Busulfan pharmacokinetics and cd4 reconstitution after stem cell transplant in patients with myeloid neoplasms.
Patil NR, Bazydlo M, Peres E, Janakiraman N, and Farhan S. Busulfan pharmacokinetics and cd4 reconstitution after stem cell transplant in patients with myeloid neoplasms. Biol Blood Marrow Transplant 2018; 24(3):S367-S367.
Biol Blood Marrow Transplant
Background: In recipients of allogeneic stem cell transplant, T-cell recovery is crucial to regain immune competence. Antithymocyte globulin (ATG) and fludarabine have been shown to influence CD4+ T-cell recovery. To explore the impact of busulfan pharmacokinetics (Bu PK) on CD4+ reconstitution, we performed retrospective analysis of patients with myeloid disorders in the last 10 years who received four days of fludarabine and busulfan (FluBu4) with or without measuring Bu PK and those who got busulfan with cyclophosphamide (BuCy).
Methods: We reviewed patients' demographics, transplant data, CD3 and CD34 dose, ATG use, disease risk index (DRI), cytogenetics, chimerism, relapse, infection and survival data. Immune reconstitution was assessed by CD3, CD4, and CD8 counts and immunoglobulin levels.
Results: 86 patients were included in the study. 56 patients received FluBu4, of whom 21 had Bu PK measured. BuCy was given in 30 patients. There were 54 males and 32 females with a median age of 59 years. DRI was high or very high in 57%, 53% and 69% of patients in the FluBu4 with PK, no PK and BuCY, respectively (P = .372). 36 patients had matched related donor, 39 had matched unrelated donor and 11 had mismatched unrelated donor SCT. Post-transplantation graft versus host disease prophylaxis consisted of methotrexate and tacrolimus in all patients. Patients receiving unrelated donor transplants received ATG 4.5 mg/kg pre-transplantation in divided doses. ATG was given in 57%, 63% and 48% of patients in the FluBu4 with PK, no PK and BuCY, respectively (P = .502). After adjusting for sex, age, ATG, DRI disease risk, and month, the CD4 count for patients who received FluBu4 with PK was only 68% as high as the CD4 count for patients who received BuCy (P = .038). While the CD4 count for patients who received FluBu4 without PK was 74% as high as the CD4 count for patients who received BuCy (P = .129). After adjusting for patient characteristics, the CD4 count of patients who received FluBu4 with and without PK was only 70% of that of patients who received BuCy (P = .044).
Conclusion: In this small cohort of consecutive patients from a single center, we found that in patients with myeloid disorders who received fludarabine busulfan for 4 days incorporating Bu PK might negatively influence CD4+ recovery. This will need to be examined in larger retrospective multicenter studies and prospective clinical trials.