title: Myeloablative allogeneic bone marrow transplant using T cell depleted allografts followed by post-transplant GM-CSF in high-risk myelodysplastic syndromes.
abstract: Allogeneic blood and marrow transplantation (alloBMT) remains the only curative treatment for patients with myelodysplastic syndromes (MDS), but its application has been limited by the older age range of patients with this disease. T cell depletion decreases transplant-related toxicity related to graft-versus-host disease (GVHD), but does not improve overall survival because of increased risk for relapse and graft failure. Myeloid growth factors have been used to speed engraftment following alloBMT, but data suggest that they may also have anti-tumor properties. We treated 43 patients (median age 56) with MDS/AML with high-risk features using a myeloablative T cell depleted alloBMT followed by prolonged systemic GM-CSF. The current event-free survival at 1 and 3 years was 47% and 34%, respectively with a median follow-up of 22.8 months in surviving patients. The toxicities compared favorably with those seen using reduced intensity conditioning regimens and included grade III/IV GVHD (10%), graft failure (9%), and cumulative treatment-related mortality (28%). The cumulative incidence of relapse remained high at 38%; however, 3/10 patients receiving donor lymphocyte infusions achieved durable complete remissions. These results suggest that it is possible to maintain treatment intensity while minimizing toxicity in older, high-risk MDS patients.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States.
authors.forename: Erica D
authors.initials: ED
authors.lastname: Warlick
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Donnell
authors.forename: Michael
authors.initials: M
authors.lastname: Borowitz
authors.forename: Nichon
authors.initials: N
authors.lastname: Grupka
authors.forename: Lauren
authors.initials: L
authors.lastname: Decloe
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.forename: Ivan
authors.initials: I
authors.lastname: Borrello
authors.forename: Robert
authors.initials: R
authors.lastname: Brodsky
authors.forename: Ephraim
authors.initials: E
authors.lastname: Fuchs
authors.forename: Carol Ann
authors.initials: CA
authors.lastname: Huff
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
authors.forename: William
authors.initials: W
authors.lastname: Matsui
authors.forename: Richard
authors.initials: R
authors.lastname: Ambinder
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jones
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor