Cord blood research advances have been reported from the United States and Netherlands

06-20-2006

Study 1: Umbilical cord blood donors are readily available for children with lysosomal and peroxisomal storage disease.

"The Cord Blood Transplantation Study (COBLT), sponsored by the National Heart, Lung, and Blood Institute, is a phase II multicenter study designed to evaluate the use of cord blood in allogeneic transplantation.

"In this report, we evaluated the outcomes of cord blood transplantation in 69 patients with lysosomal and peroxisomal storage diseases," investigators in the United States report.

According to P.L. Martin and colleagues at Duke University, Medical Center in Durham, "Patients with mucopolysaccharidoses I to III, mucolipidoses (ML) II (n=36), adrenoleukodystrophy (n=8), metachromatic leukodystrophy (n=6), Krabbe disease (n=16), and Tay-Sachs disease (n=3) were enrolled between August 1999 and June 2004.

"All patients received the same preparative regimen, graft-versus-host disease (GVHD) prophylaxis, and supportive care. End points included survival, engraftment, GVHD, and toxicity. Sixty-nine patients (64% men; 81% white) with a median age of 1.8 years underwent transplantation with a median cell dose of 8.7x107/kg."

"One-year survival was 72% (95% confidence interval, 61%-83%). The cumulative incidence of neutrophil engraftment by day 42 was 78% (95% confidence interval, 67%-87%) at a median of 25 days. Grade II to IV acute GVHD occurred in 36% of patients," the authors said.

Martin concluded, "Cord blood donors are readily available for rapid transplantation. Cord blood transplantation should be considered as frontline therapy for young patients with lysosomal and peroxisomal storage diseases."

Martin and colleagues published their study in Biology of Blood and Marrow Transplantation (Results of the Cord Blood Transplantation Study (COBLT): Outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant, 2006;12(2):184-194).

For additional information, contact J. Kurtzberg, Duke University, Medical Center, Box 3350, Durham, NC 27710, USA.

Study 2: Unrelated umbilical cord blood transplantation is successful in children with Shwachman-Diamond syndrome.

"Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic insufficiency and variable degrees of neutropenia. SDS patients are at risk of developing myelodysplasia, aplastic anemia, and leukemic transformation.

"The role and timing of allogeneic hematopoietic stem cell transplantation (HSCT) in SDS remain controversial," investigators in the United States report.

According to R. Vibhakar and colleagues at the University of Iowa Hospital & Clinic, "We report three SDS patients with severe aplasia transplanted using unrelated umbilical cord blood (UCB).

"Patients received melphalan (180 mg/m2), etoposide (1200 mg/m2), antithymocyte globulin (90 mg/kg), and total lymphoid irradiation (500cGy); graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and prednisone."

"Myeloid engraftment occurred promptly with absolute neutrophil count >500cells/mm3 on day 15+/-5 and all patients displayed 100% donor chimerism by 2 months post-transplant.

"The major complication of transplant was GVHD, with all patients developing grade II or III acute GVHD, one progressing to chronic extensive GVHD. Patients are alive 309, 623, and 2029 days post-transplant," said researchers.

"Factors important in HSCT outcome for SDS may include transplantation at a young age, avoidance of cyclophosphamide, and adequate GVHD prophylaxis. Importantly," Vibhakar concluded, "these cases also suggest that unrelated UCB, in the absence of a matched family member, is an excellent alternative stem cell source for SDS patients undergoing HSCT."

Vibhakar and colleagues published their study in Bone Marrow Transplantation (Successful unrelated umbilical cord blood transplantation in children with Shwachman-Diamond syndrome. Bone Marrow Transplant, 2005;36(10):855-861).

For additional information, contact F. Goldman, University of Iowa Hospital & Clinic, Division Pediatrics Hematology Oncology, 200 Hawkins Dr., Iowa City, IA 52242, USA.

Study 3: Cotransplantation of a second unrelated cord blood unit enhanced engraftment of umbilical cord blood-derived stem cells in NOD/SCID mice.

"Umbilical cord blood (UCB) is considered as an attractive alternative source of hematopoietic stem cells for allogeneic stem cell transplantations in patients who lack human leukocyte antigen (HLA)-matched donors. However, the low cell dose adversely affects hematopoietic recovery and therefore limits application of UCB transplantation in adults. Transplantation of multiple UCB units could be a strategy to overcome cell dose limitations," investigators in Netherlands report.

A.J. Nauta and colleagues at Leiden University proposed, "To investigate the effect of double cord transplantation, nonobese diabetic/severe combined immunodeficient mice were transplanted with human hematopoietic progenitor cells (CD34+) derived from two UCB units with RLA disparity. Human cell engraftment and donor origin was determined by flow cytometry."

The results indicated, "Double CB transplantation resulted in increased engraftment levels in the bone marrow and peripheral blood in comparison with recipients of a single unit. Because this effect could be due to the higher cell dose (2.105, vs. 1.105 cells), double CB transplantation was compared with single units containing equal cell numbers (2.105)."

"In some cases," continued investigators, "engraftment levels in recipients of single units containing 2.105 cells were significantly higher than after transplantation of 1.105 cells. These engraftment levels were similar to those observed after double CB transplantation. Chimerism analysis indicated that increased engraftment in recipients of two units was predominantly derived from one unit, whereas in other cases the contribution of the two units was similar."

"These results indicate," concluded the authors, "that engraftment may be enhanced by addition of a second unrelated CB that might be attributed to a cell dose effect or due to a graft-facilitating effect."

Nauta and colleagues published their study in Experimental Hematology (Enhanced engraftment of umbilical cord blood-derived stem cells in NOD/SCID mice by cotransplantation of a second unrelated cord blood unit. Exp Hematol, 2005;33(10):1249-1256).

For additional information, contact A.J. Nauta, Leiden University, Medical Center, Laboratory Exptl Hematology, Dept. Hematology, D2-P, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.

Keywords: Leiden, Netherlands, Blood Transfusion, Bone Marrow, Cell Transplant, Cord Blood, Diabetes, Endocrinology, Hematology, Hematopoietic, Immunology, Medical Device, Peripheral Blood, Progenitor Cell, Stem Cell Research, Transfusion Medicine.

This article was prepared by Hematology Week editors from staff and other reports. Copyright 2006, Hematology Week via NewsRx.com.