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Fourth complete remission with immunosuppression withdrawal and irinotecan after both autologous and allogeneic transplants for diffuse large B cell lymphoma

Diffuse large B cell lymphoma (DLBCL) relapsing a second time after high-dose therapy and autologous transplantation is rarely cured. Allogeneic transplant has been curative in lymphoma [1], but the true applicability has not been fully determined. Treatment of a third relapse after sequential autologous and allogeneic transplants would not be expected to result in a durable remission. We present here a patient with multiply-relapsed, large B cell nonHodgkin lymphoma (NHL) after both autologous transplant in second remission and allogeneic transplant in third remission. She is now in an exceptional sustained fourth complete remission after withdrawal of immunosuppression and treatment with irinotecan. A 29-year-old Taiwanese woman presented in 1999 with several weeks of right sided facial swelling and ipsilateral supraclavicular adenopathy unresponsive to antibiotics. A submandibular lymph node biopsy revealed follicular and diffuse large cleaved cell lymphoma. Computed tomography (CT), fluorine-18, 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET), and bone marrow biopsy demonstrated stage IIA disease. She had no International Prognostic Index (IPI) risk factors. She received an abbreviated, three-cycle regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by radiation localized to the right neck and supraclavicular region (180 cGy617 fractions, for a total of 3060 Gy) [2]. She tolerated the treatments well and follow-up imaging revealed no evidence of disease. The patient remained disease-free for 7 years, including 5 years of radiographic surveillance. Seven years after combined modality therapy, she presented with a new, left-sided neck mass. Excisional biopsy demonstrated DLBCL with plasmacytoid differentiation. Clinical stage IIIS disease was established by CT, FDG PET, and bone marrow biopsy with two adverse IPI risk factors. She received an institutional review board approved protocol for cytoreduction with two cycles of rituximab combined with augmented ifosfamide, carboplatin, and etoposide (R-ICE) [ifosfamide 10 000 mg/m over 2 days and etoposide 200 mg/m Q12 h63 doses with carboplatinum at an area under the curve of 5]. Doses were augmented compared with our original report of ICE as second-line therapy before autologous stem cell transplantation (ASCT) for primary refractory or relapsed DLBCL [3]. Follow-up CT and PET-imaging did not show any residual disease. The stem cell harvest yielded 17.6610 CD34þ cells. Autologous transplant with 7.0610 CD34þ cells/kg followed conditioning with carmustine, etoposide, cytarabine, and melphalan (BEAM). She also received a single dose of rituximab 1 month after autologous transplantation. Approximately 7 months after ASCT, the patient noticed new left cervical adenopathy coupled with fevers and progressive jaundice in the preceding