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Edited by
Laurie J. Mckenzie, University of Texas MD Anderson Cancer Center, Houston,Denise R. Nebgen, University of Texas MD Anderson Cancer Center, Houston
The incidence of cancer during gestation has risen due to multiple factors such as advanced maternal age and improvement in cancer treatment, which has resulted in longer life span and a rising number of survivors who will then become pregnant. Whether a woman is diagnosed with cancer during pregnancy or becomes pregnant after surviving the disease, navigating treatment for both the mother and the fetus can seem daunting for patients as well as their care providers, as there is a higher risk of morbidity for these patients. This chapter aims to describe safe diagnostic and therapeutic options during pregnancy and includes special considerations regarding survivors’ treatment. Breast cancer, lymphoma, leukemia and cervical cancer are the focus of the chapter and obstetric management of patients with these malignancies is addressed, including antenatal care, delivery considerations and breastfeeding.
Survivors of childhood ALL treated with CNS-directed chemotherapy are at risk for neurocognitive deficits that emerge during treatment and impact functional and quality of life outcomes throughout survivorship. Neurocognitive monitoring is the recommended standard of care for this population; however, information on assessment timing and recommendations for assessment measures are limited. We examined the role of serial neurocognitive monitoring completed during protocol-directed therapy in predicting parent-reported neurocognitive late effects during survivorship.
Participants and Methods:
Parents of 61 survivors of childhood ALL completed a semi-structured survey focused on parent perspective of neurocognitive late effects as part of a quality improvement project. Survivors completed protocol-directed treatment for newly diagnosed ALL on two consecutive clinical trials (St. Jude Total Therapy Study 15, 47.5%; Total Therapy 16, 52.5%). The majority of survivors were White (86.9%), 52.5% were male, and 49% were treated for low risk disease. Mean age at diagnosis was 7.77 years (standard deviation [SD] = 5.31). Mean age at survey completion was 15.25 years (SD = 6.29). Survivors completed neurocognitive monitoring at two prospectively determined time points during and at the end of protocol-directed therapy for childhood ALL.
Results:
During survivorship, parents reported that 73.8% of survivors experienced neurocognitive late effects, with no difference in frequency of endorsement by protocol (p = .349), age at diagnosis (p = .939), patient sex (p = .417), or treatment risk arm (p = .095). In survivors with late effects, 44.3% sought intervention in the form of educational programming (i.e., 504 or Individualized Education Program). Among the group with late effects, compared to those without educational programming, those with educational programming had worse verbal learning (CVLT Trials 1-5 Total, Mean[SD]; T = 56.36 [11.19], 47.00 [10.12], p = .047) and verbal memory (CVLT Short Delay Free Recall, Z = 0.86 [0.67], -0.21 [1.01], p = .007); Long Delay Free Recall, Z = 0.91 [0.92], -0.25 [1.25], p = .020) during therapy. Compared to those without educational programming, survivors with educational programming had lower estimated IQ (SS = 109.25 [13.48], 98.07 [15.74], p = .045) and greater inattention [CPT Beta T = 56.80 [13.95], 75.70 [22.93], p = .017) at the end of therapy.
Conclusions:
Parents report that nearly three quarters of children treated for ALL with chemotherapy only experience neurocognitive late effects during early survivorship, with no difference in frequency by established risk factors. Of those with late effects, nearly half required educational programming implemented after diagnosis, suggesting a significant impact on school performance. Results from neurocognitive monitoring beginning during therapy has utility for predicting educational need in survivors experiencing late effects. Our findings provide direction on the timing and content of neurocognitive monitoring, which is the recommended standard of care for childhood cancer patients treated with CNS-directed therapy.
The purpose of this study using archival data was to examine processing speed (PS) and its relation with academic fluencies in children who were diagnosed with, and treated with chemotherapy for, acute lymphoblastic leukemia (ALL) before vs. after five years of age. Chemotherapy is the first-line treatment for childhood leukemias, and the impact of cancer treatment on academic and global functioning may include a steady decline in functions over time (Baron & Rey-Casserly, 2013). Specifically, this research initiative examined age and gender factors in PS and academic fluencies in this population.
Participants and Methods:
Sixty-eight participants (39 M, 29 F; mean age 10.6 years) diagnosed with ALL and who were previously treated with chemotherapy were included. Thirty-seven participants (23 M, 14 F) were <5 years of age at the time of diagnosis and onset of chemotherapy, while 31 participants (16M, 15 F) were >5 years of age at diagnosis and treatment. Participants ranged in age from 6 to 17 years at the time of their neuropsychological evaluation. Participants were given the WISC-V (PS subtests) and WJ-IV academic fluencies (math and reading). To evaluate research questions and hypotheses, correlational tests, independent samples t-tests, and analyses of variance (ANOVA) were used. Results at the p< .05 level are reported.
Results:
There were significant correlations between PS and WJ math fluency (r=.510) and reading fluency (r=.392). Independent samples t-test analyses revealed that children who scored below 85 (standard score) on PS composite score demonstrated poorer performance on WJ math fluency (t(60)=-3.971, p=.000, d=1.065) and reading fluency (t(56)=-3.041, p=.004, d=0.896) compared to children whose PS scores were > 85. For children whose PS scores were <85, mean scores were in the low average range for WJ-IV math fluency (M=81.05) and reading fluency (M=84.50). No significant differences were found for age or gender in relation to PS and academic fluencies.
Conclusions:
Findings are important in highlighting the need for school accommodations in pediatric survivors of ALL. Processing speed is one of the most vulnerable functions impacted by cancer therapies and was positively correlated with reading and math fluencies in this study. Mean scores for math and reading fluencies were low average for age. In terms of academic accommodations, due to the slow processing speed of these boys and girls, regardless of their age at diagnosis and onset of chemotherapy, the provision for extra time for ALL survivors is recommended to ensure they are given the opportunity to maximize their learning potential and demonstrate their true academic abilities. Parents are encouraged to practice basic fluencies at home as early as possible. Inhospital and home-bound schooling supports are recommended to maintain educational progress. For children at higher risk for late effects and neurocognitive decline, rehabilitation similar to that which TBI survivors receive can be effective, as well. Future prospective research, including longitudinal tracking, with more homogeneous samples of pediatric survivors of ALL is expected to extend and refine findings of the present study.
You are seeing a patient referred by her primary care provider for consultation at your tertiary center’s high-risk obstetrics unit. She is a 27-year-old primigravida at 16+3 weeks’ gestation with intermittent swelling of her arms and face that appears within several minutes of brushing her hair and resolves upon lowering her arms. First-trimester dating sonography was concordant with menstrual dates, and fetal morphology appeared normal, with a low risk of aneuploidy; apart from HIV-negative status, results of other routine baseline prenatal investigations are not yet available to you. She has not experienced abdominal cramps or vaginal bleeding. Her medications include only routine prenatal vitamins.
The diagnosis of leukemia in a child is traumatic life experience that negatively affects parents and especialy the mother which is the “caregiver” who assists and coordinates all stages of treatment.
Objectives
To determine the prevalence of psychological distress among mothers of tunisian children with leukemia and to investigate their coping strategies.
Methods
A cross-sectional study was conducted at Aziza Othmana hospital department of pedo-oncology in Tunisia between June and July 2021. HADS scale was used to estimate the prevalence of anxiety and depression and coping strategies were measured via arabic version of the brief cope scale.
Results
We included 31 mothers, their middle age was 41 years old. In this study we didn’t include mothers with psychiatric history. Acute lymphoblastic leukemia was the most frequent type of cancer in our sample (94%). The middle age of the children was 10 years old and all of them were under chemotherapy. Clinically significant levels of anxiety and depression were reported by 58% and 49% of mothers, respectively. In our study, 81% of the participants practiced prayer and all mothers turned to religion as a coping strategy. Approach coping styles (especially acceptance and planning) were more frequently used than avoidant coping styles (especially substance use and denial).
Conclusions
Mothers are profoundly affected by a child’s cancer diagnosis, they should have early assessment of their mental health needs to have access to appropriate interventions.
Hematologic abnormalities occur commonly in the elderly. The prevalence of anemia appears to increase with age and may be caused by various underlying etiologies, including iron deficiency, anemia of inflammation, or myelodysplastic syndrome. Thrombocytopenia due to underlying comorbidities, medications, or immune thrombocytopenia (ITP) may also occur. Hematologic malignancies such as chronic lymphocytic leukemia (CLL) and multiple myeloma also become more prevalent with age. A systematic approach to the evaluation of these hematologic abnormalities is imperative to help guide diagnosis and management. For acute or progressive conditions, a multidisciplinary team of both geriatricians and hematologists is essential to ensure proper diagnosis, frailty assessment, and initiation of appropriate therapies. Novel therapies for the various hematological malignancies are well tolerated, turning life-threatening illnesses into chronic disease that can be managed while preserving quality of life.
This study evaluates the cost-effectiveness of tisagenlecleucel (a CAR T-cell therapy), versus blinatumomab, for the treatment of pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) in the Irish healthcare setting. The value of conducting further research, to investigate the value of uncertainty associated with the decision problem, is assessed by means of expected value of perfect information (EVPI) and partial EVPI (EVPPI) analyses.
Methods
A three-state partitioned survival model was developed. A short-term decision tree partitioned patients in the tisagenlecleucel arm according to infusion status. Survival was extrapolated to 60 months; general population mortality with a standardized mortality ratio was then applied. Estimated EVPI and EVPPI were scaled up to population according to the incidence of the decision.
Results
At list prices, the incremental cost-effectiveness ratio was EUR 73,086 per quality-adjusted life year (QALY) (incremental costs EUR 156,928; incremental QALYs 2.15). The probability of cost-effectiveness, at the willingness-to-pay threshold of EUR 45,000 per QALY, was 16 percent. At this threshold, population EVPI was EUR 314,455; population EVPPI was below EUR 100,000 for each parameter category.
Conclusions
Tisagenlecleucel is not cost effective, versus blinatumomab, for the treatment of pediatric and young adult patients with R/R ALL in Ireland (at list prices). Further research to decrease decision (parameter) uncertainty, at the defined willingness-to-pay threshold, may not be of value. However, there is a high degree of uncertainty underpinning the analysis, which may not be captured by EVPI analysis.
Mastocytosis is a diverse group of rare diseases due to a clonal proliferation of neoplastic mast cells that can involve a wide variety of organ systems. The two main categories of mastocytosis are cutaneous mastocytosis (CM) showing only skin involvement, and systemic mastocytosis (SM) with at least one extracutaneous organ involved. In many cases of SM, the bone marrow (BM) shows varying degrees of infiltration. Most cases of CM develop during childhood, while adult patients in their fifth and sixth decades tend to present with SM [1]. The clinical course can vary from spontaneous regression in young children with CM to a highly aggressive course primarily seen in adult patients. Even within the category of SM, the presentation can range from indolent to aggressive, and it is thus divided into five subcategories as outlined in the most recent edition of the 2016 World Health Organization (WHO) classification of mastocytosis (Table 12.1) [2]. Of note, mastocytosis is now considered a distinct clinicopathologic entity that is separate from other myeloproliferative neoplasms.
Myeloid and lymphoid neoplasms with eosinophilia (MLNE) and rearrangements of PDGFRA, PDGFRB and FGFR1 were recognized as a standalone category in the 2008 WHO classification. PCM1-JAK2 was added to this family as a new provisional entity in the 2016 WHO classification [1, 2]. The features shared by neoplasms in this category include a common presentation with eosinophilia or hypereosinophilia in peripheral blood and an increased number of eosinophilic forms in bone marrow (BM). Some cases present as acute leukaemia. Some cases may lack hypereosinophilia. The underlying mechanism is the overexpression of an aberrant tyrosine kinase as a result of a fusion gene, or rarely of a mutation, and a diagnosis and classification requires the demonstration of the specific gene fusions. The cell of origin is a mutated pluripotent stem cell that has the potential to involve myeloid, lymphoid or both lineages, concomitantly or sequentially, leading to clinically complex and heterogeneous manifestations. A common scenario is the presentation as a chronic myeloproliferative neoplasm (MPN), usually with eosinophilia followed within a variable time period and depending on the gene fusion involved, by a progression to acute myeloid leukaemia (AML) or mixed phenotype acute leukaemia (usually in the BM), and B- or T-lymphoblastic leukaemia/lymphoma (B-/T-ALL) in BM or in an extramedullary site. Thus it is critical to recognize the clinicopathologic features of these neoplasms, identify the molecular genetic lesions and classify them accordingly. An accurate diagnosis and classification have important therapeutic and prognostic implications.
During the last five decades environmental health researchers have documented environmental pollution’s profound impact on human bodies, including how human bodies bioaccumulate industrial chemicals and how those toxicants contribute to cancers and other chronic ailments. However, the relationship between toxicants and disease is often difficult to discern in mainstream sources of medical information. Previous research has identified the way print media systematically obscures the environmental causation frame in favor of a genetic and lifestyle frame. However, less has been said about medical publishing websites, which have become very influential. To address this gap I analyze WebMD’s coverage of leukemia, whose development is linked to over twenty toxicants. Similar to the print media research, I found WebMD’s coverage systematically obscures the environmental causation frame by failing to identify most toxicants associated with leukemia and by emphasizing a genetic and lifestyle causation frame. Building on previous research, I also identify rhetorical devices through which WebMD further downplays the environmental causation frame. As well, I discuss public health implications and sources of the problem.
High-dose chemotherapy and haematopoietic stem cell transplantation are essential for patients with paediatric haematologic diseases, although cardiotoxicity remains a concern. Heart rate variability analysis can evaluate autonomic nervous function interactions with cardiac function.
Objective:
This study aimed to characterise heart rate variability differences between patients undergoing chemotherapy and controls, and the effects of haematopoietic stem cell transplantation on the autonomic nervous system in patients with haematological malignancies.
Methods:
Nineteen patients (11 male, median age: 11.6 years) who received conventional chemotherapy followed by transplantation and 19 non-transplant patients (10 male, median age: 11.5 years) receiving chemotherapy only between 2006 and 2018 for haematological malignancies were retrospectively enrolled. Data from 24-hour Holter monitoring were recorded after chemotherapy and before and after transplantation. Heart rate variability was analysed in patients and 32 matched normal controls.
Results:
There were significant differences between patients and normal controls in all heart rate variability analysis parameters apart from coefficient of variation of RR interval and standard deviation of the average normal RR interval for all 5-minute segments during sleeping. There was a significant difference in the cumulative anthracycline dose and heart rate variability during sleep between the non-transplant and pre-transplant groups. We observed no remarkable differences in time-domain analysis parameters between before and after transplantation, although the low-frequency component of power-spectrum analysis during awake hours was significantly decreased after transplantation.
Conclusion:
Conventional chemotherapy for paediatric haematologic diseases may be a risk factor for autonomic dysfunction. Further declines in heart rate variability after transplantation appear minor.
Acquired MDM2 inhibitor resistance is commonly caused by loss-of-function TP53 mutations. In addition to the selection of TP53-mutant cells by MDM2 inhibitors, MDM2 inhibitor-induced DNA damage may promote the formation of TP53 mutations. Here, we cultivated 12 sublines of the intrinsically MDM2 inhibitor-resistant TP53 wild-type acute myeloid leukaemia cell line PL21 for 52 passages in the presence of ineffective concentrations of the MDM2 inhibitor nutlin-3 but did not observe loss-of-function TP53 mutations. This suggests that MDM2 inhibitors select TP53-mutant cells after mutations have occurred, but do not directly promote TP53 mutations. Unexpectedly, many sublines displayed increased sensitivity to the anti-cancer drugs cytarabine, doxorubicin, or gemcitabine. Consequently, therapies can affect the outcome of next-line treatments, even in the absence of a therapy response. This finding is conceptually novel. A better understanding of such processes will inform the design of improved therapy protocols in the future.