Lymphoma is potentially curable with chemotherapy. Even for late-stage aggressive NHL long-term remissions can be obtained with chemotherapy; however, the cure rate is less than 50% for this group of patients. Late-stage indolent NHL is a challenging disease with no potential for cure.

The concept of using autologous bone-marrow or peripheral blood stem-cell transplantation (autoSCT) in NHL is to reduce tumour burden and obtain cures with high doses of chemotherapy. After high-dose chemotherapy re-infusion of bone marrow or peripheral blood stem cells collected before chemotherapy will enable recovery of normal marrow function. The mortality is less than 1% with current technology and supportive care. Cost-analysis study has shown that this treatment is as cost effective as salvage courses of conventional chemotherapy for NHL. Patients with Hodgkin's disease who go into relapse after first-line chemotherapy and then enter remission after salvage chemotherapy may obtain a significant survival benefit with autoSCT. Similarly relapsed aggressive NHL that are sensitive to chemotherapy may also benefit from autoSCT.

Allogeneic blood stem cells (from siblings or unrelated donors) can be used to treat lymphomas as well. The advantage of allogeneic blood stem-cell transplantation (alloSCT) include a stem-cell source free of tumour, and donor white cells with potential anticancer effect. The disadvantage is higher treatment-related morbidity and mortality from infections and graft-versus-host disease, resulting in alloSCT being limited to younger patients. Many studies of conventional alloSCT for NHL and Hodgkin's disease report mortality rates of over 40%.

A more tolerable alloSCT-conditioning regimen allowing for engraftment of allogeneic donor stem cells with less intensive chemotherapy and immunosuppressive therapy is known as reduced-intensity blood-stem-cell transplant (RIST) or non-myeloablative blood-stem-cell transplantation (NMBSCT). RIST has enabled older patients to be treated. It also provides a platform for further treatment with lymphocytes of the donor, called donor- lymphocyte infusion, to further enhance a graft-versus-lymphoma (GVL) effect. Circumstantial evidence for a GVL phenomenon includes the fact that patients with chemotherapy-resistant disease may still obtain a complete remission with RIST. Response frequently occurs months after the initial treatment, coinciding with near-complete donor-cell repopulation of the marrow or the development of graft-versus-host disease. Reported mortality rates were initially up to 30% but has now improved to less than 5%.

In a meta-analysis of 40 published RIST studies including 368 patients who are elderly and heavily pre-treated, over 66% responses were found, with most of the cases in complete remission. These patients included those who had no longer responded to chemotherapy or had relapsed after autoSCT. Among the patients who had complete remission were some who were also in complete molecular remission, which suggested a possible cure.

RIST is still a new treatment and randomised controlled clinical trials will be required to validate its efficacy. However, the higher response rates and lasting remissions seem promising. Blood-stem-cell transplantation will continue to improve and evolve, potentially forming a platform for more streamlined biological therapies.

Dr Toh Han Chong
Consultant
Medical Oncology