Salvage chemotherapy with mitoxantrone, fludarabine, cytarabine, and cisplatin (MIFAP) in relapsing and refractory lymphoma

Purpose: The aim of the study was to evaluate the feasibility and efficacy of the combination of mitoxantrone, fludarabine, cytarabine, and cisplatin (MIFAP) in patients with prognostically unfavorable recurrent and refractor y Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Methods: Forty-s ix patients (median age 43 years, range 18-63) with relapsed (n = 15) or re fractory (n = 31) malignant lymphoma were enrolled (HD, n = 13; low-grade/t ransformed NHL, IE = 4; high-grade NHL, n = 29). A total of 39 patients (85 %) showed multiply relapsed diseases with a duration of prier remission of < 12 months (n = 8) or had lymphoma being resistant to prior chemotherapy ( n = 31). The MIFAP therapy consisted of fludarabine (15 mg/m(2), q. 12 h, d ay 1-4), cytarabine (50 mg/m(2) by continuous infusion (CI) over 22 h, day 1-4), cisplatin (25 or 30 mg/m(2) by CI over 24 h, day 1-4), and mitoxantro ne (4 mg/m(2), day 2-5). Results: Thirteen patients (28%) achieved complete remission (CR) and 15 patients (33%) partial remission (PR), for an overal l response (OR) rate of 61%. Twenty-two patients responding to MIFAP (10 CR , 12 PR) have been consolidated by high-dose therapy (HDT) with hematopoiet ic stem cell transplantation (SCT). After a median followup of 12 months, 1 6 patients are in continuous CR (CCR) (Iz = 14) or CCRu (unconfirmed) (n = 2). The median duration of event-free survival (EFS) and overall survival ( OS) were 6.5 and 19.3 months, respectively. Probabilities of EFS and OS aft er 3 years were 19% and 40%. Responders consolidated by subsequent HDT show ed rates for 3-year EFS and OS of 40% and 66%, respectively. Unfavorable pr ognostic factors for EFS by univariate analysis were refractory lymphoma an d the presence of B-symptoms. Significant prognostic factors for OS were NH L, refractory lymphoma, B-symptoms, and bone marrow involvement. The major toxicities were leukocytopenia and thrombocytopenia of the World Health Org anization (WHO) grade IV in nearly all courses (median duration 10 and 11 d ays). In contrast, non-hematological side effects were moderate, predominan tly of WHO grades I and II. Treatment-related mortality with MIFAP was 4% ( two patients with septicemia by Aspergillus fumigatus). Conclusions: MIFAP is an effective salvage protocol for patients with poor-risk recurrent or r efractory HD and NHL. The observed toxicity seems to be acceptable consider ing the unfavorable prognosis and intensive pretreatment. The results in pa tients responding to MIFAP and afterwards undergoing HDT with autologous st em cell support are even comparable to those published in patients with pro gnostically more favorable diseases.