Gemcitabine-based combination chemotherapy as salvage treatment for refractory or relapsing aggressive non-Hodgkin's lymphoma

Although CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) or more intensive chemotherapy regimens with or without rituximab can cure around 50% of advanced-stage aggressive non-Hodgkin's lymphoma (NHL), a substantial proportion of the patients develop refractory or relapsing diseases. However, high-dose chemotherapy followed by autologous stem cell transplantation usually rescues a limited number of patients. Historically, traditional chemotherapy regimens, including ESHAP (etoposide, methylprednisolone, highdose Ara-C, and cisplatin), ICE (ifosfamide, carboplatin, and etoposide), DHAP (high-dose Ara-C, cisplatin, and dexamethasone), and EPOCH (etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone) are used for salvage treatment in refractory or relapsing NHL [1]; however, the use of these regimens is often limited by the relatively severe toxicities. For example, high-dose Ara-C-containing regimens (ESHAP and DHAP) have significant hematological, skin, conjunctival, and mucosal toxicities [2,3]. Accumulated cardiac toxicity would be a major problem of anthracycline-containing regimens (EPOCH) for patients after standard first-line CHOP-based regimens [4]. Previous studies using ICE for a salvage chemotherapy regimen usually enrolled transplant-eligible patients, and the hematological toxicity remained significant, although the aggressive prophylactic granulocyte colony stimulating factor (G-CSF) was used [5]. Therefore, a safe and effective salvage chemotherapy regimen is needed for the treatment of relapsing or refractory aggressive NHL, irrespective of the initial response to chemotherapy, patients' age, or patients' comorbidities.