The Treatment of Hematologic Malignancies With Single or Double Umbilical Cord Blood Unit Transplantation Followed by Graft-Versus-Host Disease Prophylaxis With Tacrolimus and Mycophenolate Mofetil
An increasing number of patients with fatal malignant and nonmalignant diseases are being
treated with SCT. Unfortunately only about 30% of patients who could benefit from this
procedure have a HLA-matched related donor (MRD), and only an additional 20% can find a
suitable HLA-matched unrelated donor (MUD) 1. This problem is magnified in patients of
minority groups who are often underrepresented in the donor pool. In an attempt to expand
the number of patients who could be helped by transplantation alternative donor sources has
been explored including UCB. Transplantation using UCB has numerous advantages including:
ease of procurement, lack of donor attrition, absence of risk to mothers and donors,
potential reduced risk of GVHD, and less stringent criteria for HLA matching 2. However
these benefits are limited by the delayed engraftment, extended post-transplant neutropenia
and thrombocytopenia, increased infection rate, and relative decreased cell dose of the
graft.
Pediatric Experience in UCB SCT (Related and Unrelated Donors) Related UCB SCT
By November 1996, 74 patients had been treated with a related UCB SCT and the data had been
reported to the International Cord Blood Transplant Registry (ICBTR) 3. Twenty patients
received HLA 1-3 antigen mismatched grafts. Pretransplant conditioning therapy,
post-transplant use of hematopoietic growth factors and prophylaxis for acute GVHD varied
between institutions.
For recipients of HLA-matched or HLA-1 antigen mismatched UCB grafts, the actuarial
probability of hematopoietic recovery at 60 days after transplantation was 91% ± 8%. Median
times to neutrophil recovery (defined as time to achieve an absolute neutrophil count [ANC]
> 0.5 x 109/L) and platelet recovery (defined as platelet count >50 x 109/L untransfused for
7 days) were 22 days (range, 9 to 46) and 51 days (range, 15 to 117) after transplantation,
respectively. Four patients never had signs of hematopoietic recovery and one patient had
early recovery but cells were entirely host in origin. Of the 5 patients without donor cell
engraftment, 4 had undergone UCB SCT for the treatment of a bone marrow failure syndrome and
one for the treatment of Hunter's syndrome.
Acute GVHD has occurred very infrequently in recipients of HLA-matched and HLA-1 antigen
mismatched UCB SCT. The actuarial probability of grade II-IV GVHD at 100 days after
transplantation was 3%. Notably, only one patient has been reported to have grade III-IV
aGVHD.
Of the 15 recipients of 2 and 3 antigen disparate haploidentical transplants, 12 were
evaluable for GVHD (3 died of graft failure). Moderate to severe GVHD occurred in 3
patients. As shown in Table 1, donor-recipient pairs mismatched at the maternal allele
appeared to be much less likely to develop grade II-IV GVHD than donor-recipient pairs
mismatched at the paternal allele. This observation supports the hypothesis that partial
tolerance may develop to the non-inherited maternal allele (NIMA) during gestation as
opposed to the non-inherited paternal allele (NIPA)
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the safety (as assessed by the day 100 non-relapse mortality) and feasibility of single or double UCB SCT in patients with hematological malignancies receiving GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
+100 days
Yes
Brian G. Engelhardt, M.D.
Principal Investigator
Vanderbilt University
United States: Food and Drug Administration
BMT 050674
NCT00244036
September 2005
September 2009
Name | Location |
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Vanderbilt University Medical Center | Nashville, Tennessee 37232-2516 |