A novel reduced intensity conditioning can induce 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 induce 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
ACCESSION: BIOSIS:PREV201100424894
PROVIDER: biosis
PUBMED: 22276300
Notes: - Meeting Abstract: 2351 - "Source: Biosis"
Citation Impact
MSK Authors
  1. Nancy Kernan
    434 Kernan
  2. Glenn Heller
    350 Heller
  3. Sergio Andres Giralt
    610 Giralt
  4. Craig Steven Sauter
    199 Sauter
  5. Doris Ponce
    149 Ponce
  6. Juliet N Barker
    249 Barker
  7. Marissa N Lubin
    78 Lubin