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Clinical Trial
. 2011 Dec 8;118(24):6438-45.
doi: 10.1182/blood-2011-08-372508. Epub 2011 Oct 5.

Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions

Hongtao Liu  1 , Elizabeth S Rich, Lucy Godley, Olatoyosi Odenike, Loren Joseph, Susana Marino, Justin Kline, Vu Nguyen, John Cunningham, Richard A Larson, Paula del Cerro, Linda Schroeder, Lisa Pape, Wendy Stock, Amittha Wickrema, Andrew S Artz, Koen van Besien
Affiliations
Clinical Trial

Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions

Hongtao Liu et al. Blood. .

Abstract

We conducted a 45 patient prospective study of reduced-intensity conditioning (RIC) and transplantation of unrelated umbilical cord blood (UCB) and CD34(+) stem cells from a haploidentical family member. Median age was 50 years; weight was 80 kg. Fifty-eight percent had active disease. Neutrophil engraftment occurred at 11 days (interquartile range [IQR], 9-15) and platelet engraftment at 19 days (IQR, 15-33). In the majority of patients, early haploidentical engraftment was replaced by durable engraftment of UCB by 100 days, with regular persistence of minor host and/or haplo-hematopoiesis. Percentage of haplochimerism at day 100 correlated with the haplo-CD34 dose (P = .003). Cumulative incidence of acute GVHD (aGVHD) was 25% and chronic GVHD (cGVHD) was 5%. Actuarial survival at 1 year was 55%, progression-free survival (PFS) was 42%, nonrelapse mortality (NRM) was 28%, and relapse was 30%. RIC and haplo-cord transplantation results in fast engraftment of neutrophils and platelets, low incidences of aGVHD and cGVHD, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay, and promising long-term outcomes. UCB cell dose had no impact on time to hematopoietic recovery. Therefore, UCB selection can prioritize matching, and better matched donors can be identified rapidly for most patients. This study is registered at http://clinicaltrials.gov as NCI clinical trial no. NCT00943800.

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Figures

Figure 1
Figure 1
Haplo-cord SCT RIC regimen.
Figure 2
Figure 2
Cumulative incidence of neutrophil and platelet engraftment. (A) Neutrophils. (B) Platelets.
Figure 3
Figure 3
The evolution of haplo to cord engraftment during the first 6 months after transplantation. The error bars indicate the 25% to 75% IQR. (A) Unfractionated peripheral blood and (B) CD3-positive cells.
Figure 4
Figure 4
Quantity of haplo CD34+ cells infused versus fraction of haplo chimerism at day 100. A higher number of CD34+ cells infused, correlates with a greater proportion of donor chimerism derived from the haploallograft at day 100.
Figure 5
Figure 5
Cumulative incidence of acute GVHD (grade II-IV).
Figure 6
Figure 6
Transplant outcomes. (A) Cumulative incidence of relapse and TRM. (B) Progression-free survival by disease status at transplantation. (C) Overall survival.
See this image and copyright information in PMC

References

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