DISCUSSION
Non-Hodgkin lymphoma is a heterogenous disease that has been reported to
be consistently increasing in many parts of the world. Amongst the NHL,
DLBCL is one of the most frequent types of aggressive NHL that accounts
for 41% of the newly diagnosed adult NHL in Asia (14, 16). Although CR
was achievable in 60% to 80% of patients, the durable remission was
only seen in 35-45% of patients (17, 18). With AHSCT, the OS has
improved, especially in RR-NHL (5, 8, 19, 20). AHSCT is now widely used
as standard therapy in relapsed NHL (8) and most guidelines recommended
it as consolidation following salvage chemotherapy (9, 21).
Several studies have reported good outcomes following HDT-ASHCT (20,
22). In this study, the three-year OS and EFS of 70.7% and 62.1%
respectively is comparable to that of other centres worldwide, where the
OS rate ranges from 68-74%, and the progression-free survival rate of
60-69% (5, 19). The low transplant-related mortality of AHSCT, which is
comparable to other centres (16, 26), implied that supportive care in
our centres was non-inferior.
In this study, AHSCT at CR expectedly yielded better OS and EFS when
compared to those who were transplanted in PR and is consistent with
other studies (23, 24). Patients who were transplanted in CR1 appeared
to have better OS and EFS and this is especially evident in high-risk
patients who were transplanted in CR1. Our findings were consistent to
what was reported by Caballero et al. (2003), Nakaya et al. (2017), and
Zhao et al. (2017). Similarly, a study by Kansai Medical University
Hospital showed that upfront AHSCT provided better outcomes compared to
those who did not undergo ASHCT (16), and this is further supported by a
meta-analysis which found that high risk patients may benefit from
upfront AHSCT (4). However, appropriate timing in transplantation
remains debatable. Its role in the upfront setting remains
controversial.
IPI scoring had been used as a clinical tool for risk stratification of
patients with DLBCL and is considered valuable as a prognosis indicator
in aggressive lymphoma (1, 28, 29).Through the revised IPI score,
patients with high-risk IPI with DLBCL continue to have sub-optimal
outcomes with a predicted five-year survival of 50–55% (3). Accurate
molecular classification is extremely important for precision medicine
in malignant lymphomas. Increasing, molecular and genotyping cell of
origin (COO) are methods being used but limited as needs cost for
Next-Generation Sequencing (NGS). In the early 2000, a study
demonstrated that DLBCL could be differentiated based on gene expression
profiling methods (GEP) into distinct molecular subtypes through their
cell of origin (COO) (33), coupled with many other studies confirming
the prognostic significance for molecular subtyping of COO subtypes of
ABC DLBCLs having a poorer PFS (1,33 – 36) . In this study, IPI was not
found to be predictive and this may be due to the relatively small
number of DLBCL in this cohort, with a significant proportion of
lymphomas were not classifiable. This raised the issue of the importance
of the mutation profiling besides the possible downfall when using the
clinical prognostic score alone in malignant lymphomas.
The limitations of this study are the sample size is relatively small
and there is a relatively significant proportion of lymphoma were not
classified according to the new WHO classification. The follow up period
is also relatively short.
Despite these limitations, our study illustrates the outcomes of HDT and
AHSCT in NHL patients in a resource limited country with a comparable
TRM. Due to the higher incidence of aggressive lymphoma in Asian
population, there is a need for Asian countries to construct multicentre
databases to spur the kind of research demonstrated in developed
countries, to find the most feasible treatment modalities such as
upfront AHSCT which may be a cost-effective strategy to reduce the risk
of relapse. Moving forward, we recommend larger studies in randomized
and selected cohort with longer duration of follow up to be conducted to
validate our findings.