Efetividade e toxicidade de protocolo de condicionamento em transplante autólogo de célula-tronco hematopoética para pacientes com linfoma

Abstract

Introduction: In recent decades, Autologous Hematopoietic Stem Cell Transplantation (auto-HSCT) has been used as a potential rescue therapy for patients with lymphoma. Currently, numerous types of conditioning protocols for performing auto-HSCT are known and used in order to improve the overall survival (OS) and disease-free survival (DFS) of these patients. Until today, no protocol has been considered superior and produced better results than the others. Objective: Determine the maximum tolerated dose of lomustine in a conditioning protocol (lomustine, etoposide, cytarabine and melphalan – LEAM) and evaluate the toxicities of this protocol in comparison to the historical series of the service. Method: A quantitative, type 3.3 prospective cohort. The first step of the study was carried out to determine the maximum tolerated dose (MTD) of lomustine. The second step consisted in comparing it with the historical series of patients undergoing transplantation who used CBV (carmustine, etoposide and cyclophosphamide) prior to auto-HSCT. Results: To determine the maximum tolerated dose (MTD) of lomustine administered on D-4, followed by etoposide (1 g/m2 (D-3), cytarabine (4 g/m2 (D-2), and melphalan (140 mg/m2 (D-1), a total of 14 patients were submitted to the protocol. The lomustine dose was escalated according to 200 mg/m2 intervals. The initial cohort consisted of lomustine at a dose of 200 mg/m2 (L200), followed by a cohort with lomustine 400 mg/m2 (L400). Because L400 exceeded the MTD, a third cohort with lomustine in a dose of 300 mg/m2 was created (L300). Six patients were treated in L200 (1 DLT, died of sepsis), two patients were treated in L400 (2 DLT, grade 4 gastrointestinal toxicity) and 6 patients were treated in L300 (1 DLT, neurological grade 4, reversible), with lomustine 300mg/m2 being considered the MTD. In the second phase of the study, 32 patients submitted to the LEAM protocol participated. The main toxicities found among the patients were mucositis (53.1%), diarrhea (68.8 %) and dermal toxicity (34.4%). The patients were then compared to the historical series, in which 64 patients were submitted to the CBV protocol. The groups were similar with regard to the stage, medical diagnosis, age and sex. The beginning of neutropenia and its duration was statistically lower in the LEAM group when compared to the CBV group, p = 0.00 and 0.035, respectively. There was no difference between the toxicities found in the two groups, but the overall survival of the patients submitted to the LEAM protocol was higher when compared to the CBV group (p = 0.050). Conclusion: The LEAM protocol proved to be a viable conditioning regimen of rapid administration, associated with a short duration of neutropenia and acceptable toxicity. Overall survival was better in the LEAM protocol when compared to the historical series of the service.