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.