Journal Article

Haploidentical, G-CSF-primed, unmanipulated bone marrow transplantation for patients with high-risk hematological malignancies: an update

Bavaro, P, Olioso, P, Mengarelli, A, Dentamaro, T, Picardi, A, Di Piazza, F, Ferrari, A, Testi, M, Chierichini, A, Santarone, S, Cupelli, L, Pennese, E, Cudillo, L, Arcese, W, Di Bartolomeo, P, Cerretti, R, De Angelis, G, Tirindelli, M C

2015

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/250/1904 / 692/699/1541/1990 / 692/700/565/545/576/1955 / Adolescent / Adult / Aged / Analysis / Antilymphocyte serum / Bone marrow / Bone Marrow Transplantation / Cancer / Care and treatment / Cell Biology / Child / Child, Preschool / Conditioning / Cyclosporins / Disease prevention / Disease-Free Survival / Female / Fludarabine / Follow-Up Studies / Globulins / Graft vs Host Disease - mortality / Graft vs Host Disease - prevention & control / Graft-versus-host reaction / Granulocyte colony-stimulating factor / Granulocyte Colony-Stimulating Factor - administration & dosage / Health aspects / Hematologic Neoplasms - mortality / Hematologic Neoplasms - therapy / Hematology / Histocompatibility antigen HLA / Humans / Immunosuppressive agents / Internal Medicine / Italy / Leukocytes (neutrophilic) / Male / Median (statistics) / Medicine / Medicine & Public Health / Methotrexate / Middle Aged / Mortality / Multivariate analysis / Myeloablative Agonists - administration & dosage / original-article / Public Health / Risk / Statistical analysis / Stem cell transplantation / Stem Cells / Survival / Survival Rate / Thymocytes / Time Factors / Transplantation / Transplantation Conditioning / Transplants & implants