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Article ; Online: Progestogens and pregnancy loss.

Carp, H J A

Climacteric : the journal of the International Menopause Society

2018 Volume 21, Issue 4, Page(s) 380–384

Abstract: Progestational agents are often prescribed to prevent pregnancy loss. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. Progestogens have therefore been used at all ... ...

Abstract	Progestational agents are often prescribed to prevent pregnancy loss. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. Progestogens have therefore been used at all stages of pregnancy including luteal-phase support prior to pregnancy, threatened miscarriage, recurrent miscarriage, and to prevent preterm labor. In luteal support, a Cochrane review reported that progestogens were associated with a higher rate of live births or ongoing pregnancy in the progesterone group (odds ratio 1.77, 95% confidence interval (CI) 1.09-2.86). Evidence suggests that progestogens are also effective for treating threatened miscarriage. Again, in a Cochrane Database review, progestogens were associated with a reduced odds ratio of 0.53 (95% CI 0.35-0.79) when progestogens were used. In recurrent miscarriage, progestogens also seem to have a beneficial effect. A meta-analysis of progestational agents showed a 28% increase in the live birth rate (relative risk 0.72, 95% CI 0.53-0.97). For the last 30 years, progestogens have been used to prevent preterm labor. Recent meta-analyses also report beneficial effects. This review summarizes the literature and the author's experience using progestogens to prevent pregnancy loss.
MeSH term(s)	Abortion, Habitual/prevention & control ; Abortion, Threatened/prevention & control ; Female ; Humans ; Obstetric Labor, Premature/prevention & control ; Pregnancy ; Progesterone/adverse effects ; Progesterone/therapeutic use ; Progestins/adverse effects ; Progestins/therapeutic use ; Randomized Controlled Trials as Topic
Chemical Substances	Progestins ; Progesterone (4G7DS2Q64Y)
Language	English
Publishing date	2018-03-22
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Review
ZDB-ID	1469153-x
ISSN	1473-0804 ; 1369-7137
ISSN (online)	1473-0804
ISSN	1369-7137
DOI	10.1080/13697137.2018.1436166
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Zs.A 5245: Show issues

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Article ; Online: FDU-Net: Deep Learning-Based Three-Dimensional Diffuse Optical Image Reconstruction.

Deng, Bin / Gu, Hanxue / Zhu, Hongmin / Chang, Ken / Hoebel, Katharina V / Patel, Jay B / Kalpathy-Cramer, Jayashree / Carp, Stefan A

IEEE transactions on medical imaging

2023 Volume 42, Issue 8, Page(s) 2439–2450

Abstract: Near-infrared diffuse optical tomography (DOT) is a promising functional modality for breast cancer imaging; however, the clinical translation of DOT is hampered by technical limitations. Specifically, conventional finite element method (FEM)-based ... ...

Abstract	Near-infrared diffuse optical tomography (DOT) is a promising functional modality for breast cancer imaging; however, the clinical translation of DOT is hampered by technical limitations. Specifically, conventional finite element method (FEM)-based optical image reconstruction approaches are time-consuming and ineffective in recovering full lesion contrast. To address this, we developed a deep learning-based reconstruction model (FDU-Net) comprised of a Fully connected subnet, followed by a convolutional encoder-Decoder subnet, and a U-Net for fast, end-to-end 3D DOT image reconstruction. The FDU-Net was trained on digital phantoms that include randomly located singular spherical inclusions of various sizes and contrasts. Reconstruction performance was evaluated in 400 simulated cases with realistic noise profiles for the FDU-Net and conventional FEM approaches. Our results show that the overall quality of images reconstructed by FDU-Net is significantly improved compared to FEM-based methods and a previously proposed deep-learning network. Importantly, once trained, FDU-Net demonstrates substantially better capability to recover true inclusion contrast and location without using any inclusion information during reconstruction. The model was also generalizable to multi-focal and irregularly shaped inclusions unseen during training. Finally, FDU-Net, trained on simulated data, could successfully reconstruct a breast tumor from a real patient measurement. Overall, our deep learning-based approach demonstrates marked superiority over the conventional DOT image reconstruction methods while also offering over four orders of magnitude acceleration in computational time. Once adapted to the clinical breast imaging workflow, FDU-Net has the potential to provide real-time accurate lesion characterization by DOT to assist the clinical diagnosis and management of breast cancer.
MeSH term(s)	Humans ; Female ; Deep Learning ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional ; Phantoms, Imaging ; Breast Neoplasms/diagnostic imaging ; Algorithms
Language	English
Publishing date	2023-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	622531-7
ISSN	1558-254X ; 0278-0062
ISSN (online)	1558-254X
ISSN	0278-0062
DOI	10.1109/TMI.2023.3252576
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Zs.A 2546: Show issues

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Article ; Online: Cancer diagnosis among women with recurrent pregnancy loss: a retrospective cohort study.

Cahen-Peretz, Adva / Haas, Jigal / Hadi, Efrat / Carp, Howard / Hershko Klement, Anat

Reproductive biomedicine online

2021 Volume 43, Issue 6, Page(s) 1057–1062

Abstract: Research question: What is relationship between unexplained recurrent pregnancy loss (RPL) and risk of cancer morbidity?: Design: A retrospective observational cohort study was conducted, based on data from a tertiary medical centre. RPL cases ( ... ...

Abstract	Research question: What is relationship between unexplained recurrent pregnancy loss (RPL) and risk of cancer morbidity? Design: A retrospective observational cohort study was conducted, based on data from a tertiary medical centre. RPL cases (exposed) were defined as women presenting with three or more unexplained confirmed pregnancy losses at 5-24 weeks, whose first visit to the RPL clinic was between 1990 and 2010. The unexposed group included women giving birth who were not RPL patients; these were matched by age and year of giving birth/admission (1:5 ratio). Data from the RPL and the live birth registries were cross-linked to the Israeli national cancer registry according to the unique ID number and merged into one database. Results: The study group comprised 937 RPL patients who were matched by maternal age (P = 1.0) and admission date (P = 0.84) to 4685 women achieving a live birth. There was no difference in overall cancer incidence between groups (adjusted odds ratio [OR] 0.76, 95% confidence interval [CI] 0.55-1.03; P = 0.08). The secondary RPL group showed a trend towards decreased cancer morbidity incidence compared with primary RPL (adjusted OR 0.65, 95% CI 0.41-1.03; P = 0.07). Analysis by cancer type showed a similar risk for breast cancer among women with RPL compared with live birth, but a significantly lower risk for gynaecological cancers among women with RPL (adjusted OR 0.25, 95% CI 0.08-0.79; P = 0.018). Conclusions: Unexplained RPL may be related to a lower risk of gynaecological cancers, possibly explained by hyper-responsive immunological mechanisms involving uterine natural killer cells.
MeSH term(s)	Abortion, Habitual/immunology ; Abortion, Habitual/pathology ; Adult ; Cohort Studies ; Databases, Factual ; Female ; Humans ; Incidence ; Maternal Age ; Neoplasms/epidemiology ; Neoplasms/immunology ; Neoplasms/pathology ; Pregnancy ; Retrospective Studies
Language	English
Publishing date	2021-08-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2113823-0
ISSN	1472-6491 ; 1472-6483
ISSN (online)	1472-6491
ISSN	1472-6483
DOI	10.1016/j.rbmo.2021.08.001
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Zs.A 5792: Show issues

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Article ; Online: Recurrent miscarriage and hCG supplementation: a review and metaanalysis.

Carp, H J A

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology

2010 Volume 26, Issue 10, Page(s) 712–716

Abstract: Human chorionic gonadotropin (hCG) has been used to prevent subsequent miscarriages after previous recurrent miscarriages. In addition to the luteotrophic effects, hCG has uterine immune and autocrine actions. hCG also affects cytokine expression. A ... ...

Abstract	Human chorionic gonadotropin (hCG) has been used to prevent subsequent miscarriages after previous recurrent miscarriages. In addition to the luteotrophic effects, hCG has uterine immune and autocrine actions. hCG also affects cytokine expression. A Cochrane database systematic review has indicated that hCG seems to prevent further miscarriages, (OR for miscarriage = 0.26, 95% CI 0.14-0.52). However, the trials in the Cochrane database were not matched for the number of miscarriages, 1°, 2° or 3° aborter status, maternal age, etc. and no account was made for chromosomally abnormal pregnancies. All of these impact on the subsequent prognosis and may confound the results. The previous trials in the literature all assessed urinary (u-hCG) rather than recombinant hCG (r-hCG), raising the question whether the effect on pregnancy outcome is due to hCG itself, or other urinary proteins present in u-hCG. A new trial is indicated in which r-hCG is compared to u-hCG and the most effective compared to placebo. Treatment and placebos arms should be stratified for the prognostic factors above and the results corrected for fetal chromosomal aberrations. Until such a trial is carried out, the use of hCG supplementation is empiric.
MeSH term(s)	Abortion, Habitual/diagnosis ; Abortion, Habitual/immunology ; Abortion, Habitual/prevention & control ; Autocrine Communication ; Chorionic Gonadotropin/pharmacology ; Chorionic Gonadotropin/therapeutic use ; Female ; Humans ; Pregnancy ; Prognosis ; Uterus/drug effects
Chemical Substances	Chorionic Gonadotropin
Language	English
Publishing date	2010-10
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Review
ZDB-ID	639237-4
ISSN	1473-0766 ; 0951-3590
ISSN (online)	1473-0766
ISSN	0951-3590
DOI	10.3109/09513590.2010.488779
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Zs.A 2284: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 608: Show issues

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Article ; Online: X-linked genes exhibit miR6891-5p-regulated skewing in Sjögren's syndrome.

Shaw, Teressa M / Zhang, Wei / McCoy, Sara S / Pagenkopf, Adam / Carp, Diana M / Garg, Shivani / Parker, Maxwell H / Qiu, Xueer / Scofield, Robert H / Galipeau, Jacques / Liang, Yun

Journal of molecular medicine (Berlin, Germany)

2022 Volume 100, Issue 9, Page(s) 1253–1265

Abstract: Many autoimmune diseases exhibit a strikingly increased prevalence in females, with primary Sjögren's syndrome (pSS) being the most female-predominant example. However, the molecular basis underlying the female-bias in pSS remains elusive. To address ... ...

Abstract	Many autoimmune diseases exhibit a strikingly increased prevalence in females, with primary Sjögren's syndrome (pSS) being the most female-predominant example. However, the molecular basis underlying the female-bias in pSS remains elusive. To address this knowledge gap, we performed genome-wide, allele-specific profiling of minor salivary gland-derived mesenchymal stromal cells (MSCs) from pSS patients and control subjects, and detected major differences in the regulation of X-linked genes. In control female MSCs, X-linked genes were expressed from both paternal and maternal X chromosomes with a median paternal ratio of ~ 0.5. However, in pSS female MSCs, X-linked genes exhibited preferential expression from one of the two X chromosomes. Concomitantly, pSS MSCs showed decrease in XIST levels and reorganization of H3K27me3
MeSH term(s)	Female ; Genes, X-Linked ; Histones/genetics ; Humans ; MicroRNAs/genetics ; Sjogren's Syndrome/genetics
Chemical Substances	Histones ; MIRN6891 microRNA, human ; MicroRNAs
Language	English
Publishing date	2022-05-10
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1223802-8
ISSN	1432-1440 ; 0946-2716
ISSN (online)	1432-1440
ISSN	0946-2716
DOI	10.1007/s00109-022-02205-3
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Article: Recurrent spontaneous abortions in antiphospholipid syndrome: natural killer cells - an additional mechanism in a multi factorial process.

Carp, H J A / Shoenfeld, Y

Rheumatology (Oxford, England)

2007 Volume 46, Issue 10, Page(s) 1517–1519

MeSH term(s)	Abortion, Habitual/immunology ; Antibodies, Antiphospholipid/immunology ; Antiphospholipid Syndrome/immunology ; Female ; Humans ; Killer Cells, Natural/immunology ; Pregnancy
Chemical Substances	Antibodies, Antiphospholipid
Language	English
Publishing date	2007-10
Publishing country	England
Document type	Comment ; Editorial
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kem219
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Zs.B 240: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 497: Show issues

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Article: Anti-phospholipid antibodies and infertility.

Carp, H J A / Shoenfeld, Y

Clinical reviews in allergy & immunology

2007 Volume 32, Issue 2, Page(s) 159–161

Abstract: Antiphospholipid syndrome (APS) or the presence of antiphospholipid antibodies (aPL), usually presents as pregnancy loss. However, aPL have also been reported to affect implantation, placentation, and early embryonic development. The binding of aPl to ... ...

Abstract	Antiphospholipid syndrome (APS) or the presence of antiphospholipid antibodies (aPL), usually presents as pregnancy loss. However, aPL have also been reported to affect implantation, placentation, and early embryonic development. The binding of aPl to beta2GP1 may lead to breakdown of the phospholipid adhesion molecules between different elements of trophoblast. As aPL affect placental growth and function, aPl may prevent implantation presenting as infertility. Lupus anticoagulant and anticardiolipin antibody have been implicated in the prothrombotic effects of APS. Antibodies to other phospholipids such as anti-phosphatidylserine, phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl glycerol, phosphatidyl Inositol etc. may be more relevant in infertility. Their role remains to be clarified. There is theoretical evidence from animal models and clinical infertility practice that aPL has a role in infertility. However, a large-scale meta-analysis has failed to confirm the association. To determine whether infertility or even pregnancy loss is associated with aPL, it is necessary to know that the embryo is chromosomally normal. Pregestational diagnosis has shown that up to 60% of embryos may be chromosomally aneuploid in failed in vitro fertilization (IVF); hence, may confound our understanding concerning the association between aPL and infertility, failed IVF or even pregnancy loss.
MeSH term(s)	Abortion, Habitual/immunology ; Animals ; Antibodies, Antiphospholipid/immunology ; Antiphospholipid Syndrome/complications ; Antiphospholipid Syndrome/immunology ; Female ; Humans ; Infertility, Female/etiology ; Infertility, Female/immunology ; Male ; Pregnancy ; beta 2-Glycoprotein I/immunology
Chemical Substances	Antibodies, Antiphospholipid ; beta 2-Glycoprotein I
Language	English
Publishing date	2007-10-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1239045-8
ISSN	1559-0267 ; 1080-0549
ISSN (online)	1559-0267
ISSN	1080-0549
DOI	10.1007/s12016-007-0010-2
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Zs.A 1844: Show issues

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Article ; Online: Fluorescence lifetime of injected indocyanine green as a universal marker of solid tumours in patients.

Pal, Rahul / Lwin, Thinzar M / Krishnamoorthy, Murali / Collins, Hannah R / Chan, Corey D / Prilutskiy, Andrey / Nasrallah, MacLean P / Dijkhuis, Tom H / Shukla, Shriya / Kendall, Amy L / Marshall, Michael S / Carp, Stefan A / Hung, Yin P / Shih, Angela R / Martinez-Lage, Maria / Zukerberg, Lawrence / Sadow, Peter M / Faquin, William C / Nahed, Brian V /

Feng, Allen L / Emerick, Kevin S / Mieog, J Sven D / Vahrmeijer, Alexander L / Rajasekaran, Karthik / Lee, John Y K / Rankin, Kenneth S / Lozano-Calderon, Santiago / Varvares, Mark A / Tanabe, Kenneth K / Kumar, Anand T N

Nature biomedical engineering

2023 Volume 7, Issue 12, Page(s) 1649–1666

Abstract: The surgical resection of solid tumours can be enhanced by fluorescence-guided imaging. However, variable tumour uptake and incomplete clearance of fluorescent dyes reduces the accuracy of distinguishing tumour from normal tissue via conventional ... ...

Abstract	The surgical resection of solid tumours can be enhanced by fluorescence-guided imaging. However, variable tumour uptake and incomplete clearance of fluorescent dyes reduces the accuracy of distinguishing tumour from normal tissue via conventional fluorescence intensity-based imaging. Here we show that, after systemic injection of the near-infrared dye indocyanine green in patients with various types of solid tumour, the fluorescence lifetime (FLT) of tumour tissue is longer than the FLT of non-cancerous tissue. This tumour-specific shift in FLT can be used to distinguish tumours from normal tissue with an accuracy of over 97% across tumour types, and can be visualized at the cellular level using microscopy and in larger specimens through wide-field imaging. Unlike fluorescence intensity, which depends on imaging-system parameters, tissue depth and the amount of dye taken up by tumours, FLT is a photophysical property that is largely independent of these factors. FLT imaging with indocyanine green may improve the accuracy of cancer surgeries.
MeSH term(s)	Humans ; Indocyanine Green ; Fluorescence ; Neoplasms/diagnostic imaging ; Fluorescent Dyes
Chemical Substances	Indocyanine Green (IX6J1063HV) ; Fluorescent Dyes
Language	English
Publishing date	2023-10-16
Publishing country	England
Document type	Journal Article
ISSN	2157-846X
ISSN (online)	2157-846X
DOI	10.1038/s41551-023-01105-2
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Article ; Online: Age-Related Declines in Occipital GABA are Associated with Reduced Fluid Processing Ability.

Simmonite, Molly / Carp, Joshua / Foerster, Bradley R / Ossher, Lynn / Petrou, Myria / Weissman, Daniel H / Polk, Thad A

Academic radiology

2018 Volume 26, Issue 8, Page(s) 1053–1061

Abstract: Rationale and objectives: Healthy aging is associated with pervasive declines in cognitive, motor, and sensory functioning. There are, however, substantial individual differences in behavioral performance among older adults. Several lines of animal ... ...

Abstract	Rationale and objectives: Healthy aging is associated with pervasive declines in cognitive, motor, and sensory functioning. There are, however, substantial individual differences in behavioral performance among older adults. Several lines of animal research link age-related reductions of gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, to age-related cognitive, motor, and sensory decline. Our study used proton magnetic resonance spectroscopy (MRS) at 3T to explore whether occipital GABA declines with age in humans and whether individual differences in occipital GABA are linked to individual differences in fluid processing ability. Materials and methods: We used a MEGA-PRESS sequence that combines frequency spectral editing with a point-resolved spectroscopy sequence to quantify GABA. Spectra were obtained from a 30 × 30 × 25 mm voxel placed in the occipital cortex of 20 young adults (mean age 20.7 years) and 18 older adults (mean age 76.5 years). Participants also performed 11 fluid processing tasks outside the scanner, the results of which were z-scored and averaged to calculate a summary measure of fluid processing ability. Regression analysis was employed to determine the relationship between GABA concentrations in the occipital cortex and a summary measure of fluid processing ability. Results: Occipital GABA was significantly lower in older participants compared to the younger participants. We also observed a significant positive relationship between occipital GABA and fluid processing ability. In fact, higher GABA was associated with better task performance in 10 of the 11 tasks. Conclusion: These findings suggest that GABA levels decline with age in humans and are associated with declines in fluid processing ability.
MeSH term(s)	Aged ; Aging/physiology ; Aging/psychology ; Cognition/physiology ; Female ; Humans ; Magnetic Resonance Spectroscopy/methods ; Male ; Occipital Lobe/diagnostic imaging ; Occipital Lobe/metabolism ; Young Adult ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2018-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1355509-1
ISSN	1878-4046 ; 1076-6332
ISSN (online)	1878-4046
ISSN	1076-6332
DOI	10.1016/j.acra.2018.07.024
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Zs.A 4594: Show issues

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Article ; Online: Impact of central nervous system involvement in adult patients with Philadelphia-negative acute lymphoblastic leukemia: a GRAALL-2005 study.

Orvain, Corentin / Chantepie, Sylvain / Thomas, Xavier / Escofrre-Barbe, Martine / Huguet, Francoise / Desbrosses, Yohan / Guillerm, Gaelle / Uzunov, Madalina / Leguay, Thibaut / Barbieux, Sarah / Vey, Norbert / Chevallier, Patrice / Malfuson, Jean-Valere / Lepretre, Stephane / Baumann, Michael / Aykut, Murat / Chaib, Abdelaziz / Joris, Magalie / Zerazhi, Hacene /

Stussi, Georg / Chapiro, Jacques / Berthon, Celine / Bonmati, Caroline / Jourdan, Eric / Carp, Diana / Marcais, Amb Roise / Gallego-Hernanz, Maria-Pilar / Vaida, Iona / Bilger, Karin / Villate, Alban / Pasquier, Florence / Chalandon, Yves / Maury, Sebastien / Lheritier, Veronique / Ifrah, Norbert / Dombret, Herve / Boissel, Nicolas / Hunault-Berger, Mathilde

Haematologica

2023 Volume 108, Issue 12, Page(s) 3287–3297

Abstract: Whereas the prognosis of adult patients with Philadelphia-negative acute lymphoblastic leukemia (ALL) has greatly improved since the advent of pediatric-inspired regimens, the impact of initial central nervous system (CNS) involvement has not been ... ...

Abstract	Whereas the prognosis of adult patients with Philadelphia-negative acute lymphoblastic leukemia (ALL) has greatly improved since the advent of pediatric-inspired regimens, the impact of initial central nervous system (CNS) involvement has not been formerly re-evaluated. We report here the outcome of patients with initial CNS involvement included in the pediatric-inspired prospective randomized GRAALL-2005 study. Between 2006 and 2014, 784 adult patients (aged 18-59 years) with newly diagnosed Philadelphia-negative ALL were included, of whom 55 (7%) had CNS involvement. In CNSpositive patients, overall survival was shorter (median 1.9 years vs. not reached, HR=1.8 [1.3-2.6], P<0.001). While there was no statistical difference in cumulative incidence of relapse between CNS+ and CNS- patients (HR=1.5 [0.9-2.5], P=0.11), non-relapse mortality was significantly higher in those with initial CNS disease (HR=2.1 [1.2-3.5], P=0.01). This increase in toxicity was mostly observed in patients randomized to the high-dose cyclophosphamide arm and in those who received allogeneic stem cell transplantation. Exploratory landmark analyses did not show any association between either cranial irradiation or allogeneic stem cell transplantation and outcome. Despite improved outcome in young adult ALL patients with pediatric-inspired protocols, CNS involvement is associated with a worse outcome mainly due to excess toxicity, without improved outcome with allogeneic SCT.
MeSH term(s)	Young Adult ; Humans ; Prospective Studies ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications ; Cyclophosphamide ; Hematopoietic Stem Cell Transplantation ; Central Nervous System ; Treatment Outcome
Chemical Substances	Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2023-12-01
Publishing country	Italy
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.282332
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