1.
Augmented myeloablative conditioning with thiotepa in acute myeloid leukemia - improved outcomes with similar toxicity
Sheth, V., Nachmias, B., Grisariu, S., Avni, B., Or, R., Shapira, M.
Leukemia & lymphoma. 2018;:1-8
Abstract
Myeloablative doses of busulfan (Bu) with fludarabine (Flu) have reduced toxicity, however, limited by an increased relapse rate. We aimed to improve outcome of Flu-Bu regimen by augmentation with thiotepa (TT) (10 mg/kg). Eighty-nine patients with AML, 44 patients conditioned with Flu-Bu (group 1), and 45 patients augmented with TT (Flu-Bu-TT, group 2), were retrospectively analyzed. Primary objectives were toxicity and outcomes. Major toxicities were comparable: mucositis (p = 1.0), sepsis (p = .7), severe venocclusive disease of liver (VOD) (p = 1.0), and non-relapse mortality (NRM) (22 vs. 22%, p = .7). Five-year disease-free survival was significantly better in group 2 compared to group 1 (62 vs. 38%, p = .02). Five-year overall survival (OS) showed trend toward benefit in group 2 (62 vs. 42%, p = .06). Lower relapse rate in group 2 (14 vs. 46%, p = .005) contributed to better outcomes. Augmented regimen has better disease-free survival (DFS) (mainly due to reduced relapse rate) and similar toxicities as compared to Flu-Bu. Key points Assessing the addition of TT to myeloablative conditioning (Flu, Bu) in patients undergoing allogeneic stem cell transplant for acute myeloid leukemia with regard to relapse rate, disease-free survival and toxicity. Addition of thiotepa improves disease-free survival and shows trend toward benefit in overall survival, by reducing relapses without additional toxicity.
2.
Active acute leukaemia: should transplant be offered to all patients?
Avni, B., Shapira, M. Y., Resnick, I. B., Stepensky, P., Or, R., Grisariu, S.
Hematological Oncology. 2017;35(4):797-803
Abstract
The probability of achieving long term remission for patients with refractory acute leukaemia is very low. Allogeneic stem cell transplantation (SCT) is offered to these patients in order to improve their dismal outcome. We retrospectively analyzed 361 acute leukaemia patients, who underwent allogeneic SCT in the Hadassah's bone marrow transplantation department between the years 2005 and 2012 and identified 84 patients with active leukaemia at transplantation. Median age was 34years. Sixty four patients were diagnosed with acute myeloid leukaemia (AML), 18 patients with acute lymphoblastic leukaemia and two with biphenotypic leukaemia. The majority of patients were diagnosed with de-novo AML and transplanted at relapse. In the surviving patients, median follow up was 15months. One year OS was 20%. At time of last follow up, 13 patients were alive (15.5%): ten patients with AML and two patients with acute lymphoblastic leukaemia. In the univariate analysis, factors associated with significantly better overall survival were as follows: matched unrelated donor (p=0.006), matched donor (p=0.014) and occurrence of acute graft-versus-host disease (aGVHD) (p=0.019). Karnofsky performance score at SCT and occurrence of cGVHD were found to be borderline significant. Only matched unrelated donor and aGVHD were found to affect overall survival significantly in the multivariate analysis. Other than performance score at SCT, none of the pretransplant patients' characteristics were found to influence survival. In conclusion, as none of the pretransplant characteristics were found to influence the ability to select the patients that will benefit from HSC transplantation, this work supports offering HSCT to all active leukaemia eligible patients with reasonable performance status. Copyright © 2016 John Wiley & Sons, Ltd.Copyright © 2016 John Wiley & Sons, Ltd.
3.
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
Eder, S., Labopin, M., Arcese, W., Or, R., Majolino, I., Bacigalupo, A., de Rosa, G., Volin, L., Beelen, D., Veelken, H., et al
European Journal of Haematology. 2016;96(1):90-7
Abstract
Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting. Copyright © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.