TY - JOUR
T1 - A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders
AU - Shenoy, S.
AU - Grossman, W. J.
AU - DiPersio, J.
AU - Yu, L. C.
AU - Wilson, D.
AU - Barnes, Y. J.
AU - Mohanakumar, T.
AU - Rao, A.
AU - Hayashi, R. J.
PY - 2005
Y1 - 2005
N2 - Bone marrow transplantation (BMT) benefits nonmalignant diseases but is limited by regimen-related toxicity, graft-versus-host disease (GVHD), donor availability, and graft rejection (GR). To overcome some of these barriers, we developed a new conditioning strategy for these patients. In total, 16 patients received Campath-1H (33/48 mg; days -21 to -19), fludarabine (150 mg/m2; days -8 to -4), melphalan (140/70 mg/m2; day -3), and transplant using related/unrelated stem cells. GVHD prophylaxis included cyclosporine/methylprednisolone for cord cells. Other recipients also received methotrexate. Risk factors for GR included multiple transfusions (6), low stem cell numbers (1), and immunologic/metabolic disorders (3). Donor engraftment was present in 14/16 recipients. Neutrophils (ANC >0.5 × 109/l) and platelets (>50 × 109/l) engrafted at a median of 13 and 24 days. Two patients died of Pseudomonas sepsis prior to engraftment, one of CMV disease, and another of intracranial hemorrhage. With median follow-up of 281 days (78-907), 12/16 are stable/improved, or cured. Acute GVHD was absent (n = 10) or mild and transient (grade 1-2 skin) (n = 4). There was no chronic GVHD. Toxicities were predominantly early infections within 100 days, and correlated with lymphopenia (CD4+ T and B cells). Stable engraftment and low incidence of significant GVHD, irrespective of age or stem cell source, make this reduced-intensity regimen attractive for nonmalignant disorders.
AB - Bone marrow transplantation (BMT) benefits nonmalignant diseases but is limited by regimen-related toxicity, graft-versus-host disease (GVHD), donor availability, and graft rejection (GR). To overcome some of these barriers, we developed a new conditioning strategy for these patients. In total, 16 patients received Campath-1H (33/48 mg; days -21 to -19), fludarabine (150 mg/m2; days -8 to -4), melphalan (140/70 mg/m2; day -3), and transplant using related/unrelated stem cells. GVHD prophylaxis included cyclosporine/methylprednisolone for cord cells. Other recipients also received methotrexate. Risk factors for GR included multiple transfusions (6), low stem cell numbers (1), and immunologic/metabolic disorders (3). Donor engraftment was present in 14/16 recipients. Neutrophils (ANC >0.5 × 109/l) and platelets (>50 × 109/l) engrafted at a median of 13 and 24 days. Two patients died of Pseudomonas sepsis prior to engraftment, one of CMV disease, and another of intracranial hemorrhage. With median follow-up of 281 days (78-907), 12/16 are stable/improved, or cured. Acute GVHD was absent (n = 10) or mild and transient (grade 1-2 skin) (n = 4). There was no chronic GVHD. Toxicities were predominantly early infections within 100 days, and correlated with lymphopenia (CD4+ T and B cells). Stable engraftment and low incidence of significant GVHD, irrespective of age or stem cell source, make this reduced-intensity regimen attractive for nonmalignant disorders.
KW - Campath-1H
KW - Metabolic disorders
KW - Nonmalignant
KW - Reduced-intensity transplant regimen
KW - Stem cell
UR - http://www.scopus.com/inward/record.url?scp=14644418544&partnerID=8YFLogxK
U2 - 10.1038/sj.bmt.1704795
DO - 10.1038/sj.bmt.1704795
M3 - Article
C2 - 15592491
AN - SCOPUS:14644418544
SN - 0268-3369
VL - 35
SP - 345
EP - 352
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 4
ER -