Long-term disease-free survival after nonmyeloablative cyclophosphamide fludarabine conditioning and related unrelated allotransplantation for acute myeloid leukemia myelodysplasia

• Published in: Bone marrow transplantation (Basingstoke) Vol. 45; no. 8; pp. 1300 - 1308
• Main Authors: Nelson, R P, Yu, M, Schwartz, J E, Robertson, M J, Hromas, R, Fausel, C A, Vance, G H, Dlouhy, S R, Baute, J A, Cox, E A, Wood, L L, Srivastava, S, Robertson, K A, Haut, P R, Farag, S S, Abonour, R, Cornetta, K, Cripe, L D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2010; Nature Publishing Group
• Subjects: 692/699/67/1990/1673; 692/699/67/1990/283/1897; 692/700/565/1436; 692/700/565/545/576/1955; Acute myeloid leukemia; Adolescent; Adult; Age Factors; Aged; Analysis; Bone marrow; Care and treatment; Cell Biology; Conditioning; Cyclophosphamide; Cyclophosphamide - therapeutic use; Diagnosis; Disease-Free Survival; Female; Fludarabine; Follow-Up Studies; Graft vs Host Disease - drug therapy; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cell Transplantation - mortality; Hematopoietic stem cells; Histocompatibility antigen HLA; Humans; Immunological tolerance; Immunosuppression; Immunotherapy; Internal Medicine; Leukemia; Leukemia, Myeloid, Acute - therapy; Male; Medicine; Medicine & Public Health; Methods; Middle Aged; Mucositis; Mud; Mycophenolate mofetil; Mycophenolic acid; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - therapy; original-article; Peripheral blood; Prophylaxis; Public Health; Stem cell transplantation; Stem Cells; Survival; Survival Analysis; Transplantation; Transplantation Conditioning - methods; Transplantation, Homologous; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use; Young Adult; United States; minimal intensity; leukemia; myelodysplasia; nonmyeloablative; transplantation
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2009.348

A total of 50 consecutive patients (median age, 57.5 years) with AML ( n =30) or myelodysplasia (MDS, n =20) underwent HLA matched related donor (MRD, n =27) or unrelated donor (MUD, n =23) peripheral blood hematopoietic cell transplantation after nonmyeloablative CY/fludarabine (Flu) conditioning. GVHD prophylaxis included CsA ( n =19)±mycophenolate mofetil ( n =31). At a median follow-up of 59 months, 21 patients (42%) were alive without evidence of disease. By Kaplan–Meier analysis, year 1–4 disease-free survival (DFS) and OS estimates were 0.50/0.58, 0.40/0.46, 0.37/0.43 and 0.37/0.41. MUD recipients were engrafted quickly (13.5 days) compared to MRD recipients (16 days) and relapsed/progressed less frequently ( P =0.005). Overall grade 3/4 acute GVHD (aGVHD) occurred in 26% in the absence of antecedent mucositis and was associated with chronic GVHD (cGVHD) and poor OS. Extensive cGVHD developed in 51.2% of 100 day survivors. Rates of aGVHD, cGVHD and survival were similar between MRD and MUD recipients. Of 14 survivors with cGVHD, 5 (35.7%) experienced resolution off immunosuppression, suggesting that tolerance with HLA matched grafts is possible at an advanced age by this method. This study provides further evidence for prolonged DFS after CY/Flu MRD allotransplantation for AML/MDS, and extends the findings to older patients and those with unrelated donors.