Energy balance and hematologic malignancies
Health care providers should encourage, not discourage, this partnership. Many parents of children with cancer explore the use of integrative therapies IT to help manage the side effects associated with cancer therapy, to augment the efficacy of conventional medications, and to provide psychological support for coping with the diagnosis of cancer. The high prevalence of IT use, especially the dietary supplements used in combination with conventional agents, has brought attention to the potential for adverse interactions.
Although there has been a significant increase in research on IT for cancer, there is still a paucity of data to guide clinical practice incorporating IT for children with hematological malignancies. Similar to the situation in adults, the integration of complementary therapies in the management of children with leukemia and lymphoma is controversial. Most surveys demonstrate that the biologically active herbs and other dietary supplements are the most common type of IT in use with conventional therapies, 1 , 4 yet there are very few clinical trials in adults or children examining their safety and efficacy.
Adverse events have been reported, 5 especially related to contamination of botanical products from China or India with heavy metals such as lead, mercury, and arsenic, which have, among other things, the potential to interfere with cognitive development in the young child. Microbial contamination of herbal products may be associated with even more significant risks in immunocompromised children, especially for those children undergoing stem cell transplantation.
Direct toxicities of dietary supplements have been observed, but the prevalence is unknown as systematic reporting is not legally mandated. The non-biologically based therapies are generally considered safe. For example, in a review of adverse events observed among children receiving acupuncture, the incidence rate of side effects is estimated to be only 1.
Although there is a low risk of interference with conventional therapies, training programs for IT practitioners often have little to no standards for training with children, let alone children receiving intensive conventional treatment for hematological malignancies. With the greater use of IT by children with hematological malignancies, increasing scientific attention is being directed towards the investigation of these therapies.
Preclinical and phase I studies are often not done, and this may impact the conduct of phase III trials. Additional barriers to research efforts in children with cancer exist. For example, investigations of non-pharmacologic therapies such as acupuncture are further hampered by the lack of validated assessment tools in children. The rarity of childhood cancer further reduces the incentive for many IT providers to scientifically evaluate therapies in children.
Integrative therapies that have been investigated for use as a supportive care therapy in children with hematological malignancies reviewed in Ladas et al 10 and Myers et al Most parents are also interested in the potential anti-cancer properties of herbs and other supplements; however, in this area clinical trial data are nonexistent. Preclinical studies have investigated a limited number of botanicals in the setting of childhood leukemia and lymphoma. For example, in preclinical studies of curcumin treatment of patient acute lymphoblastic leukemia ALL cells, modulation of leukemia cell resistance was achieved through a reduction in multiple drug resistance gene mRNA levels.
At the current time, no active clinical research trials investigating botanicals or other dietary supplements in children with hematological malignancies are in progress. In addition to evaluation of direct anti-cancer activity, the investigation of the interactions of specific dietary supplements with conventional chemotherapy and radiation therapy is an area of pressing need.
Antioxidants are one of the most common classes of supplements used by patients with cancer; these supplements are used for direct cytotoxic effects, for synergy with conventional therapy or to mitigate conventional therapy-induced toxicity. In a prospective observational study conducted among children with ALL, low plasma 16 and dietary antioxidant 17 levels directly correlated with treatment-related toxicity. Studies evaluating the impact of supplementation on toxicity and leukemia-free survival have not been completed.
The effect of immune-enhancing dietary supplements in children with hematological malignancies is also a priority area for research. Popular immune-enhancing herbs and dietary supplements include astragalus, echinacea, beta-glucans, and mushroom extracts especially reishi, maitake, and shitaki. No clinical trials specifically in children have been reported in the English language literature.
There are many aspects of childhood cancer therapy where IT may have a beneficial role, especially as a component of the multidisciplinary approach often utilized in childhood cancer therapy. The aims of the IT interventions are to assist with the minimization of pain and suffering and to provide practical, emotional and physical support. These therapies may be a particularly good resource for children whose illness or conventional treatment involve an extended period in the hospital, such as children with newly diagnosed ALL or acute myeloid leukemia, children undergoing stem cell transplants, and children in the end-of-life setting.
Children may become fatigued and often have reduced muscle tone. IT interventions such as yoga, karate, and massage can help maintain movement, muscle tone, and strength. Massage or reflexology may ease muscle pain associated with corticosteroid or vincristine therapy. Long conventional treatment durations such as those for ALL include therapy for up to 3 consecutive years can also lead parents to search for more comprehensive approaches to the management of side effects or to investigate IT that may minimize long-term effects of cancer therapy.
On the other hand, IT that require numerous patient visits or require radical lifestyle modification may be unreasonable given the demands of conventional treatment regimens.
The decision to use a particular IT will in part be based on the developmental stage of the child. Children with fear of needles and discomfort with the invasiveness of the conventional treatment such as intrathecal chemotherapy injections and bone marrow aspirations may have added anxiety with the use of acupuncture; in this instance, acupressure or massage may be more appropriate options. Young children often have a fear of strangers and may assume that all health care providers may induce unintentional pain.
Introduction of the relatively non-invasive IT modalities of reflexology, energy therapies, or aromatherapy may be a more effective strategy.
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This is particularly true for younger patients who may not have the language skills to articulate their fears, yet have strong imaginations to understand concepts such as energy fields, guided imagery, and meditation. Children and adolescents may be hesitant in using IT because of the fear of what the therapy may feel like; therefore, an effective strategy may be to first observe a session on another patient, parent, or sibling. The health care provider must consider several important factors in children with cancer prior to supporting or discouraging the use of IT.
Childhood cancers are generally quite different than those cancers observed in adults. Children also tend to tolerate chemotherapy better, as they are less likely to have comorbid conditions. Therefore, it is critical that therapies that may interfere with or encourage refusal or delay of conventional therapies be avoided in the child with cancer. An often under-recognized observation is that IT are used frequently among children enrolled on clinical trials.
The decision to include IT should be based on the available evidence and not include those therapies that require a tremendous burden with unproven benefit or that might lead to obstacles for the child to adhere to the conventional therapy. Massage therapy, one of the most commonly reported IT among children with cancer, is used most often to cope with side effects associated with anticancer therapy, including pain, nausea, and fatigue.
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Several dietary supplements have demonstrated efficacy for symptom control, especially for side effects for which there are limited conventional treatment options. Glutamine is safe and beneficial in reducing the severity of mucositis in children undergoing stem cell transplantation. Adult survivors of childhood leukemia and lymphoma are at risk for medical and psychosocial sequelae that may adversely affect their health status.
The use of IT as a component of a healthy lifestyle may provide support to survivors for coping with many of the late effects of cancer therapy. For example, yoga and meditation may help to reduce the feelings of anxiety associated with cancer recurrence, may lessen the functional impact of disturbances in balance or gait, or assist with maintenance of a healthy weight. Acupuncture may provide relief to patients who are challenged with fatigue, recurrent pain or infertility.
As more parents of children with cancer seek integrative care, pediatric institutions face the need to answer questions from patients and healthcare providers about integrating these therapies in the care of children with hematological malignancies. In a study performed at a pediatric institution with an established IT consultation service, consultations were most frequently requested by oncology patients for assistance with symptom management and with questions on various therapies, especially herbs and dietary supplements.
Similarly, we need to offer easy-to-understand information about integrative approaches. We can encourage patients and parents to talk with us when they hear of anecdotal use of unproven modalities, and discourage the use of most biologically based IT until studies are undertaken to prove their safety and efficacy. Most of all, we can remind them that we are their partners in care, that we care about and take seriously their wishes to use IT in the best interests of their child.
The goal of an integrative approach in the care of children with hematological malignancies is to provide IT modalities that are deemed safe and effective in conjunction with effective conventional medical treatments. There is significant need for research evaluating the roles of IT for direct treatment of hematological malignancies and for symptom control of toxicities related to conventional therapies.
Healthcare providers should consider how IT services may be beneficial for children with leukemia or lymphoma.
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This work was supported in part by funding to the Integrative Therapies Program for Children with Cancer through the Tamarind Foundation. Disclosures Conflict-of-interest disclosure: The author declares no competing financial interests. Off-label drug use: None disclosed. Institutional subscriptions are also available.
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Kelly 1 Kara M. This heterogeneity is driven not only by tumor genetics, but also by other cell states, such as rare cancer stem cells CSCs. Single cell genomic techniques are ideally placed to unravel such multi-layered heterogeneity and provide entirely new insights into cancer biology. Arguably, the best characterized CSC-propagated malignancies are chronic myeloid neoplasms, which are excellent tractable disease models for cancer biology. Mead will specifically review new insights that have been gained through single cell multi-omic analysis of CSC populations in chronic myeloid neoplasms and address how this might be applied to improve precision medicine approaches and outcomes for patients.
Dan A. Adam J. Hitoshi Takizawa will discuss how dormant HSCs are activated to self-renew and differentiate to increase blood production upon enhanced hematopoietic need. It remains unclear how HSCs and progenitor cells HSPCs integrate the peripheral demand signal to facilitate hematopoietic production and what the biological consequence of HSPCs activation is on cell fate decision.
To that end, he will also discuss the mechanistic insights on how HSPCs sense pathogen insult through innate immune receptors and orchestrate hematopoiesis for host defense and tissue homeostasis. Marieke Essers will discuss infections associated with extensive consumption of differentiated hematopoietic cells, representing a high risk for health.
The mechanisms coordinating the rapid and efficient regeneration of these differentiated cells during such stress conditions remain unclear.
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In addition to identifying how HSCs respond under inflammatory conditions, she will also focus on investigating the response of the BM niche to inflammatory stress and how different components of the BM niche support the response of quiescent HSCs to inflammatory stress in vivo. Tannishtha Reya will address how high-resolution in vivo imaging can be used to map normal stem cell behavior and interactions within living animals. She will describe how these interactions are driven by adhesive signals, and how they change during cancer formation.
She will also highlight mechanisms that drive therapy resistance in the treatment of cancers. Reya's research focuses on the signals that control stem cell self-renewal and how these signals are hijacked in cancer. Using a series of genetic models, she has studied how classic developmental signaling pathways influence hematopoietic stem cell growth and regeneration as well as leukemia development when such pathways are dysregulated.