Outcomes following HSCT Using Fludarabine, Busulfan, and Thymoglobulin: A Matched Comparison to Allogeneic Transplants Conditioned with Busulfan and Cyclophosphamide

Abstract

We have reported a lower incidence of acute graft versus host disease (aGVHD) with a novel conditioning regimen using low dose rabbit anti-thymocyte globulin (TG, Thymoglobulin) with fludarabine and intravenous busulfan (FluBuTG). To assess further this single center experience, we performed a retrospective matched pair analysis comparing outcomes of adult patients transplanted using the FluBuTG conditioning regimen with matched controls from patients reported to the CIBMTR receiving a first allogeneic hematopoietic stem cell transplant (HCT) after standard oral busulfan and cyclophosphamide (BuCy). 120 cases and 215 matched controls were available for comparison. Patients receiving FluBuTG had significantly less treatment related mortality (12% vs 34%, p<0.001) and grades II–IV aGVHD (15% vs 34% p<0.001) compared to BuCy patients. The risk of relapse was higher in the FluBuTG patients (42% vs 20%, p<0.001). The risks of chronic GVHD (cGVHD) and disease free survival (DFS) were similar in the cases and controls. These results suggest that the novel regimen FluBuTG decreases the risk of aGVHD and transplant mortality after HLA-identical sibling HCT, but is associated with an increased risk of relapse, resulting in similar DFS. Whether these conditioning regimens may be more suitable for specific patient populations based on relapse risk requires testing in prospective randomized trials.

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

“…[29][30][31][32] Administration of rabbit-anti-human T lymphocyte antibodies has been increasingly used by transplant programs because the antibodies can partially prevent aGVHD and cGVHD without impacting rates of relapse and non-EBV infections (except when used at a high dose, for example, 48 mg/kg thymoglobulin). 9,20,[33][34][35][36][37][38][39][40][41] Thus, our findings that in patients conditioned with rabbit-ATG, the PTLD occurrence is relatively high (8.1%) and that the vast majority of PTLD's occurring before day 100 are important. This suggests that monitoring EBV DNAemia in the first 100 days is warranted, together with preemptive (at the time of high/rising EBV DNAemia) or prompt (early in the course of PTLD) administration of rituximab- [42][43][44] or EBV-specific T lymphocytes.…”

Toxic erythema of chemotherapy following i.v. BU plus fludarabine for allogeneic PBSC transplant

“…Additional studies evaluating BU were reviewed but did not report on cutaneous toxicity. 2,3,5,[7][8][9][10][11][12][13][14] Toxic erythema of chemotherapy after high-dose BU TL Parker et al development of erosions and desquamation may be the first sign of TEC; the former may be misdiagnosed as herpetic viral infections. Lastly, the duration of the cutaneous toxicity may be weeks and to date, we have found no specific therapy that alters the clinical course.…”

“…BU plus fludarabine (IVBuFlu; þ / À antithymocyte globulin (ATG)) appears to be a highly effective conditioning regimen prior to allo-SCT for patients with AML or myelodysplasic syndrome. [1][2][3][4][5] Several reports suggest that IVBuFlu combines the efficacy of a fully myeloablative regimen with the low treatment-related mortality generally seen with reduced intensity or even nonmyeloablative regimens. 3,4,6 For example, de Lima et al 4 reported a nonrelapse mortality at 12 months of 3%.…”

“…The decrease in treatment-related mortality appears to be due to a lower incidence of sinusoidal obstructive syndrome (venoocclusive disease) and severe acute GVHD, with the latter hypothesized to be due to less widespread tissue injury. [1][2][3][4][5] Compared with other myeloablative regimens, an important advantage of BU-based therapy is the ability to modify the dose of BU based upon the pharmacokinetics of the drug in an individual patient. Because of the efficacy and low incidence of serious toxicity, IVBuFlu þ / À ATG has become a popular regimen for patients with myeloid neoplasia.…”

An addition of medium-dose ATG to conditioning regimens favours the long-term survival of patients with allogeneic hematopoietic stem cell transplantation

“…It seemed that the relapse rate was higher when ATG was added to the conditioning regimen. Moreover, an increase in the risk of relapse of leukemia with an ATG conditioning regimen has been reported by other authors [30]. On the other hand it has been indicated that the use of polyclonal ATG as part of conditioning prior to Allo-SCT improved the survival rate [15].…”