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Haematological Malignancies
Capturing Alloreactivity in Multiple Myeloma
Gordon Cook
Director, Blood and Marrow Transplantation Programme, Leeds Teaching Hospitals Trust, and
Consultant Haematologist and Honorary Senior Lecturer, University of Leeds
Abstract
Allogeneic stem cell transplantation (alloSCT) has been utilised in the management of both malignant and non-malignant haematological
disorders for several decades and has established its role in producing long-term remissions. In the context of multiple myeloma (MM),
compared with conventional therapies alloSCT induces the highest rate of remissions, resulting in long-term disease-free survival in over
30% of patients. However, it is associated with the highest rate of treatment-related mortality of all the interventions for MM. Following the
introduction of new biological agents for the management of MM, the question of what role alloSCT has in MM is raised. This article aims
to review where we are with alloSCT in MM, drawing from our experience thus far to plan the future role of alloSCT if we are to capitalise
on a potential donor antimyeloma immune therapeutic effect.
Keywords
Allogeneic stem cell transplantation, multiple myeloma, adoptive immunotherapy, immunomodulatory agents
Disclosure: The author has no conficts of interest to declare.
Received: 27 March 2009 Accepted: 23 June 2009
Correspondence: Gordon Cook, Director, Blood and Marrow Transplantation, St James’s Institute of Oncology, Bexley Wing, St James’s University Hospital, Leeds,
LS9 7TF, UK. E: Gordon.Cook@leedsth.nhs.uk
Allogeneic stem cell transplantation (alloSCT) has been utilised in while maintaining acceptable toxicity and extending the spectrum of
the management of leukaemia for several decades and has patients with MM who would and could benefit from alloSCT.
established its role in producing long-term remission. In the context
of multiple myeloma (MM), alloSCT induces the highest rate of The survival of patients with MM ranges from a few weeks to >20
remissions, including molecular remission, resulting in long-term years, but there is good evidence that the median survival of patients
disease-free survival (DFS) in <30% of patients.
1–3
However, has increased over the last decade
9
to between three and four years.
it is associated with the highest rate of treatment-related This improvement is probably due to improvements in supportive
mortality (TRM) of all of the interventions for MM, resulting from care, the introduction of novel therapies and the increased use of
conditioning-related end-organ damage and the unwanted high-dose therapy, which has made decision-making for younger
immunological toxicity of graft-versus-host disease (GvHD), in patients with a human leukocyte antigen (HLA)-matched sibling
addition to immune-suppression-related opportunistic infection.
4
donor even more difficult. MM has a median age at presentation of
approximately 70 years and only 15% of patients are <60 years of
The effectiveness of alloSCT results from the combination of age, with the result that only a minority of patients are eligible for
high-dose chemotherapy and the adoptive transfer of immune- consideration for alloSCT, even when reduced-intensity conditioning
competent donor immune-effector cells (graft-versus-myeloma [GvM] (RIC) alloSCT is included. Myeloablative alloSCT is associated with a
effect). The former aims to cytoreduce and is combined with high TRM, most likely due to a combination of factors, including
autologous stem-cell rescue as first-line therapy in suitably fit advanced age of patients, myeloma-related organ damage
patients;
5,6
however, all patients ultimately relapse. The GvM (particularly renal impairment), disease-associated immune
immunological effect is best demonstrated by the use of donor dysfunction and infection risk with the effects of previous treatment.
lymphocyte infusions (DLIs) to re-induce disease responses following Analysis of prognostic factors is essential to compare outcomes
relapse post-alloSCT. Although less potent than that seen with chronic within and between clinical trials and, in particular, to assess whether
myeloid leukaemia, it significantly contributes to the DFS effect noted certain treatments, such as alloSCT or ‘new agents’, can overcome
with alloSCT in MM.
7,8
The published evidence surrounding these two the effect of prognostic factors that would be associated with a poor
main factors in alloSCT for MM suggests that they are not mutually outcome with conventional therapy. The International Staging System
exclusive in their contribution to long-term DFS in MM, although the (ISS) is considered the standard prognostic model and identifies
relevant contribution of each to this effect remains to be clarified. three risk categories based on levels of β
2
-microglobulin and
There is evidence that both the method and degree of cytoreduction albumin.
10
Cytogenetic and molecular genetic abnormalities have
and the GvM effect contribute to long-term DFS in MM. As such, the also been shown to be useful predictors of outcome, with the
challenge for transplant physicians is how to harness the GvM effect presence of chromosome 13 deletion – t(4;14), t(14;16), t(14;20) – and
© TOUCH BRIEFINGS 2009 61
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