title: Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation.
abstract: It is unknown whether the severity, timing, and quality of graft-versus-host disease (GVHD) may be different after nonmyeloablative as compared with myeloablative hematopoietic stem cell transplantation (HSCT). Therefore, GVHD incidence, morbidity of skin, liver, and gut, requirements for immunosuppressive therapy, and survival were retrospectively analyzed in 44 patients who underwent nonablative HSCT and 52 who underwent ablative HSCT (median ages, 56 and 54 years, respectively). The nonablative transplantation regimen consisted of low-dose total body irradiation (TBI), preceded in some patients by fludarabine administration and followed in all patients by immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). Those who underwent myeloablative HSCT were prepared with different TBI- and non-TBI-containing regimens and received CSP plus methotrexate or MMF for GVHD prophylaxis. The cumulative incidence of grades II-IV acute GVHD was lower after nonablative transplantation (64% vs 85%; P =.001), but there were no differences in the cumulative incidence of chronic GVHD requiring treatment (73% vs 71%; P =.96). Nonablative transplantation was associated with the delayed initiation of steroid treatment for GVHD (0.95 months vs 3.0 months; P <.001) and with the use of fewer systemic immunosuppressants in the first 3 months after transplantation (P </=.04). This corresponded to more prevalent skin and more severe gut morbidity 6 to 12 months after nonablative transplantation. Our results show that nonablative HSCT is associated with a syndrome of acute GVHD occurring after day 100 in many patients. This "late-onset acute GVHD" should be taken into consideration in the design of prospective studies comparing GVHD resulting from the two types of transplantation procedures.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, Seattle, WA, 98109-1024, USA. mielcar@u.washington.edu
authors.forename: Marco
authors.initials: M
authors.lastname: Mielcarek
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Wendy
authors.initials: W
authors.lastname: Leisenring
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002066:Busulfan; D002423:Cause of Death; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007422:Intestines / Q000473:pathology; D015993:Life Tables; D008099:Liver / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D009928:Organ Specificity; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014740:Vidarabine / Q000031:analogs & derivatives*; D014861:Washington / Q000453:epidemiology; D014916:Whole-Body Irradiation
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014740:Vidarabine; D002066:Busulfan; D009173:Mycophenolic Acid; C024352:fludarabine; D008727:Methotrexate