Do patients with classic Hodgkin's lymphoma treated with ABVD in low-middle income countries have a higher risk of neutropenia/febrile neutropenia without G-CSF support? a single-center retrospective study

Abstract

Abstract Introduction: Patients with Hodgkin lymphoma (cHL) who receive adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy commonly experience neutropenia; however, the incidence of febrile neutropenia is rare. Various retrospective studies have suggested that ABVD can be administered safely without dose delays or the need for granulocyte-colony stimulating factor (G-CSF) support. Nonetheless, it is important to note that most of these studies were conducted in high-income countries, where patients have timely access to emergency departments and outpatient clinics. There is a notable lack of data regarding the effects of omitting G-CSF support for patients in low and low-middle income countries, where emergency healthcare resources may be limited. Methods: This retrospective, single-center study aimed to evaluate the incidence of grade 3-4 neutropenia and febrile neutropenia in newly diagnosed patients with classic Hodgkin lymphoma (cHL) treated at a public Lymphoma Clinic (Hospital Municipal da Vila Santa Catarina) in São Paulo, Brazil. Eligible patients were 18 years or older and received at least two cycles of ABVD at our center. Patients who received primary G-CSF support were excluded from the analysis. The cumulative incidence of neutropenia was assessed while considering competitive risks such as death, disease progression, or treatment modification. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier estimates and compared using the log-rank test. Results: A total of 146 patients were diagnosed with Hodgkin's lymphoma between February 2019 and March 2024. Eight patients were excluded from the analysis: five were initially treated at other facilities, one lacked reliable laboratory results, and one patient died before treatment initiation. The final cohort comprised 138 patients, with a median age of 36 years and a well balanced between male and female patients (50% each). At diagnosis, 61.6% of patients presented with stage IV disease, and 81.2% exhibited B symptoms, reflecting the expected delays in diagnosis within low- and middle-income countries (LMIC). Most patients (68.8%) received a total of six cycles of ABVD. In this cohort, 47 patients (34%) developed neutropenia of any grade, with 27% experiencing grade 3 neutropenia and 6% grade 4 neutropenia. The incidence of febrile neutropenia was 2.17% (n=4), and notably, no patients required admission to the intensive care unit or died due to febrile neutropenia. Furthermore, there was no impact on OS or PFS for patients who presented with neutropenia. Conclusions: The omission of G-CSF support in patients treated with ABVD appears to be both safe and resource-saving in LMIC. Despite the observed higher incidence of stage IV disease and B symptoms—indicative of delays in diagnosis and referral and suggesting a more clinically challenging population—febrile neutropenia was infrequent and did not adversely affect progression-free survival (PFS) or overall survival (OS). To our knowledge, this study represents the largest cohort of classic Hodgkin lymphoma (cHL) patients from low- and middle-income countries (LMIC) assessed for neutropenia and febrile neutropenia following ABVD treatment.