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

Bone Marrow Transplant. 2015 Jun:50 Suppl 2:S24-30. doi: 10.1038/bmt.2015.91.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Marrow Transplantation*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease* / mortality
  • Graft vs Host Disease* / prevention & control
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Hematologic Neoplasms* / mortality
  • Hematologic Neoplasms* / therapy
  • Humans
  • Male
  • Middle Aged
  • Myeloablative Agonists / administration & dosage
  • Survival Rate
  • Time Factors
  • Transplantation Conditioning*

Substances

  • Myeloablative Agonists
  • Granulocyte Colony-Stimulating Factor