Direct intrabone transplant of unrelated cord-blood cells in acute leukaemia: A phase I/II study

Stem Cells and Cell Therapy Centre, San Martino Hospital, Genoa, Italy.
The Lancet Oncology (Impact Factor: 24.69). 09/2008; 9(9):831-9. DOI: 10.1016/S1470-2045(08)70180-3
Source: PubMed


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.
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 x 10(7)/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 website, number NCT 00696046.
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 x 10(9)/L) was 23 days (range 14-44) and median time to recovery of platelets in 27 patients (>/=20 x 10(9)/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).
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.

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    • "The first strategy to overcome the low cell contents in a single CB unit was to increase the infused stem cell dose using double unit of CB12) or ex vivo expanded CB13). Other efforts for enhancing the engraftment kinetics to overcome the limitations of low cell dose were intraosseous injection of CB14,15) and cotransplantation of third-party MSCs16). "
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    ABSTRACT: Cord blood (CB) has been used as an important and ethical source for hematopoietic stem cell transplantation (SCT) as well as cell therapy by manufacturing mesenchymal stem cell, induced pleuripotential stem cell or just isolating mononuclear cell from CB. Recently, the application of cell-based therapy using CB has expanded its clinical utility, particularly, by using autologous CB in children with refractory diseases. For these purposes, CB has been stored worldwide since mid-1990. In this review, I would like to briefly present the historical development of clinical uses of CB in the fields of SCT and cell therapy, particularly to review the experiences in Korea. Furthermore, I would touch the recent banking status of CB.
    Korean Journal of Pediatrics 03/2014; 57(3):110-116. DOI:10.3345/kjp.2014.57.3.110
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    • "Relatively rapid engraftment with cord blood was observed in this case, similar to that previously reported [5], and this was believed to be one reason for reduced transplantation-related complications. The reduced toxicity conditioning regimen, which has been reported to induce high antileukemic activity in patients with active and advanced AML with reduced RRT [3] [4], is also considered to contribute to reduced complica- tions. "
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    ABSTRACT: Although hematopoietic stem cell transplantation (HSCT) has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML), there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT) using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.
    02/2014; 2014:918708. DOI:10.1155/2014/918708
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    • "First, we were able to document the feasibility and the safety of this approach for islet infusion. The direct islet infusion in the BM was performed according to the same procedure used in our institution for the administration of cord blood cells in patients with acute leukemia (28). The procedure was easy and reproducible and, thus far, we have recorded no AEs related to the islet infusion in the iliac crest. "
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    ABSTRACT: The liver is the current site of choice for pancreatic islet transplantation, even though it is far from being ideal. In mice we have recently shown that the bone marrow (BM) may be a valid alternative to the liver and here we report a pilot study to test feasibility and safety of BM as a site for islet transplantation in humans. Four patients who developed diabetes after total pancreatectomy were candidates for the autologous transplantation of pancreatic islet. Since the patients had contraindications for intraportal infusion, islets were infused in the BM. In all recipients islets engrafted successfully, as shown by measurable post-transplantation C-peptide levels and histopathological evidence of insulin producing cells and/or molecular markers of endocrine tissue on BM biopsies performed during follow-up. Thus far we have recorded no adverse events related to the infusion procedure or the presence of islets in the BM. Islet function was sustained up to the maximum follow-up of 944 days. The encouraging results of this pilot study open new perspectives in identifying alternative sites for islet infusion in patients with type 1 diabetes. Moreover, this is the first unequivocal example of successful engraftment of an endocrine tissue in the BM in humans.
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