TY - JOUR
T1 - A pilot study of tacrolimus and mycophenolate mofetil graft-versus-host disease prophylaxis in childhood and adolescent allogeneic stem cell transplant recipients
AU - Osunkwo, Ifeyinwa
AU - Bessmertny, Olga
AU - Harrison, Lauren
AU - Cheung, Ying Kuen
AU - Van De Ven, Carmella
AU - del Toro, Gustavo
AU - Garvin, James
AU - George, Diane
AU - Bradley, M. Brigid
AU - Wolownik, Karen
AU - Wischhover, Cheryl
AU - Levy, Joseph
AU - Skerrett, Donna
AU - Cairo, Mitchell S.
N1 - Funding Information:
We thank Linda Rahl and Erin Morris, RN, for their expert editorial assistance and all the nurses and allied health professionals who participated in the superb care of our AlloSCT recipients. We would also like to thank Les Shaw, PhD, at the University of Pennsylvania for his helpful suggestions on MPA monitoring and MMF dose adjustments. Presented in part at the American Society of Hematology, December 2002, Philadelphia, PA, and the American Society of Blood and Marrow Transplantation, February 2003, Keystone, CO. Supported in part by grants from the Pediatric Cancer Research Foundation, the Pediatric Cancer Foundation, and the Swim Across America Foundation.
PY - 2004/4
Y1 - 2004/4
N2 - Tacrolimus (FK506)/mycophenolate mofetil (MMF) has been demonstrated to be an effective salvage therapy for steroid-resistant chronic graft-versus-host disease (GVHD), but its effectiveness as prophylaxis for acute GVHD (aGVHD) is unknown. We investigated the safety and efficacy of FK506/MMF in preventing aGVHD and sparing the use of methotrexate and methylprednisolone in childhood and adolescent allogeneic stem cell transplant (AlloSCT) recipients. Thirty-four childhood and adolescent patients (median age, 7 years; range, 0.5-21 years; 24 males and 10 females) undergoing 37 AlloSCTs for malignant (n = 22) and nonmalignant (n = 12) disorders received FK506 (0.03 mg/kg/d by continuous intravenous infusion) and MMF (15 mg/kg per dose orally or intravenously twice daily). Stem cell sources included 22 umbilical cord blood donors (21 unrelated and 1 related), 6 related bone marrow donors, and 9 related peripheral blood donors. Malignant diagnoses included 7 acute lymphoblastic leukemias, 3 acute myeloid leukemias, 1 acute promyelocytic leukemia, 2 non-Hodgkin lymphomas, 4 Hodgkin diseases, 3 chronic myeloid leukemias, and 2 neuroblastomas; nonmalignant diagnoses included 2 β-thalassemias, 1 sickle cell disease, 4 aplastic anemias, 1 Wiskott-Aldrich syndrome, 1 Hurler syndrome, 2 hemophagocytic lymphohistiocytoses, and 1 myelodysplastic syndrome. The probability of developing grade ≥II aGVHD was 45.4% ± 9.7% (7 related bone marrow/related peripheral blood; 5 umbilical cord blood), and for chronic GVHD it was 38.1% ± 19.7%. FK506/MMF was well tolerated. Three patients had grade III to IV neurotoxicity (disorientation and leukoencephalopathy); 4 patients developed grade III to IV nephrotoxicity (all received concomitant nephrotoxins). Patients who achieved target mycophenolic acid levels (1.0-3.5 μg/mL) before day +30 had a significantly reduced incidence of developing grade ≥II aGVHD (16.7% ± 15.2% versus 100%; P < .02). These results suggest that FK506/MMF is well tolerated and may be a safe and effective methotrexate- and methylprednisolone-sparing alternative GVHD prophylaxis regimen after AlloSCT. Further pharmacokinetic and pharmacodynamic studies are ongoing in pediatric and adolescent AlloSCT recipients to define optimal MMF dosing.
AB - Tacrolimus (FK506)/mycophenolate mofetil (MMF) has been demonstrated to be an effective salvage therapy for steroid-resistant chronic graft-versus-host disease (GVHD), but its effectiveness as prophylaxis for acute GVHD (aGVHD) is unknown. We investigated the safety and efficacy of FK506/MMF in preventing aGVHD and sparing the use of methotrexate and methylprednisolone in childhood and adolescent allogeneic stem cell transplant (AlloSCT) recipients. Thirty-four childhood and adolescent patients (median age, 7 years; range, 0.5-21 years; 24 males and 10 females) undergoing 37 AlloSCTs for malignant (n = 22) and nonmalignant (n = 12) disorders received FK506 (0.03 mg/kg/d by continuous intravenous infusion) and MMF (15 mg/kg per dose orally or intravenously twice daily). Stem cell sources included 22 umbilical cord blood donors (21 unrelated and 1 related), 6 related bone marrow donors, and 9 related peripheral blood donors. Malignant diagnoses included 7 acute lymphoblastic leukemias, 3 acute myeloid leukemias, 1 acute promyelocytic leukemia, 2 non-Hodgkin lymphomas, 4 Hodgkin diseases, 3 chronic myeloid leukemias, and 2 neuroblastomas; nonmalignant diagnoses included 2 β-thalassemias, 1 sickle cell disease, 4 aplastic anemias, 1 Wiskott-Aldrich syndrome, 1 Hurler syndrome, 2 hemophagocytic lymphohistiocytoses, and 1 myelodysplastic syndrome. The probability of developing grade ≥II aGVHD was 45.4% ± 9.7% (7 related bone marrow/related peripheral blood; 5 umbilical cord blood), and for chronic GVHD it was 38.1% ± 19.7%. FK506/MMF was well tolerated. Three patients had grade III to IV neurotoxicity (disorientation and leukoencephalopathy); 4 patients developed grade III to IV nephrotoxicity (all received concomitant nephrotoxins). Patients who achieved target mycophenolic acid levels (1.0-3.5 μg/mL) before day +30 had a significantly reduced incidence of developing grade ≥II aGVHD (16.7% ± 15.2% versus 100%; P < .02). These results suggest that FK506/MMF is well tolerated and may be a safe and effective methotrexate- and methylprednisolone-sparing alternative GVHD prophylaxis regimen after AlloSCT. Further pharmacokinetic and pharmacodynamic studies are ongoing in pediatric and adolescent AlloSCT recipients to define optimal MMF dosing.
KW - Allogeneic stem cell transplantation
KW - Graft-versus-host disease
KW - Mycophenolate mofetil
KW - Tacrolimus
UR - https://www.scopus.com/pages/publications/11144354112
U2 - 10.1016/j.bbmt.2003.11.005
DO - 10.1016/j.bbmt.2003.11.005
M3 - Article
C2 - 15077223
AN - SCOPUS:11144354112
SN - 1083-8791
VL - 10
SP - 246
EP - 258
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -