A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies

Abstract

Cytokine-mobilized peripheral blood is increasingly used instead of bone marrow as the source of cells for allogeneic transplantation. Although cells lead to faster hematologic recovery, their effects on graft-versus-host disease, relapse, and survival are less certain. Between January 1996 and February 2000, 228 patients with chronic myeloid leukemia, acute myeloid leukemia, or myelodysplasia were randomized to receive either bone marrow or peripheral blood allografts from HLA-matched siblings. All patients received busulfan and cyclophosphamide as conditioning chemotherapy and cyclosporine and methotrexate as graft-versushost disease prophylaxis. We compared the times to neutrophil and platelet recovery, acute and chronic graft-versus-host disease, relapse, and overall survival between the groups. The median times to neutrophil recovery were 19 days and 23 days and the times to platelet recovery were 16 days and 22 days in the peripheral blood and bone marrow groups, respectively (P < .0001 for both comparisons). The cumulative incidence of grades II to IV acute graft-versus-host disease 100 days after transplantation was 44% in both groups (hazard ratio, 0.99; 95% confidence interval, 0.66-1.49; P > .9), and the incidence of extensive chronic graftversus-host disease at 30 months after transplantation was 40% with peripheral blood and 30% with bone marrow (hazard ratio, 1.23; 95% confidence interval, 0.78-1.96; P ‫؍‬ .37). There was no statistically significant difference in the probability of relapse of the underlying disease between the groups. The probabilities of survival at 30 months after transplantation were 68% and 60% in the peripheral blood and bone marrow groups, respectively (hazard ratio, 0.62; 95% confidence interval, 0.39-0.97; P ‫؍‬ .04). In patients with chronic myeloid leukemia, acute myeloid leukemia, and myelodysplasia undergoing allogeneic transplantation from matched siblings, the use of peripheral blood instead of bone marrow leads to faster hematologic recovery, similar risk of graft-versus-host disease, and improved survival. IntroductionTraditionally, cells for allografting have been harvested directly from the pelvis of donors under general anesthesia. Hematopoietic progenitor cells also circulate in the peripheral blood, and their numbers are increased by administration of cytokines such as granulocyte colony-stimulating factor (G-CSF), allowing collection by leukapheresis. In autologous transplantation, such mobilized blood cells have largely replaced bone marrow as the source of cells for transplantation because their use leads to more rapid neutrophil and platelet recovery 1,2 and faster immune reconstitution. 3 However, enthusiasm for the adoption of mobilized blood cells for allogeneic transplantation has been tempered by 3 main considerations. 4 First, there was concern that the use of cytokines such as G-CSF may cause complications in healthy donors. Second, the peripheral blood harvest contains 10-fold more T cells than bone marrow, 5-7 which may be harmful because T cel...

Reduced risk of acute GVHD following mobilization of HLA-identical sibling donors with GM-CSF alone

“…Nevertheless, the incidence of grades 2-4 acute GVHD observed in the G-CSF group in this trial (49%) is clearly in line with rates (21-64%) reported in the PBPC arms of several randomized trials. [1][2][3][4][5][6][7] The lack of any grade 3-4 acute GVHD in the GM-CSF group is noteworthy given the large proportion of patients transplanted for high-risk disease.…”

“…[1][2][3][4][5][6][7][8] Nevertheless, in only a minority of the randomized comparative trials did this translate into an overall survival advantage and some studies suggested the use of G-CSF mobilized PBPC was associated with a greater risk of either acute or chronic graft-versus-host disease (GVHD), or both. 6,[8][9][10] In two recent retrospective studies in patients with aplastic anemia or children with leukemia performed by the International Bone Marrow Transplant Registry, transplantation of G-CSF mobilized PBPC was associated with higher rates of GVHD.…”

“…Lineage negative (negative for CD3, CD14, CD11b, CD19) CD34 þ cells were measured by a modification of the technique of Roscoe et al 25 Lymphocyte subsets were enumerated by mixing samples containing 1 Â 10 6 leukocytes with the following four cocktails of fluorescent conjugated antibodies (Beckman-Coulter, Fullerton, CA, USA): (1) CD3-FITC, CD-4-PE, CD8-ECD, and CD45-PE-Cy5; (2) CD3-FITC, CD56-PE, CD19-ECD, and CD45-PE-Cy5; (3) CD2-FITC and CD45-PE-Cy5, and (4) IgG 1 -FITC, IgG 1 -PE, IgG 1 -ECD, and CD45-PE-Cy5. After 30 min incubation at 41C, a red cell lysis procedure was performed using 0.15 M NH 4 Cl and samples were fixed with 1% paraformaldehyde. All flow cytometry analyses were performed on side scatter-CD45 gated lymphocytes using a Coulter Elite cytometer equipped with an argon laser (Beckman-Coulter).…”

Overcoming various comorbidities by G-CSF-primed unmanipulated BM SCT in adult patients with AML

“…However, a higher incidence of chronic GVHD in PBSCT compared to SCT using sBM may be more acceptable with current management strategies. 1,2,8,9,15 Moreover, based on a meta-analysis performed in 2001, PBSCT involves a slightly increased risk of acute GVHD. 16 More importantly, recent studies have found no significant difference between PBSCT and SCT using pBM in terms of engraftment, although PBSCT involved a significantly increased risk of acute and/or chronic GVHD.…”

“…1,2 In addition, allogeneic G-CSF-primed bone marrow (pBM) stem cells appear to be similar to PBSCs in terms of engraftment potential. [3][4][5][6][7] Overall, allogeneic hematopoietic SCT using pBM results in more rapid engraftment with a lower incidence of chronic GVHD than SCT using PBSCs.…”