Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia

A. Bacigalupo, M. T. Van Lint, D. Occhini, F. Gualandi, T. Lamparelli, G. Sogno, E. Tedone, F. Frassoni, J. Tong, A. M. Marmont

Research output: Contribution to journalArticlepeer-review

Abstract

Eighty-one patients with acute myeloid leukemia (ANLL, n = 44) or acute lymphoblastic leukemia (ALL, n = 37), aged 10 to 50 years were randomized to receive 1 mg/kg per day (n = 41, group A) or 5 mg/kg per day (n = 40, group B) of cyclosporine A (CyA) from day -1 to day +20 after bone marrow transplant (BMT). All patients received CyA orally thereafter. All patients were prepared with cyclophosphamide (CY) 120 mg/kg and fractionated total body irradiation (TBI), and received unfractionated BM from an HLA-identical sibling. The two groups were comparable for diagnosis, disease status, French-American-British (FAB) classification, WBC count at diagnosis, cytogenetic abnormalities, extramedullary disease before BMT, donor/recipient age and sex, number of cells infused, and number of days with intravenous (IV) CyA. Median follow-up for surviving patients in group A was 983 v 632 days in group B. Patients in group A had lower serum levels of CyA (295 v 686 ng/mL, P = .004), lower bilirubin levels (1.9 v 2.6 mg/dL, P = .07), lower creatinine levels (0.9 v 1.4 mg/dL, P = .06), and a lower proportion of CD8+ cells in the peripheral blood (PB) within day +21 (19% v 28%, P = .07). First day to 0.5 × 109/L neutrophils was comparable in the two groups (13 v 14 days; P= . 1 ). In a Cox model, the actuarial risk of acute grafts-v-host disease (GVHD) grade II+, after stratification for age () was significantly lower in group B patients (0.54, P = .04). The actuarial risk of developing chronic GVHD was comparable (P = .9). Actuarial transplant-related mortality (TRM) at 240 days was 28% and 26% (P = .8) in group A and B: the major cause of death was GVHD in group k (P = .02) and multiorgan toxicity in group B (P = .07). The actuarial risk of relapse at 2 years overall was 20% in group A and 52% in group B (P = .001); it was 9% v 43%, respectively, for patients in first remission (P = .0001) and 48% v 63% for patients in non-first complete remission (CR) (P = .1). Actuarial 2-year disease-free survival (DFS) in group A and B was 58% v 32% (P = .02) for all patients, 71% v 35% (P = .01), in first remissions, and 30% v 23% (P = .2) in advanced disease. In conclusion, protection from GVHD-related death with high-dose CyA is offset by significant organ toxicity and leukemia relapse: As a consequence, long-term DFS is clearly superior in patients receiving low-dose CyA after Cy and fractionated TBI.

Original languageEnglish
Pages (from-to)1423-1428
Number of pages6
JournalBlood
Volume77
Issue number7
Publication statusPublished - Apr 1 1991

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of 'Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia'. Together they form a unique fingerprint.

Cite this