What is Stem Cell: [StemCells] Unrelated CB for acute leukemia

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

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
Click here to read The Summary online

The Lancet Oncology
www.thelancet.com/journals/lanonc

http://www.medicalnewstoday.com/articles/117780.php

The Lancet Oncology Early Online Publication, 9 August 2008

Lancet Oncology DOI:10.1016/S1470-2045(08)70180-3

Articles

Direct intrabone transplant of unrelated cord-blood cells in acute
leukaemia: a phase I/II study
Dr Francesco Frassoni MD a , Francesca Gualandi MD b, Marina
Podestà PhD a, Anna Maria Raiola MD a, Adalberto Ibatici MD a,
Giovanna Piaggio PhD b, Prof Mario Sessarego MD c, Nadia
Sessarego PhD a, Prof Marco Gobbi MD d, Nicoletta Sacchi PhD e,
Myriam Labopin MD f and Andrea Bacigalupo MD b

Summary
Background
Cord-blood transplants are associated with delayed or failed
engraftment in about 20% of adult patients. The aim of this phase
I/II study was to establish the safety and efficacy of a new
administration route (intrabone) for cord-blood cells, measured by
the donor-derived neutrophil and platelet engraftment.

Methods
Adult patients with acute leukaemia, for whom an unrelated stem-cell
transplantation was indicated and no suitable unrelated human
leucocyte antigen (HLA)-matched donor had been identified, were
included in the study and underwent a cord-blood transplant in San
Martino Hospital, Genoa, Italy. Eight patients were in first complete
remission, ten in second complete remission, and 14 had advanced-
stage, refractory disease. HLA matching was 5/6, 4/6, and 3/6 for 9,
22, and one patient, respectively. Cord-blood cells were concentrated
in four 5-mL syringes, and were infused in the superior-posterior
iliac crest under rapid general anaesthesia. Median transplanted cell
dose was 2·6×107/kg (range 1·4–4·2). The primary endpoint was the
probability of neutrophil and platelet recovery after intrabone cord-
blood transplantantion. Secondary endpoints included the incidence of
acute graft-versus-host disease, relapse, and overall survival. This
trial is registered on the ClinicalTrials.gov website, number NCT
00696046.

Findings
Between March 31, 2006, and Jan 25, 2008, 32 consecutive patients
with acute myeloid leukaemia (n=20) or acute lymphoblastic leukaemia
(n=12) underwent a cord-blood transplant (median age 36 years [range
18–66]). No complications occurred during or after the intrabone
infusion of cells. Four patients with advanced-stage disease died
within 12 days of the procedure. Median time to recovery of
neutrophils in 28 patients (≥0·5×109/L) was 23 days (range 14–44) and
median time to recovery of platelets in 27 patients (≥20×109/L) was
36 days (range 16–64). All patients were fully chimeric from 30 days
after transplantation to the last follow-up visit, suggesting an
early complete donor engraftment. No patient developed grade III–IV
acute graft-versus-host disease. Causes of death were transplant
related (n=5), infection (n=7), and relapse (n=4). 16 patients were
alive and in haematological remission at a median follow-up of 13
months (range 3–23).

Interpretation
Our preliminary data suggest that direct intrabone cord-blood
transplantation overcomes the problem of graft failure even when low
numbers of HLA-mismatched cord-blood cells are transplanted, thus
leading to the possibility of use of this technique in a large number
of adult patients.

Funding
This work was supported by grants from the Associazione Italiana
Ricerca contro il Cancro (FF), Compagnia di San Paolo Torino (FF),
Progetto CARIGE Cellule Staminali (FF), the EUROCORD III (QLRT 2001-
01918) (FF), Ministero della Salute (Ricerca Finalizzata Ministeriale
2005) (FF), and the Associazione Italiana Leucemie, Sezione Ligure.

Affiliations

a. Stem Cells and Cell Therapy Centre, San Martino Hospital, Genoa,
Italy
b. Division of Haematology and Bone Marrow Transplant Unit, San
Martino Hospital, Genoa, Italy
c. Department of Internal Medicine, University of Genoa, Genoa, Italy
d. Department of Haematology, University of Genoa, Genoa, Italy
e. Italian Bone Marrow Donor Registry, Genoa, Italy
f. Hôpital Saint Antoine AP-HP, Université Pierre et Marie Curie,
Paris, France

Correspondence to: Dr Francesco Frassoni, Stem Cells and Cell Therapy
Centre, San Martino Hospital, 16132 Genoa, Italy

http://www.thelancet.com/journals/lanonc/article/PIIS1470204508701803/
abstract?iseop=true

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