDT and ASCT in the upfront treatment of HIV-NHL at high risk, in terms of efficacy and toxicity. We report the mature results of a multicenter prospective study including HDT and ASCT as consolidation after first-line treatment of HIV-NHL at high-risk.
Patients and methods. Inclusion criteria: untreated aggressive HIV-NHL (including DLBCL, plasmablastic, anaplastic lymphoma), aa-IPI 2-3, age 18-60, CD4+ count >50/mcl and availability of effective HAART.. Patients (pts) received R-CHOP (no Rituximab for CD20 negative lymphoma) for 6 cycles and, if responsive, underwent stem cells collection after Cyclophosphamide 4gr/ms + G-CSF followed by HDT with BEAM and ASCT. Involved-field radiotherapy on previous bulky or residual disease was recommended. Patients (pts) received HAART during the entire treatment program.
Results: From January 2007 to July 2014, 29 pts were registered and 25 entered the study. Median age was 48 years (range, 27-62). Nineteen pts had DLBCL, 5 plasmablastic, 1 anaplastic lymphoma. ECOG PS was >1 in 14 pts (56%); Ann-Arbor stage III/IV, 7(28%)/18(72%); B symptoms, 16 (64%); LDH >n.v., 18 (88%); aaIPI 2/3, 13 (52%)/12 (48%). Eighteen pts (72%) had a prior history of HIV-positivity, and 17 (68%) were on HAART at NHL diagnosis. In 7 pts HIV and NHL diagnosis were concomitant. Fourteen pts (56%) had detectable HIV-viremia (range 40->500.000 cp/mL). Median CD4+ count was 255/mcl (51-571). Ten pts (40%) had HCV infection. Twenty-two pts received (R)-CHOP-21 and 3 pts with plasmablastic histology received CHOP-14. One pt is on treatment and 24/25 are evaluable for (R)-CHOP response. One pt died of hepatic failure and 1 due to cerebral hemorrhage, 2 had prolonged cytopenia (plus severe hepatic toxicity in 1) and 1 infectious complications that lead to withdrawal from the trial [however 1 achieved a complete remission (CR) and 2 died of progressive disease]; 19 pts completed (R)-CHOP according to the study: 14 had CR, 4 partial remission (PR) and 1 disease progression (PD). On an intention to treat basis: ORR 79.2%, CR 62.5%, PR 16.7%. Seventeen/18 pts collected stem cells (median CD34+ cells 7.4 x 10e6/Kg, range 2.6-10.1) and 1 failed mobilization. Two pts had early disease progression after collection, 1 did not receive HDT because of cardiac ejection fraction <50% at evaluation before BEAM and 14 actually received ASCT according to the protocol. Lymphoma stage IV and aa-IPI 3 were significantly associated with the risk of not receiving ASCT (p.02 and p.03 respectively, Fisher exact test). HDT-related toxicities included 5 grade II, 5 grade III and I grade IV gastrointestinal toxicity and 2 grade II and 1 grade III hepatic toxicity. Prior to engraftment, 1 VZV infection, 1 Clostridium difficile colitis, 1 sigmoiditis, 1 CMV reactivation and 9 FUO were registered. There were no transplant-related deaths. One case of CMV reactivation, 1 bacterial pneumonia and no opportunistic infections were registered during subsequent observation. After a median f-up of 50 ms (2-89), 5-years OS and PFS of the entire series were 74.6% (+8.9%) and 70.9% (+9.2%), respectively (Figure 1). All transplanted pts (100%) are alive and relapse-free after a median of 38.5 ms (1-82) after transplant (Figure 2).
Conclusions: This is the first prospective trial addressing the role of HDT and ASCT in first line treatment of HIV-LNH. Almost 60% of pts were able to complete the entire treatment program and the ASCT was well tolerated. The OS in this series of pts at high risk is satisfactory and no relapse occurred in pts who received ASCT, after a prolonged follow-up. Further improvement could result from an increase in the rate of patients who receive ASCT. HDT with ASCT seems an effective way to consolidate first response and improve outcome in HIV-NHL at high risk .
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.