title: A new minimally ablative stem cell transplantation procedure in high-risk patients not eligible for nonmyeloablative allogeneic bone marrow transplantation.
abstract: Nonmyeloblative stem cell transplantation (NST, SCT) aims to induce host-versus-graft tolerance for subsequent immunotherapy of underlying disease with alloreactive donor lymphocytes, focusing on well-tolerated conditioning suitable for elderly individuals or for other risk factors. However, there is a subset of high-risk patients who cannot tolerate NST. A new protocol consisting of fludarabine 30 mg/m(2) x 6 days (days -8 to -2), very-low-dose busulfan (2 mg/kg x 2 days, days -6 to -5), without anti thymocyte globulin (ATG), was employed in 11 high-risk patients aged 26-58 years. Graft-versus-host-disease (GVHD) prophylaxis consisted of low-dose and short-course cyclosporine-A (CSA) alone. One patient died during the nadir due to pulmonary complications. Other patients showed rapid three-lineage engraftment, without complete aplasia; 6/10 patients did not require platelet transfusion and 8/10 had full donor chimerism without transient mixed chimerism. Owing to intentional selection of highly poor-risk patients, overall mortality was high and only one patient survived. Acute GVHD (>/=grade I) occurred in 8/10 evaluable patients, 5/8 while off CSA; 5/8 developed grade III-IV acute GVHD. It appears that our modified, minimally ablative stem cell transplantation (MST) may be used for high-risk patients in need of allo-SCT. Furthermore, although the MST conditioning is not myeloablative, it results in myeloablation of the host hematopoietic system, mediated by alloreactive lymphocytes.
authors.affiliation: Department of Bone Marrow Transplantation & Cancer Immunotherapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. shapiram@hadassah.org.il
authors.forename: M Y
authors.initials: MY
authors.lastname: Shapira
authors.forename: R
authors.initials: R
authors.lastname: Or
authors.forename: I B
authors.initials: IB
authors.lastname: Resnick
authors.forename: M
authors.initials: M
authors.lastname: Bitan
authors.forename: A
authors.initials: A
authors.lastname: Ackerstein
authors.forename: S
authors.initials: S
authors.lastname: Samuel
authors.forename: S
authors.initials: S
authors.lastname: Elad
authors.forename: I
authors.initials: I
authors.lastname: Zilberman
authors.forename: S
authors.initials: S
authors.lastname: Miron
authors.forename: S
authors.initials: S
authors.lastname: Slavin
mesh_terms: D000328:Adult; D002066:Busulfan / Q000008:administration & dosage; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality / Q000628:therapy; D018579:Patient Selection; D010865:Pilot Projects; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine