Refractory Hodgkin lymphoma responds to pentostatin (2′-deoxycoformycin)

Hodgkin lymphoma in children and young adults is characterized by a high sensitivity to radiation and cytotoxic agents, resulting in cure of most, but not all, patients. The majority of young adults respond to combined-modality regimen with multi-agent chemotherapy and involved-field radiotherapy. However, there is a debate about the optimal therapeutic management in advanced stage cases of Hodgkin lymphoma because one third of these patients do not achieve a prolonged disease-free survival [1–3]. Even with high-dose chemotherapy and autologous stem cell transplantation as salvage therapy, 40 – 70% of the patients with refractory or recurrent Hodgkin lymphoma will fail to attain a durable second remission [4]. We report a 21-year old patient with heavily pretreated advanced refractory Hodgkin lymphoma who achieved a near complete metabolic response after pentostatin treatment. Pentostatin (20-deoxycoformycin) is a purine analog that inhibits adenosine deaminase. This compound is highly lymphocytotoxic and is approved by the Food and Drug Administration (FDA) for hairy cell leukemia [5]. It is also active in cutaneous and peripheral T-cell lymphomas, but there are no studies in Hodgkin lymphoma [6,7]. A 19-year-old man was diagnosed with stage IV nodular sclerosis Hodgkin lymphoma after presenting with fatigue and night sweats. After 6 cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine), he achieved only partial response and relapsed in the lungs and mediastinum. Subsequently, 2 courses of ICE (ifosfamide, carboplatin and etoposide), autologous bone marrow transplantation and adjuvant radiation therapy to the relapse area in the lungs insured a brief remission for 6 months. Neither additional 2 courses of gemcitabine nor 8 courses of COPP (cyclophosphamide, vincristine, procarbazine and prednisone) provided any significant response. The patient’s low back and chest pain worsened, with weight loss and fatigue. Round-theclock opioids were needed to control the pain. He was then enrolled on a phase I/II investigational agent protocol with MDX060-01, which is a CD30 antibody, but his disease progressed. After an extensive search of the Internet, the patient self-referred himself to the University of Texas M. D. Anderson Cancer Center, to be considered for an investigational protocol with pentostatin (20-deoxycoformycin) for advanced lymphoma. An 18-FDG positron-emission tomography (fluorodeoxyglucose PET) scan revealed extensive disease, involving nodal and extra-nodal sites (Figure 1, panel A). The patient received pentostatin at 5 mg m intravenous infusions for 3 consecutive days every 3 weeks. After 2 cycles, a repeat PET scan revealed striking interval reduction in extent and degree of metabolic activity at all nodal and extra-nodal sites (Figure 1, panel B). The patient’s pain resolved and he discontinued all opioids. After an additional 2 cycles, restaging by PET (Figure 1, panel C) and CT scans (data not shown) revealed an ongoing metabolic and morphologic response (decrease of aortocaval node lymph node size from 1.7 to 1.3 cm). With the earlier course, the patient encountered significant nausea during the 3 days infusion of pentostatin, despite prophylactic ondansetron. This was subsequently controlled with systemic pre-treatment with dexamethasone 10 mg