Researchers from Italy have reported that the injection of umbilical cord blood directly into the pelvic bones of patients with leukemia appears promising. These results were recently published in an early online publication of the Lancet Oncology on August 9, 2008.

Transplantation of bone marrow, peripheral blood stem cells, and umbilical cord blood is accomplished by intravenous infusion. The original studies of human bone marrow transplantation were carried out by direct infusion into bone marrow spaces. However, this approach was abandoned as there was no advantage in speed or rate of engraftment over intravenous infusion. Since these early days of transplantation, there have been sporadic attempts to evaluate intra-osseous infusion of stem cells, but no advantage over intravenous infusion was ever found. The reason for this is thought to be that direct infusion of stem cells into the marrow cavity is in fact identical to intra-arterial or intra-venous infusion, and most stem cells enter the general circulation before homing into marrow spaces throughout the body.

Umbilical cord blood transplantation is associated with relatively high graft failure rates thought to be due to the relatively low dose of stem cells in each collection. Researchers have suggested that the infusion of stem cells from two separate cord blood collections alleviates the graft failure problem. However, Italian researches have posed the question of whether or not intra-osseous infusion would be better.

The current trial evaluated direct infusion of umbilical cord blood into the pelvic bones. This trial included 32 patients with acute myeloid leukemia (AML) and 12 with acute lymphoblastic leukemia (ALL); median age was 36 years. Overall, 14 patients had advanced-stage disease that did not respond to standard therapies, and no patient had a suitable donor for the stem cell transplant.

• No complications occurred during the infusion of stem cells into the bone marrow.
• 28 of the 32 patients recovered neutrophil function and 27 recovered platelet function.
• The median time to recovery of 500 neutrophils was 28 days and the median time to recovery of platelets to 20,000 was 36 days.
• No patient developed acute, severe GVHD.

• At 13 months 16 patients were alive and in complete remission.
• Five patients died from treatment-related complications of the transplant, seven died from infection, and four patients died from a relapse of their disease.

The researchers concluded that these results “[lead] to the possibility of use of this technique in a large number of adult patients.” Although this technique is still under investigation, it provides promise for the future of patients with leukemia.

Comments: These data are not convincingly better than would be expected with intravenous infusion of cord blood stem cells. Only a randomized trial would answer the question of whether this is superior to intravenous infusion. However, given the fact that all studies in the past have failed to show a benefit from intra-osseous infusion of stem cells, this study must be looked upon with skepticism.

Related News:

Equivalent Results from Umbilical Cord Blood and Related Donor Stem Cell Transplants (2/7/2007)

Umbilical Cord Blood Transplants Successful in Children with High-Risk Acute Lymphocytic Leukemia (7/15/2005)

Co-Infusion of Peripheral Blood Stem Cells May Improve Umbilical Cord Blood Transplants in Adults (7/12/2005)

European Study Updates Results of Umbilical Cord Blood Transplants in Adults (4/22/2005)

Are Two Umbilical Cord Blood (UCB) Units Better Than One for Transplantation? (2/15/2005)

Japanese Study Shows Umbilical Cord Blood Transplants Superior to Unrelated Donor Transplants for Adults with Leukemia (1/10/2005)

Umbilical Cord Blood: Acceptable Source of Stem Cells for Adult Transplants (12/2/2004)

Reference: Frassoni F, Gualandi F, Podesta M, et al. Direct intrabone transplant of unrelated cord-blood cells in acute leukaemia: a Phase I/II study. Lancet Oncology [early online publication]. August 9, 2008. DOI:10.1016/S1470-2045(08)70180-3.