Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials

Abstract

Purpose: Considerable uncertainty exists regarding relative effects of allogeneic peripheral blood stem cells transplantation (PBSCT) versus bone marrow transplantation (BMT) on outcomes of patients with hematologic malignancies.

Patients and methods: To provide the totality of research evidence related to the effects of PBSCT versus BMT, we conducted an individual-patient data meta-analysis using data from nine randomized trials enrolling 1,111 adult patients.

Results: Compared with BMT, PBSCT led to faster neutrophil (odds ratio [OR] = 0.31; 95% CI, 0.25 to 0.38; P < .00001) and platelet engraftment (OR = 0.52; 95% CI, 0.44 to 0.61; P < .00001). PBSCT was associated with a significant increase in the development of grade 3-4 acute graft-versus-host disease (GVHD; OR = 1.39; 95% CI, 1.03 to 1.88) and extensive (47% v 31% at 3 years; OR = 1.89; 95% CI, 1.47 to 2.42; P < .000001) and overall chronic GVHD (68% v 52% at 3 years; OR = 1.92; 95% CI, 1.47 to 2.49; P < .000001), but not grade 2-4 acute GVHD (54% v 53%; P = .49). PBSCT was associated with a decrease in relapse (21% v 27% at 3 years; OR = 0.71; 95% CI, 0.54 to 0.93; P = .01) in both late-stage-(33% v 51% at 3 years; OR = 0.59; 95% CI, 0.38 to 0.93; P = .02) and early-stage-disease patients (16% v 20% at 3 years; OR = 0.69; 95% CI, 0.49 to 0.98; P = .04). Nonrelapse mortality was not different between groups. Overall and disease-free survival were only statistically significantly improved in patients with late-stage disease (overall survival: 46% v 31% at 3 years; OR = 0.64; 95% CI, 0.46 to 0.90; P = .01; disease-free survival: 41% v 27% at 3 years; OR = 0.63 95% CI, 0.45 to 0.87; P = .01).

Conclusion: PBSCT is associated with a decreased relapse rate in hematologic malignancies and improvement in overall and disease-free survival in patients with late-stage disease. PBSCT is also associated with a significant risk of extensive chronic GVHD.

Fig 1.

The patient distribution according to the type of diagnosis and its prognostic features (favorable = early-stage disease; unfavorable = late-stage disease; see text for details). BMT, bone marrow transplantation; PBSCT, peripheral blood stem-cell transplantation; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; MDS = myelodysplastic syndrome; HD, Hodgkin’s disease; NHL, non-hodgkin lymphoma; CLL, chronic lymphocytic leukemia; MM, multiple myeloma; IMF, idiopathic myelofibrosis.

Fig 2.

Summary forest plot showing the effects of allogeneic peripheral blood stem cell transplantation (PBSCT) versus bone marrow transplantation (BMT). If the square is to the left of the solid line then odds ratio (OR) is better in the group receiving PBSC, but if the CI crosses this line, then this result is not statistically significant (P < .05). GVHD, graft-versus-host disease; c, chronic; a, acute; O – E, observed – expected; Var., variance; Redn., reduction; SD, standard deviation.

Fig 3.

(A) Time-to-event plots showing the absolute risk for development of grade 2-4 acute graft-versus-host-disease (GVHD) in patients with hematologic malignancies. (B) Time-to-event plots showing the absolute risk for development of grade 3-4 acute GVHD in patients with hematologic malignancies. PBSCT, peripheral blood stem-cell transplantation; BMT, bone marrow transplantation; abs diff, absolute difference.

Fig 4.

(A) Time-to-event plots showing the absolute risk for development of extensive stage of chronic graft-versus-host disease (GVHD) in the patients with hematologic malignancies. (B) Time-to-event plots showing the absolute risk for development of any stage of chronic GVHD in patients with hematologic malignancies. PBSCT, peripheral blood stem-cell transplantation; BMT, bone marrow transplantation; Abs diff, absolute difference.

Fig 5.

Time-to-event plots showing the risk of relapse in patients with hematologic malignancies treated with allogeneic peripheral blood stem-cell transplantation (PBSCT) versus bone marrow transplantation (BMT). Abs diff, absolute difference.

Fig 6.

Time-to-event plots showing the risk of relapse in patients with hematologic malignancies treated with allogeneic peripheral blood stem-cell transplantation (PBSCT) versus bone marrow transplantation (BMT). (A) In early-stage disease and (B) in late-stage disease. Abs diff, absolute difference.

Fig 7.

(A) Relapse-related mortality. Time-to-event plots showing the absolute risk reductions in relapse mortality in patients with hematologic malignancies treated with allogeneic peripheral blood stem-cell transplantation (PBSCT) versus bone marrow transplantation (BMT). (B) Time-to-event plots showing the absolute risk reductions in death without relapse (nonrelapse mortality) in patients with hematologic malignancies treated with allogeneic PBSCT versus BMT. Abs diff, absolute difference.

Fig 8.

Survival curves showing the absolute risk reductions in disease-free survival in patients with hematologic malignancies treated with allogeneic peripheral blood stem-cell transplantation (PBSCT) versus bone marrow transplantation (BMT). Differences at 3- and 5-year outcome, together with the SEs, and two-sided P values are given in the box. Abs diff, absolute difference.

Fig 9.

Survival curves showing the absolute risk reductions in disease-free survival in patients with hematologic malignancies treated with allogeneic peripheral blood stem-cell transplantation (PBSCT) versus bone marrow transplantation (BMT). (A) In early-stage disease, (B) in late-stage disease. Abs diff, absolute difference.

Fig 10.

Forest plot illustrating the effect of peripheral blood stem-cell transplantation (PBSCT) versus bone marrow transplantation (BMT) on overall survival. Note: inclusion of Egyptian trial (N = 29) from which data on individual patients were not available (data from this trial were extracted from the paper). Inclusion of this trial did not change the results significantly (see the main text for details). NS, not significant; OR, odds ratio; EBMT, European Group for Blood and Marrow Transplantation; O – E, observed – expected; Var., variance; Redn., reduction; SD, standard deviation.

Fig 11.

Survival curves showing the absolute risk reductions in death in patients with hematologic malignancies treated with allogeneic peripheral blood stem-cell transplantation (PBSCT) versus bone marrow transplantation (BMT). Abs diff, absolute difference.

Fig 12.

Survival curves showing the absolute risk reductions in death in patients with hematologic malignancies treated with allogeneic peripheral blood stem-cell transplantation (PBSCT) versus bone marrow transplantation (BMT). (A) In early-stage disease, (B) in late-stage disease. Abs diff, absolute difference.