Case Summaries presented by Joseph M. Connors, MD, Clinical Director, Centre for Lymphoid Cancer, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada
When considering the management of a patient whose Hodgkin lymphoma has relapsed despite high dose chemoradiotherapy and autologous hematopoietic stem cell transplantation, it is useful to consider three distinct scenarios, as described in the following case summaries.
Patient 1
Patient 1 is a 26-year-old man who presented with night sweats, fevers, and cough. On examination, he was found to have palpable bilateral supraclavicular lymphadenopathy and wheezing but no other localizing symptoms. Open lymph node biopsy of a supraclavicular node revealed nodular sclerosing Hodgkin lymphoma. CT and FDG-PET demonstrated abnormally enlarged lymph nodes in the supraclavicular fossae, mediastinum, and retrocrural and retroperitoneal regions bilaterally but no other abnormal masses. The largest lymph node mass was 6 cm in greatest diameter.
For his stage IIIB classical Hodgkin lymphoma, the patient was treated with six cycles of standard ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine), after which both CT and PET scanning were negative, indicating a complete response. Four months later, the patient noted recurrent night sweats and detected supraclavicular lymphadenopathy. Biopsy confirmed relapsed Hodgkin lymphoma, and CT/PET demonstrated recurrence in the neck and mediastinum. The patient was then treated with two cycles of GDP chemotherapy (gemcitabine, dexamethasone, cisplatin) with good response, followed by high-dose BEAM chemotherapy (carmustine [BiCNU], etoposide, cytarabine, melphalan) and autologous stem cell transplant, after which CT/PET scanning was once again negative. Six months later, night sweats recurred, and relapse in the neck and mediastinal nodes could be seen on CT/PET scanning.
Patient 2
Patient 2 had a similar initial presentation (stage IIIB, nodular sclerosing Hodgkin lymphoma) and was treated with six cycles of ABVD; however, postchemotherapy CT/PET remained positive for disease in the neck and mediastinum, and involved-field radiation (3,500 cGy in 20 fractions) to the abnormal nodes in the neck and mediastinum was added. Nine months later, the Hodgkin lymphoma recurred within the previously irradiated lymph nodes, prompting treatment with two cycles of GDP followed by high-dose chemotherapy and autologous stem cell transplant, but in another 9 months, a second in-field relapse occurred.
Patient 3
Patient 3 presented with bulky (> 10 cm) stage IIB nodular sclerosing Hodgkin lymphoma, but his disease progressed during the fifth cycle of ABVD. Despite subsequent treatment with GDP, high-dose BEAM, autologous stem cell transplant, and involved-field radiation to the neck and mediastinum, the lymphoma once again recurred in-field in the neck and mediastinum.
Discussion
These three patients illustrate the three distinct scenarios that may unfold on the way to re-emergence of Hodgkin lymphoma after autologous stem cell transplant. Patient 1 had node-only relapse of previously unirradiated node-only classical Hodgkin lymphoma after transplant and is potentially curable with extended-field radiation with or without MOPP-type chemotherapy (mechlorethamine, vincristine, procarbazine, prednisone). Patient 2 had chemotherapy-sensitive late relapse (> 6 months after autologous stem cell transplant) of Hodgkin lymphoma that had not been primarily resistant to the original ABVD plus involved-field radiotherapy. Preliminary data indicate such a patient may be curable with further chemotherapy followed by allogeneic stem cell transplant, but this technique remains experimental and is best offered within the context of a clinical trial. Patient 3 had ABVD-resistant Hodgkin lymphoma and experienced rapid relapse despite high-dose chemotherapy, stem cell transplant, and involved-field radiotherapy.
This latter situation—relapse of Hodgkin lymphoma after autologous transplant in a manner not approachable with potentially curative radiation or allogeneic transplant—is the most common one encountered (~70% of patients) and requires planned management aimed at minimizing toxicity, controlling symptoms, and ensuring the best possible quality of life even though the Hodgkin lymphoma cannot be cured (Table 1). This can usually be best accomplished by judicious use of involved-field radiation for localized symptoms such as a painful mass or bone lesion and single-agent chemotherapy. Reliance on single-agent chemotherapy eliminates concerns that arise when multiple agents are used and cause toxicity, although only one of the agents may be having a beneficial effect.
Desirable characteristics of the single agent include a high response rate, minimal toxicity, durability of response, convenient scheduling, and oral administration. If possible, the single agent chosen should avoid difficult-to-control nausea, marked myelotoxicity, hair loss, or need for frequent administration. Durability of response is particularly desirable because it allows treatment-free intervals.
No single agent possesses all of those useful characteristics, but vinblastine, gemcitabine, and lomustine are often helpful and well tolerated. Preliminary data indicate that bendamustine (Treanda) may also prove useful for this purpose, but more experience is needed (and myelotoxicity can be a major issue). More recently, brentuximab vedotin (Adcetris), an anti-CD30 antibody-drug conjugate, has been shown to be very well tolerated and highly effective for palliation of recurrent Hodgkin lymphoma and should be strongly considered for this use.1-5 ■
Suggested Readings
1. Younes A, Gopal AK, Smith SE, et al: Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol 30:2183-2189, 2012.
2. Sureda A, Robinson S, Canals C, et al: Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin’s lymphoma: An analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 26:455-462, 2008.
3. Horning S, Fanale M, deVos S, et al: Defining a population of Hodgkin lymphoma patients for novel therapeutics: An international effort. Ann Oncol 19(suppl 4): Abstract 118, 2008.
4. Sirohi B, Cunningham D, Powles R, et al: Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin lymphoma. Ann Oncol 19:1312-1319, 2008.
5. Lavoie JC, Connors JM, Phillips GL, et al: High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: Long-term outcome in the first 100 patients treated in Vancouver. Blood 106:1473-1478, 2005.
