1. INTRODUCTION
Non-Hodgkin lymphoma (NHL) is a pathologically and prognostically
diverse group of hematological malignancies with variable clinical
outcomes. NHL accounted for approximately 80% of all lymphoid neoplasms
and in Malaysia, lymphoma is the sixth most common cancer and accounted
for about 4.3% of all cancers. Survival had improved significantly for
NHL in the past decades in many countries including Asian regions. Risk
stratification based on prognostic indices for each subtype of NHL is an
important tool which has been validated to predict outcomes (1). Diffuse
large B-cell lymphoma (DLBCL) is the most common form of aggressive
lymphoma (2), accounting for 30–40% of newly diagnosed NHL globally.
In patients with DLBCL, the international prognostic index (IPI), which
includes variables such as age, performance status (PS), lactate
dehydrogenase (LDH), number of extra-nodal involvement and staging is
used to prognosticate patients (1, 3).
Autologous hematopoietic stem cell transplantation (AHSCT) was first
used as frontline, consolidative treatment for aggressive NHL in the
early ‘90s (4). Subsequently, high dose therapy (HDT) followed by AHSCT
has been widely adopted for cases of relapsed or refractory NHL
(RR-NHL). In selected centres, upfront AHSCT has also been considered a
feasible form of management for poor risk patients (5, 6). Prior to
rituximab being introduced, many studies have demonstrated the role of
AHSCT in improving event-free survival (EFS) and overall survival (OS)
in patients who had RR-NHL (7, 8). One such trial, PARMA, has
established HDT-AHSCT as the standard of care for relapsed or refractory
DLBCL (RR-DLBCL). The trial demonstrated a significantly better
five-year EFS and OS for the AHSCT group compared to the salvage therapy
group(8). Hence, the role of HDT-AHSCT as a standard treatment in
RR-DLBCL was recommended by the US National Comprehensive Cancer Network
(NCCN) (9).
In pre-rituximab era, survival benefit was demonstrated with ASHCT in
patients who had achieved CR after salvage chemotherapy (8). Other
studies have reported that about a third of patients who achieved
partial remission (PR) also experienced better long-term EFS with ASHCT
when compared with chemotherapy alone (7, 10).
In the post Rituximab era, a registry study done recently in the United
States concluded there has been limited improvement in the survival of
adult patients with DLBCL beyond the introduction of rituximab (11). An
international retrospective multicohort non-Hodgkin lymphoma research
study (SCHOLAR-1) also demonstrated the poor outcomes in patients with
refractory DLBCL. These data are particularly important because it
represents a large cohort with refractory DLBCL, which supported the
need for more effective therapies (12). Novel agents such as
bendamustine and polatuzumab are used for aggressive and relapsed cases
in many developed countries, however these therapies are expensive and
not easily available to many resource-limited countries such as
Malaysia. Therefore, effective upfront therapy would likely benefit to
reduce relapse and become the mainstay treatment in RR-DLBCL especially
in a resource limited country.
Although evidence regarding the use of AHSCT in NHL are widely
available, data in resource limited countries within South East Asian
(SEA) region are lacking, despite incidence of aggressive lymphoma
subtypes such as T cell and DLBCL being higher in such populations
(13-15). This is especially pertinent when the novel agents for
treatment of relapsed refractory NHL are expensive and are not freely
accessible to many patients. Therefore, it is crucial that we have local
data to establish the effectiveness of AHSCT, which is relatively less
expensive when compared to novel agents, and to determine the possible
predictive factors which can translate to better outcome.