Treatment strategies for Hodgkin lymphoma recurring following autologous hematopoietic stem cell transplantation

Erin-Siobhain R. Currin; Ajay K. Gopal

doi:10.5045/kjh.2012.47.1.8

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Korean J Hematol 2012; 47(1):

Published online March 31, 2012

https://doi.org/10.5045/kjh.2012.47.1.8

Treatment strategies for Hodgkin lymphoma recurring following autologous hematopoietic stem cell transplantation

Erin-Siobhain R. Currin¹, and Ajay K. Gopal^2*

Author Info. +

¹Department of Internal Medicine, University of Washington School of Medicine, Seattle, WA, USA.

²Division of Medical Oncology, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Correspondence to : Correspondence to Ajay K. Gopal, M.D. Division of Medical Oncology, University of Washington, Fred Hutchinson Cancer Research Center Seattle Cancer Care Alliance, Mailstop G3-200, 825 Eastlake Ave E, Seattle, WA 98109, USA. Tel: +1-206-288-2035, Fax: +1-206-288-1130, agopal@u.washington.edu

Received: March 3, 2012; Accepted: March 20, 2012

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Hodgkin lymphoma (HL) represents one of the great success stories in hematology going from a uniformly fatal disease, to one that is curable in the vast majority of cases. Despite this success, some patients experience relapse. To address this unmet need a variety of agents, classes of drugs, and strategies have demonstrated activity in HL recurring after autologous hematopoietic stem cell transplantation. These include chemotherapeutics (gemcitabine-based combinations, bendamustine), histone deacetylase (HDAC) inhibitors (panobinostat), immunomodulatory agents (lenalidomide), mTOR inhiobitors (everolimus), monoclonal antibodies (rituximab), and antibody-drug conjugates (brentuximab vedotin) as well the potential of long-term disease control via allogeneic transplantation. Such advances reflect our increased understanding of the biology of HL and hold promise for continued improved outcomes for those suffering with this condition.

Keywords Hodgkin lymphoma, Antibody drug conjugates, allogeneic transplant, HDAC inhibitor, IMID, mTOR

Article

Review Article

Korean J Hematol 2012; 47(1): 8-16

Published online March 31, 2012 https://doi.org/10.5045/kjh.2012.47.1.8

Treatment strategies for Hodgkin lymphoma recurring following autologous hematopoietic stem cell transplantation

Erin-Siobhain R. Currin¹, and Ajay K. Gopal^2*

¹Department of Internal Medicine, University of Washington School of Medicine, Seattle, WA, USA.

²Division of Medical Oncology, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Correspondence to: Correspondence to Ajay K. Gopal, M.D. Division of Medical Oncology, University of Washington, Fred Hutchinson Cancer Research Center Seattle Cancer Care Alliance, Mailstop G3-200, 825 Eastlake Ave E, Seattle, WA 98109, USA. Tel: +1-206-288-2035, Fax: +1-206-288-1130, agopal@u.washington.edu

Received: March 3, 2012; Accepted: March 20, 2012

Abstract

Keywords: Hodgkin lymphoma, Antibody drug conjugates, allogeneic transplant, HDAC inhibitor, IMID, mTOR

Abstract

Fig 1.

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Figure 1.

Proposed Mechanism of Action of Brentuximab Vedotin Antibody Drug Conjugate (ADC). Depiction of CD30 ligation by ADC followed by CD30-ADC internalization, lysosomal cleavage of linker and intracellular release of anti-tubulin agent MMAE leading to cell cycle arrest and apoptosis. Abbreviation: RS, Reed-Sternberg.

Blood Research 2012; 47: 8-16https://doi.org/10.5045/kjh.2012.47.1.8

Table 1 . Selected traditional chemotherapeutic regimens for relapsed Hodgkin lymphoma..

^a)Excluding auto-HCT..

Abbreviations: No., number; ORR, overall response rate; CR, complete response; auto-HCT, autologous stem cell transplant; NMT, non-myeloablative stem cell transplant; GVD, gemcitabine, vinorelbine and pegylated liposomal doxorubicin; GDP, gemcitabine, dexamethasone and cisplatin; GCD, gemcitabine, carboplatin, and dexamethasone; ABVD, adriamycin, bleomycin, vinblastine, dacarbazine; --, data not available..

Table 2 . Selected biologic agents and small molecules for relapsed Hodgkin lymphoma..

^a)Excluding auto-HCT.

Abbreviations: No., number; ORR, overall response rate; CR, complete response; allo, allogeneic; auto-HCT, autologous stem cell transplant..

Table 3 . Selected series of reduced intensity allogeneic transplant for relapsed Hodgkin lymphoma..

^a)Excluding auto-HCT, ^b)Included regimens under RIC definition: carmustine 300 mg/m² IV, etoposide 600-800 mg/m² IV, cytarabine 800-1,600 mg/m² IV, melphalan 100-140 mg/m² IV (BEAM regimen); Flu plus 2-4 Gy TBI or 1-2 low dose alkylating agents..

Abbreviations: RIC, reduced intensity chemotherapy; No., number; Ref., refractory; NRM, non-relapse mortality; PFS, progression free survival; OS, overall survival; yrs, years; NMT, nonmyeloablative therapy; TBI, total body irradiation; mos, months; MUD, matched unrelated donor; MMUD, mis-matched unrelated donor; MRD, matched related donor; MMRD, mis-matched related donor; HLA haplo, HLA haploidentical donor; Flu, fludarabine; Cy, cyclophosphamide; ATG, antithymocyte globulin; Flu-M, fludarabine-melphalan..