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Autologous Transplantation in Relapsed or
Refractory Hodgkin’s Lymphoma – The Challenges
Professor of Haematology, Hôpital Saint Louis, Paris
Abstract Failure to initiate treatment remains a challenge in Hodgkin’s lymphoma (HL). For years, chemotherapy and stem cell transplantation
salvaged less than half of relapses. Nowadays, positron emission tomography can predict the outcome under treatment. Two targeted
agents are dramatically improving therapy, alone or in association with chemotherapy or stem cell transplantation. Brentuximab vedotin
is an immunoconjugate anti-CD30 and anti-programmed death 1 nivolumab induces blockade of immune checkpoint. How to use them
are discussed in the context of relapses/refractory HL.
Keywords Hodgkin’s lymphoma, brentuximab, nivolumab, PET scan
Disclosure: Christian Gisselbrecht has no disclosures in relation to this article. No funding was received for the publication of this article.
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation
and reproduction provided the original author(s) and source are given appropriate credit.
Received: 24 August 2015 Published Online: 16 November 2015 Citation: European Oncology & Haematology, 2015;11(2):121–2
Correspondence: Christian Gisselbrecht, Professor of Haematology, Hôpital Saint Louis, Paris 75010, France. E: firstname.lastname@example.org
Approximately 10 % of patients with localised Hodgkin’s lymphoma (HL)
and 20 % with disseminated HL fail to respond to or relapse after a
The standard of care indicated by a randomised study 1 is salvage
chemotherapy followed by consolidation with autologous stem cell
transplant (ASCT). Salvage chemotherapy followed by ASCT induces
long-term remission in ~50 % of patients. 2 However, there is a limited
impact on survival. 1,3 The increase in the cumulative incidence of
second malignancies in the transplanted patients compared with
conventionally treated HL patients is still a major issue. 4 The main point
is to achieve a major response with complete remission (CR) prior
to transplantation, because a suboptimal response to pretransplant
salvage chemotherapy is the major determinant of ASCT failure. 5 The
introduction of the pretransplantation positron emission tomography
(PET) scan has changed the paradigm of treatment. Standardisation of
criteria of responses with PET scan was based on the Deauville criteria
or the Five-Point Scale 6. In a series of 111 consecutive patients, a
5-year progression-free survival (PFS) of 23 % and 79 % (p<0.001)
and a 5-year overall survival (OS) of 55 % and 90 % (p=0.001) were
documented in patients with or without 18-Fluoro-deoxyglucose (FDG)-
avid lymphoma lesions at ASCT, respectively. 7
Patients with a positive PET after a second-line salvage therapy have a
worse event-free survival (EFS) and require new approaches.
The European intergroup study Hodgkin disease relapse 2 (HDR2)
showed that adding sequential high-dose chemotherapy after salvage
chemotherapy and before ASCT does not improve a prognosis and is
associated with additional adverse effects. 8
Tou ch MEd ica l MEdia
Transplantation Strategy –
Auto or Allo or Tandem?
A single ASCT is appropriate for intermediate-risk patients. Various
conditioning regimens have been used as chemotherapy prior to
ASCT. However, there have been no prospective comparison trials.
BEAM (carmustine, etoposide, cytarabine and melphalan) has been
one of the most popular regimens since its introduction in the 1980s.
More data regarding newer regimens, including active agents such as
bendamustine, busulfan and fotemustine, are required.
To improve the outcomes of patients with high-risk disease,
tandem transplantation could be proposed provided they display
chemosensitivity and that there is no progression between the two
transplants. The LYmphoma Study Association (LYSA) reported a
prospective multicentre trial that evaluated a risk-adapted salvage
treatment without a PET scan with a single or tandem ASCT for 245
relapse or refractory patients. 9
Of the poor-risk patients, 105 (70 %) received a tandem ASCT, whereas
92 intermediate-risk patients (97 %) received a single ASCT. The
5-year PFS and OS estimates were 73 % and 85 %, respectively, for
the intermediate-risk group and 46 % and 57 %, respectively, for the
poor-risk group. The outcomes for the primary refractory and poor-risk/
relapsed HL groups were similar.
As improvements in OS after an allogeneic haematopoietic cell
transplantation (allo-SCT) has been reported (following the introduction
of reduced intensity conditioning [RIC] regimens, improvements in
human leukocyte antigen [HLA] typing, and more careful patient
selection), this strategy was also tested in HL. A large, prospective