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Fludarabine-based conditioning secures engraftment of second hematopoietic stem cell allografts (HSCT) in the treatment of initial graft failure.
Biol Blood Marrow Transplant. 2007 Nov; 13(11):1313-23.BB

Abstract

Graft failure is associated with a high mortality rate. To date, regimens invoked for second transplants have resulted in inconsistent engraftment with high transplant-related mortality (TRM). We here report 16 consecutive patients, aged 4-59 years, who received second HSCT (HSCT-2) at a median of 45 days following primary or secondary failure of an initial unmodified (N = 3) or T cell-depleted (TCD) (N = 13) HSCT (HSCT-1). HSCT-1 was administered after myeloablative total body irradiation (TBI)- or alkylator-based conditioning for acute leukemias (N = 7), MDS (N = 6), CML (N = 2), and Fanconi anemia (N = 1). All patients experienced 1 or more infectious complications between HSCT-1 and HSCT-2, and 10 patients had active infections at the time of HSCT-2. Cytoreduction regimens used for HSCT-2 included fludarabine (Flu) in combination with cyclophosphamide (CTX) (N = 9), or thiotepa (Thio) (N = 5). In addition, 1 patient received Flu alone and 1 patient Thio combined with CTX. Antithymocyte globulin (ATG) (N = 11) or Alemtuzumab (N = 3) was added pretransplant to prevent rejection. For HSCT-2, donors included HLA-matched (N = 3) or mismatched (N = 8) related, or matched (N = 2) or mismatched (N = 3) unrelated donors. The primary graft donor was used in 6 of 16 cases. The grafts administered were unmodified peripheral blood stem cell transplantation (PBSCT) (N = 5) or bone marrow transplantation (BMT) (N = 3), TCD PBSCT (N = 8). All patients achieved engraftment at a median of 12 days and evaluable patients achieved complete donor chimerism. Six patients are alive with a median follow-up of 49 months, including 4/9 conditioned with Flu/CTX. In this series, outcome was statistically superior for younger patients (<or=20 years). In summary, second HSCT using the combination of a fludarabine- and ATG-based, nonmyeloablative regimen and higher numbers of CD34+ progenitor cells has been associated with acceptable toxicity and allowed consistent engraftment with hematopoietic reconstitution in patients with previous graft failure.

Authors+Show Affiliations

Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

17950918

Citation

Chewning, Joseph H., et al. "Fludarabine-based Conditioning Secures Engraftment of Second Hematopoietic Stem Cell Allografts (HSCT) in the Treatment of Initial Graft Failure." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 13, no. 11, 2007, pp. 1313-23.
Chewning JH, Castro-Malaspina H, Jakubowski A, et al. Fludarabine-based conditioning secures engraftment of second hematopoietic stem cell allografts (HSCT) in the treatment of initial graft failure. Biol Blood Marrow Transplant. 2007;13(11):1313-23.
Chewning, J. H., Castro-Malaspina, H., Jakubowski, A., Kernan, N. A., Papadopoulos, E. B., Small, T. N., Heller, G., Hsu, K. C., Perales, M. A., van den Brink, M. R., Young, J. W., Prockop, S. E., Collins, N. H., O'Reilly, R. J., & Boulad, F. (2007). Fludarabine-based conditioning secures engraftment of second hematopoietic stem cell allografts (HSCT) in the treatment of initial graft failure. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 13(11), 1313-23.
Chewning JH, et al. Fludarabine-based Conditioning Secures Engraftment of Second Hematopoietic Stem Cell Allografts (HSCT) in the Treatment of Initial Graft Failure. Biol Blood Marrow Transplant. 2007;13(11):1313-23. PubMed PMID: 17950918.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fludarabine-based conditioning secures engraftment of second hematopoietic stem cell allografts (HSCT) in the treatment of initial graft failure. AU - Chewning,Joseph H, AU - Castro-Malaspina,Hugo, AU - Jakubowski,Ann, AU - Kernan,Nancy A, AU - Papadopoulos,Esperanza B, AU - Small,Trudy N, AU - Heller,Glenn, AU - Hsu,Katharine C, AU - Perales,Miguel A, AU - van den Brink,Marcel R M, AU - Young,James W, AU - Prockop,Susan E, AU - Collins,Nancy H, AU - O'Reilly,Richard J, AU - Boulad,Farid, Y1 - 2007/09/07/ PY - 2007/07/08/received PY - 2007/07/10/accepted PY - 2007/10/24/pubmed PY - 2007/12/12/medline PY - 2007/10/24/entrez SP - 1313 EP - 23 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 13 IS - 11 N2 - Graft failure is associated with a high mortality rate. To date, regimens invoked for second transplants have resulted in inconsistent engraftment with high transplant-related mortality (TRM). We here report 16 consecutive patients, aged 4-59 years, who received second HSCT (HSCT-2) at a median of 45 days following primary or secondary failure of an initial unmodified (N = 3) or T cell-depleted (TCD) (N = 13) HSCT (HSCT-1). HSCT-1 was administered after myeloablative total body irradiation (TBI)- or alkylator-based conditioning for acute leukemias (N = 7), MDS (N = 6), CML (N = 2), and Fanconi anemia (N = 1). All patients experienced 1 or more infectious complications between HSCT-1 and HSCT-2, and 10 patients had active infections at the time of HSCT-2. Cytoreduction regimens used for HSCT-2 included fludarabine (Flu) in combination with cyclophosphamide (CTX) (N = 9), or thiotepa (Thio) (N = 5). In addition, 1 patient received Flu alone and 1 patient Thio combined with CTX. Antithymocyte globulin (ATG) (N = 11) or Alemtuzumab (N = 3) was added pretransplant to prevent rejection. For HSCT-2, donors included HLA-matched (N = 3) or mismatched (N = 8) related, or matched (N = 2) or mismatched (N = 3) unrelated donors. The primary graft donor was used in 6 of 16 cases. The grafts administered were unmodified peripheral blood stem cell transplantation (PBSCT) (N = 5) or bone marrow transplantation (BMT) (N = 3), TCD PBSCT (N = 8). All patients achieved engraftment at a median of 12 days and evaluable patients achieved complete donor chimerism. Six patients are alive with a median follow-up of 49 months, including 4/9 conditioned with Flu/CTX. In this series, outcome was statistically superior for younger patients (<or=20 years). In summary, second HSCT using the combination of a fludarabine- and ATG-based, nonmyeloablative regimen and higher numbers of CD34+ progenitor cells has been associated with acceptable toxicity and allowed consistent engraftment with hematopoietic reconstitution in patients with previous graft failure. SN - 1083-8791 UR - https://www.unboundmedicine.com/medline/citation/17950918/Fludarabine_based_conditioning_secures_engraftment_of_second_hematopoietic_stem_cell_allografts__HSCT__in_the_treatment_of_initial_graft_failure_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(07)00350-3 DB - PRIME DP - Unbound Medicine ER -