Safety and outcome after fludarabine–thiotepa–TBI conditioning for allogeneic transplantation: a prospective study of 30 patients with hematologic malignancies

Abstract

Summary:Fludarabine, thiotepa and total body irradiation (TBI) has been used as conditioning in haplo-identical transplantation. We studied this conditioning regimen in adults undergoing matched sibling transplantation and alternative donor transplantation. A total of 30 consecutive patients underwent matched related, haplo-identical related or matched unrelated donor transplantation with fludarabine, thiotepa and TBI conditioning. All but four had advanced hematologic malignancies. For haploidentical transplant, ATG was added to the regimen. All patients received peripheral blood stem cells; these were Tcell depleted for 2-antigen or 3-antigen mismatched related transplantation. Additional graft-versus-host disease prophylaxis consisted of tacrolimus and minimethotrexate. One recipient of haplo-identical transplant failed to engraft; all other evaluable patients had prompt engraftment. Four patients died of regimen-related toxicity. In all, 14 additional patients died of regimenrelated causes including four from failure to thrive with persistent thrombocytopenia and four from delayed pulmonary toxicity. Six patients relapsed. Progressionfree survival at 12 months was 47% (90% CI: 25-69%) for recipients of HLA-identical sibling transplants and 30% (90% CI: 14-46%) for all patients. Five of six longterm survivors have extensive chronic GVHD. As a result of the delayed complications and a relatively high recurrence rate, we abandoned this regimen. Bone Marrow Transplantation (2003) 32, 9-13. doi:10.1038/ sj.bmt.1704088 Keywords: transplantation; TBI; fludarabine; thiotepa; toxicity Allogeneic transplantation is curative for only a limited proportion of patients with advanced hematologic malignancies. Its impact is limited because of high recurrence rates and because of treatment-related complications in patients with considerable comorbidities. We studied a conditioning regimen containing fludarabine, thiotepa and total body irradiation (TBI). A similar regimen had previously been used in recipients of haplo-identical transplants. 1 Based on its reported favorable toxicity profile and its excellent antileukemic and immunosuppressive properties, we expanded its use to recipients of HLAidentical transplants and matched unrelated donor transplantation. We report safety data of 30 consecutive patients treated with this regimen. Patients and methods Patients and protocol designPatients were eligible if they had hematologic malignancies including acute and chronic leukemia and myeloproliferative disorders, non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma. Patients with acute leukemia in first remission were enrolled only if they had adverse prognostic characteristics at diagnosis.Eligibility criteria included, Karnofsky performance status greater than or equal to 60%, bilirubin less than or equal to 2 mg/dl, creatinine less than 1.5 times normal.The trial was designed as a single-arm phase II equivalence trial using methodology developed by Thall et al. 2 The four elementary patient outcomes, each defined ...

Thiotepa‐based versus total body irradiation‐based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

“…After a prospective study using fludarabine, thiotepa and TBI (12 Gy), van Besien et al . suggested abandoning this regimen due to delayed complications and relatively high recurrence rate . A modified regimen, consisting of thiotepa and 10 Gy TBI (phase II single‐centre trial), was also considered to be too toxic, with a 90‐d transplant‐related mortality of 44% .…”