Factors affecting microbial contamination rate of cord blood collected for transplantation.

BACKGROUND: Collection and processing of cord blood (CB) is associated with significant risk of microbial contamination and hence relevant standards mandate microbial screening of the final product. This study aimed to determine the contamination rate and associated risk factors during 14 years of banking at the Sydney Cord Blood Bank. STUDY DESIGN AND METHODS: CB was collected and processed using a closed system and tested for contamination using blood culture bottles (BacT/ALERT, bioMérieux) incubated for a minimum of 5 days. Four microbial screening methods were used with different combinations of inoculated bottles (adult or pediatric) and associated sample volumes (10 or 1 mL). RESULTS: Of 13,344 CB units screened, 537 (4.0%) tested positive for contamination, with Bacteroides spp. (20.9%), Staphylococcus spp. (18.6%), and Propionibacterium spp. (13.7%) being the most common isolates. The contamination rate reduced from 10% in 1997 to 1.1% in 2009. Multivariate analysis demonstrated the following variables were independently associated with higher contamination rates: vaginal delivery, collection by obstetric staff, and use of an anaerobic bottle in addition to an aerobic bottle (which facilitated a larger sample inoculation volume than pediatric bottles). CONCLUSIONS: This study demonstrates that contamination rates of CB collected for transplantation can be substantially reduced by collection after cesarean delivery and utilizing trained CB collection staff. These data also indicate that the common practice of testing using a pediatric (aerobic) bottle with its attendant small volume of the final CB product may be suboptimal for sensitive detection of contaminating anaerobic microbes.

Failure to lactate: a possible late effect of cranial radiation.

We conducted a retrospective review of the lactation experience of female survivors who received 24 Gy cranial radiotherapy as CNS prophylaxis for acute lymphoblastic leukemia in childhood prior to 1982 and who attend the Long-Term Follow-Up Clinic at Sydney Children's Hospital, Randwick, Australia. Median time since diagnosis is 28 years (range 25-37 years). Twelve have produced offspring. Ten report minimal or no breast changes during pregnancy and failure to lactate postpartum. All patients remain in remission. These data suggest a high risk of failure of lactation in women treated during childhood with 24 Gy cranial irradiation. Awareness of this possibility can assist in counseling.

No longer a biological waste product: umbilical cord blood.

Haematopoietic stem cell transplantation is an accepted curative therapy for many cancers and inherited non-malignant diseases, including bone marrow failure syndromes, haemoglobinopathies, and inborn errors of metabolism. Stem cells can be used from the bone marrow or blood of matched siblings or appropriately matched unrelated volunteers, but many patients do not have a suitably matched donor. Umbilical cord blood (UCB) has been successfully used as an alternative stem cell source. It has the advantage of tolerance for a degree of human leukocyte antigen (HLA) incompatibility not possible with adult bone marrow, resulting in greater likelihood of finding an appropriate match. UCB is also stored fully tested and cryopreserved, leading to rapid availability. Greatest clinical experience in UCB transplants has been in treating paediatric leukaemia. Results using well matched UCB grafts are equivalent or better than with unrelated bone marrow transplant. Cell dose and the degree of HLA matching are critical determinants in the success of UCB transplant. The use of UCB in older children and adult patients has been limited by the fixed, low cell dose available in a UCB unit, relative to recipient weight. This can be overcome by strategies such as using two or more UCB units. Early animal studies suggest that UCB may have the potential to differentiate into other cell types, including nervous tissue, and may in future play a role in the treatment of disorders such as Alzheimer disease and Parkinson disease.

Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice.

OBJECTIVE: Optimizing cord blood donor selection based mainly on cell dose and human leukocyte antigen (HLA) disparities may further improve results of unrelated cord blood transplants (UCBT). MATERIALS AND RESULTS: We analyzed 550 UCBTs for hematologic malignancies reported to the Eurocord Registry. Main outcomes and prognostic factors were analyzed in univariable and multivariable analyses incorporating center and period effects and using death and relapse as competitive risks for nonfatal endpoints. Nucleated cell (NC) dose before freezing and number of HLA disparities had a significant influence on outcome. Cumulative incidence (CI) of neutrophil and platelet recovery was associated with the number of HLA mismatches, number of NC before freezing, and use of granulocyte colony-stimulating factor. Coexistence of HLA class I and II disparities and high CD34 cell dose in the graft were associated with graft-vs-host disease grades III-IV. CI of disease relapse was higher in matched transplants showing a graft-vs-leukemia effect increased in HLA-mismatched transplants. Overall 3-year survival was 34.4%. Prognostic factors for survival were recipient age, gender, and disease status. CONCLUSION: Our results provide indications for a better choice of cord blood units according to cord blood cell content and HLA.

Osteochondroma after total body irradiation: an age-related complication.

BACKGROUND: The discovery of a mass lesion in a long-term cancer survivor causes significant anxiety. The causes of such a mass include benign osteochondroma, which has been reported following focal irradiation and total body irradiation (TBI). PROCEDURE: To establish the incidence of osteochondromas following TBI, the medical records of all children treated at the Sydney Children's Hospital who received TBI as part of the conditioning prior to bone-marrow transplantation between 1978 and 1997 were reviewed. RESULTS: Five of 58 children who received TBI as part of the conditioning therapy for bone-marrow transplantation and who have been followed for at least 30 months post-irradiation, developed osteochondromas. All five of the patients had been under 5 years of age when they received TBI (mean 2.4 years), giving an incidence of osteochondroma of 24% in those who received TBI in the first 5 years of life. No osteochondromas have been diagnosed among the 37 patients who were aged between 5 years and 15 years at the time of receiving TBI. The mean latent time to diagnosis of osteochondroma was 4.6 years (range 2.5-9 years). Two patients developed multiple osteochondromas. Two patients required resection of their osteochondromas because of symptoms. Neither showed malignant degeneration. CONCLUSIONS: Younger patients are at increased risk of osteochondroma following TBI. Review of the available literature suggests a low malignant potential of radiation-induced osteochondromas. Knowledge about the behaviour of post-irradiation osteochondromas will help clinicians manage patients appropriately.

Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis.

Results of unrelated cord blood transplantation (UCBT) in childhood acute myeloid leukemia (AML) have not been previously reported. We analyzed 95 children receiving UCB transplants for AML (20 in first complete remission [CR1], 47 in CR2, and 28 in more advanced stage). Poor prognosis cytogenetic abnormalities were identified in 29 cases. Most patients received a 1 or 2 HLA antigens-mismatched UCB transplants. The median number of collected nucleated cells (NCs) was 5.2 x 107/kg. Cumulative incidence (CI) of neutrophil recovery was 78% +/- 4%, acute graft-versus-host disease (GVHD) was 35% +/- 5%, and 100-day transplantation-related mortality (TRM) was 20% +/- 4%. In multivariable analysis, a collected NC dose higher than 5.2 x 107/kg was associated with a lower 100-day TRM. The 2-year CI of relapse was 29% +/- 5% and was associated with disease status. The 2-year leukemia-free survival (LFS) was 42% +/- 5% (59% +/- 11% in CR1, 50% +/- 8% in CR2, and 21% +/- 9% for children not in CR). Children with poor prognosis cytogenetic features had similar LFS compared with other patients (44% +/- 11% vs 40% +/- 8%). In CR2, LFS was not influenced by the length of CR1 (53% +/- 11% in CR1 < 9.5 months compared with 50% +/- 12% in later relapses). We conclude that UCBT is a therapeutic option for children with very poor-prognosis AML and who lack an HLA-identical sibling.

Results of consecutive trials for children newly diagnosed with acute myeloid leukemia from the Australian and New Zealand Children's Cancer Study Group.

Despite improvements in the treatment of acute myeloid leukemia (AML), approximately 50% of children die of the disease. Clinical trials in adult patients with AML indicate that idarubicin may have superior efficacy when compared to daunorubicin in the remission-induction phases of chemotherapy. We conducted consecutive clinical trials in children with newly diagnosed AML in which daunorubicin (group 1, n = 102) or idarubicin (group 2, n = 160) was used during the remission-induction (RI) and the early consolidation phases of chemotherapy. Idarubicin was given at a dose of either 10 mg/m(2) (group 2A, n = 106) or 12 mg/m(2) (group 2B, n = 53). A high rate of RI was achieved for all groups (95% group 1, 90% group 2A, 94% group 2B). There were no significant differences in 5-year event-free survival (EFS) or in overall survival (OS) when the 3 groups were compared (group 1: EFS 50%, OS 56%; group 2A: EFS 50%, OS 60%; group 2B: EFS 34%, OS 50%). RI deaths resulting from treatment toxicity were low-2% for group 1 and 5% for group 2. More gastrointestinal, pulmonary, and renal toxicity but fewer infections were observed in patients receiving idarubicin (P <.001, P =.04, P =.03, respectively). Following RI chemotherapy, all patients received 3 to 4 more courses of identical chemotherapy and then underwent either autologous (n = 156) or an allogeneic bone marrow transplantation (BMT) (n = 35). OS was higher in allogeneic BMT patients than in autologous BMT patients (79% vs 63%; P =.23). We conclude that daunorubicin is as effective as idarubicin for remission-induction therapy for childhood AML and has reduced toxicity.