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J Cornish

Publications and source records attributed to J Cornish.

At least 19 recordsLinked to original sources
PubMed2007

Haematopoietic stem cell transplantation trends in children over the last three decades: a survey by the paediatric diseases working party of the European Group for Blood and Marrow Transplantation.

This paper describes the trends in haematopoietic stem cell transplantation (HSCT) activity for children in Europe over the last three decades. We analysed 31,713 consecutive paediatric HSCTs reported by the European Group for Blood and Marrow Transplantation (EBMT) centres between 1970 and 2002. Data were taken from the EBMT registry and were compared according to period and centre category (paediatric or combined). Since 1996, there has been a significant increase in the number of HSCTs performed exclusively by paediatric centres, as well as in the number of alternative donor HSCTs, and in the use of peripheral blood stem cells (P<0.0001). The number of allogeneic HSCTs (allo-HSCTs) for acute lymphoblastic leukaemia, acute myeloblastic leukaemia and chronic myeloid leukaemia remained stable, whereas it increased for myelodysplastic syndromes and lymphomas, and decreased significantly for non-malignant diseases (P<0.0001). Multivariate analysis showed that younger age, human leukocyte antigen genoidentical donors, HSCT performed after 1996 and transplant centres performing more than 10 allo-HSCT/year were all associated with decreased transplant-related mortality (TRM) (P<0.0001). The number of autologus HSCTs (auto-HSCTs) for acute leukaemia decreased significantly, whereas it increased for solid tumours (P<0.0001). Multivariate analysis showed that both auto-HSCT performed before 1996 and paediatric solid tumours (P<0.0001) had higher TRM. Indications for paediatric HSCT have changed considerably during the last seven years. These changes provide tools for decision making in health-care planning and counselling.

Blood Transfusion↗
PubMed2006

A meta-analysis on the influence of inflammatory bowel disease on pregnancy.

BACKGROUND: Inflammatory bowel disease (IBD) has a typical onset during the peak reproductive years. Evidence of the risk of adverse pregnancy outcomes in IBD is important for the management of pregnancy to assist in its management. AIM: To provide a clear assessment of risk of adverse outcomes during pregnancy in women with IBD. DESIGN: The Medline literature was searched to identify studies reporting outcomes of pregnancy in patients with IBD. Random-effect meta-analysis was used to compare outcomes between women with IBD and normal controls. PATIENTS AND SETTING: A total of 3907 patients with IBD (Crohn's disease 1952 (63%), ulcerative colitis 1113 (36%)) and 320 531 controls were reported in 12 studies that satisfied the inclusion criteria. RESULTS: For women with IBD, there was a 1.87-fold increase in incidence of prematurity (<37 weeks gestation; 95% CI 1.52 to 2.31; p<0.001) compared with controls. The incidence of low birth weight (<2500 g) was over twice that of normal controls (95% CI 1.38 to 3.19; p<0.001). Women with IBD were 1.5 times more likely to undergo caesarean section (95% CI 1.26 to 1.79; p<0.001), and the risk of congenital abnormalities was found to be 2.37-fold increased (95% CI 1.47 to 3.82; p<0.001). CONCLUSION: The study has shown a higher incidence of adverse pregnancy outcomes in patients with IBD. Further studies are required to clarify which women are at higher risk, as this was not determined in the present study. This has an effect on the management of patients with IBD during pregnancy, who should be treated as a potentially high-risk group.

Birth Weight↗
PubMed2006

Comparison of long-term outcomes after allogeneic hematopoietic stem cell transplantation from matched sibling and unrelated donors.

Long-term survivors of hematopoietic stem cell transplants remain at risk of potentially fatal complications that detract from life quality. Long-term morbidity and mortality were compared between matched recipient cohorts surviving 2 or more years and defined by donor type, HLA matched sibling donor (MSD) or volunteer unrelated donor (URD). Patients were previously entered into the prospective multicenter International Unrelated Search and Transplant Study. Thirty-nine centers provided data on 108 URD and 355 MSD recipients surviving more than 2 years. Long-term survival, performance status, chronic GvHD (c-GvHD), secondary malignancy, endocrine dysfunction, cataracts, bone necrosis and dental pathology were compared between cohorts. Twelve year survival was 77+/-5% for the MSD and 67+/-11% for the URD cohort (P=0.1). Late death occurred in 105 of 463 recipients alive at 2 years, 73 after 355 (21%) MSD and 32 after 108 (30%) URD transplants, P=0.10. Of 105 deaths, the cause was relapse in 60 and unrelated to relapse in 45 cases. Cumulative incidence of extensive c-GvHD (P=0.002), cataracts (P=0.02) and bone necrosis (P=0.02) was higher after URD transplants. No long-term difference in endocrine dysfunction, secondary malignancy and major dental pathology was detected. This landmark study will assist physicians counseling patients pre-transplant and with their long-term care post transplant.

Adolescent↗
PubMed2006

Meta-analysis: Alvimopan vs. placebo in the treatment of post-operative ileus.

BACKGROUND: Alvimopan is a selective, competitive mu-opioid receptor antagonist with limited oral bioavailability which may be used to reduce length of post-operative ileus. AIM: The study compared alvimopan with placebo following bowel resection or total abdominal hysterectomy. METHODS: A meta-analysis of randomized-controlled trials published between 2001 and 2006 of alvimopan vs. placebo was performed. The primary efficacy end-points were composite measures of passage of flatus, stool, and tolerance of solid food (GI-3) and passage of stool and tolerance of solid food (GI-2). The incidence of treatment emergent adverse events was assessed. RESULTS: Five trials matched the selection criteria, reporting on 2195 patients. A total of 1521 (69.3%) had alvimopan and 674 (30.7%) placebo. GI-3 significantly improved (hazard ratio 1.30; 95% confidence intervals 1.16, 1.45, P < 0.001), as did GI-2 (hazard ratio 1.61; 95% confidence intervals 1.26, 2.05, P < 0.001) on alvimopan 12 mg. Time to discharge (hazard ratio 1.26; 95% confidence intervals 1.13, 1.40, P < 0.001), time to bowel motion (hazard ratio 1.74; 95% confidence intervals 1.29, 2.35, P < 0.001), and time to solid food (hazard ratio 1.14; 95% confidence intervals 1.01, 1.30, P < 0.04) also improved significantly. No difference was noted in the incidence of treatment emergent adverse events. CONCLUSIONS: Alvimopan showed significant advantages over placebo in restoring gastro-intestinal function, and reduced time to discharge following major abdominal surgery, with acceptable side effects.

Adolescent↗
PubMed2006

Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo.

Several hormones that regulate nutritional status also impact on bone metabolism. Preptin is a recently isolated 34-amino acid peptide hormone that is cosecreted with insulin and amylin from the pancreatic beta-cells. Preptin corresponds to Asp(69)-Leu(102) of pro-IGF-II. Increased circulating levels of a pro-IGF-II peptide complexed with IGF-binding protein-2 have been implicated in the high bone mass phenotype observed in patients with chronic hepatitis C infection. We have assessed preptin's activities on bone. Preptin dose-dependently stimulated the proliferation (cell number and DNA synthesis) of primary fetal rat osteoblasts and osteoblast-like cell lines at periphysiological concentrations (>10(-11) M). In addition, thymidine incorporation was stimulated in murine neonatal calvarial organ culture, likely reflecting the proliferation of cells from the osteoblast lineage. Preptin did not affect bone resorption in this model. Preptin induced phosphorylation of p42/p44 MAP kinases in osteoblastic cells in a dose-dependent manner (10(-8)-10(-10) M), and its proliferative effects on primary osteoblasts were blocked by MAP kinase kinase inhibitors. Preptin also reduced osteoblast apoptosis induced by serum deprivation, reducing the number of apoptotic cells by >20%. In vivo administration of preptin increased bone area and mineralizing surface in adult mice. These data demonstrate that preptin, which is cosecreted from the pancreatic beta-cell with amylin and insulin, is anabolic to bone and may contribute to the preservation of bone mass observed in hyperinsulinemic states such as obesity.

Animals↗
PubMed2006

Topical issues in unrelated donor haematopoietic stem cell transplants: a report from a workshop convened by the Anthony Nolan Trust in London - 2005.

Over more than three decades, The Anthony Nolan Trust (ANT) has provided an unrelated donor (UD) for over 4000 children and adults lacking a suitable family member donor, and has remained at the forefront of developments in haematopoietic stem cell transplantation (HSCT) and bone marrow register management. These three decades have seen major changes in clinical practice of UD-HSCT, including new indications, increased use of alternative haematopoietic cell sources, significant improvement of the outcome as a result of better support care, less-toxic conditioning regimens, and better donor selection, and expansion to older patients with higher comorbidities. In order to foster our goal of improving UD-HSCT availability and outcome in a progressively more complex clinical scenario, a new initiative from ANT was launched in 2005 to convene an experts workshop to address the topical issues in this field. Four consecutive panels addressed factors influencing donor selection and transplant outcome, the use of cord blood, regulatory and accreditation issues, and future developments in this field. This report summarizes the discussions held in this workshop, which will likely develop into a periodic event where transplant clinicians, scientists and registry members will meet to share their experience and vision in the field of UD-HSCT.

Donor Selection↗
PubMed2006

Lactoferrin and bone; structure-activity relationships.

The maintenance of the mechanical integrity of the skeleton depends on bone remodeling, the well-coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts. The coupled action of osteoblasts and osteoclasts is regulated by the action of many local and circulating hormones and factors as well as central regulation by a neurological mechanism. We have previously shown that lactoferrin can promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and acts as a survival factor. Lactoferrin also affects osteoclasts, potently inhibiting their formation. In vivo, local injection of lactoferrin results in substantial increases in bone formation and bone area. In a critical bone-defect model in vivo, lactoferrin was also seen to promote bone growth. The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through low-density lipoprotein-receptor protein-1 (LRP1), a member of the low-density lipoprotein-receptor-related proteins that are primarily known as endocytic receptors; however, LRP1 is not necessary for the anti-apoptotic actions of lactoferrin. Lactoferrin also induces the activation of p42/44 mitogen-activated protein kinase (MAPK) signalling and the PI3-kinase-dependent phosphorylation of Akt in osteoblasts. In this study, we examined other properties of lactoferrin and the way they affect osteogenic activity. The degree of glycosylation, iron-binding, and the structure-activity relationships indicate that lactoferrin maintains osteogenic activity in deglycosylated, holo, and apo forms, and in with various small fragments of the molecule. These data suggest that lactoferrin signals through more than 1 membrane-bound receptor to produce its anabolic skeletal effects, and that it signals through diverse pathways. We conclude that lactoferrin might have a physiological role in bone growth and healing and a potential therapeutic role as an anabolic factor in osteoporosis.

Amino Acid Sequence↗
PubMed2005

Survey on haematopoietic stem cell transplantation for children in Europe.

A recent report, prepared in March 2003, regarding the paediatric transplantation activity registered between 1970 and 2002 in the European Bone Marrow Transplantation (EBMT) database showed a decrease in the number of registrations in 2001 and in 2002. In order to validate this observation, the Paediatric Diseases Working Party (PDsWP) secretariat distributed a questionnaire to 395 institutions participating in the EBMT Registry. Each institution was requested to check the number of transplants they reported and to confirm or to correct the figures. As of 15 March 2004, replies had been received from 135 centres reporting a median of 48 transplants per centre over the study period, total 17 891 (58% of the total number). Among them, 55 confirmed their original figures, while 80 corrected the numbers. The overall number of autologous and allogeneic SCTs performed and not reported were 461 and 692, respectively. Most of the teams that corrected their figures stated that their data managers could provide missing data to the EBMT; 260 other teams, each reporting a median of 15 transplants during the study period, total 12 866 (42% of the total number) chose not to reply. A report prepared in March 2004, following the PDsWP survey, showed an increasing number of transplants performed on patients below 18 years of age between 1973 and 2002 and reported to the EBMT Registry (328 autologous and 628 allogeneic) as compared to the 2003 report. This first PDsWP survey, reaching more than 50% of activity in the field, illustrates that the decrease in activity we observed in the 2003 report does not correspond to a decrease in the number of transplants that were actually performed. It demonstrates the compliance of most major paediatric institutions and confirms the important role of cooperation between National Registries and EBMT Registries.

Adolescent↗
PubMed2005

Factors affecting the outcome of stem cell transplantation from unrelated donors for childhood acute lymphoblastic leukemia in third remission.

Between July 1990 and March 2002, 35 consecutive children with ALL in third complete remission (CR3) underwent stem cell transplantation (SCT) from unrelated donors (UD). All patients received CAMPATH-1M 5-20 mg daily for 5 days. Grafts were T-cell depleted in 30 patients, 29 by CAMPATH antibodies and one by CD34 selection. Median follow-up was 3.8 years (0.3-9.3). Event-free survival (EFS) at 3 years was 35% (SE 8%); relapse rate and transplant-related mortality (TRM) at 3 years was 42 and 23%. Short first complete remission (CR1) <2.5 years was associated with lower EFS (P=0.001), higher TRM (P=0.019) and higher relapse rate (P=0.023). Short second complete remission (CR2) <2.5 years was associated with lower EFS (P=0.003) and higher TRM (0.009). Higher relapse rate and lower EFS were associated with isolated first extramedullary relapse (P=0.019, 0.012). There was no significant difference in outcome between mismatched unrelated donor stem cell transplantation (MMUD-SCT) and matched unrelated donor stem cell transplantation (UD-SCT). We conclude that UD-SCT is an effective treatment of ALL in CR3. The outcome remains limited by TRM and a high relapse rate. Short duration of CR1 and of CR2 and extramedullary site at first relapse are particularly adverse. MMUD should also be considered in high-risk patients, since the outcome of MMUD appears similar to MUD.

Alemtuzumab↗
PubMed2004

Osteoblastic cells express phospholipid receptors and phosphatases and proliferate in response to sphingosine-1-phosphate.

Sphingosine-1-phosphate (S1P) is a naturally occurring polar phospholipid that exerts growth-factor--like effects in a number of cell types, potentially by endocrine, paracrine, and intracrine mechanisms. The biological actions of S1P are mediated in part by its specific binding to at least four members of the edg/lp family of G protein-coupled receptors (edg 1, 3, 6, and 8), and further regulated by the actions of specific cell membrane-bound lipid phosphate phosphatases (LPPs). Recent evidence has suggested that S1P may act as an osteoblast growth factor. In the current study, we demonstrate expression in osteoblastic cells of the S1P receptors edg 1, edg 5 and edg 8; the lipid phosphate phosphatases LPP-1, LPP-2, and LPP-3, and the S1P phosphatase mSPP1. S1P exerts dose-dependent mitogenic effects in cultures of primary rat osteoblastic cells and SaOS-2 cells. S1P also activates p42/44 mitogen-activated protein (MAP) kinases in osteoblastic cells, and the proliferative effects of S1P in these cultures are partially abrogated by PD-98059 and U-0126, specific inhibitors of p42/44 MAP kinase signaling. S1P-induced p42/44 MAP kinase activation in osteoblastic cells is dependent on functional Gi proteins and intracellular calcium fluxes, but not on protein kinase A, phospha-tidylinositol-3 kinase, or protein Kinase C. These data demonstrate (1) the expression by osteoblastic cells of several cell membrane-bound components of phospholipid signaling and (2) that S1P is a potent osteoblast mitogen, the proliferative action of which is mediated by a signaling pathway that involves Gi proteins, intracellular calcium, and p42/44 MAP kinases.

Animals↗
PubMed2004

Lactoferrin promotes bone growth.

We have demonstrated bovine or human lactoferrin to be an anabolic factor in skeletal tissue. In vitro, lactoferrin stimulates the proliferation of bone forming cells, osteoblasts, and cartilage cells at physiological concentrations (above 0.1 microg/ml). The magnitude of this effect exceeds that observed in response to other skeletal growth factors such as IGF-1 and TGFbeta. DNA synthesis is also stimulated in a bone organ culture system likely reflecting the proliferation of cells of the osteoblast lineage. Lactoferrin is also a potent osteoblast survival factor. In TUNEL and DNA fragmentation assays, lactoferrin decreased apoptosis, induced by serum withdrawal, by up to 70%. In addition, lactoferrin has powerful effects on bone resorbing cells, osteoclasts, decreasing osteoclast development at concentrations > 1 microg/ml in a murine bone marrow culture system. However, lactoferrin did not alter bone resorption in calvarial organ culture, suggesting that it does not influence mature osteoclast function. In vivo, local injection of lactoferrin in adult mice resulted in increased calvarial bone growth, with significant increases in bone area and dynamic histomorphometric indices of bone formation after only 5 injections. Taken together, these data demonstrate that the naturally-occurring glycoprotein lactoferrin is anabolic to bone in vivo, an effect which is consequent upon its potent proliferative and anti-apoptotic actions in osteoblasts, and its ability to inhibit osteoclastogenesis. Lactoferrin may therefore have a physiological role in bone growth, and a potential therapeutic role in osteoporosis.

Animals↗
PubMed2003

Adrenomedullin--a regulator of bone formation.

Bone growth and maintenance are highly regulated processes. Throughout life, bone constantly undergoes remodelling, maintaining a balance between bone formation by osteoblasts and bone resorption by osteoclasts. This balance depends on the coordinated activities of many systemic hormones and locally acting factors in the bone microenvironment. Understanding the mechanisms of action of these factors provides a better appreciation of the cellular and molecular basis of bone remodelling. Adrenomedullin has recently been found to stimulate the proliferation of osteoblasts in vitro, and to increase indices of bone formation when administered either locally or systemically in vivo. Adrenomedullin receptors, as well as adrenomedullin itself, are expressed in primary osteoblasts and in osteoblast-like cell lines. In this paper we discuss the anabolic effect of adrenomedullin in bone, and present new evidence for a possible role of adrenomedullin in the regulation of cartilage cells. We show that adrenomedullin stimulates proliferation of primary chondrocytes in culture and that mRNA for adrenomedullin and for adrenomedullin receptors are expressed in these cells. Studies of structure-activity relationships have demonstrated that osteotropic effects of adrenomedullin can be retained in peptide fragments of the molecule which lack the parent molecule's vasodilatory properties. Thus, these small peptides, or their analogues, are attractive candidates as anabolic therapies for osteoporosis.

Adrenomedullin↗
PubMed2003

Interleukin-18 is a novel mitogen of osteogenic and chondrogenic cells.

IL-18 was identified due to its ability to induce interferon-gamma (IFNgamma) production by T cells. It is a pleiotropic factor that shares structural features with IL-1 and functional activities with IL-12. IL-18 has a role in T cell development, where it has been demonstrated to act cooperatively with IL-12 to regulate IFNgamma. In bone, IL-18 is mainly produced by macrophages, but is also expressed by osteoblasts and inhibits osteoclast formation through granulocyte-macrophage colony-stimulating factor (GM-CSF) and not IFNgamma production by T cells. We have investigated the effects of IL-18 on mature osteoclast activity and for potential actions on osteoblasts or chondrocytes. The effects of IL-18 on mature osteoclast activity were determined using two assays: isolated mature osteoclast cell culture and neonatal murine calvarial organ culture. IL-18 did not affect bone resorption in either assay system. The actions of IL-18 on osteogenic cells (primary cell cultures of fetal rat and neonatal mouse osteoblasts, as well as neonatal mouse calvarial organ culture) and primary chondrocytes (canine) were assessed by proliferation assays (quantification of cell numbers and thymidine incorporation). In each assay system, IL-18 acted as a mitogen to the osteogenic and chondrogenic cells. Since IL-18 signal transduction may involve IFNgamma or GM-CSF, we assessed their involvement in the IL-18 response. IL-18 did not induce IFNgamma production by primary osteoblasts, but, of greater significance, IFNgamma had the opposing action to IL-18 in that it inhibited the primary osteoblast cell proliferation. Although IL-18 rapidly induced GM-CSF production by primary osteoblasts, IL-18 was still mitogenic in osteoblast preparations established from GM-CSF-deficient mice. Combined, these studies indicate that IL-18 may have an autocrine/paracrine mitogen role for both osteogenic and chondrogenic cells, independent of the production of IFNgamma or GM-CSF.

Animals↗
PubMed2002

Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo.

Fat mass is an important determinant of bone density, but the mechanism of this relationship is uncertain. Leptin, as a circulating peptide of adipocyte origin, is a potential contributor to this relationship. Recently it was shown that intracerebroventricular administration of leptin is associated with bone loss, suggesting that obesity should be associated with low bone mass, the opposite of what is actually found. Since leptin originates in the periphery, an examination of its direct effects on bone is necessary to address this major discrepancy. Leptin (>10(-11) m) increased proliferation of isolated fetal rat osteoblasts comparably with IGF-I, and these cells expressed the signalling form of the leptin receptor. In mouse bone marrow cultures, leptin (>or=10(-11) m) inhibited osteoclastogenesis, but it had no effect on bone resorption in two assays of mature osteoclasts. Systemic administration of leptin to adult male mice (20 injections of 43 micro g/day over 4 weeks) reduced bone fragility (increased work to fracture by 27% and displacement to fracture by 21%, P<0.001). Changes in tibial histomorphometry were not statistically significant apart from an increase in growth plate thickness in animals receiving leptin. Leptin stimulated proliferation of isolated chondrocytes, and these cells also expressed the signalling form of the leptin receptor. It is concluded that the direct bone effects of leptin tend to reduce bone fragility and could contribute to the high bone mass and low fracture rates of obesity. When administered systemically, the direct actions of leptin outweigh its centrally mediated effects on bone, the latter possibly being mediated by leptin's regulation of insulin sensitivity.

Animals↗
PubMed2002

Amylin and adrenomedullin: novel regulators of bone growth.

Bone growth is regulated by circulating hormones and locally generated factors. Understanding their mechanisms of action enables us to obtain a better appreciation of the cellular and molecular basis of bone remodelling, and could therefore be valuable in approaches to new therapies. In this review, we consider the actions on bone tissue of the peptide hormones amylin and adrenomedullin, known to circulate at picomolar concentrations. Adrenomedullin is also produced locally in bone. Amylin and adrenomedullin are related peptides with some homology to both calcitonin and calcitonin gene-related peptide. These peptides have recently been found to stimulate the proliferation of osteoblasts in vitro, and to increase indices of bone formation when administered either locally or systemically in vivo. In addition, amylin inhibits bone resorption. Both amylin and adrenomedullin have also been found to act on chondrocytes, stimulating their proliferation in culture and increasing tibial growth plate thickness when administered systemically to adult mice. Like the peptides themselves, the receptors for the calcitonin family are also related to each other. Each peptide seems to act through its own distinct high affinity receptor, as well as through other receptors for the family, usually with lower affinity. Characterisation of the putative receptors expressed in osteoblasts, has provided some understanding of the physiological effects of amylin and adrenomedullin in these cells. Studies of structure-activity relationships have demonstrated that osteotropic effects of amylin and adrenomedullin can be retained in peptide fragments of the molecule whilst losing the parent molecule's effects on carbohydrate metabolism or vasodilatory properties respectively. Thus, these small peptides, or their analogues, are attractive candidates as anabolic therapies for osteoporosis.

Adrenomedullin↗
PubMed2001

Effectiveness of propranolol for cocaine dependence treatment may depend on cocaine withdrawal symptom severity.

Propranolol may reduce symptoms of autonomic arousal associated with early cocaine abstinence and improve treatment outcome. This trial was an 8-week, double-blind, placebo-controlled trial of propranolol in 108 cocaine dependent subjects. The primary outcome measure was quantitative urinary benzoylecgonine levels. Secondary outcome measures included treatment retention, addiction severity index results, cocaine craving, mood and anxiety symptoms, cocaine withdrawal symptoms, and adverse events. Propranolol treated subjects had lower cocaine withdrawal symptom severity but otherwise did not differ from placebo treated subjects in any outcome measure. However, in a secondary, exploratory analysis, subjects with more severe cocaine withdrawal symptoms responded better to propranolol in comparison to placebo. In these subjects, propranolol treatment was associated with better treatment retention and lower urinary benzoylecgonine levels as compared with the placebo treatment. Propranolol may be useful only for the treatment of cocaine dependent patients with severe cocaine withdrawal symptoms.

Adolescent↗
PubMed2001

Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia.

In order to compare the outcomes of unrelated umbilical cord blood transplants (UCBTs) or bone marrow transplants, 541 children with acute leukemia (AL) transplanted with umbilical cord blood (n = 99), T-cell-depleted unrelated bone marrow transplants (T-UBMT) (n = 180), or nonmanipulated (UBMT) (n = 262), were analyzed in a retrospective multicenter study. Comparisons were performed after adjustment for patient, disease, and transplant variables. The major difference between the 3 groups was the higher number in the UCBT group of HLA mismatches (defined by serology for class I and molecular typing for DRB1). The donor was HLA mismatched in 92% of UCBTs, in 18% of UBMTs, and in 43% of T-UBMTs (P <.001). Other significant differences were observed in pretransplant disease characteristics, preparative regimens, graft-versus-host disease (GVHD) prophylaxis, and number of cells infused. Nonadjusted estimates of 2-year survival and event-free survival rates were 49% and 43%, respectively, in the UBMT group, 41% and 37% in the T-UBMT group, and 35% and 31% in the UCBT group. After adjustment, differences in outcomes appeared in the first 100 days after the transplantation. Compared with UBMT recipients, UCBT recipients had delayed hematopoietic recovery (Hazard ratio [HR] = 0.37; 95% confidence interval [95CI]: 0.27-0.52; P <.001), increased 100 day transplant-related mortality (HR = 2.13; 95CI: 1.20-3.76; P <.01) and decreased acute graft-versus-host disease (aGVHD) (HR = 0.50; 95CI: 0.34-0.73; P <.001). T-UBMT recipients had decreased aGVHD (HR = 0.25; 95CI: 0.17-0.36; P <.0001) and increased risk of relapse (HR = 1.96; 95CI: 1.11-3.45; P =.02). After day 100 posttransplant, the 3 groups achieved similar results in terms of relapse. Chronic GVHD was decreased after T-UBMT (HR = 0.21; 95CI: 0.11-0.37; P <.0001) and UCBT (HR = 0.24; 95CI: 0.01-0.66; P =.002), and overall mortality was higher in T-UBMT recipients (HR = 1.39; 95CI: 0.97-1.99; P <.07). In conclusion, the use of UCBT, as a source of hematopoietic stem cells, is a reasonable option for children with AL lacking an acceptably matched unrelated marrow donor.

Analysis of Variance↗