Lomustine, cytarabine, cyclophosphamide, etoposide – An effective conditioning regimen in autologous hematopoietic stem cell transplant for primary refractory or relapsed lymphoma: Analysis of toxicity, long-term outcome, and prognostic factors
Alok Gupta1, Anant Gokarn1, Deepan Rajamanickam1, Sachin Punatar1, Ravi Thippeswamy1, Libin Mathew1, Bhausaheb Bagal1, Sadhana Kannan2, Navin Khattry1
1 Department of Medical Oncology, Bone Marrow Transplant Unit, ACTREC, Tata Memorial Centre, Mumbai, Maharashtra, India
2 Department of Biostatistics, ACTREC, Tata Memorial Centre, Mumbai, Maharashtra, India
Department of Medical Oncology, Bone Marrow Transplant Unit, Room No. 247, Paymaster Shodhika, ACTREC, Tata Memorial Centre, Sector 22, Kharghar, Mumbai - 410 210, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT) is the treatment of choice for patients with relapsed and refractory (RR) lymphoma. We analyzed toxicity and long-term outcome with lomustine, cytarabine, cyclophosphamide, etoposide (LACE) conditioning in patients with primary refractory or relapsed lymphoma undergoing autologous transplant.
Materials and Methods: One-hundred patients with primary refractory (23), chemotherapy sensitive relapse (74) or RR (3) Hodgkin lymphoma (HL - 70 patients), and non-HL (NHL - 30 patients) underwent HSCT with LACE (lomustine 200 mg/m 2 day-7, etoposide 1000 mg/m 2 day-7, cytarabine 2000 mg/m 2 day-6 to day-5, and cyclophosphamide 1800 mg/m 2 day-4 to day-2) conditioning between November 2007 and December 2013. At transplant, 68 patients were in complete remission (CR), 29 in partial remission, 2 had stable disease, and 1 had progressive disease. Patients were followed up for development of transplant-related toxicities and long-term survival outcome.
Results: The incidence of grades 3–4 oral mucositis and grades 3–4 diarrhea was 8% and 4%, respectively. Median days to myeloid and platelet engraftment were 10 and 13. Transplant-related mortality was 7%. At median follow-up of 3 years, probability of overall survival (OS) and progression-free survival (PFS) at 3 years was 70% and 58% in entire cohort, 78% and 62% in HL and 51% and 46% in NHL subgroup, respectively. International Prognostic Score (IPS) >2 at relapse prognosticated for poor OS (P = 0.002) and PFS (P < 0.001) in HL subgroup. Positron emission tomography positivity pretransplant (HL subgroup) and at day + 100 (NHL subgroup) predicted for poor survival.
Conclusion: We conclude that LACE is effective and well-tolerated conditioning regimen. IPS at relapse is the most important prognostic factor in HL transplant.