Autologous Hematopoietic Stem Cell Transplantation (AHCT) in Patients with Chemotherapy-Sensitive, Relapsed/Refractory (CSRR) Human Immunodeficiency Virus (HIV)-Associated Lymphoma (HAL): Results from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0803)/AIDS Malignancy Consortium (AMC-071) Trial
Authors: Alvarnas J , Le Rademacher J , Wang Y , Little Richard F. , Akpek G , Ayala E , Devine S , Kaplan L , Noy A , Popat U , Thompson J , Horowitz M H , Mendizabal A , Navarro W H. , Ambinder R ,   Blood and Marrow Transplant Clinical Trials Network (BMT CTN),   The AIDS Malignancy Consortium (AMC)
Published: October 2019

Background: HIV infection is associated with increased risk of non-Hodgkin (NHL) and Hodgkin lymphoma (HL). Historically HIV-infected patients had inferior outcomes and increased treatment-related morbidity and mortality over uninfected patients. Highly active antiretroviral therapy (HAART) improved the prognosis for patients with HAL and permitted treatment identical to that in uninfected patients. The role of AHCT in HIV-infected patients, however, remains under investigation. This BMT CTN 0803/ AMC-071 trial, sponsored by the National Heart, Lung and Blood Institute and National Cancer Institute, was designed to prospectively assess overall survival (OS) after AHCT in patients with CSRR HAL.

Methods : Patients with treatable HIV-1 infection, age > 15 years, adequate organ function and CSRR aggressive NHL or HL were included. Mobilization and collection followed institutional guidelines. Patients underwent AHCT using the BEAM regimen [carmustine 300 mg/m2 (day -6), etoposide 100 mg/m2 twice daily (days -5 to -2), cytarabine 100 mg/m2 (days -5 to -2), melphalan 140 mg/m2 (day -1)]. Patients received AHCT on day 0 and standard supportive care through discharge. HAART was withheld during the preparative regimen and until therapy-related GI toxicity resolved. The primary trial objective was estimation of one-year OS. Secondary objectives included lymphoma response post-transplant, progression-free survival (PFS), transplant-related mortality (TRM), infection-related complications and recovery of hematological function (RHF) post-AHCT. RHF was defined as ANC > 1500/µl, untransfused hemoglobin > 10 gm/dL and platelet > 200,000/µl. Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Results : Between July 2010 and May 2013, 43 patients were enrolled; 3 progressed prior to AHCT and were excluded from analysis. Forty patients underwent AHCT (5 female, 35 male). Median age was 46.9 years (range, 22.5-62.2). Lymphoma subtypes included diffuse large B-cell lymphoma (40%), plasmablastic lymphoma (5%), Burkitt/Burkitt-like lymphoma (17.5%) and HL (37.5%). All patients received < 2 salvage regimens. Prior to transplant, 30 patients (75%) were in complete remission (CR), 8 (20%) were in partial remission (PR) and 2 (5%) had relapsed/progressive disease (RPD). Pre-HCT HIV viral load (VL) was undetectable in 31 patients (77.5%) and detectable in 9 (22.5%) with a median VL of 84 copies/mL (interquartile range [IQR], 58-234). Median CD4 count was 250.5/µL (range 39-797, IQR 175-307). All 40 patients completed BEAM and underwent HCT. At day 100 post-HCT, 39 patients were assessed for disease response (1 inevaluable due to early death): 36 (92.3%) were in CR, one (2.6%) in PR and two (5.1%) had RPD. By one-year post-HCT, 5 patients died (3 from recurrent/persistent disease, 1 from organ failure [cardiac arrest] and 1 from invasive fungal infection). Cumulative incidence of TRM was 5.2% (95% confidence interval [CI]: 0.9%-15.7%). With a median follow-up of 24 months post-AHCT, estimated probability of one-year OS was 86.6% (95% CI: 70.8%-94.2%) (Figure 1). By one-year, 5 patients relapsed post-HCT, 3 of whom subsequently died. The cumulative incidence of relapse/progression at one-year post-HCT was 12.5% (95% CI: 4.5%-24.8%). Estimated probability of one-year PFS was 82.3% (95% CI: 66.3%-91.1%) (Figure 2). Within one-year of HCT, 13 patients experienced grade 3 and 2 patients grade 4 toxicities (1 patient with mucositis and 1 patient with dyspnea/hypoxia/ cardiac arrhythmia/hypotension). Seventeen patients (42.5%) developed a total of 42 episodes of infection within one-year post-HCT, including 9 with an infection severity grade of severe. Median time to neutrophil engraftment (> 500/µl) was 11 days (range, 9-32).Median time to platelet transfusion-independent engraftment >20,000/µl was 18 days (range, 9-176); 1 patient died prior to platelet recovery. Eleven (28.9%) of 38 evaluable patients and 24 (75%) of 32 evaluable patients achieved RHF by 100 days and 1-year post-HCT, respectively.

Discussion : Patients with HAL may successfully undergo AHCT with favorable outcomes. AHCT should be considered the standard of care for patients with relapsed/refractory HAL who meet standard eligibility criteria.

Figure 1 Figure 1.

Figure 2 Figure 2.

Disclosures

No relevant conflicts of interest to declare.