Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia

• Published in: Journal of clinical oncology Vol. 28; no. 17; pp. 2859 - 2867
• Main Authors: GYURKOCZA, Boglarka, STORB, Rainer, BRUNO, Benedetto, PETERSEN, Finn B, MARIS, Michael B, AGURA, Edward, YEAGER, Andrew, BETHGE, Wolfgang, SAHEBI, Firoozeh, APPELBAUM, Frederick R, MALONEY, David G, SANDMAIER, Brenda M, STORER, Barry E, CHAUNCEY, Thomas R, LANGE, Thoralf, SHIZURU, Judith A, LANGSTON, Amelia A, PULSIPHER, Michael A, BREDESON, Christopher N, MAZIARZ, Richard T
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10-06-2010
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Child; Child, Preschool; Disease-Free Survival; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Humans; Leukemia, Myeloid, Acute - surgery; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Original Reports; Prognosis; Transplantation Conditioning - adverse effects; Transplantation Conditioning - methods; Treatment Outcome; Tumors; Young Adult; Human; Acute myelogenous leukemia; Cancerology; Allogeneic hematopoietic stem cell transplantation; Stem cell; Hematopoietic cell; Homograft; Graft; Malignant hemopathy; Non myeloablative treatment; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2009.27.1460

Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning regimens imposes prohibitively high risks of morbidity and mortality for patients with high-risk acute myeloid leukemia (AML) who are older or have comorbid conditions. Here, we examined outcomes after nonmyeloablative allogeneic HCT in such patients.
Two hundred seventy-four patients (median age, 60 years) with de novo or secondary AML underwent allogeneic HCT from related (n = 118) or unrelated donors (n = 156) after conditioning with 2 Gy of total-body irradiation (TBI) with or without fludarabine. A calcineurin inhibitor and mycophenolate mofetil were used for postgrafting immunosuppression.
With a median follow-up of 38 months in surviving patients, the estimated overall survival at 5 years was 33%. The estimated 5-year relapse/progression and nonrelapse mortality rates were 42% and 26%, respectively. The cumulative incidences of grades 2, 3, and 4 acute graft-versus-host disease (GVHD) were 38%, 9%, and 5%, respectively. The cumulative incidence of chronic GVHD at 5 years was 44%. Patients in first and second complete remission had better survival rates than patients with more advanced disease (37% and 34% v 18%, respectively). Patients with HLA-matched related or unrelated donors had similar survivals. Unfavorable cytogenetic risk status was associated with increased relapse and subsequent mortality. Chronic GVHD was associated with lower relapse risk.
Allogeneic HCT from related or unrelated donors after conditioning with low-dose TBI and fludarabine, relying almost exclusively on graft-versus-leukemia effects, can result in long-term remissions in older or medically infirm patients with AML.