Intrabone Administration Of Unrelated Cord-Blood Cells Is Successful In Enabling More Patients With Acute Leukaemia To Undergo Transplantation

Main Category: Lymphoma / Leukemia
Also Included In: Transplants / Organ Donations;  Cancer / Oncology
Article Date: 09 Aug 2008 - 1:00 PDT

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Intrabone administration of unrelated umbilical-cord-blood cells overcomes the problem of graft failure seen with intravenous administration and is associated with a low incidence of graft-versus-host disease*, making the technique potentially useful in a large number of adult patients with acute leukaemia, according to findings from a phase I/II study, published early Online and in the September edition of The Lancet Oncology.

Cord-blood transplantation is an effective treatment for haematological malignancies, but only a small number of adult patients can undergo this procedure due to the high proportion of graft failures that occur (as a result of the low number of nucleated cells contained in a cord-blood unit) and the high incidence of graft-versus-host disease that follows. Dr Francesco Frassoni (San Martino Hospital, Genoa, Italy) and colleagues investigated intrabone injection of cord-blood cells as an alternative to intravenous injection, to assess whether this new approach was able to ensure engraftment and shorten the time to complete haemopoietic recovery.

Between March 31, 2006, and Jan 25, 2008, the safety and efficacy of intrabone injection was assessed in 32 patients with acute myeloid leukaemia or acute lymphoblastic leukaemia. A suitable unrelated cord-blood unit was found for each patient, and human leucocyte antigen (HLA) matching was 5/6 for nine patients, 4/6 for 22 patients, and 3/6 for one patient. The cord-blood cells were concentrated in 5-mL syringes and were injected into the superior-posterior iliac crest under rapid general anaesthesia. The primary endpoint was the probability of neutrophil and platelet recovery, and secondary endpoints were incidence of graft-versus-host disease, relapse, and overall survival.

Of 28 assessable patients, all achieved complete neutrophil recovery (median time to recovery 23 days [range 14-44]) and 27 patients achieved complete platelet recovery (median time to recovery 36 days [range 16-64]). All 27 patients showed complete reconstitution of haemopoiesis from cord-blood cells, and no patient had secondary graft failure. Importantly, no patients developed grade III-IV acute graft-versus-host disease. Overall survival was 45% at 1 year, with a median follow-up of 13 months (range 3-23).

Dr Frassoni concludes: "This technique might be possible in a large number of adult patients. The decreased incidence of acute graft-versus-host disease is intriguing. If these findings are proven in a larger series of patients, direct intrabone injection will have the potential to affect the current practice of haemopoietic stem-cell transplantation".

*Graft-versus-host disease is a common complication after an allogeneic transplant, in which immune cells from the donor attack the body of the recipient, and can range from mild to life-threatening. When the immune cells do not recognise HLA expressed on the recipient's cells they attack those cells, making HLA matching important for such transplants.

"Direct intrabone transplant of unrelated cord-blood cells in acute leukaemia: a phase I/II study"
Francesco Frassoni, Francesca Gualandi, Marina Podestà, Anna Maria Raiola, Adalberto Ibatici, Giovanna Piaggio, Mario Sessarego, Nadia Sessarego, Marco Gobbi, Nicoletta Sacchi, Myriam Labopin, Andrea Bacigalupo
The Lancet Oncology, Aug 9th 2008 - DOI:10.1016/S1470-2045(08)70180-3
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The Lancet Oncology
www.thelancet.com/journals/lanonc