Search

Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD., (© 2014 John Wiley & Sons Ltd.)

We compared outcome and toxicity in two paediatric groups undergoing SCT and treated with busulphan (BU) by the oral route of administration. One group receiving the standard dose of 1 mg/kg q.i.d. for a total of 16 doses was compared with age- and disease-matched patients receiving 2 mg/kg of BU b.i.d. for a total of eight doses. Seventy-two patients from two Swedish paediatric transplantation centres were included; one centre used a standard q.i.d. administration (n=37) and the second centre used a b.i.d. administration setting (n=35). Our primary objective was to determine the incidence of veno-occlusive disease (VOD), graft-versus-host disease (GVHD), relapse frequency and transplant-related mortality in both cohorts. A total of 17 autologous and 55 allogeneic transplantations was performed for malignant (n=47) and non-malignant (n=25) diseases in the two centres during the period 1990-2005. No significant difference in the incidence of VOD, graft rejection, GVHD, relapse rate or overall survival was observed between the two centres. The clinical outcome of SCT for paediatric patients conditioned with oral BU at a dose of 2 mg/kg for eight doses is comparable to that found for children conditioned using the standard regimen given 1 mg/kg q.i.d. for 16 doses.

To investigate which factors impact on survival, relapse, relapse free survival, transplant-related mortality (TRM) and graft-versus-host disease (GVHD) in children who undergo allogeneic stem cell transplantation, we included all 181 children transplanted due to leukemia at our unit. At the end of follow up 54% of the patients were alive, 27% had died due to relapse while 19% had died of other causes. Survival was similar in recipients of related (55%) and unrelated grafts (48%). Risk factors identified in univariate analysis were brought into a multivariable analysis. However, an unrelated donor was not identified as a risk factor for any of the five end-points analysed. A donor positive for three to four herpes viruses increased the risk of acute GVHD, TRM and death. A female to male transplant increased the risk of TRM, particularly if combined with a mismatch. Early stage of disease as well as human leukocyte antigen (HLA)-matching independently predicted survival. The risk of relapse increased after 1992. Chronic GVHD independently decreased the risk of relapse (relative risk RR, 0.39) and death (RR 0.42). We conclude that in children with leukemia other specific donor characteristics such as HLA-matching, gender, parity, and exposure to herpes viruses were more important for outcome than relationship., (Copyright 2004 Blackwell Munksgaard)

Background: Previous studies have suggested that altered expression or dysfunction of the tumor suppressor gene p53 or the oncogene MDM2 could indicate disease progression in children with leukemia who would fail to achieve complete remission or who would relapse. While these studies mainly have described aberrations of MDM2 and p53 function at the DNA and mRNA-level, we have examined p53 and MDM2 expression at the protein level. Mutation of the p53 tumor suppressor gene may result in cellular accumulation of the p53 protein, due to prolonged half-life of the abnormal protein. The p53 protein can also be rendered nonfunctional by overexpression of proteins that bind to p53, such as MDM2. Both pathways have been proposed to disrupt cell cycle regulation in humans. Recent studies have shown that increased expressions of MDM2 as well as of p53 can be detected at the protein level in the absence of gene amplification., Procedure: Forty-three bone marrow samples were analyzed immunohistochemically for p53 and MDM2. Twenty-nine bone marrow samples were obtained in children with active, prognostically unfavorable leukemia and MDS. Fourteen bone marrow samples were from children with non-malignant hematological disorders., Results: p53 protein was expressed in 12 patients and MDM2 in 17 patients with leukemia. In the control group MDM2 expression was detected in one child, while p53 was not found in any of the samples., Conclusions: Our findings of p53 or MDM2 positive cells in a majority of children with unfavorable prognostic features suggests that dysfunction of the p53-dependent cell growth control have a role in the development of high risk leukemias., (Copyright 2000 Wiley-Liss, Inc.)

Forty patients with leukemia receiving HLA-identical sibling marrow and treated with four doses of methotrexate (MTX) in combination with cyclosporin A (CSA) for prevention of graft-versus-host disease (GVHD) were compared with retrospective controls consisting of 57 patients treated with MTX alone and 30 patients treated with CSA alone. Follow-up time ranged from 2.6 to 6.7 years after bone marrow transplantation. Patients in the MTX + CSA group were older and received a smaller marrow cell dose, but were otherwise comparable regarding disease status, donor/recipient sex match and seropositivity for cytomegalovirus (CMV) and other herpes viruses. Engraftment was slowest in the MTX + CSA group and fastest in the CSA group (p = 0.005 vs MTX and p less than 0.001 vs CSA). The incidence of moderate to severe acute GVHD (grade II-IV) was 8% among patients on MTX + CSA and 26% and 47% in the MTX (p = 0.028) and CSA (p = 0.0001) groups respectively. The corresponding figures for chronic GVHD were 25, 42 and 40% (n.s.). The incidence of CMV interstitial pneumonia was 0% in patients treated with MTX + CSA compared to 23% in the MTX treated patients (p = 0.01) and 11% in the CSA treated patients (p = 0.05). The actuarial 3-year survival in the three groups was similar, 56% for the MTX + CSA patients and 53% for both the MTX and CSA patients (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: The aim of the study was to evaluate long-term ovarian function after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. Subjects and methods: Predictive factors for ovarian function were evaluated among 92 adult or pubertal female survivors transplanted at Huddinge and Helsinki University Hospital during 1978-2000, at a mean age of 9±4.3 years (range 1-19). At the time of the study a meanGS.D. of 13±5.5 years (range 6-27) had elapsed since the HSCT and the mean age of the participants was 22±6.3 years (range 9-41). Results: Spontaneous puberty based on breast development occurred in 40 and menarche in 30 of the 70 girls who were prepubertal at transplantation. Six out of 20 girls who received HSCTafter initiation of pubertal development recovered their ovarian function. Younger age at HSCT, conditioning without total body irradiation (TBI), and a non-leukemia diagnosis predicted the spontaneous menarche. The incidence of menarche was higher after fractioned vs single fraction TBI (P<0.05), cyclophosphamide (Cy) vs busulfan (Bu)-based conditioning (P<0.05), and among leukemia patients transplanted at first remission vs later remissions (P<0.01) and with no cranial irradiation (cranial radiotherapy, CRT) vs given CRT (14-24 Gy) (P<0.01). The majority of recipients conditioned with only Cy vs TBI (P<0.001) or vs Bu-based regimens (P<0.01) showed preserved ovarian function and required no estrogen replacement at their latest follow-up visit at a mean age of 23±6.3 years (range 15-41). Ten women became pregnant. Conclusions: Patients conditioned with TBI or Bu-based regimes are at high risk of ovarian failure. Intensive antileukemia therapy before HSCT including CRT especially among relapsed patients may further decrease the possibility of spontaneous menarche. [ABSTRACT FROM AUTHOR]

Summary:A total of 52 children, age 9 or over and at least 3 years (median=8) beyond SCT for leukaemia (n=32) or nonmalignant diseases, participated in a single-centre study of health and quality of life (QoL). QoL and self-esteem were assessed with SCHQ-CF87, a generic multidimensional self-report instrument, and with ‘I think I am’. As a group, the children had good QoL, but were below norm in the bodily pain (P<0.05), general health and self-esteem dimensions (P<0.01). Lansky or Karnofsky function levels were at a median of 90. Sense of coherence (SOC-13) was normal and correlated with SCHQ-CF87. Most children were subjectively and objectively in good health according to a self-assessment symptom inventory or by a medical record-based scoring of late effects, although pain was commonly reported. A total of 25% of the patients were rated as having moderate to severe late effects, without considering cataracts or infertility. Neither age at SCT, gender, malignant vs nonmalignant disease, nor stature influenced QoL significantly. Children with moderate to severe chronic graft-versus-host disease or cognitive deficits had lower QoL in some dimensions. No correlation was, however, found between the physician-rated total late effects score and overall QoL. Contrarily, QoL was clearly related to the degree of self-rated symptoms.Bone Marrow Transplantation (2005) 36, 171–176. doi:10.1038/sj.bmt.1705021 Published online 6 June 2005 [ABSTRACT FROM AUTHOR]