Forty-eight toddlers participated in a word-learning task to assess gesture input on mapping nonce words to unfamiliar objects. Receptive fast mapping and expressive naming for target object-word ...pairs were tested in three conditions - with a point, with a shape gesture, and in a no-gesture, word-only condition. No statistically significant effect of gesture for receptive fast-mapping was found but age was a factor. Two year olds outperformed one year olds for both measures. Only one girl in the one-year-old group correctly named any items. There was a significant interaction between gesture and gender for expressive naming. Two-year-old girls were six times more likely than two-year-old boys to correctly name items given point and shape gestures; whereas, boys named more items taught with the word only than with a point or shape gesture. The role of gesture input remains unclear, particularly for children under two years and for toddler boys.
Identification of language disorders in children younger than 3 years remains challenging despite agreement that early intervention improves outcomes. This study of twin language and gesture ...development substantiated the twinning effect, an unexplained lag in expressive and receptive language seen in twins, for a group of 88, 16- to 18-month-old twins who did not present with extreme perinatal risk. A valid, parent-report measure revealed word production of 10th percentile and less for 15 twins. Pregnancy complications, but not a positive family history of speech, language, or learning disorders or other case history factors, significantly increased the odds of this early expressive delay. The twinning effect was more pronounced for gesture than for spoken vocabulary: 29 twins fell below gesture norms. This was unexpected. Because gesture signals early communicative intentionality, twins with early expressive delay who present with limited gestures, with or without additional risk factors, warrant priority consideration for early intervention.
Loneliness may compromise health-related quality of life (HRQOL) outcomes and the immunological impacts of loneliness via neuroendocrinological mechanisms likely have consequences for patients who ...have undergone a hematopoietic stem cell transplantation (HSCT).
Loneliness (pre-transplant), immunological recovery (Day 30, Day 100, 1-year post-transplant), and HRQOL (Day 100, 1 year) were measured in a sample of 205 patients completing a HSCT (127 autologous, 78 allogenic).
Greater levels of pre-transplant loneliness predicted poorer HRQOL at Day 100 and 1-year follow-up. Loneliness also was associated with higher absolute neutrophil to absolute lymphocyte (ANC/ALC) ratios in the entire sample at Day 30, which in turn was associated with Day 100 HRQOL.
Findings demonstrate that pretransplant loneliness predicts HRQOL outcomes and associates with inflammatory immunological recovery patterns in HSCT patients. The balance of innate neutrophils to adaptive lymphocytes at Day 30 present a distinct profile in lonely individuals, with this immunity recovery profile predicting reduced HRQOL 100 days after the transplant. Addressing perceptions of loneliness before HSCT may be an important factor in improving immunological recovery and HRQOL outcomes.
Aim
The aim of study was to investigate whether depression and anxiety symptoms and illness perception prior to hematopoietic stem cell transplantation (HSCT) predict health related quality of life ...(HRQOL) at Day 100 and 1 year following HSCT.
Methods
A total of 205 patients who underwent HSCT (N = 127 autologous transplants, N = 78 allogeneic transplants) were included in this prospective study. Baseline assessment was assessed prior to transplantation and post HSCT data were collected at Day 100 and 1 year. At baseline we assessed depressive symptoms (Patient Health Questionnaire‐9), anxiety symptoms (Generalized Anxiety Disorder‐7), illness perception (Brief Illness Perception Questionnaire), and HRQOL (Functional Assessment of Cancer Therapy‐BMT).
Results
Patients who expressed a greater level of concern about the severity, course, and ability to exert control over one's illness (i.e., illness perception) and who reported a greater level of depression and anxiety symptoms prior to HSCT reported lower HRQOL at both Day 100 and 1 year posttransplant, with a similar degree of association observed at the two follow‐up time points.
Conclusions
Our findings suggest that pretransplant perceptions about their illness and negative mood are significant predictors of HRQOL following HSCT. Illness perception, depression, and anxiety are potentially modifiable risk factors for less than optimal outcome after HCSCT and intervention strategies should be explored.
While HSCT continues to remain a promising form of treatment and advances in transplant medicine have led to reduced morbidity and mortality from HSCT, HRQOL remains an important consideration. Our study suggests that addressing possibly modifiable psychological risk factors prior to and/or during recovery from HSCT has the potential to improve this important aspect of patient experience during transplant and also health outcomes.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Cedazuridine (CED), a cytidine deaminase (CDA), inhibitor allows oral availability of decitabine (DEC); 5 daily doses of the fixed-dose combination (FDC) of 35 mg DEC/100 mg CED standard dose (SD) ...provides equivalent exposure to an IV DEC regimen of 20 mg/m2 D1-5 (Garcia-Manero et al, 2020). Attenuated HMA regimens (e.g., 3 days IV DEC) have shown activity in LR-MDS (Jabbour, et al. 2017).
This Phase 1/2 study explores lower dose oral DEC/CED regimens in LR-MDS patients.
Phase 1/2 study in lower-risk-MDS (IPSS low risk and lntermediate-1) subjects requiring treatment. Phase 1: explored 28-day regimens, dose ranges 5-20 mg DEC/100mg CED; duration ranges 5-10 days. Primary endpoints: recommended Phase 2 dose (RP2D) based on safety and dose-limiting toxicity (DLT). Secondary endpoints: clinical activity per 2006 IWG (transfusion independence TI, LFS, OS). Phase 2: randomized 81 LR-MDS 1:1 to receive Phase 1 RP2D vs 35 mg DEC/100 mg CED (SD) for 3days (SD-3Day) (reflecting attenuated HMA regimen for LR-MDS). Similar efficacy and safety endpoints as Phase 1.
Phase 1: 47 patients treated with five different DEC/CED regimens. DLT (myelosuppression-associated) increased with higher treatment doses and longer duration. Hematologic improvement (HI) % across dosing regimens: 30% (14/47), 8-week RBC transfusion-independent rate: 33% (7/21); mOS: 31 months (95%Cl:19,NE); mLFS 23 months (95%Cl:14,32). Based on clinical efficacy and safety, 10mg DEC/100mgCED D1-5 every 28D (LD-5Day) was selected as RP2D. Phase 2: Baseline: Int-1 (65-73%), 48% prior MDS treatment (21%ESA, 26% luspatercept), 46% RBC transfusion-dependent (TD); 14% platelet TD. At cutoff, 80 subjects had received a median of 4.5 treatment cycles, ~10 patients received subsequent transplant. PK data showed LD-5Day exposure about half SD-3Day exposure. Reported adverse event terms with LD-5Day were similar to SD-5day, with most common grade ≥3 from myelosuppression. By cycle 8, average neutrophil counts were higher in LD-5Day regimen vs SD-3Day regimen; platelet changes were similar. Of 8 all-cause deaths at data cutoff, only 1 was within 30 days (in SD-3Day group).
This Phase 1/2 study suggests LD-5Day regimen is tolerable (less neutropenia) and potentially an optimal regimen for LR-MDS (longer term efficacy analysis vs SD-3Day regimen pending).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. This portion of the ...NCCN Guidelines for AML focuses on management and provides recommendations on the workup, diagnostic evaluation, and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients.
Acute myeloid leukemia O'Donnell, Margaret R; Appelbaum, Frederick R; Coutre, Steven E ...
Journal of the National Comprehensive Cancer Network
6, Issue:
10
Journal Article
Nonmyeloablative allogeneic stem-cell transplantation (alloNST) is the focus of investigations searching for less-toxic transplantation regimens. We report studies on the kinetics of lymphodepletion ...and safety of pentostatin (PT) conditioning in alloNST. Patients with hematologic malignancy received mobilized blood from human leukocyte antigen-matched related (n=4) or unrelated (n=8) donors. PT 4 mg/m2 was administered on days -21, -20, and -19 and 200 cGy of total-body irradiation was administered on day -1, followed by cyclosporine A and mycophenolate mofetil. Mononuclear cell adenosine deaminase after PT was inhibited 84%. The absolute CD3+ cells decreased significantly by day -7 (49%) and CD19+ cells declined 92% by day -1. CD4+ cells were depressed more than CD8+ cells. Neutrophils and monocytes were minimally affected by PT. Median posttransplant peripheral blood chimerism on day 70 showed 95% donor leukocytes and 82.5% donor CD3 lymphocytes. PT demonstrated lymphodepleting effects and promising safety, supporting alloNST as early as 7 days after initiation of PT.
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