title: Haploidentical, G-CSF-primed, unmanipulated bone marrow transplantation for patients with high-risk hematological malignancies: an update.
abstract: Ninety-seven patients affected by high-risk hematological malignancies underwent G-CSF primed, unmanipulated bone marrow (BM) transplantation from a related, haploidentical donor. All patients were prepared with an identical conditioning regimen including Thiotepa, Busilvex, Fludarabine (TBF) and antithymocyte globulin given at myeloablative (MAC = 68) or reduced (reduced intensity conditioning (RIC) = 29) dose intensity and received the same GvHD prophylaxis consisting of the combination of methotrexate, cyclosporine, mycofenolate-mofetil and basiliximab. Patients were transplanted in 1st or 2nd CR (early phase: n = 60) or in > 2nd CR or active disease (advanced phase: n = 37). With a median time of 21 days (range 12-38 days), the cumulative incidence (CI) of neutrophil engraftment was 94 ± 3%. The 100-day CI of III-IV grade acute GvHD and the 2-year CI of extensive chronic GvHD were 9 ± 3% and 12 ± 4%, respectively. Overall, at a median follow-up of 2.2 years (range 0.3-5.6), 44 out of 97 (45%) patients are alive in CR. The 5-year probability of overall survival (OS) and disease-free survival (DFS) for patients in early and advanced phase was 53 ± 7 vs 24 ± 8% (P = 0.006) and 48 ± 7 vs 22 ± 8% (P = 0.01), respectively. By comparing MAC with RIC patient groups, the transplant-related mortality was equivalent (36 ± 6 vs 28 ± 9%) while the relapse risk was lower for the MAC patients (22 ± 6 vs 45 ± 11%), who showed higher OS (48 ± 7 vs 29 ± 10%) and DFS (43 ± 7 vs 26 ± 10%). However, all these differences did not reach a statistical significance. In multivariate analysis, diagnosis and recipient age were significant factors for OS and DFS. In conclusion, this analysis confirms, on a longer follow-up and higher number of patients, our previous encouraging results obtained by using MAC and RIC TBF regimen as conditioning for G-CSF primed, unmanipulated BM transplantation from related, haploidentical donor in patients with high-risk hematological malignancies, lacking an HLA-identical sibling or unrelated donor and in need to be urgently transplanted.
authors.affiliation: Stem Cell Transplant Unit, Rome Transplant Network, Department of Hematology, "Tor Vergata" University Hospital, Rome, Italy.
authors.forename: W
authors.initials: W
authors.lastname: Arcese
authors.affiliation: Stem Cell Transplant Unit, Rome Transplant Network, Department of Hematology, "Tor Vergata" University Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Picardi
authors.affiliation: Bone Marrow Transplant Center, Department of Hematology, Spirito Santo Hospital, Pescara, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Santarone
authors.affiliation: Stem Cell Transplant Unit, Rome Transplant Network, Department of Hematology, "Tor Vergata" University Hospital, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: De Angelis
authors.affiliation: Stem Cell Transplant Unit, Rome Transplant Network, Department of Hematology, "Tor Vergata" University Hospital, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Cerretti
authors.affiliation: Stem Cell Transplant Unit, Rome Transplant Network, Department of Hematology, "Tor Vergata" University Hospital, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cudillo
authors.affiliation: Bone Marrow Transplant Center, Department of Hematology, Spirito Santo Hospital, Pescara, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Pennese
authors.affiliation: Bone Marrow Transplant Center, Department of Hematology, Spirito Santo Hospital, Pescara, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Bavaro
authors.affiliation: Bone Marrow Transplant Center, Department of Hematology, Spirito Santo Hospital, Pescara, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Olioso
authors.affiliation: Hematology, Department of Specialties, Sant'Andrea Hospital, Rome, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Dentamaro
authors.affiliation: Hematology, Department of Specialties, Sant'Andrea Hospital, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cupelli
authors.affiliation: Hematology, Department of Specialties, San Giovanni Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Chierichini
authors.affiliation: Hematology, Department of Oncology, Sant'Andrea Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ferrari
authors.affiliation: Department of Oncology, Regima Elena National Cancer Institute, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mengarelli
authors.affiliation: Hematology Stem Cell Transplant Transfusion Medicine and Cellular Therapy, Rome, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Tirindelli
authors.affiliation: Laboratory of Immunogenetics and Transplant Biology-IME Foundation, Policlinic of Tor Vergata, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Testi
authors.affiliation: Stem Cell Transplant Unit, Rome Transplant Network, Department of Hematology, "Tor Vergata" University Hospital, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Di Piazza
authors.affiliation: Bone Marrow Transplant Center, Department of Hematology, Spirito Santo Hospital, Pescara, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Di Bartolomeo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D015996:Survival Rate; D013997:Time Factors; D019172:Transplantation Conditioning
chemical_list: D019653:Myeloablative Agonists; D016179:Granulocyte Colony-Stimulating Factor