Caitlin W Elgarten1,2, Danielle E Arnold3, Nancy J Bunin1,4, Alix E Seif1,4. 1. Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 2. Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 3. Division of Immunology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 4. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
BACKGROUND: Optimal graft versus host disease (GVHD) prophylaxis prevents severe manifestations without excess immunosuppression. Standard prophylaxis includes a calcineurin inhibitor (CNI) with low-dose methotrexate. However, single-agent CNI may be sufficient prophylaxis for a defined group of patients. Single-agent CNI has been used for GVHD prophylaxis for human leukocyte antigen (HLA)-matched sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the Children's Hospital of Philadelphia for over 20 years. Here, we describe outcomes using this prophylactic strategy in a recent cohort. PROCEDURE: We performed a single-institution chart review and retrospective analysis of consecutive children undergoing MSD BMT who received single-agent CNI for GVHD prophylaxis between January 2002 and December 2014. RESULTS: Fifty-two children with a median age of 6.1 years (interquartile range [IQR] 2.5-8.3) and donor age of 6 years (IQR 3-10), with malignant and nonmalignant diseases (n = 35 and 17, respectively) were evaluated. Forty-three (82.6%) received oral prophylaxis with single-agent tacrolimus after initial intravenous therapy. Rates of GVHD were consistent with reported rates on dual prophylaxis: the overall incidence of grades 2-4 acute GVHD was 25.5%, grades 3-4 GVHD 9.8%, and chronic GVHD 10.4%. The cumulative incidence of relapse among children with malignancy was 20% at a median of 237 days (IQR 194-318) post-transplant. Two-year overall survival was 82.7% (95% confidence interval [CI]: 69.4-90.6%) and event-free survival was 78.9% (95% CI: 65.1-87.7%). No patient experienced graft failure. CONCLUSIONS: Single-agent CNI is a safe, effective approach to GVHD prophylaxis in young patients undergoing HLA-identical sibling BMT. Additionally, single-agent oral tacrolimus is a reasonable alternative to cyclosporine in this population.
BACKGROUND: Optimal graft versus host disease (GVHD) prophylaxis prevents severe manifestations without excess immunosuppression. Standard prophylaxis includes a calcineurin inhibitor (CNI) with low-dose methotrexate. However, single-agent CNI may be sufficient prophylaxis for a defined group of patients. Single-agent CNI has been used for GVHD prophylaxis for human leukocyte antigen (HLA)-matched sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the Children's Hospital of Philadelphia for over 20 years. Here, we describe outcomes using this prophylactic strategy in a recent cohort. PROCEDURE: We performed a single-institution chart review and retrospective analysis of consecutive children undergoing MSD BMT who received single-agent CNI for GVHD prophylaxis between January 2002 and December 2014. RESULTS: Fifty-two children with a median age of 6.1 years (interquartile range [IQR] 2.5-8.3) and donor age of 6 years (IQR 3-10), with malignant and nonmalignant diseases (n = 35 and 17, respectively) were evaluated. Forty-three (82.6%) received oral prophylaxis with single-agent tacrolimus after initial intravenous therapy. Rates of GVHD were consistent with reported rates on dual prophylaxis: the overall incidence of grades 2-4 acute GVHD was 25.5%, grades 3-4 GVHD 9.8%, and chronic GVHD 10.4%. The cumulative incidence of relapse among children with malignancy was 20% at a median of 237 days (IQR 194-318) post-transplant. Two-year overall survival was 82.7% (95% confidence interval [CI]: 69.4-90.6%) and event-free survival was 78.9% (95% CI: 65.1-87.7%). No patient experienced graft failure. CONCLUSIONS: Single-agent CNI is a safe, effective approach to GVHD prophylaxis in young patients undergoing HLA-identical sibling BMT. Additionally, single-agent oral tacrolimus is a reasonable alternative to cyclosporine in this population.
Authors: F Locatelli; M Zecca; R Rondelli; F Bonetti; G Dini; A Prete; C Messina; C Uderzo; M Ripaldi; F Porta; G Giorgiani; E Giraldi; A Pession Journal: Blood Date: 2000-03-01 Impact factor: 22.113
Authors: D Weisdorf; R Hakke; B Blazar; W Miller; P McGlave; N Ramsay; J Kersey; A Filipovich Journal: Transplantation Date: 1991-06 Impact factor: 4.939
Authors: K Atkinson; M M Horowitz; R P Gale; D W van Bekkum; E Gluckman; R A Good; N Jacobsen; H J Kolb; A A Rimm; O Ringdén Journal: Blood Date: 1990-06-15 Impact factor: 22.113
Authors: N Watanabe; K Matsumoto; H Muramatsu; K Horibe; T Matsuyama; S Kojima; K Kato Journal: Bone Marrow Transplant Date: 2009-11-16 Impact factor: 5.483
Authors: H M Shulman; K M Sullivan; P L Weiden; G B McDonald; G E Striker; G E Sale; R Hackman; M S Tsoi; R Storb; E D Thomas Journal: Am J Med Date: 1980-08 Impact factor: 4.965