Gemcitabine, dexamethasone and cisplatin is an active andnon-toxic chemotherapy regimen in relapsed or refractory Hodgkin’s disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group

Baetz, Tara; Belch, Andrew R.; Couban, Stephen; Imrie, Kevin; Yau, Jonathan C.; Myers, Robert E.; Ding, Keyue; Paul, Narinder; Shepherd, L. E.; Iglesias, J.; Meyer, Ralph M.; Crump, Michael

doi:10.1093/annonc/mdg496

Cited by 153 publications

(99 citation statements)

References 29 publications

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“…over 30 min on days 1 and 8, dexamethasone 40 17,18 Filgrastim was added during the second cycle in the event of febrile neutropenia during the first cycle or a low neutrophil count on a treatment day.…”

Section: Salvage Chemotherapymentioning

confidence: 99%

Different response to salvage chemotherapy but similar post-transplant outcomes in patients with relapsed and refractory Hodgkin's lymphoma

Puig¹,

Pintilie²,

Seshadri³

et al. 2010

Haematologica

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BackgroundThe use of high-dose chemotherapy and autologous stem-cell transplantation in patients with relapsed Hodgkin's lymphoma is supported by two randomized clinical trials but its benefit in patients with primary refractory disease is less clear. Aiming to shed light on this issue, we analyzed and compared the outcomes of patients with relapsed or refractory Hodgkin's lymphoma treated with second-line chemotherapy and planned autologous stem-cell transplantation. Design and MethodsWe retrospectively analyzed data on 157 consecutive patients with Hodgkin's lymphoma referred to our institution for consideration of autologous stem-cell transplantation between 1999 and 2006. Of those, 73 met the definition of having primary refractory disease, ie. progressive disease during first line chemotherapy or within 3 months of completion of the treatment. Those patients achieving complete remission, partial remission and stable disease with symptomatic improvement after two or three cycles of salvage chemotherapy proceeded to stem cell mobilization and autologous transplantation. ResultsFrom first relapse/progression, the 3-year overall survival was 76% (95% CI: 66%-89%) for the refractory cohort and 91% (95% CI: 84%-98%) for the relapsed cohort (P=0.034); the overall response rate to second-line chemotherapy was 51% and 83% (P<0.0001), respectively. Threeyear progression-free survival post-transplant was 49% in refractory patients and 67% in relapsed patients (P=0.21); overall survival was 75% and 91% (P=0.097), respectively. ConclusionsUsing the group with relapsed disease as a reference, we can conclude that the subset of patients with chemosensitive primary refractory Hodgkin's lymphoma do benefit from autologous stem-cell transplantation.Key words: Hodgkin's lymphoma, transplantation, refractory.Citation: Puig N, Pintilie M, Seshadri T, al-Farsi K, Nagy T, Franke N, Tsang R, Keating A, Crump M, and Kuruvilla J. Different

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Section: Salvage Chemotherapymentioning

confidence: 99%

Different response to salvage chemotherapy but similar post-transplant outcomes in patients with relapsed and refractory Hodgkin's lymphoma

Puig¹,

Pintilie²,

Seshadri³

et al. 2010

Haematologica

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“…14 Other promising gemcitabine-based combinations are summarized (Table 1). 15,16 In medically fit patients, gemcitabine-based regimens represent a reasonable option to cytoreduce disease before an allo-HCT. Reports of serious pulmonary toxicity after combining gemcitabine and brentuximab vedotin preclude prospective investigation of this combination.…”

Section: Salvage Therapies For Relapsed Hl After Auto-hctmentioning

confidence: 99%

Managing Hodgkin lymphoma relapsing after autologous hematopoietic cell transplantation: a not-so-good cancer after all!

Kharfan‐Dabaja

Hamadani

Sibai

et al. 2014

Bone Marrow Transplant

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Hodgkin lymphoma (HL) relapsing after an autologous hematopoietic cell transplant (HCT) poses a therapeutic challenge. In this setting, salvage chemotherapy (for example, gemcitabine-based, ifosfamide-containing and others) or immunotherapy (for example, brentuximab vedotin) is essential as a bridging-cytoreduction strategy to an allogeneic HCT. Myeloablative allogeneic hematopoietic cell transplantation in relapsed HL is associated with high rates of non-relapse mortality. In carefully selected patients with chemosensitive disease, allografting following lower-intensity conditioning regimens can provide durable disease control rates of about 25-35%. Promising early results with haploidentical and umbilical cord transplantation are noteworthy and are expanding this procedure to patients for whom HLA-matched related or unrelated donors are not available. Unfortunately, a significant number of HL patients relapsing after an autologous HCT are not candidates for allografting because of the presence of resistant disease, donor unavailability or comorbidities. Brentuximab vedotin is approved for HL relapsing after a prior autograft. Rituximab and bendamustine are also active in this setting, albeit with short durations of remission. Histone deacetylase inhibitors (for example, panobinostat, mocetinostat), mTOR inhibitors (for example, everolimus) and immunomodulatory agents (lenalidomide) have shown activity in phase II trials, but currently are not approved for this indication. Second autologous HCT are rarely performed but this approach should not be considered standard practice at this time. The need for effective agents for post autograft failures of HL largely remains unmet. Continuous efforts to ensure early referral of such patients for allogeneic HCT or investigational therapies are the key to improving outcomes of this not-so-good lymphoma.

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“…Non-etoposide salvage/priming regimens (e.g., gemcitabinecontaining regimens) may have similar activity in relapsed/refractory lymphoma patients. [96][97][98] Infuse higher doses of autologous stem cells. Decrease proliferative stress during engraftment.…”

Section: Stem Cell Collection/transplant Interventionsmentioning

confidence: 99%

Does autologous transplantation directly increase the risk of secondary leukemia in lymphoma patients?

Hake

Graubert

Fenske

2006

Bone Marrow Transplant

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Patients who undergo autologous stem cell transplantation (ASCT) for lymphoma have a significant risk of therapy-related acute myeloid leukemia and myelodysplasia (t-AML/MDS). Compared to that seen in other indications such as breast cancer, multiple myeloma or germ cell tumors, there is a substantially increased risk for t-AML/MDS following ASCT for lymphoma. This risk has largely been attributed to the extent of pre-transplant chemotherapy and radiation therapy. In many of the larger series to date, it has not been possible to directly implicate autologous transplantation itself as a risk factor for t-AML/MDS. Although pre-transplant therapy is certainly an important factor in the development of t-AML/MDS, specific components of the autologous transplantation procedure itself may also contribute to the risk of t-AML/MDS. Specifically, priming chemotherapy, total body irradiation, and the extensive cellular proliferation which occurs during engraftment may all play a role in the development of t-AML/MDS. Furthermore, there is an increasing body of evidence that certain inherited polymorphisms in genes governing drug metabolism, DNA repair and leukemogenesis may influence susceptibility to t-AML/MDS. In this paper, we review the evidence implicating the above risk factors for t-AML/MDS, present a potential mechanism for t-AML/ MDS and propose interventions to reduce the rate of t-AML/MDS in lymphoma patients.

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Gemcitabine, dexamethasone and cisplatin is an active andnon-toxic chemotherapy regimen in relapsed or refractory Hodgkin’s disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group

Cited by 153 publications

References 29 publications

Different response to salvage chemotherapy but similar post-transplant outcomes in patients with relapsed and refractory Hodgkin's lymphoma

Different response to salvage chemotherapy but similar post-transplant outcomes in patients with relapsed and refractory Hodgkin's lymphoma

Managing Hodgkin lymphoma relapsing after autologous hematopoietic cell transplantation: a not-so-good cancer after all!

Does autologous transplantation directly increase the risk of secondary leukemia in lymphoma patients?

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