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-versushost 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.

The hematopoietic system in the context of regenerative medicine

“…Support for this shift has come from numerous large, multicenter, randomized trials performed to-date, which have collectively shown that engraftment/reconstitution is often faster and more robust with mPB than with marrow, and may be associated with a decreased relapse rate, but this appears to depend upon the patient population and malignancy in question [125, 126]. However, as originally feared, these studies have also revealed that the use of mPB is associated with a significantly higher rate of chronic (and perhaps acute) GVHD than marrow, and offers no significant improvement in survival [114, 115, 124, 127–137].…”

Rapid donor T‐cell engraftment increases the risk of chronic graft‐versus‐host disease following salvage allogeneic peripheral blood hematopoietic cell transplantation for bone marrow failure syndromes

“…These data suggest the deleterious effect iron overload has on transplant outcome may be overcome by aggressive post-transplant phlebotomy in these types of patients. Numerous studies have clearly defined an increased risk of chronic-GVHD with the use of PBPC compared to BM [19,47,48]. Although highly successful in preventing graft-failure, this transplant approach led to a high incidence of chronic-GVHD [49,50].…”

Novel strategies for improving hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation or intensive chemotherapy

“…Stem cell source is one of the main factors affecting engraftment kinetics [18,[23][24][25]. As example in one large study assessing the impact of graft source on unrelated donor allo-HCT in adults with acute leukemia, median times to neutrophil (defined as achievement of an absolute neutrophil count of ≥500 cells/mm 3 for 3 consecutive days) and platelet (defined as achievement of ≥20,000 platelets/mm 3 unsupported by transfusion for 7 days) recoveries were 14 (range, 5-28) and 19 (range, 7-112) days respectively after peripheral blood stem cell transplantation (PBSCT), 19 (range 6-41) and 28 (range, 10-150) days respectively after bone marrow transplantation, and 24 (range, 12-68) and 52 (range, 22-275) days, respectively after UCBT [18].…”