A chemotherapy-only regimen of busulfan, melphalan, and fludarabine, and rabbit antithymocyte globulin followed by allogeneic T-cell depleted hematopoietic stem cell transplantations for the treatment of myeloid malignancies Journal Article

Authors: Spitzer, B.; Jakubowski, A. A.; Papadopoulos, E. B.; Fuller, K.; Hilden, P. D.; Young, J. W.; Barker, J. N.; Koehne, G.; Perales, M. A.; Hsu, K. C.; van den Brink, M. R.; Kernan, N. A.; Prockop, S. E.; Scaradavou, A.; Castro-Malaspina, H.; O'Reilly, R. J.; Boulad, F.
Article Title: A chemotherapy-only regimen of busulfan, melphalan, and fludarabine, and rabbit antithymocyte globulin followed by allogeneic T-cell depleted hematopoietic stem cell transplantations for the treatment of myeloid malignancies
Abstract: We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplantations (HSCT) without the need for total body irradiation, thereby reducing toxicity while maintaining low rates of graft-versus-host disease (GVHD) and without increasing relapse. We investigated the myeloablative combination of busulfan (Bu) and melphalan (Mel), with the immunosuppressive agents fludarabine (Flu) and rabbit antithymocyte globulin (r-ATG) as cytoreduction before a TCD HSCT. No post-transplantation immunosuppression was administered. Between April 2001 and May 2008, 102 patients (median age, 55 years) with a diagnosis of primary or secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) underwent cytoreduction with Bu/Mel/Flu, followed by TCD grafts. TCD was accomplished by CD34+-selection followed by E-rosette depletion for peripheral blood stem cell grafts and, for bone marrow grafts, by soybean agglutination followed by E-rosette depletion. Donors included matched and mismatched, related and unrelated donors. Risk stratification was by American Society for Blood and Marrow Transplantation risk categorization for patients with primary disease. For patients with secondary/treatment-related MDS/AML, those in complete remission (CR) 1 or with refractory anemia were classified as intermediate risk, and all other patients were considered high risk. Neutrophil engraftment occurred at a median of 11 days in 100 of 101 evaluable patients. The cumulative incidences of grades II to IV acute and chronic GVHD at 1 year were 8.8% and 5.9%, respectively. Overall- and disease-free survival (DFS) rates at 5 years were 50.0% and 46.1%, respectively, and the cumulative incidences of relapse and treatment-related mortality were 23.5% and 28.4%, respectively. Stratification by risk group demonstrated superior DFS for low-risk patients (61.5% at 5 years) compared with intermediate- or high-risk (34.2% and 40.0%, respectively, P =.021). For patients with AML, those in CR1 had superior 5-year DFS compared with those in ≥CR2 (60% and 30.6%, respectively, P =.01), without a significant difference in incidence of relapse (17.1% and 30.6%, respectively, P =.209). There were no differences in DFS for other patient, donor, or disease characteristics. In summary, cytoreduction with Bu/Mel/Flu and r-ATG secured consistent engraftment of TCD transplantations. The incidences of acute/chronic GVHD and disease relapse were low, with favorable outcomes in this patient population with high-risk myeloid malignancies. © 2017 The American Society for Blood and Marrow Transplantation
Keywords: adult; treatment outcome; middle aged; survival rate; major clinical study; overall survival; busulfan; fludarabine; cancer combination chemotherapy; disease free survival; melphalan; herpes zoster; high risk patient; survival time; acute graft versus host disease; chronic graft versus host disease; engraftment; myeloablative conditioning; myelodysplastic syndrome; neutrophil; allogeneic hematopoietic stem cell transplantation; soybean; t cell depletion; leukemia relapse; cd34 selection; adenovirus infection; cytomegalovirus infection; thymocyte antibody; autologous peripheral blood stem cell transplantation; leukemia remission; refractory anemia; intermediate risk patient; viremia; herpes virus infection; antigen antibody reaction; acute myeloid leukemia; myeloid malignancies; mortality rate; epstein barr virus infection; t-cell depleted; low risk patient; bone marrow cancer; human; male; female; article; human herpesvirus 6; chemotherapy-only; hematopoietic stem cell transplantations; bk virus infection; e rosette
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 23
Issue: 12
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2017-12-01
Start Page: 2088
End Page: 2095
Language: English
DOI: 10.1016/j.bbmt.2017.07.004
PROVIDER: scopus
PUBMED: 28711727
PMCID: PMC6010191
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
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MSK Authors
  1. Nancy Kernan
    383 Kernan
  2. Farid Boulad
    255 Boulad
  3. Susan E Prockop
    161 Prockop
  4. Miguel-Angel Perales
    384 Perales
  5. Katharine C Hsu
    139 Hsu
  6. Juliet N Barker
    229 Barker
  7. Guenther Koehne
    175 Koehne
  8. James W Young
    257 Young
  9. Richard O'Reilly
    487 O'Reilly
  10. Barbara Spitzer
    28 Spitzer
  11. Patrick Dale Hilden
    85 Hilden
  12. Kirsten N Cobbs
    1 Cobbs