Mitoxantrone-DHAP with GM-CSF: An Active but Myelosuppressive Salvage Therapy for Relapsed Refractory Aggressive Non-Hodgkin's Lymphoma

• Published in: Leukemia & lymphoma Vol. 35; no. 5-6; pp. 527 - 536
• Main Authors: Haq, Rashida, Sawka, Carol A., Franssen, Edmée, Berinstein, Neil L.
• Format: Journal Article
• Language: English
• Published: United States Informa UK Ltd 01.11.1999; Taylor & Francis
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; cisplatin; Cisplatin - administration & dosage; Cisplatin - adverse effects; cytarabine; Cytarabine - administration & dosage; Cytarabine - adverse effects; dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Disease-Free Survival; Drug Administration Schedule; Female; Gastrointestinal Diseases - chemically induced; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Hematopoietic Stem Cell Mobilization; Humans; Life Tables; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - mortality; M-DHAP+GM-CSF; Male; Middle Aged; Mitoxantrone - administration & dosage; Mitoxantrone - adverse effects; Neutropenia - chemically induced; Neutropenia - complications; Neutropenia - prevention & control; Relapsed lymphoma; Remission Induction; Salvage Therapy; salvage treatment; Sepsis - etiology; Sepsis - mortality; Survival Analysis; Thrombocytopenia - chemically induced; Treatment Outcome
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428199909169617

This study was designed to evaluate the efficacy and toxicity of dose intensifying DHAP (dexmethasone, cytarabine and cisplatin) salvage chemotherapy by adding mitoxantrone with GM-GSF support in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). From March 1992 to January 1995, 22 patients with intermediate and high grade (aggressive) NHL refractory or relapsed after adriamycin containing chemotherapy regimens were treated with M-DHAP+GM-CSF, (dexamethasone 40 mg IV days 1-4, cisplatin 100 mg m2 IV by continuous infusion over 24 hours on day 1, cytarabine 2 gm m2, IV every 12 hours for 2 doses on day 2, mitoxantrone 10 mg m2 IV on days 3 and 4 and GM-CSF 250-500 μg m2 SC daily beginning day 5 until absolute neutrophil count recovery. Most patients had poor prognostic factors including primary refractory disease (18 22), bulky disease (12 22), elevated LDH (9 22), or bone marrow involvement (8 22). All 22 patients were evaluable. The overall response rate was 41% (CR 23% and PR 18%). There were three toxic deaths, all related to sepsis. Median progression free survival (PFS) and overall survival (OS) rates were 5.2 months and 11.8 months respectively. At the same time of the analysis two patients were alive after high-dose therapy and bone marrow transplant at 34 and 36 months follow-up and two were alive with disease. The maximal acceptable dosage of mitoxantrone was 10 mg m2 × 2 due to serious hematologic toxicity. Treatment delays and dose reductions compromised delivering the optimal dose intensity of M-DHAP. A poor prognostic group of patients with refractory or recurrent aggressive lymphoma, many of whom were not eligible for high-dose therapy and stem cell transplantation were treated with repeated cycles of dose intensified DHAP with growth factor support. Although M-DHAP had therapeutic activity even in patients considered to have primary refractory disease, myelosuppression was dose limiting and frequently limited the number of cycles. Therefore, if M-DHAP is to be further evaluated, therapeutic results may be improved further by incorporating strategies to reduce myelotoxicity such as the use of growth factors to reduce platelet transfusion requirements or the use of autologous stem cell support after each cycle.