Glutathione-S-transferase P1 may predispose children to a decline in pulmonary function after stem cell transplant

RATIONALE: Pulmonary complications after hematopoietic stem cell transplant (SCT) are associated with increased mortality. Genetic markers for those at risk for pulmonary impairment post-SCT have not been widely investigated. METHODS: Forty-nine patients were retrospectively selected from a single institution's biorepository with linked clinical data. All subjects performed pre-SCT PFTs. Genotyping was conducted using the Infinium Exome-24 BeadChip. Four single nucleotide polymorphisms (SNPs) were selected (rs1800871, rs1695, rs1800629, rs12477314) and evaluated for association with PFT parameters as change over time from baseline. Associations between SNPs and PFT parameters were assessed and adjusted for the following confounding variables: age, gender, and race. RESULTS: Using the recessive genetic model, patients with one or two minor alleles for the glutathione S-transferase P1 (GSTP1) SNP rs1695 had a lower decline in FEV1 and FEF25-75 at 1-year post-SCT compared to patients who were homozygous for the ancestral allele (adjusted P-values <0.01 and 0.02, respectively). No other SNPs were significantly associated with other PFT parameters. CONCLUSIONS: Our findings suggest that GSTP1 genotype may be associated with lung function during the first year post-SCT. Identifying and investigating genes that predispose patients to pulmonary complications after SCT may allow for more personalized patient management based on pre-emptive genetic testing. The glutathione S-transferase gene merits further investigation

Mentoring future Kenyan oncology researchers

This is a summary of the 1st Academic Model Providing Access to Healthcare (AMPATH) Oncology Institute research grant writing workshop organized in collaboration with the Kenya Medical Research Institute (KEMRI) and held in Kisumu, Kenya from January 16th to 18th, 2013. The goal of this meeting was to mentor future Kenyan scientists and prioritize research topics that would lead to improved cancer care and survival for the citizens of Kenya

Chaplain care in pediatric oncology: Insight for interprofessional collaboration

Background Although attending to spiritual and religious needs is part of high quality care of pediatric cancer patients, oncology clinicians may not understand the role of the chaplain, resulting in underutilization of resources and failure to fully integrate the chaplain into the clinical team. We provide a description of what the chaplain does in the care of pediatric oncology patients. Methods We conducted a qualitative content analysis of chaplain chart notes over a one‐year period on the pediatric oncology service at a freestanding children's hospital. Using criteria designed to capture multiple potential factors in chaplain referral, we selected 30 patients for thematic analysis. Results In 2016, 166 pediatric patients were diagnosed with cancer and received ongoing care at our institution. From the 30 patients selected, 230 chaplain encounters were documented in the medical chart. Three major themes emerged. (1) The chaplains provided a rich description of spiritual and psychosocial aspects of the patient and family's experience; (2) chaplains provided diverse interventions, both religious and secular in nature; and (3) chaplains provided care within a longitudinal relationship. All three themes depend on the empathic listening by a chaplain. Conclusions The chaplains’ observations about patient and family beliefs, experiences, and emotional/spiritual states have the potential to inform the interdisciplinary care of the patient. Chaplain documentation provides insight into how spiritual care interventions and close relationships may promote patient and family well‐being. In future work, we will explore how to give voice to their insights in caring for pediatric oncology patients

Low serum albumin levels prior to pediatric allogeneic HCT are associated with increased need for critical care interventions and increased 6-month mortality

Poor nutritional status in HCT patients is a negative prognostic factor. There are no pediatric studies evaluating albumin levels prior to HCT and need for critical care interventions. We hypothesized that pediatric patients with low albumin levels, routinely measured 30 days (±10 days) prior to allogeneic HCT, have a higher risk of critical care interventions in the post-transplant period. We performed a 5-year retrospective study of pediatric patients who underwent allogeneic HCT for any indication. Patients were categorized based on albumin level. Hypoalbuminemia was defined as <3.1 g/dL. A total of 73 patients were included, with a median age of 7.4 years (IQR 3.3, 13.2). Patients with hypoalbuminemia had higher needs for critical care interventions including non-invasive ventilation (44% vs 8%, P=.01), mechanical ventilation (67% vs 17%, P<.01), and vasoactive therapy (56% vs 16%, P=.01). Patients with hypoalbuminemia also had a higher 6-month mortality (56% vs 17%, P=.02). Our data demonstrate that children undergoing allogeneic HCT with hypoalbuminemia in the pretransplant period are more likely to require critical care interventions and have higher 6-month mortality. These findings identify an at-risk population in which nutritional improvements may be instituted prior to HCT in hopes of improving outcomes

Health-Care Providers' Perspectives towards Childhood Cancer Treatment in Kenya

BACKGROUND: This study explored perspectives of health-care providers on childhood cancer treatment in Kenya. MATERIALS AND METHODS: A self-administered questionnaire was completed by 104 health-care providers in January and February 2013. RESULTS: Seventy six percent of the health-care providers believed cancer to be curable. More doctors than other health-care providers had this positive opinion (p=0.037). The majority of health-care providers (92%) believed that most children with cancer will not be able to finish their treatment due to financial difficulties. They considered that prosperous highly-educated parents adhere better with treatment (88%) and that doctors adhere better with treatment for prosperous highly-educated parents (79%). According to 74% of health-care providers, quality of care is better for prosperous highly-educated parents (74%). Most health-care providers reported giving more explanation (71%), work with greater accuracy (70%) and use less difficult vocabulary (55%) to prosperous more educated families. Only 34% of health-care providers reported they feel more empathy towards patients from prosperous families. Reasons for non-adherence with the protocol according to health-care providers are: family refuses drugs (85%), inadequate supply of drugs at pharmacy (79%), child looks ill (75%), and financial difficulties of parents (69%). CONCLUSIONS: Health-care providers' health beliefs and attitudes differ for patients with families having high versus low socio-economic backgrounds

Factors influencing time to diagnosis and treatment among pediatric oncology patients in Kenya

Early diagnosis and start of treatment are fundamental goals in cancer care. This study determines the time lag and the factors that influence the time to diagnosis and start of treatment. Study participants were parents of childhood cancer patients diagnosed between August 2013 and July 2014 in a hospital in Kenya. Patient, physician, diagnosis, treatment, health care system, and total delay were explored using a questionnaire. Demographic and medical data were collected from the patients' medical records. Parents of 99 childhood cancer patients were interviewed (response rate: 80%). Median total delay was 102 (9–1021) days. Median patient delay (4 days) was significantly shorter than health care system delay (median 87 days; P < .001). Diagnosis delay (median 94 days) was significantly longer than treatment delay (median 6 days; P < .001). days. Lack of health insurance at diagnosis and use of alternative medicine before attending conventional health services were associated with a significantly longer patient delay (P = .041 and P = .017, respectively). The type of cancer had a significant effect on treatment delay (P = .020). The type of health facility attended affected only patient delay (P = .03). Gender, age at diagnosis, stage of disease, parents' education level or income, and distance from hospital did not have a significant effect on the length of any type of delay. Training on childhood cancer should be included in the curricula for medical training institutes. In-service workshops should be held for the health workers already working. Families must be obligated to get health insurance. Families should be encourage to attend conventional health facilities and informed on symptoms of cancer through mass media

Genetic Variants Associated With Vincristine‐Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149215/1/cpt1324_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149215/2/cpt1324.pd

Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation.

Reliable, non-invasive methods for diagnosing and prognosing sinusoidal obstruction syndrome (SOS) early after hematopoietic cell transplantation (HCT) are needed. We used a quantitative mass spectrometry-based proteomics approach to identify candidate biomarkers of SOS by comparing plasma pooled from 20 patients with and 20 patients without SOS. Of 494 proteins quantified, we selected six proteins [L-Ficolin, vascular-cell-adhesion-molecule-1 (VCAM1), tissue-inhibitor of metalloproteinase-1, von Willebrand factor, intercellular-adhesion-molecule-1, and CD97] based on a differential heavy/light isotope ratio of at least 2 fold, information from the literature, and immunoassay availability. Next, we evaluated the diagnostic potential of these six proteins and five selected from the literature [suppression of tumorigenicity-2 (ST2), angiopoietin-2 (ANG2), hyaluronic acid (HA), thrombomodulin, and plasminogen activator inhibitor-1] in samples from 80 patients. The results demonstrate that together ST2, ANG2

A Metabolomics Approach for Early Prediction of Vincristine-Induced Peripheral Neuropathy

Vincristine is a core chemotherapeutic drug administered to pediatric acute lymphoblastic leukemia patients. Despite its efficacy in treating leukemia, it can lead to severe peripheral neuropathy in a subgroup of the patients. Peripheral neuropathy is a debilitating and painful side-effect that can severely impact an individual’s quality of life. Currently, there are no established predictors of peripheral neuropathy incidence during the early stage of chemotherapeutic treatment. As a result, patients who are not susceptible to peripheral neuropathy may receive sub-therapeutic treatment due to an empirical upper cap on the dose, while others may experience severe neuropathy at the same dose. Contrary to previous genomics based approaches, we employed a metabolomics approach to identify small sets of metabolites that can be used to predict a patient’s susceptibility to peripheral neuropathy at different time points during the treatment. Using those identified metabolites, we developed a novel strategy to predict peripheral neuropathy and subsequently adjust the vincristine dose accordingly. In accordance with this novel strategy, we created a free user-friendly tool, VIPNp, for physicians to easily implement our prediction strategy. Our results showed that focusing on metabolites, which encompasses both genotypic and phenotypic variations, can enable early prediction of peripheral neuropathy in pediatric leukemia patients

Use of Flow Cytometry Immunophenotyping for Diagnosis of Acute Leukemia at Moi Teaching and Referral Hospital, Eldoret, Kenya

The main objective of the study was to compare morphological and flow cytometric diagnosis in patients previously diagnosed with leukemia. The retrospective study was carried out at Moi Teaching and Referral Hospital and patient’s data for the period of July 2013 and June 2014 was used. After Institutional Research Ethics approval was granted. Consecutive sampling was done and information was extracted from patient’s files. Data for all who were previously diagnosed with leukemia through both morphology and immunophenotyping was recorded. The data was collected using a data collection form where socio-demographic data, morphological and flow cytometry results were recorded. The findings were based on 33 patients who underwent both flow cytometry and bone marrow morphology tests for diagnosis of leukemia between July 2013 and June 2014. The ages of the patients ranged from 3 to 76 years. The ratio of male to female was 1:1.1.Using the Bone marrow morphology, 17 patients had AML and 15 had ALL, one case was inconclusive There were five categories for the flow cytometry. They comprised of B-ALL-6 cases, T-ALL-13 cases, AML-10 cases, Biphynotypic-1 case and inconclusive-1case. There was concordance between the morphological and flow cytometry on 25 out of the 33 cases. As a conclusion we can say that at MTRH, Flow cytometry had a role to play to confirm a definite and a probable diagnosis of patients with acute leukemia.