A novel reduced intensity conditioning can cnduce a high incidence of sustained donor engraftment after double unit cord blood transplantation (CBT) without anti-thymocyte globulin Meeting Abstract

Authors: Ponce, D. M.; Sauter, C.; Lubin, M.; Gonzales, A. M.; Heller, G.; Castro-Malaspina, H.; Giralt, S.; Kernan, N. A.; Papadopoulos, E. B.; Scaradavou, A.; Barker, J. N.
Abstract Title: A novel reduced intensity conditioning can cnduce a high incidence of sustained donor engraftment after double unit cord blood transplantation (CBT) without anti-thymocyte globulin
Meeting Title: 52nd Annual Meeting of the American Society of Hematology (ASH)
Abstract: CBT can be curative for patient's with high-risk hematologic malignancies. However, patients of older age, those with extensive prior therapy, or significant co-morbidities may not tolerate high-dose myeloablative conditioning. Reduced intensity (RI) or non-myeloablative (NMA) conditioning has been successfully used in CBT, especially in patients with lymphomas: However, patients with myeloid malignancies without extensive prior therapy have an increased risk of graft rejection following NMA CBT. Further, the addition of anti-thymocyte globulin (ATG) to enhance engraftment increases the risk of serious infections and Epstein-Barr virus post-transplant lymphoproliferative disease, and could-increase the risk of relapse. Therefore, we investigated the efficacy and safety of a novel ATG-free RI conditioning prior to double unit CBT in patients with acute leukemias and myelodysplasia with the hypothesis that this regimen can induce a high incidence of sustained donor engraftment. Conditioning consisted-of cyclophosphamide 50 mg/kg. (day -6), fludarabine 30 mg/m(2)/day X 5 (days -6 to -2); thiotepa 5 mg/kg/day X 2 (days -5 and -4), and total body irradiation 200 cGy X 2 (days -2 and -1). All patients received cyclosporine-A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Between 10/01/07-04/30/10, 20 patients were transplanted. The median age was 56 years (range 18-69). Thirteen (65%) had AML (9 CR1, 4 CR2), 4(20%) had ALL (3 CR1, 1 CR3), and 3 (15%) had MDS (with one patient also having follicular lymphoma). The majority had high-risk disease. Indications for RI conditioning were the risk factors for transplant-related mortality (TRM) with high-dose conditioning of age >= 50 years, and/or extensive prior therapy, and/or significant co-morbidities. Thirteen patients had only 1 of these risk factors, whereas 7 had >= 2 risk factors. Units were predominantly 4-5/6 HLA-matched to the recipient (one 6/6, twenty-four 5/6, fifteen 4/6). The median infused cell doses of the larger units were 2.7 X 10(7) total nucleated cells/kg (range 1:46-5.56) and 0.95 X 10(5) CD34+ cells/kg (range 0.35-3.32), and 1.89 X 10(7)/kg total nucleated cells/kg (range 1.42-2.47) and 0.59 X 10(5)/kg CD34+ cells/kg (range 0.18-1.52) for the smaller Units, respectively. The cumulative incidence of sustained donor engraftment at day 45 was 95% (95%CI: 81-100). The single patient with graft failure was 100% donor in the day 21 bone marrow, but died early post-transplant of multi-organ failure without count recovery. The median time to neutrophil recovery >= 0.5 X 10(9)/1 was 25 days (range 13-43). The median total donor chimerism in the day 21 bone marrow was 94% (both units combined, range 71-100), and sustained engraftment was accounted for by one unit in 18/19 engrafting patients. The incidence of grade II-IV acute GVHD, at day 100 was 55% (95%CI: 32-78), and 46% (95%CI: 21-71) of patients have had late acute GVHD requiring ongoing therapy or chronic GVHD to date. The incidence of day 100 transplant-related-mortality (TRM) was 20% (95%CI: 2-38). Notably, mine of the 13 patients with only one risk factor died of transplant-related causes. By contrast, 5/7(71%) patients with >= 2 risk factors died of TRM by day 100 (p=0.03, Table 1). Two additional patients died of relapse. With a median follow-up of 13 months (range 3-31), 1 year progression-free survival is 74% (95%CI: 55-94) (Figure 1).We demonstrate that this ATG-free RI conditioning is associated with a high incidence of sustained onor engraftment, and acceptable toxicities in older patients without other risk factors. While longer follow-up is needed, progression-free survival is encouraging provided multiple risk factors are not present. This conditioning combined with double unit grafts warrants further investigation, and may also be a promising alternative to high-dose conditioning in younger patients.[GRAPHICS].
Keywords: pharmacology; methods and techniques; oncology (human medicine, medical sciences); clinical immunology (human medicine, medical sciences); hematology (human medicine, medical sciences); donor engraftment, donor chimerism, cell count recovery
Journal Title: Blood
Volume: 116
Issue: 21
Meeting Dates: 2010 Dec 4-7
Meeting Location: Orlando, FL
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2010-11-19
Start Page: 971
End Page: 972
Language: English
PROVIDER: biosis
PUBMED: 22276300
Notes: --- - Meeting Abstract: 2351 - 52nd Annual Meeting of the American-Society-of-Hematology (ASH) - Orlando, FL, USA - December 04 -07, 2010 - Amer Soc Hematol - "Source: Biosis"