Unrelated umbilical cord blood transplantation (UCBT) has become a standard therapeutic option for pediatric patients who may benefit from hematopoietic stem cell transplantation but lack an adequate HLA-identical related donor. UCB has the advantages of rapid availability and presumably lower risk of severe, acute graft-versus-host disease (GVHD) despite donor-recipient human leukocyte antigen (HLA) disparity. Double-unit UCBT (DUCBT) extends access to transplantation to patients who were previously disqualified on the basis of the available cell dose in a single unit. Recent studies report high engraftment rate, low incidence of severe acute GVHD and a relatively low transplantation-related mortality in DUCBT. (

Barker Blood. 2005;105:1343–1347
). It is unknown, however, whether patients with advanced hematological malignancies and patients with the severe co-morbidities would benefit from DUCBT. Seven patients, 5 males and 2 females, age 5.2–15 yrs (median 14 yr), 5 with advanced hematological malignancies; were given DUCBT. The diagnoses were AML (n=3; refractory n=1, 2CR n=1, 3CR n=1)), ALL (n=4; 1CR Ph+ I n =1, 2CR Ph+ n=1, both MRD+, 2CR n=2). Five of seven were non-Caucasian (71%). Co-morbidities included recent invasive fungal infection (n=3), acute pancreatitis (n=1), and bulbar paralysis (n=1). Conditioning regimes were FTBI and melphalan d (n=3) and fludarabine and melphalan (n=4). Myeloid engraftment occurred in all patients. The median time to an absolute neutrophil count >500 was 34 days (range 26–74 days). Three patient remained platelet transfusion dependent after day 100. In the remaining 4 patients the median time to a platelet count >20,000 unsupported were 51 days (range 44–69 days). All patients (100%) experienced Grades II-III acute GVHD. There were no patients with Grade IV GVHD and no deaths from acute GVHD. Four patients developed extensive chronic GVHD of the skin only. The 100 day transplant related mortality was 0%. One patient died on day + 200 from respiratory failure. None of the patient suffered relapse. The disease-free survival is 80% with a median day +348 post transplant (range 116–1069). The observation that DUCBT may be associated with a reduced risk of relapse in patients with high-risk leukemia deserves further evaluation. Larger studies will be needed to investigate potential mechanisms by which DUCBT could mediate an anti-leukemic effect and to confirm the clinical experience.

Topics:
pediatrics, recurrence risk, umbilical cord blood transplantation, graft-versus-host disease, acute, transplantation, human leukocyte antigens, graft-versus-host disease, hematologic neoplasms, melphalan, fludarabine

Disclosure: No relevant conflicts of interest to declare.

2006, The American Society of Hematology
2006
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