Allogeneic peripheral blood stem cell and bone marrow transplantation for hematologic malignancies: Meta-analysis of randomized controlled trials

The Stem Cell Trialist’s Collaborative Group. An individual-patient data meta-analysis using data from 9 randomized trials enrolling 1,111 patients (pts.) to compare allogeneic peripheral blood stem cell transplantation (PBSCT) with bone marrow transplantation (BMT) has recently been completed (Hematology J2004;5:s89). Here, we report the results of this analysis for patients suffering from CML in 1st chronic phase (CP1) (n=422) or accelerated phase/blast crisis (AP/BC) (n=50). Overall survival at five years (70%) was not significantly different in patients who were transplanted with peripheral blood (PB) as compared to bone marrow (BM) cells if all pts. [absolute difference (AD) 3.3 %, p=0.16] or pts. in CP1 [AD 1.1 %, p=0.72] were considered. However, pts. transplanted for AP or BC survived significantly longer following PBSCT than BMT [AP 40 %, p=0.015]. The difference between two subgroups was significant (test of interaction chi²=4.3;p=0.04). Disease-free survival (DFS) was significantly better after PBSCT for all pts. [AD 15.2 %, p=0.004], for pts. in CP1 [AD 11.5 %, p=0.069], and AP/BC [AD 30.3 %, p=0.009]. Test of interaction between two subgroups was chi²=4.3;p=0.07. Relapse rates for all pts. [AD 18.6 %, p=0.00005] and pts. in CP1 [AP 17.0 %, p=0.0002] were significantly lower after PBSCT; no statistical difference was found for pts. in AP/BC most likely due to small patient numbers. Extensive chronic GVHD occurred more often after PBSCT [AD 20%, p<0.00001 ) than after BMT.Treatment-related mortality (TRM) at 5 yrs was 27% for all pts and 26% for patients in CP phase with no significant differences between pts. transplanted with PB instead of BM.TRM was higher in the BMT arm (62% vs. 22%, p=0.02) for pts. in AP/BC. The difference between two subgroups was statistically significant (chi²=5.5;p=0.02). Pts. with CML in AP/BC should be offered a transplant with G-CSF mobilized PB. For pts. in CP1 the decision to use PB or BM needs to value the higher risk of attracting extensive cGVHD against the lower risk of relapse after PBSCT. Further follow up will be necessary to see if the difference in relapse rates after BMT as compared to PBSCT continues to increase over time.

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Acute and Chronic Graft-Versus-Host Disease After Allogeneic Peripheral-Blood Stem-Cell and Bone Marrow Transplantation: A Meta-Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.16.3685 ◽

2001 ◽

Vol 19 (16) ◽

pp. 3685-3691 ◽

Cited By ~ 318

Author(s):

Corey Cutler ◽

Satyendra Giri ◽

Suriya Jeyapalan ◽

David Paniagua ◽

Akila Viswanathan ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Bone Marrow Transplantation ◽

Graft Versus Host Disease ◽

Peripheral Blood ◽

Marrow Transplantation ◽

Peripheral Blood Stem Cell ◽

Meta Analysis ◽

Chronic Gvhd ◽

Graft Versus Host

PURPOSE: Controversy exists as to whether the incidence of graft-versus-host disease (GVHD) is increased after peripheral-blood stem-cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT). We performed a meta-analysis of all trials comparing the incidence of acute and chronic GVHD after PBSCT and BMT reported as of June, 2000. Secondary analyses examined relapse rates after the two procedures. METHODS: An extensive MEDLINE search of the literature was undertaken. Primary authors were contacted for clarification and completion of missing information. A review of cited references was also undertaken. Sixteen studies (five randomized controlled trials and 11 cohort studies) were included in this analysis. Data was extracted by two pairs of reviewers and analyzed for the outcomes of interest. Meta-analyses, regression analyses, and assessments of publication bias were performed. RESULTS: Using a random effects model, the pooled relative risk (RR) for acute GVHD after PBSCT was 1.16 (95% confidence interval [CI], 1.04 to 1.28; P= .006) when compared with traditional BMT. The pooled RR for chronic GVHD after PBSCT was 1.53 (95% CI, 1.25 to 1.88; P < .001) when compared with BMT. The RR of developing clinically extensive chronic GVHD was 1.66 (95% CI, 1.35 to 2.05; P < .001). The excess risk of chronic GVHD was explained by differences in the T-cell dose delivered with the graft in a meta-regression model that did not reach statistical significance. There was a trend towards a decrease in the rate of relapse after PBSCT (RR = 0.81; 95% CI, 0.62 to 1.05). CONCLUSION: Both acute and chronic GVHD are more common after PBSCT than BMT, and this may be associated with lower rates of malignant relapse. The magnitude of the transfused T-cell load may explain the differences in chronic GVHD risk.

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