Cancer Patients Undergoing Bone Marrow Research Articles

Low-dose Oral Ketamine as a Procedural Analgesia in Pediatric Cancer Patients Undergoing Bone Marrow Aspirations at a Resource-limited Cancer Hospital in India.

Aim:Many pediatric cancer patients undergo repeated bone marrow aspirations (BMAs) for diagnostic and treatment evaluation purposes. Full anesthesia is the standard of care during this procedure in high-income countries. At hospitals with low resources in low/middle-income countries many children undergo these painful procedures without sufficient pain relief. This study aimed to evaluate the usefulness of low-dose oral ketamine as a procedural analgesic in a low-resource pediatric cancer care department.Materials and Methods:Pediatric patients, 4–15 years of age, who underwent BMAs between September 31 and November 30, 2018, were invited to participate. The study was designed as a placebo-controlled, single-blinded trial with three trial groups. Group K received 1.0 mg/kg of ketamine and Group KM received 1.0 mg/kg ketamine with an addition of 0.2 mg/kg midazolam, mixed in juice 30 min before procedures. Group P received placebo consisting of plain juice. All three groups also received the hospital's current standard treatment for procedural pain in BMAs. Patients and caregivers assessed the procedural pain, as did the performing doctors. For the patients, Faces Pain Scale – Revised was used and the Numeric Rating Scale-11 for caregivers and doctors.Results:A total of 87 patients were included in the study distributed with 29 in Group K, 29 in Group KM, and 29 in Group P. Seven patients were excluded, one patient denied participation and the remaining did not meet the inclusion criteria. There was no significant difference between the pain reported by the groups. A total of 69% patients in Group KM and 35% in Group K had somnolence reported as a side effect compared to 14% in Group P.Conclusion:We found no significant effects on the procedural pain in any of the treatment groups compared to placebo. There were only mild side effects. The doses of ketamine might be insufficient for this painful and stressful procedure.

Intestinal helminths regulate lethal acute graft-versus-host disease and preserve the graft-versus-tumor effect in mice.

Donor T lymphocyte transfer with hematopoietic stem cells suppresses residual tumor growth (graft-versus-tumor [GVT]) in cancer patients undergoing bone marrow transplantation (BMT). However, donor T cell reactivity to host organs causes severe and potentially lethal inflammation called graft-versus-host disease (GVHD). High-dose steroids or other immunosuppressive drugs are used to treat GVHD that have limited ability to control the inflammation while incurring long-term toxicity. Novel strategies are needed to modulate GVHD, preserve GVT, and improve the outcome of BMT. Regulatory T cells (Tregs) control alloantigen-sensitized inflammation of GVHD, sustain GVT, and prevent mortality in BMT. Helminths colonizing the alimentary tract dramatically increase the Treg activity, thereby modulating intestinal or systemic inflammatory responses. These observations led us to hypothesize that helminths can regulate GVHD and maintain GVT in mice. Acute GVHD was induced in helminth (Heligmosomoides polygyrus)-infected or uninfected BALB/c recipients of C57BL/6 donor grafts. Helminth infection suppressed donor T cell inflammatory cytokine generation and reduced GVHD-related mortality, but maintained GVT. H. polygyrus colonization promoted the survival of TGF-β-generating recipient Tregs after a conditioning regimen with total body irradiation and led to a TGF-β-dependent in vivo expansion/maturation of donor Tregs after BMT. Helminths did not control GVHD when T cells unresponsive to TGF-β-mediated immune regulation were used as donor T lymphocytes. These results suggest that helminths suppress acute GVHD using Tregs and TGF-β-dependent pathways in mice. Helminthic regulation of GVHD and GVT through intestinal immune conditioning may improve the outcome of BMT.

A Randomized Trial of Hypnosis for Relief of Pain and Anxiety in Adult Cancer Patients Undergoing Bone Marrow Procedures

Pain and anxiety are closely associated with bone marrow aspirates and biopsies. To determine whether hypnosis administered concurrently with the procedure can ameliorate these morbidities, the authors randomly assigned 80 cancer patients undergoing bone marrow aspirates and biopsies to either hypnosis or standard of care. The hypnosis intervention reduced the anxiety associated with procedure, but the difference in pain scores between the two groups was not statistically significant. The authors conclude that brief hypnosis concurrently administered reduces patient anxiety during bone marrow aspirates and biopsies but may not adequately control pain. The authors explain this latter finding as indicating that the sensory component of a patient's pain experience may be of lesser importance than the affective component. The authors describe future studies to clarify their results and address the limitations of this study.

Enteral nutrition during bone marrow transplantation in patients with pediatric cancer: a prospective cohort study.

Cancer patients undergoing bone marrow transplantation (BMT) often require nutritional therapy due to treatment toxicities. The aim here was to evaluate the use of tube feeding and its applicability, indications, contraindications and complications in these patients. Prospective observational study conducted at a public university in São Paulo between January 2002 and August 2007. The patients were followed up daily in the BMT unit by a research dietitian. Tube feeding was indicated when oral supplementation proved to be insufficient, when the patient had severe malnutrition or there was an impediment to use of oral feeding. It was contraindicated in the presence of gastrointestinal toxicity of grade 3 and 4 or other conditions that implied a risk or hindered its use or placement. Complications of tube feeding were divided into minor and major, according to whether they had life-threatening implications. Forty-two (47.2%) patients had indications for tube feeding: the main reasons were transplantation inadequate food and supplement intake, insufficient intake with malnutrition or weight loss, severe malnutrition or need for oral fasting. Thirty-one (73.8%) received tube feeding: 11 autologous and 20 allogenic patients (P = 0.04). The main contraindications were severe gastrointestinal toxicities and sinusitis. Minor complications from tube feeding were more prevalent in patients with allogenic BMT, but no major complications were observed. Enteral nutrition is a feasible procedure in patients undergoing BMT and should be encouraged. The main difficulty in BMT patients, in relation to tube feeding, is gastrointestinal toxicities.

The Analgesic Effect of Magnetic Acupressure in Cancer Patients Undergoing Bone Marrow Aspiration and Biopsy: A Randomized, Blinded, Controlled Trial

Context Bone marrow aspiration and biopsy (BMAB) is a frequently performed and painful procedure. Objectives To evaluate the efficacy of magnetic acupressure in reducing pain in cancer patients undergoing BMAB. Methods Cancer patients without previous acupuncture or acupressure experience were stratified by the number of prior BMAB and randomized to having magnetic acupressure delivered to either the large intestine 4 (LI4) acupoint or a sham site. The primary study endpoint was the patient’s pain intensity rating during the procedure using a visual analogue scale (VAS). Results Seventy-seven eligible patients received magnetic acupressure: 37 were randomized to treatment at the LI4 site arm and 40 at the designated sham site arm. There was no significant difference between the median pain scores of patients treated at the LI4 site and the sham site ( P = 0.87). However, severe pain (VAS ≥ 7) was reported in only one patient (2.7%) treated at the LI4 site compared with eight patients (20%) at the sham site ( P = 0.03). No patients experienced significant magnetic acupressure-related toxicities. Conclusion Magnetic acupressure at the LI4 acupoint requires minimal training and expense and is well tolerated. Although its use did not significantly reduce median pain scores in patients undergoing BMAB, it does appear to reduce the proportion of patients with severe pain associated with this invasive procedure.

Pharmacokinetic and Maximum Tolerated Dose Study of Micafungin in Combination with Fluconazole versus Fluconazole Alone for Prophylaxis of Fungal Infections in Adult Patients Undergoing a Bone Marrow or Peripheral Stem Cell Transplant

In this dose escalation study, 74 adult cancer patients undergoing bone marrow or peripheral blood stem cell transplantation received fluconazole (400 mg/day) and either normal saline (control) (12 subjects) or micafungin (12.5 to 200 mg/day) (62 subjects) for up to 4 weeks. The maximum tolerated dose (MTD) of micafungin was not reached, based on the development of Southwest Oncology Group criteria for grade 3 toxicity; drug-related toxicities were rare. Commonly occurring adverse events considered related to micafungin were headache (6.8%), arthralgia (6.8%), hypophosphatemia (4.1%), insomnia (4.1%), maculopapular rash (4.1%), and rash (4.1%). Pharmacokinetic profiles for micafungin on days 1 and 7 were similar. The mean half-life was approximately 13 h, with little variance after repeated or increasing doses. Mean maximum concentrations of the drug in serum and areas under the concentration-time curve from 0 to 24 h were approximately proportional to dose. There was no clinical or kinetic evidence of interaction between micafungin and fluconazole. Five of 12 patients (42%) in the control group and 14 of 62 (23%) in the micafungin-plus-fluconazole groups had a suspected fungal infection during treatment which resulted in empirical treatment with amphotericin B. The combination of micafungin and fluconazole was found to be safe in this high-risk patient population. The MTD of micafungin was not reached even at doses up to 200 mg/day for 4 weeks. The pharmacokinetic profile of micafungin in adult cancer patients with blood or marrow transplants is consistent with the profile in healthy volunteers, and the area under the curve is proportional to dose.

Difficulties in screening for adjustment disorder, Part I: Use of existing screening instruments in cancer patients undergoing bone marrow transplantation

Although success rates for bone marrow transplantation (BMT) continue to improve, there is still a high level of morbidity and physical and emotional distress associated with BMT. To date, limited research has focused on the assessment of and screening for specific psychiatric disorders of patients facing BMT. This is especially true with regard to identifying adjustment disorder (AD), despite the fact that AD is the most prevalent psychiatric diagnosis in cancer patients. A sample of 95 BMT patients were interviewed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (SCID) and completed several commonly used self-report instruments to determine if these tools could be used to identify patients with adjustment disorder in need of further assessment and intervention. Of these patients, 34.7% were diagnosed with adjustment disorder, 11.6% with major depression, and 5.3% with generalized anxiety disorder. The instruments were not found to be predictive of AD. However, the results of a regression analysis showed that the Social Subscale of the Functional Assessment of Cancer Therapy-General (R2 delta = 0.04, F = 4.30, p < 0.05) was a significant predictor of adjustment disorder. We conclude that there is little efficacy in using existing scales for detecting adjustment disorders in cancer patients undergoing bone marrow transplantation, and that other tools for identifying patients with adjustment disorder who might benefit from counseling are needed.

Difficulties in screening for adjustment disorder, Part II: An attempt to develop a novel self-report screening instrument in cancer patients undergoing bone marrow transplantation

Screening for adjustment disorder (AD) in cancer patients presents a significant clinical challenge. As seen in Part I of this research, conventional, existing measures are rather poor at detecting this most common of psychiatric diagnoses. Bone marrow transplantation (BMT) has a high level of morbidity that can cause significant stress for patients faced with the procedure. A sample of 95 BMT patients completed a semistructured interview and a novel self-report instrument, the Coping Flexibility Scale for Cancer (C-Flex), to determine if it could identify patients with adjustment disorder in need of further assessment and intervention. The screen yielded four factors but was not predictive of AD. However, the C-Flex was significantly related to the presence of any disorder (r = -0.44, p < 0.001) in this sample. In addition, Factor I of the screen was found to be correlated to the presence of any diagnosis (r = -0.44, p < 0.001) and to have adequate sensitivity (81.63%) and specificity (76.09%). Either because of problems with the scale or the amorphous nature of the AD category, or both, rapid identification of patients with this common problem has proven to be elusive.

Granisetron in the control of nausea and vomiting associated with bone marrow transplantation: a review of its efficacy and tolerability.

Cancer patients undergoing bone marrow transplantation (BMT) experience severe nausea and vomiting associated with high-dose chemotherapy agents; these emetic symptoms are compounded by total body irradiation used in many conditioning regimens. This paper reviews clinical experience with the 5-HT(3) receptor antagonist granisetron, both as a single agent and in combination with other anti-emetics, in patients undergoing BMT and peripheral blood stem cell transplantation (PBSCT). Clinical studies demonstrate the efficacy (47-61% with no vomiting and no worse than mild nausea) and tolerability of granisetron. Its long half-life and duration of action may be responsible for its effective 24 h control of nausea and vomiting in BMT patients.

The role of biomedical and psychosocial factors for the prediction of pain and distress in patients undergoing high-dose therapy and BMT/PBSCT.

Recent research has shown that cancer patients undergoing bone marrow transplantation (BMT) experience moderate to severe mouth pain due to treatment-related mucositis in spite of morphine therapy. Treatment-related emotional distress in BMT patients is also described widely. This study examined several biomedical, psychological and social variables as possible predictors for the intensity of treatment-related mouth pain and anxious mood in 63 cancer patients undergoing BMT or stem cell transplantation (SCT) within a prospective longitudinal design. Biomedical predictors included biomedical risk, mucositis, the mode of transplantation, total body irradiation, age and gender. Psychological predictors were depression (BDI), BMT-related distress, chronic stress and resources in everyday life (KISS), pain-related coping behaviour (KPI-17) and social support (ISSS). Among the social variables we evaluated education, being married and the living situation. Criteria variables were the intensity of mouth pain and anxious mood which were assessed daily by numeric self-rating scales for 24 days after transplantation. Results of stepwise multiple regressions indicated that psychological and social variables were important predictors of mouth pain, besides biomedical variables. Whereas the biomedical variables revealed the most predictive power during the second week after BMT, psychological predictors were more important during the early and late phases of the treatment. Daily anxious mood was best predicted by psychological and social variables. Among the biomedical variables mucositis was most strongly related to mouth pain besides mode of transplantation, risk, TBI and age. Among the psychological variables BMT-related distress was the most important predictor, with resources in private life or at work and pain-related coping modes as further significant predictors. These results imply that relevant predictors should be assessed as high risk factors for an increased vulnerability for treatment-related side-effects before treatment starts indicating an additional offer of psychological treatment in high risk patients.

Control of nosocomial Clostridium difficile transmission in bone marrow transplant patients.

This is a report of six cases of Clostridium difficile-associated diarrhea (CDAD) that occurred among cancer patients undergoing bone marrow transplantation in a tertiary-care cancer hospital. Specific infection control measures that were taken to minimize the nosocomial spread of CDAD also are discussed.

Clinical hypnosis versus cognitive behavioral training for pain management with pediatric cancer patients undergoing bone marrow aspirations

A randomized controlled trial was conducted to compare the efficacy of clinical hypnosis versus cognitive behavioral (CB) coping skills training in alleviating the pain and distress of 30 pediatric cancer patients (age 5 to 15 years) undergoing bone marrow aspirations. Patients were randomized to one of three groups: hypnosis, a package of CB coping skills, and no intervention. Patients who received either hypnosis or CB reported less pain and pain-related anxiety than did control patients and less pain and anxiety than at their own baseline. Hypnosis and CB were similarly effective in the relief of pain. Results also indicated that children reported more anxiety and exhibited more behavioral distress in the CB group than in the hypnosis group. It is concluded that hypnosis and CB coping skills are effective in preparing pediatric oncology patients for bone marrow aspiration.

A Computer-Based System for Controlling Plasma Opioid Concentration According to Patient Need for Analgesia

Microprocessor-controlled infusion pumps, which allow a patient to self-administer bolus doses of an analgesic to relieve pain, are becoming commonplace. While these patient-controlled analgesia (PCA) systems overcome the large interpatient variations in pharmacokinetics, they do not provide steady relief from pain since they rely on delivering a drug in small, incremental doses. To overcome this problem, the authors developed an algorithm and computer-pump system that allows patients to control their own plasma concentration of analgesic. This approach uses individually predetermined pharmacokinetic parameters to provide steady plasma opioid concentrations that can be increased or decreased by the patient in line with the need for more pain relief or fewer side effects. The control software uses a novel, recursive algorithm to compute the pump rates necessary to maintain constant plasma drug (e.g. morphine) concentrations at desired values and to reach a new steady concentration in response to patient requests. This report describes the mathematical approach to the problem of control of plasma opioid concentration, the application of this new drug delivery system to management of persistent pain in cancer patients undergoing bone marrow transplantation, and the magnitude of pharmacokinetic variability with morphine in this patient population. Results are presented from individual patients using this adjustable drug delivery system continuously for up to 2 weeks to control pain from oral mucositis.

The Effects of Music-Assisted Relaxation on the Distress of Pediatric Cancer Patients Undergoing Bone Marrow Aspirations

The use of music-assisted relaxation in the reduction of childrens distress associated with bone marrow aspirations was evaluated Six pediatric cancer patients ages 6 to 15 years were observed during a baseline procedure and then received music-assisted relaxation during the second of two consecutive bone marrow aspirations Childrens anticipatory and experienced feat and pain and their observed behavioral distress during the procedures were evaluated systematically using a within-subjects experimental design Analysis of the data indicated strong trends tor reductions in anticipatory fear experienced fear, and experienced pain A strong trend for reduction in anticipatory behavioral distress was found, but there was no significant reduction in total observed behavioral distress Implications for clinical applications and further research were discussed.

An observation scale for measuring children's distress during medical procedures.

The current state-of-the-art in the area of assessing pain and anxiety experienced by children undergoing painful medical procedures remains at a rudimentary level. Early studies in the preparation literature included global Likert-type rating scales of children’s distress and cooperative behaviors (Visintainer & Wolfer, 1975; Wolfer & Visintainer, 1979). More recent studies have focused on the development of more objective and operationalized behavioral observation scales which have been used specifically to measure distress in pediatric cancer patients undergoing bone marrow aspirations (BMAs) and lumbar punctures (LPs) (Jay, in press; Jay & Elliott, 1984; Jay, Ozolins, Elliott, & Caldwell, 1983; Katz, Kellerman, & Siegel, 1980; LeBaron & Zeltzer, 1984). For example, Katz et al. (1980) developed the Procedure Behavior Rating Scale (PBRS) which consisted of 13 operationally defined behaviors that were recorded as present or absent during bone marrow aspirations. The PBRS was found to be a reliable instrument and preliminary validity data (i.e., nurse ratings) were also encouraging. LeBaron and Zeltzer (1984) presented additional validity data on an eight-item version of the PBRS which they labeled the Procedure Behavior Check List.