Stem cell transplant (SCT) outcomes in high-risk (HR) and relapsed/refractory (R/R) paediatric acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) have been poor historically. Cord blood allows T-cell replete transplant (TRCB), enabling enhanced graft-versus-leukaemia. We collected data from 367 consecutive patients undergoing TRCB (112 patients) or other cell source (255 patients) SCT for paediatric AML/MDS in the UK and Ireland between January 2014 and December 2021. Data was collected about patient's demographics, disease and its treatment including previous transplant, measurable residual disease (MRD) status at transplant, HLA-match, relapse, death, graft versus host disease (GvHD) and transplant-related mortality (TRM). Univariable and multivariable analyses were undertaken. There was a higher incidence of poor prognosis features in the TRCB cohort: 51.4% patients were MRD positive at transplant, 46.4% had refractory disease and 21.4% had relapsed after a previous SCT, compared with 26.1%, 8.6% and 5.1% respectively in the comparator group (all p <0.001). Within the TRCB cohort, Event Free Survival (EFS) was 64.1%, 50% in MRD positive patients and 79% in MRD negative (p= 0.009). To allow for the imbalance in baseline characteristics, a multivariable analysis was performed: the TRCB cohort had significantly improved EFS (0.57[0.35-0.91], p=0.019), time to relapse (0.46[0.26-0.81), p=0.008), and reduced chronic GVHD (HR 0.28 [95% CI 0.11-0.70]; p=0.007), with some evidence of improved Overall Survival (OS) (0.65[0.39-1.07], p = 0.088). The effect appeared similar regardless of MRD status, (interaction p-value= 0.29). CB transplant without serotherapy may be the optimal transplant option for children with myeloid malignancy.
The literature relating to mixed Mullerian tumors of the uterine corpus has been reviewed. A critical account of the clinico-pathologic features of these tumors, their prognosis and treatment is presented.
Smoking has been associated, on epidemiologic grounds, with an increased risk of cervical neoplasia. We have investigated this association, using laboratory-based methods. A 32P post-labeling assay was performed on 97 cervical biopsies to detect and measure DNA adducts (additional products formed by the covalent binding of potential chemical carcinogens to nuclear DNA). The specimens were taken from both normal cervices as well as the histologically normal regions of cervices with invasive and intraepithelial neoplasia. A detailed smoking history was obtained from each patient and correlated with an assay of cotinine level in urine. Characteristic smoking-related DNA adducts were found, and a significant difference in their levels was detected between current and non-current smokers (P = 0.017, Mann-Whitney test). There was also a highly significant trend in median adduct levels between the three tissue types (P < 0.002). We conclude that the finding of smoking-related cervical DNA damage is suggestive of a causal association between smoking and cervical neoplasia.
The expression of cytochrome P450 isoenzymes (subfamilies) CYP1A, CYP2B, CYP2C, CYP3A and CYP4A in the histologically normal cervix was explored using a panel of polyclonal antibodies. There was variation in the intensity of immunohistochemical reaction between the isoenzymes and between the various components of the cervix. Half the subjects tested were smokers and had increased urinary cotinine levels. Statistical analysis revealed no significant differences between smokers and nonsmokers in the expression of these isoenzymes. The implications of these observations in relation to cervical carcinogenesis are discussed.
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