Standard therapy of advanced Hodgkin lymphoma

Kuruvilla, John

doi:10.1182/asheducation-2009.1.497

Cited by 65 publications

(49 citation statements)

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“…However, 2-5% and 5-10% of patients have a primary refractory disease, and 10-15% and 25-30% of patients experience relapse after conventional chemotherapy in early-stage HL and advanced-stage HL, respectively [1,2]. For these patients, several studies have demonstrated that autologous hematopoietic stem cell transplantation (HSCT) can prolong survival [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

The role of hematopoietic stem cell transplantation for relapsed and refractory Hodgkin lymphoma

et al. 2014

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on behalf of the Adult Lymphoma Working Group of the Japanese Society for Hematopoietic Cell TransplantationThe optimal treatment strategy with the use of hematopoietic stem cell transplantation (HSCT) for relapsed and refractory Hodgkin lymphoma (HL) remains unclear. We performed a retrospective analysis using registry data from the Japanese Society for Hematopoietic Cell Transplantation. Adult patients with HL who underwent a first autologous or a first allogeneic HSCT between 2002 and 2009 were included. Patients who underwent HSCT in first complete remission (CR) were excluded. Autologous and allogeneic HSCT were performed in 298 and 122 patients, respectively. For autologous HSCT, overall survival at 3 years (3yOS) was 70%, and sex, age, disease status, and performance status (PS) at HSCT were prognostic factors. OS was favorable even in patients who underwent autologous HSCT in disease status other than CR. For allogeneic HSCT, 3yOS was 43%, and sex and PS at HSCT were prognostic factors. Disease status at HSCT, previous autologous HSCT, and conditioning intensity did not affect OS. Moreover, graft-versus-host disease did not affect progression-free survival or relapse/progression rate. A first allogeneic HSCT without a previous autologous HSCT was performed in 40 patients. 3yOS was 45%, and was significantly inferior to that in patients who underwent their first autologous HSCT. This result was retained after the correction by the different patient characteristics according to the type of HSCT. In conclusion, autologous HSCT is effective in prolonging survival in patients with relapsed and refractory HL. Allogeneic HSCT might be beneficial even to relapsed HL after autologous HSCT, although establishing the role of allogeneic HSCT remains a challenge.

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Section: Introductionmentioning

confidence: 99%

The role of hematopoietic stem cell transplantation for relapsed and refractory Hodgkin lymphoma

et al. 2014

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“…6 In approximately 85% of patients chemotherapy and autologous bone marrow transplantation result in long-lasting remissions or cure but about 15% of patients still succumb to multiple relapses or have primary resistant disease. 7 Genomic instability is a hallmark of tumor cells. 8 Different pathways lead to such instability, but, in the context of HL, telomere dysfunction is a prime mechanism leading to the transition of H to RS cells.…”

Section: Introductionmentioning

confidence: 99%

Dynamic chromosomal rearrangements in Hodgkin's lymphoma are due to ongoing three-dimensional nuclear remodeling and breakage-bridge-fusion cycles

Guffei¹,

Sarkar²,

Klewes³

et al. 2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundHodgkin's lymphoma is characterized by the presence of mono-nucleated Hodgkin cells and bi-to multi-nucleated Reed-Sternberg cells. We have recently shown telomere dysfunction and aberrant synchronous/asynchronous cell divisions during the transition of Hodgkin cells to Reed-Sternberg cells. 1 Design and MethodsTo determine whether overall changes in nuclear architecture affect genomic instability during the transition of Hodgkin cells to Reed-Sternberg cells, we investigated the nuclear organization of chromosomes in these cells. ResultsThree-dimensional fluorescent in situ hybridization revealed irregular nuclear positioning of individual chromosomes in Hodgkin cells and, more so, in Reed-Sternberg cells. We characterized an increasingly unequal distribution of chromosomes as mono-nucleated cells became multi-nucleated cells, some of which also contained chromosome-poor 'ghost' cell nuclei. Measurements of nuclear chromosome positions suggested chromosome overlaps in both types of cells. Spectral karyotyping then revealed both aneuploidy and complex chromosomal rearrangements: multiple breakage-bridge-fusion cycles were at the origin of the multiple rearranged chromosomes. This conclusion was challenged by super resolution three-dimensional structured illumination imaging of Hodgkin and Reed-Sternberg nuclei. Three-dimensional super resolution microscopy data documented inter-nuclear DNA bridges in multi-nucleated cells but not in mono-nucleated cells. These bridges consisted of chromatids and chromosomes shared by two Reed-Sternberg nuclei. The complexity of chromosomal rearrangements increased as Hodgkin cells developed into multi-nucleated cells, thus indicating tumor progression and evolution in Hodgkin's lymphoma, with Reed-Sternberg cells representing the highest complexity in chromosomal rearrangements in this disease. ConclusionsThis is the first study to demonstrate nuclear remodeling and associated genomic instability leading to the generation of Reed-Sternberg cells of Hodgkin's lymphoma. We defined nuclear remodeling as a key feature of Hodgkin's lymphoma, highlighting the relevance of nuclear architecture in cancer.Key words: 3D nucleus, chromosomal rearrangements, SKY, 3D-SIM, BBF-cycles, ReedSternberg cells.Citation: Guffei A, Sarkar R, Klewes L, Righolt C, Knecht H, and Mai S. Dynamic chromosomal rearrangements in Hodgkin's lymphoma are due to ongoing three-dimensional nuclear remodeling and breakage-bridge-fusion cycles. Haematologica 2010;95(12):2038-2046. doi:10.3324/haematol.2010 Dynamic chromosomal rearrangements in Hodgkin's lymphoma are due to ongoing three-dimensional nuclear remodeling and breakage-bridge-fusion cycles © F e r r a t a S t o r t i F o u n d a t i o n

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“…However, patients with advanced stage disease continue to have suboptimal outcomes, with 5-year freedom from progression rates of 47%-79% and relapse rates of 30%-40% [4,5]. Moreover, an additional 10%-15% of patients fail to enter remission with frontline therapy (primary refractory disease).…”

Section: Introductionmentioning

confidence: 99%