The Lymphoma Working Party (LWP) of the European Bone Marrow Transplant (EBMT) and the lymphoma committee of the Center for International Blood and Bone Marrow Transplant Research (CIBMTR) collaborated on a study to assess long term outcomes of allogeneic hematopoietic stem cell transplantation (allo-HCT) in patients with follicular lymphoma (FL). The large retrospective analysis by Anna Sureda et al. was published in Cancer, on 9th Feb 2018.
The study included 1567 patients (median age = 51, range 21–74 years) with FL who had human leukocyte antigen (HLA)-identical sibling or HLA-matched unrelated donor allo-HCT between 2001–2011. The majority of patients had received HLA-matched sibling donor allo-HCT (n = 1148, 73%) compared to unrelated well-matched HLA donor allo-HCT (n = 419, 27%). The primary endpoints of the study included; overall survival (OS), progression-free survival (PFS), transplant-related mortality (TRM) and disease relapse and progression.
- Median follow-up was 55 months
- 5-year OS probability = 61% (95% CI, 59%–64%), P = 0.13
- 5-year PFS probability = 52% (95% CI, 49%–55%)
- 5-year TRM cumulative incidence = 29% (95% CI, 26%–31%)
- 5-year cumulative incidence of disease relapse/progression = 19% (95% CI, 17%–22%)
In the multivariate analysis, several factors were identified that had significant associations with patient outcomes. Factors that adversely affected OS and PFS included:
- Age at HCT = OS relative risk (RR) 03 (1.02-1.04) P > 0.0001
- Grade 3 histology = OS RR 44 (1.13-1.83) P = 0.003, PFS RR 1.42 (1.15-1.76) P = 0.001
- High number of lines of prior therapy ≥5 = OS RR 41 (1.77-3.30) P < 0.0001, PFS RR 1.93 (1.46-2.55) P < 0.0001
- Chemo-refractory disease = OS RR 59 (1.30-1.95) P < 0.0001, PFS RR 1.54 (1.28-1.86) P < 0.0001
- Low Karnofsky performance score (KPS) <80 = OS RR 23 (1.52-3.25) P < 0.0001, PFS RR 1.78 (1.23-2.58) P = 0.002
- Myeloablative conditioning (MAC) regimens = OS RR 42 (1.16-1.73) P = 0.0006, PFS RR 1.36 (1.14-1.63) P = 0.0008
Additionally, age, chemo-resistant disease, high number of prior lines of therapy, low KPS and MAC were significantly associated with TRM and chemo-resistant disease and grade 3 histology were more likely to adversely affect disease relapse and progression.
Grade 2-4 Graft versus Host Disease (GVHD) at day 100 = 20% (95% CI, 18–22%) and at year 1 = 45% (95% CI, 42–48%). The authors noted that GVHD incidence was higher in the CIBMTR group, which may have been due to a higher frequency of matched unrelated donors in this group.
The study authors then conducted a risk analysis giving a score of low, intermediate and high risk to the factors identified in the multivariate analysis. Hazard ratio (HR) for treatment failure was 1.72 (95% CI, 1.24–2.43) P = 0.0014 when comparing high risk with intermediate risk patients.
The authors noted a plateau in the relapse curve showing that there was good disease control in this group of patients. Limitations of the study included; no distinction between grade 3a and 3b histologies, exclusion of transformed histologies, and that pre-transplant therapies, post-allo-HCT maintenance treatments and chimerism kinetics on outcomes were not assessed. The authors concluded that their study was the largest of its kind and it demonstrated good long-term outcomes for allo-HCT treated relapsed FL patients. They recommended that unrelated donor allo-HCT should be started earlier on in disease treatment and to avoid MAC regimens as it was associated with poorer outcomes.