Synapse - Intravenous busulfan and melphalan, tacrolimus, and short-course methotrexate followed by unmodified HLA-matched related or unrelated hematopoietic stem cell transplantation for the treatment of advanced hematologic malignancies

Intravenous busulfan and melphalan, tacrolimus, and short-course methotrexate followed by unmodified HLA-matched related or unrelated hematopoietic stem cell transplantation for the treatment of advanced hematologic malignancies Journal Article

Authors:	Small, T. N.; Young, J. W.; Castro-Malaspina, H.; Prockop, S.; Wilton, A.; Heller, G.; Boulad, F.; Chiu, M.; Hsu, K.; Jakubowski, A.; Kernan, N. A.; Perales, M. A.; O'Reilly, R. J.; Papadopoulos, E. B.
Article Title:	Intravenous busulfan and melphalan, tacrolimus, and short-course methotrexate followed by unmodified HLA-matched related or unrelated hematopoietic stem cell transplantation for the treatment of advanced hematologic malignancies
Abstract:	Results of allogeneic hematopoietic stem cell transplantation (HCT) to treat advanced leukemia or myelodysplastic syndrome (MDS) remain poor due to excessive relapse and transplant-related mortality. To improve transplant outcome in this patient population, 43 patients (median age, 46.1 years) with high-risk or advanced lymphoid (n = 5) or myeloid malignancy (n = 38) were prospectively enrolled on a pilot trial of cytoreduction with intravenous busulfan and melphalan followed by an unmodified HLA-A, -B, and -DRβ1-matched related (n = 18) or unrelated (n = 25) HCT. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Thirty-four patients had ≥ 5% blasts at the time of HCT; 12 of these had > 20% blasts. Seventeen patients had unfavorable cytogenetics, 8 patients underwent transplantation for secondary MDS or acute myelogenous leukemia, and 4 patients had relapsed after a previous allogeneic transplantation. Although mucositis was the most significant regimen-related toxicity, requiring the addition of folinic acid rescue and failure to receive all 4 doses of methotrexate in 23 patients, the nonrelapse mortality at 30 and 100 days was low at 0% and 16%, respectively. The cumulative incidence of grade II-IV acute GVHD was 24%, and that of extensive chronic GVHD was 7%. With a minimum follow-up of 18 months, the estimated 3-year overall survival is 37% and the estimated disease-free survival (DFS) is 33%. For 18 patients with MDS (≤ RAEB-2) or high-risk myeloproliferative disorder, the estimated 3 year DFS is 61%. These data demonstrate the curative potential of this regimen in patients with high-risk myeloid malignancies. © 2007 American Society for Blood and Marrow Transplantation.
Keywords:	adolescent; adult; child; clinical article; controlled study; treatment outcome; child, preschool; middle aged; survival analysis; leukemia; acute granulocytic leukemia; overall survival; myeloproliferative disorder; busulfan; clinical trial; side effect; disease free survival; cytarabine; methotrexate; drug megadose; follow up; prospective studies; controlled clinical trial; hemolysis; steady state; mucosa inflammation; antineoplastic combined chemotherapy protocols; incidence; cytogenetics; melphalan; kidney failure; hematopoietic stem cell transplantation; continuous infusion; transplantation; cancer mortality; acute graft versus host disease; chronic graft versus host disease; engraftment; hematologic malignancy; hla matching; myelodysplastic syndrome; infant; folinic acid; hla dr antigen; transplantation conditioning; asparaginase; allogeneic hematopoietic stem cell transplantation; cancer relapse; drug blood level; hla a antigen; hla b antigen; tacrolimus; immunosuppressive agents; hla antigen; myelodysplastic syndromes; thymocyte antibody; gemtuzumab ozogamicin; mds; histocompatibility testing; liver venoocclusive disease; septic shock; refractory anemia with excess blasts; leukemia, myelocytic, acute; leukemia, lymphocytic, acute
Journal Title:	Biology of Blood and Marrow Transplantation
Volume:	13
Issue:	2
ISSN:	1083-8791
Publisher:	Elsevier Inc.
Date Published:	2007-02-01
Start Page:	235
End Page:	244
Language:	English
DOI:	10.1016/j.bbmt.2006.10.005
PUBMED:	17241929
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-33846329122&partnerID=40&md5=6a1671de9b44ec621149dccd07419d95
Notes:	--- - "Cited By (since 1996): 10" - "Export Date: 17 November 2011" - "CODEN: BBMTF" - "Source: Scopus"