Background. Reduced intensity conditioning (RIC) regimens have been widely used over the past years with the aim of reducing transplant related mortality (TRM) of allogeneic hemopoietic stem cells transplants (HSCT). The preferred source is peripheral blood (PB) cells, although this source has not been prospectively compared with bone marrow (BM) iun the setting of RIC transplants.

Aim of the study. To compare BM and PB allogeneic transplants following a RIC regimen in patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML) or idiopathic myelofibrosis (IM).

Methods and patients. This is a prospective multicenter randomized trial: eligible were patients with AML, CML and IM, aged 45–60, with an HLA identical sibling, Conditioning regimen was thiotepa 5 mg/kgx2 and cyclophopshamide 50 mg/kgx2. Graft versus host disease (GvHD) prophylaxis was low dose cyclosporin and low dose methotrexate. Patients were randomized to receive unmanipulated BM (n=36) or unmanipulated PB (n=35), after stratification for disease phase (1st remission, n=47) or advanced disease (n=24). Median age was 51 in both groups and follow up of surviving patients 760 and 756 days respectively.

Results. Engraftment was achieved in all but one patient who has autologous reconstitution. Acute GvHD grade III–IV accurred in 0% vs 12% of BM vs PB patients (p=0.03) and extensive chronic GvHD in 13% vs 37% respectively (p=0.03).

Cumulative incidence (CI) of TRM at 5 years is 6% for BM and 9% for PB (p=0.6). Relapse of the original disease occurred in 61% vs 29% of BM and PB patients (p=0.007) and the CI of relapse related death (RRD) is 39% vs 19% respectively (p=0.07). Actuarial 5 year survival is 47% in BM vs 68% in PB paitents (p=0.3). A COX proportional step down analysis shows chronic GvHD to be a significant favourable factor for RRD and survival. Conclusions. In patients receiving a RIC allogeneic graft

  • TRM is low and comparable in BM and PB transplanst;

  • acute and chronic GvHD is more frequent in PB transplants,

  • relapse is significantly decreased in PB transplants and RRD is also lower,

  • there is a non significant survival advantage for PB patients and

  • the occurrence of chronic GvHD protects against relapse and favourably influences long term survival.

Topics:
bone marrow, hematopoietic stem cell transplantation, myeloproliferative disease, stem cells, graft-versus-host disease, chronic, graft-versus-host disease, cyclosporine, disease remission, follow-up, graft-versus-host disease, acute

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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