Undergoing Bone Marrow Transplantation Research Articles

Expression Levels of Il-6 and Il-18 in Acute Myeloid Leukemia and Its Relation with Response to Therapy and Acute GvHD After Bone Marrow Transplantation.

Cytokines seem to play a crucial role in physiological and pathological conditions of acute myeloid leukemia (AML). The aim of this study was to evaluate the expression levels of interleukins-6 (IL-6) and IL-18 in patients with AML and its correlation with response to therapy and graft versus host disease (GvHD) after bone marrow transplantation. The expression levels of IL-6 and IL-18 genes were done in all patients and compared with matched control. Complete remission (CR) was used for evaluation of the effects of these cytokines on response to treatment in patients group. The expression level of these cytokines was also evaluated in patients who underwent bone marrow transplantation and experienced acute GvHD in compare with patients without aGvHD. Il-6 gene expression level was significantly higher in these patients in comparison with control but Il-18 gene expression level was not statistically significant compared to control group. Il-6 and also Il-18 expression levels were significantly higher in patients without a response to treatment according to CR compared to patient's whit response to treatment as well as patients experienced aGvHD after bone marrow transplantation. IL-6 and Il-18 are important markers in the progression of the disease and could be considered as a prognostic marker in acute leukemia. It is recommended that more studies with larger study groups and more involved cytokines are needed for more evaluation of the cytokine roles in pathophysiology and progression of acute leukemia.

MRD assessment using NGS in patients with acute myeloid leukemia undergoing hematopoietic stem cell transplantation: Meta-analysis.

e19002 Background: The presence of measurable residual disease (MRD) preceding hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML) is increasingly recognized as a risk factor for leukemic relapse and decreased survival. Over many years, attempts have been looking at developing tools to detect MRD; this includes multiparametric flow cytometry, quantitative polymerase chain reaction, and most recently, next-generation sequencing (NGS). NGS offers higher sensitivity and detection rate of disease-related gene mutations, thereby potentially improving disease outcomes. Our study sought to review the scientific literature that included NGS‐detected molecular MRD in patients with AML who underwent bone marrow transplantation. Methods: We performed a systematic search using PubMed, Google Scholar, EMBASE, and SCOPUS up until October 2020. Inclusion criteria included articles that reported the association between pre-HSCT MRD detected by NGS and post HSCT outcome in patients with AML. We extracted hazard ratios for the cumulative incidence of relapse (CIR), overall survival (OS) and leukemia free survival (LFS). A random-effect model was utilized to calculate the hazard ratio (HR) with a 95% confidence interval (CI). Results: Six studies met our inclusion criteria. Our meta-analysis showed that the detection of pre-transplant MRD by NGS was associated with increased risk of cumulative incidence of relapse (hazard ratio=2.5, CI= 1.6-3.9, with p-value <0.001) and decreased overall survival (hazard ratio=1.6, CI= 1.6-2.3, p-value 0.005). LFS was significantly higher in those who had negative MRD detection by NGS before transplantation (HR=1.9, CI= 1.3-2.8 with p-value 0.001). These results were independent of the cytogenetic risk of conditioning intensity. There was heterogeneity between our studies (I2 = 53%, 52%, and 59% for CIR, OS, and LFS, respectively). Conclusions: The application of NGS to detect MRD is a strong predictor of outcome in patients with AML who are undergoing hematopoietic stem cell transplantation. NGS-detected MRD positive status prior to HSCT is indicative of a higher risk of relapse and decreased overall survival in this meta-analysis. Despite the limitations in our study, it demonstrates the value of MRD detection by NGS in HSCT recipients.

Prevalence of growth hormone deficiency in patients with unexplained chronic fatigue after undergoing bone marrow transplantation in adulthood.

Many patients who undergo bone marrow transplantation (BMT) in adulthood experience unexplained chronic fatigue which can have a major impact on their health-related quality of life (QoL). Pre-BMT treatment regimens increase the risk of developing acquired growth hormone deficiency (GHD), which results in a clinical syndrome with decreased energy and has additionally been linked to metabolic syndrome. Using the gold-standard insulin hypoglycemic test (IHT), we evaluated the prevalence of GHD in 18 post-BMT adult patients with unexplained chronic fatigue, as well as the correlation between peak serum GH response and QoL scores, the metabolic syndrome, and insulin resistance. Peak serum GH cut-point less than 3.0 ug/L was used for the diagnosis of severe GHD. The Fatigue Severity Scale and Quality of Life in Adult GHD Assessment questionnaires were used to quantify fatigue symptoms. The prevalence of severe GHD within this sample of 18 patients was 50%. A trend between lower peak serum GH response and higher fatigue and QoL-AGHDA scores was observed. GHD may represent a remediable contributor to post-BMT chronic fatigue in adults, further studies are needed to evaluate the potential role of screening and GH replacement therapy in this vulnerable patient population. GHD may be a treatable explanation for disabling post-BMT fatigue pending results of intervention studies.

Replacement Versus Same-Site Salvage Using Hickman Catheter for Pediatric Stem Cell Transplantation Patients: A Comparative Study

Children undergoing bone marrow transplant need a double-lumen Hickman line. Therefore, changing Port-a-Cath ports to double-lumen Hickman catheter is mandatory. Several methods were described for changing Port-a-Cath ports either through the same-site or a new placement access site. The advantage of one method over the other is still debatable. We conducted this study to compare the safety and effectiveness of replacement versus salvage techniques to change ports to the Hickman lines before bone marrow transplants in pediatric patients. We included 85 pediatric patients who underwent stem cell transplants. Their age ranged from 0.2 to 15 years. According to the Hickman reinsertion technique, we classified the patients into 2 groups; the Replacement group (n = 47) and the Same-site salvage group (n = 38). We compared the data before and after Hickman insertion between both groups. Study outcomes were the catheter duration, its complications, and mortality. The mean age of all patients was 4.7 ± 3.9 years, and 65.9% were males. There was no difference in the baseline data between both groups. During Port-a- Cath first insertion; 16.5% of patients suffered complications, with 10.6% had conversion to cut down, 1.2% had a hematoma, and 4.7% had multiple site insertion. We did not report differences between groups in the complications of the first port insertion. The Hickman duration was longer in the replacement group (4 (Q1-Q2: 2-6) vs. 1 (0.5-3) months, P = 0.005). Increased age (odds ratio [OR]: 1.31, P = 0.001) and male gender (OR: 1.19, P = 0.046) were independent predictors of mortality. Endovascular same-site salvage technique could help preserve vascular access during the tunnel catheter exchange for noninfectious reasons. We recommend the use of the same-site salvage technique in pediatric transplant patients.

Three resected cases of esophageal carcinoma considered as being secondary solid tumors after bone marrow transplantation

BackgroundBone marrow transplantation is now an established treatment for some hematopoietic disorders and hematopoietic malignancies, and secondary solid tumors that develop after bone marrow transplantation have begun to attract attention.Case presentationHerein, we report 3 cases of esophageal carcinoma that developed after bone marrow transplantation. Case 1: 40-year-old female received cyclophosphamide and total body irradiation at 12 Gy for acute myeloid leukemia, followed by related bone marrow transplantation. She developed chronic graft-versus-host disease manifesting as pulmonary complications and was administered cyclosporine. Nine years after the transplantation, she was diagnosed as having esophageal carcinoma Stage II and underwent radical surgery. She died of the primary disease 17 months after the surgery. Case 2: A 45-year-old male patient received cyclophosphamide, VP-16 and total body irradiation at 13.2 Gy for acute lymphocytic leukemia, followed by related bone marrow transplantation. He developed chronic graft-versus-host disease manifesting as liver dysfunction. Fifteen years after the transplantation, he was diagnosed as having esophageal carcinoma Stage II and underwent radical surgery. Seven months after the surgery, he died of the primary disease. Case 3: A 30-year-old female patient received cyclophosphamide and total body irradiation at 3 Gy for Fanconi anemia, followed by unrelated bone marrow transplantation. She developed chronic graft-versus-host disease manifesting as a rash and was administered tacrolimus and methotrexate. Fifteen years after the transplantation, she was diagnosed as having esophageal carcinoma Stage III and underwent radical surgery. She died of sepsis 7 months after the surgery.ConclusionThe esophageal carcinomas developing after bone marrow transplantation had the characteristics of secondary solid tumors in all 3 patients, such as early onset, after total body irradiation, association with chronic graft-versus-host disease, and history of use of immunosuppressive drugs. Patients undergoing bone marrow transplantation require long-term follow-up after the transplantation, considering the possible development of secondary solid tumors, and in regard to secondary solid tumors developing in the gastrointestinal tract, it must be borne in mind that the risk of esophageal carcinoma is particularly high.

Perceptions and Misperceptions of Early Palliative Care Interventions for Patients With Hematologic Malignancies Undergoing Bone Marrow Transplantation

Hematopoietic stem cell or bone marrow transplantation (BMT) is one of the most promising and potentially curative therapeutic options available for eligible patients with hematologic malignancies (HMs) or leukemias. However, the nature and clinical course of HMs, specifically for patients undergoing BMT, are associated with significant morbidity, symptomatology, healthcare service utilization, psychosocial and end of life issues, and overall decreased quality of life. Early palliative care (PC) consultations and utilization for patients with HMs have been shown to improve patient outcomes, satisfaction, and autonomy as well as caregiver burden, shared-decision making, and holistic care management. Despite the complexity of care and complications for patients with HM undergoing BMT, early PC interventions are systematically underutilized and understudied in this population compared to patients with solid tumors or non-HMs. Herein, the authors reviewed the current literature and knowledge to assess and report the perceptions and barriers to early PC utilization in the care of patients with HMs undergoing BMT. Clinical and cultural aspects of PC perceptions as well as current PC care models and potential directions for PC implementation were reviewed to inform future research studies and clinical practice guidelines necessary for the improvement of care and quality of life for HM patients undergoing BMT.

Impact of severe oral mucositis in pediatric cancer patients on resource utilization and cancer treatment plans.

Oral mucositis is a common chemotherapy-related adverse event that may result in serious complications. Few studies have evaluated mucositis in pediatric patients. To evaluate the impact of severe mucositis on resource utilization and on treatment plans of pediatric cancer patients. Comprehensive cancer center in Amman, Jordan. Retrospective study on pediatric patients undergoing active cancer treatment with a hospital admission diagnosis of severe oral mucositis (January 2015-December 2019). Patients undergoing bone marrow transplant were excluded. Severe oral mucositis was defined as interfering with oral intake and requiring intravenous opioids. We reviewed the electronic billing system and patient medical charts to determine the resources utilized during hospitalization, cost, and the impact on subsequent treatment protocols. During the study period, 200 patients were eligible; the average age was 8.6±5.6years (SD) and 45% had acute lymphoblastic leukemia. The median hospital stay was 6days (range 2-21) with a total median cost of US$ 2,176 (range 635-13,976) per admission. The median medication cost was US$ 1,075 (range 135-9010), and 85% of the patients received antibiotics during hospitalization, at a median cost of US$ 487 (range 23-2,193). Modification of the chemotherapy treatment protocol was required in 110 patients, which included dose reduction (60%), delay (38%), and discontinuation (2%). Severe oral mucositis is associated with significant resource utilization and modification of the treatment protocols. Further studies are needed to identify strategies to reduce the impact of mucositis in this patient population.

Cannabidiol Enhances Intestinal Cannabinoid Receptor Type 2 Receptor Expression and Activation Increasing Regulatory T Cells and Reduces Murine Acute Graft-versus-Host Disease without Interfering with the Graft-versus-Leukemia Response.

Cannabidiol (CBD) is a highly lipidic phytocannabinoid with remarkable anti-inflammatory effects. The aim of this study was to evaluate CBD's effects and mechanisms of action in the treatment of mice subjected to acute graft-versus-host disease (aGVHD). aGVHD was induced by the transplantation of bone marrow cells and splenocytes from C57BL-6j to Balb-c mice. The recipient mice were treated daily with CBD, and the treatment reduced mouse mortality by decreasing inflammation and injury and promoting immune regulation in the jejunum, ileum, and liver. Analysis of the jejunum and ileum showed that CBD treatment reduced the levels of C-C motif chemokine ligand (CCL) 2, CCL3, CCL5, tumor necrosis factor α, and interferon γ (IFNγ). CCL3 and IFNγ levels were also decreased in the liver. Mechanistically, CBD also increased the number of cannabinoid receptor type 2 (CB2) receptors on CD4+ and forkhead box P3+ cells in the intestine, which may explain the reduction in proinflammatory cytokines and chemokines. Antagonists of the CB2 receptor reduced the survival rates of CBD-treated mice, suggesting the participation of this receptor in the effects of CBD. Furthermore, treatment with CBD did not interfere with the graft-versus-leukemia response. CBD treatment appears to protect aGVHD mice by anti-inflammatory and immunomodulatory effects partially mediated by CB2 receptor interaction. Altogether, our study suggests that CBD represents an interesting approach in the treatment of aGVHD, with potential therapeutic applications in patients undergoing bone marrow transplantation. SIGNIFICANCE STATEMENT: This study provides for the first time a mechanism by which cannabidiol, a phytocannabinoid with no psychoactive effect, induces immunomodulation in the graft-versus-host disease. Enhancing intestinal cannabinoid receptor type 2 (CB2) receptor expression on CD4+ and forkhead box P3+ cells and increasing the number of these regulatory cells, cannabidiol decreases proinflammatory cytokines and increases graft-versus-host disease mice survival. This effect is dependent of CB2 receptor activation. Besides, cannabidiol did not interfere with graft-versus-leukemia response, a central response to avoid primary disease relapse.

Epidemiology and outcome for viremia in children undergoing bone marrow transplant: A retrospective cohort study.

Viral infections pose a serious risk for children undergoing hematopoietic stem cell transplant (HSCT). There are few published case series of prevalence, risk factors, and outcomes examining multiple viruses simultaneously, and no pediatric Australasian data published to date. We describe the real-life experience of viremia in pediatric HSCT in a single tertiary center. All episodes of viremia in children undergoing HSCT between 2000 and 2018 were identified by matching HSCT patients' unique identification numbers with positive blood polymerase chain reaction (PCR) results for human adenovirus (HAdV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpes virus 6 (HHV-6). Paper or electronic charts and electronic pathology results were used to extract the study variables. Viremia was detected in 177/445 (39.8%) HSCT episodes, of which 46% were allogeneic and 19% autologous transplants. Viremia was disseminated in 96 (21.6%) episodes, with 80 (18%) having more than one virus. HAdV was detected in 108 (24.3% of total episodes) and frequently in autologous transplants, CMV in 71 (16.0%), EBV in 60 (13.5%), and HHV-6 in 38 (8.5%). Of 174 children, 19 (10.9%) died of a viral-associated cause, with viral mortality highest in CMV (18.3%), lowest in HHV-6 (2.6%) with HAdV and EBV similar (6.6% and 6.7%). Adenoviral (but not other virus) dissemination was significantly associated with lower lymphocyte count at time of first detection. CMV dissemination and death were significantly associated with initial and highest CMV viral loads (copies/mL). This study presents the first pediatric-specific Australasian data for viremia in HSCT. Findings may help guide clinicians in prophylaxis and treatment decisions.

Beneficial effect of angiotensin converter enzyme inhibitors on left ventricular deformation in patients with hematologic malignancies after bone marrow transplantation

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Hellenic society of lipidiology, atherosclerosis and cardiovascular disease Background/Introduction: Optimal medical treatment for heart failure may reverse myocardial dysfunction in the early stages of cardiotoxic treatment. Patients and methods 60 patients age 46,3 ± 12,9 years old, 19 male) with preserved ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive 2,5 mg enalapril bid daily or placebo. We measured at baseline, before transplantation, and after three months: i) Global Longitudinal Strain of left ventricle (LV) (GLS), ii) LV Epicardial Strain (GLSepi), iii) LV Endocardial Strain (GLSendo), by speckle tracking imaging, iv) LV End Diastolic ,End Systolic Volume and Ejection Fraction (LVEF). Results The two treatment groups had similar age, sex atherosclerotic risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with enalapril did not show a deterioration of LV GLS and GLSepi [ p = 0,540 and p = 0,422)], Conversely, patients treated with placebo group, presented a significant impairment of LV GLS and GLSepi [p = 0,041 and p = 0,028)] three months after bone marrow transplantation. No significant changes were found in LVEF after treatment with enalapril ( p = 0,692) or the placebo ( p = 0,892). Table 1 Conclusions Treatment with enalapril prevented deterioration of myocardial deformation three months after bone marrow transplantation Table 1 group baseline 3 months follow-up p Longitudinal strain apical 4 chambers view placebo -20.56 ± 2.55 -19.46 ± 2.59 0.154 enalapril -20.41 ± 3.31 -19.70 ± 3.70 0.433 Longitudinal strain apical 2 chambers view placebo -20.5 ± 1.97 -16.11 ± 10.38 0.149 enalapril -20.30 ± 3.90 -20.00 ± 3.82 0.763 Longitudinal strain apical 3 chambers view placebo -19.55 ± 2.36 -18.55 ± 2.43 0.197 enalapril -20.01 ± 4.09 -19.26 ± 3.68 0.489 Global Longitudinal Strain placebo -20.19 ± 1.76 -18.96 ± 2.08 0.041 enalapril -20.24 ± 3.58 -19.66 ± 3.65 0.540 Average Global Epicardial Strain placebo -17.82 ± 1.45 -16.60 ± 1.68 0.028 enalapril -17.84 ± 3.09 -17.16 ± 3.20 0.422 Average Global Endocardial Strain placebo -23.03 ± 2.15 -21.96 ± 2.56 0.181 enalapril -23.07 ± 4.19 -23.60 ± 4.17 0.666 EF (Simpon’s method) placebo 59.46 ± 6.59 59.69 ± 6.79 0.892 enalapril 58.65 ± 7.63 59.45 ± 9.28 0.692 Left ventricular parameters during 3 months of follow-up.

Survey of HCMV in allogenic and autologous stem cell transplantation by real-time PCR in Kermanshah, west of Iran

IntroductionHuman Cytomegalovirus (HCMV) is the most important viral pathogen in people undergoing bone marrow transplantation (BMT). HCMV detection in the early stages makes is possible to save the patients’ lives through immediate and timely treatment. The aim of this study was to investigate the status of HCMV using the real-time PCR method in BMT patients in Kermanshah, west of Iran.MethodsHCMV monitoring was done in 120 patients who underwent BMT, 38 allogeneic cases and 82 autologous cases, using the ELISA serology test before transplantation. The participants were followed up 100 days after transplantation for HCMV detection in blood samples using real-time PCR. Preemptive therapy started with Ganciclovir and Foscarnet when the viral load was > 200 HCMV DNA copies/ml.ResultsDespite preemptive therapy, infection recurred in less than 1 month. HCMV recurred more frequently in patients undergoing allogenic transplation versus those receiving autologous transplantation. Recurrence was seen in 5 patients receiving allogenic transplantation. HCMV recurrence occurred in five patients with allogeneic transplantation. Twelve patients undergoing allogeneic or autologous transplantation (83%) and a virus load of > 1000 copies/ml showed HCMV-related symptoms. Three patients died, two due to HCMV-related pneumonia and the other one due to a fungal infection.ConclusionReal-time PCR may be a useful method for quantification and monitoring of HCMV recurrence and may be helpful in choosing more efficient HCMV preemptive treatment in BMT recipients.

Impact of childhood cancer on the family: evidence from Bangladesh

BackgroundThe care of children with cancer creates emotional, financial, and social impacts for their families. Information on the impact of childhood cancer (CC) on the family is scarce in Bangladesh. Thus, the study was set out to assess the impact of CC on the families in the local context. MethodsThis cross-sectional study was conducted from January to June 2018 in three purposively selected tertiary hospitals. All the children diagnosed and treated at those hospitals during the study period were eligible for this study. Children undergoing bone marrow transplantation, or those who were seriously ill, or those transferred to another hospital, or those who died were excluded or whose parents were not willing to participate. A total of 242 children were enrolled in the study and their parents were included in the interview. Measures included socio-demographic attributes, financial burden, personal strain, social impact, mastery, and treatment cost. Informed written consent was obtained from the parents and a face-to-face interview was conducted using a semi-structured questionnaire based on (i) About you and your-family and (ii) the Impact-On-Family (IOF) scale. High scores of the scale correlated to high impact. Medical records were reviewed to collect data on the pattern of CC and treatment costs. ResultsMajor CCs included leukemia (36.0%), blastoma (18.2%), sarcoma (14.9%), and lymphoma (12.4%). The weighted score was highest for mastery (3.63) followed by financial burden (3.33), personal strain (3.27), and social impact (3.21) domains. The difference of IOFS score was significant by family type (p < 0.05), father's occupation (p < 0.05), type (p < 0.01) and duration of cancer (p < 0.01), and treatment cost (p˂0.01). Families adopted diverse coping strategies including changed lifestyle (98.3%), sought social support (86.0%), rely more on religion (98.8%), and reduced family investment (83.9%) to adjust the impact. ConclusionThe impact of CC on the family is evident at many levels. In particular, mean scores of financial burden, personal strain, social impact, and mastery domains of the IOF scale were significantly associated with the employment status of parents, residing place, treatment cost, type, and duration of cancer. The study findings could contribute to devising impact-reducing intervention programs in Bangladesh.

Retrospective analysis of 34 febrile neutropenia episodes - therapeutic implication of multiplex polymerase chain reaction in infection diagnosis

Hemato-oncologic patients on chemotherapy or undergoing bone marrow transplantation are susceptible to infections due to neutropenia. Incidences of febrile neutropenia (FN) in these patients are common, contributing to high mortality and morbidity. Lack of diagnosis of pathogens responsible for infections in these patients is a major healthcare challenge. Newer molecular diagnostics are increasingly becoming relevant. The objective of this retrospective study was to evaluate the effectiveness of Syndrome Evaluation System (SES), a multiplex molecular diagnostic platform for diagnosis of pathogens, and its impact on the management of FN. In total, 34 neutropenic episodes from 21 patients admitted during September 2013 to April 2015 were analyzed in this study. Clinical samples from patients were tested on SES and routine culture. Treatment was as per standard of care. SES showed a 5-fold higher clinical sensitivity (55.9%) as compared to automated culture (11.1%). SES results were available within 14 hours as compared to >72 hours for culture, and elucidated change in antimicrobial therapy in 50% of episodes. Mortality rates were lower when SES was used early in the episode. De-escalation of antimicrobials according to SES results was possible, which translated into substantial cost saving. Newer non-culture-based molecular technologies like SES are changing the way we manage FN. It is faster, has a higher diagnostic yield as compared to traditional culture, and helps in making rapid, evidence-based therapeutic decision-making including de-escalation of antimicrobials. It would potentially lead to a reduction in mortality and healthcare cost in the long run.

Grip Strength Changes in Bone Marrow Transplant Patients

Emerging evidence that cancers survivors may experience premature aging has prompted epidemiology research aimed at the characterization of key premature aging phenotypes. Physical functioning data relevant for premature aging phenotype classification in cancer survivors, however, remain scarce. We assessed the burden of dynapenia, a key sarcopenia indicator, and muscle strength loss in the understudied population of bone marrow transplant (BMT) patients. This study involved secondary analyses of data from patients who underwent bone marrow transplant (BMT) in a cancer Institute in South Florida (June 2018-April 2019) with traditional hematopoietic cell transplantation specific comorbidity index (HCT-CI) scores and other relevant information. T-tests for paired data assessed pre- vs. post-BMT changes in grip strength (GS) (n=9). Prevalence of dynapenia (GS<27Kg and <16Kg) in pre-BMT (n=20) and post-BMT (n=9) periods were calculated. Median age [25th-75th percentiles] age was 61 [55-68] years old. Fifty-percent were females. GS and HCT-CI scores were not correlated. Mean GS loss after BMT was 6.4 Kg (95% confidential interval: 2.5-10.4 Kg, p-value=.003) in post-BMT (median-time-after-BMT: 90 days) minus pre-BMT (median-time-before-BMT: 62 days) comparison. Proportion with dynapenia increased from 10% (1/10) to 20% (1/5) in women, and 10% (1/2) to 75% (3/4) in men. We observed substantial muscle strength loss and dynapenia burden in patients who underwent BMT. Considering that dynapenia is a major, potentially modifiable risk factor for frailty, which is not captured by HCT-TI, we speculated that dynapenia-related targeted assessments and interventions – preventive and/or rehabilitative – could offer complementary approaches for treatment enhancement in BMT patients.

Addressing the psychosocial needs of young people with thalassaemia undergoing bone marrow transplantation

Beta thalassaemia major is an inherited condition that causes severe anaemia. Patients with the condition require regular blood transfusions. One curative treatment option available is bone marrow transplantation, but a bone marrow transplant is a high-risk, painful procedure requiring prolonged hospitalisation. Undergoing such a disruptive treatment can be a source of great anxiety for young people and their families, who will need honest, sensitive and empathetic communication, person-centred care, support to socialise and access education, involvement in decision-making and signposting to financial support. This article discusses the role of children's nurses in addressing the psychosocial needs of young people with thalassaemia who undergo bone marrow transplantation and in supporting young people's families.

Protein truncation test of LYST reveals heterogenous mutations in patients with Chediak-Higashi syndrome

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder in which an immune deficiency occurs in association with pigmentation abnormalities. Most patients who do not undergo bone marrow transplantation die of a lymphoproliferative syndrome, though some patients with CHS have a relatively milder clinical course of the disease. The large size of the LYST gene, defective in CHS, has made it difficult to screen for mutations in a large number of patients. Only 8 mutations have been identified so far, and all lead to a truncated LYST protein. We conducted protein truncation tests on this gene in 8 patients with CHS. Different LYST mutations were identified in all subjects through this approach, strengthening the observation of a high frequency of truncated LYST proteins as the genetic cause of CHS.

Insertion of central venous catheters in children undergoing bone marrow transplantation: is there a platelet level for a safe procedure?

BackgroundBone marrow transplantation (BMT) is a therapeutic procedure for the management of several hematological diseases and malignancies in pediatric population. Central venous catheters (CVCs) play a pivotal role during the process of BMT. The aim of this study was to compare the complications of CVCs placements in children undergoing BMT with platelet levels above and below 50,000/μL and also to detect if there is a platelet count for a safe insertion. This prospective study included all children who had placements of tunneled CVCs during BMT at our hospital between March 2017 and March 2020. Procedures were divided into two groups accordingly to preoperative platelet counts (above and below 50,000/μL). Data were compared between both groups regarding postoperative complications including bleeding or catheter-related blood stream infections (CRBSIs).ResultsForty-six CVC insertions were performed in 40 patients. There were 20 procedures below 50,000/μL (median 27,500; range 5000–42,000) inserted with perioperative platelet transfusions, and their postoperative levels were median 59,500/μL, range 18,000–88,000. Allogeneic BMT was adopted in 39 patients (97.5%). Beta thalassemia major was the commonest indication (21/40, 52.5%), followed by acute lymphocytic leukemia in six patients (15%). There were nine postoperative complications (bleeding n = 2 and CRBSIs n = 7) encountered in all placements. Four of them occurred in insertions below 50,000/μL (two bleeding complications that managed conservatively, and two CRBSIs). Post-procedural morbidities regarding bleeding or CRBSIs did not differ significantly between both groups (p value = 0.099 and 0.695, respectively).ConclusionsPostponement of CVC insertions in thrombocytopenic children due to the fear of potential complications seems unwarranted, as it has no significant impact on the morbidity. Placements of such catheters can be safe under cover of perioperative platelet transfusions irrespective of the preoperative platelet count.

Restricted Mean Survival Time Estimation: Nonparametric and Regression Methods

In survival analyses, the log-rank test is the standard approach to comparison of survival distributions estimated from independent groups. The semiparametric proportional hazards model uses the hazard function as the conduit to assess the influence of covariates x on the survival distribution of an event time T. The accelerated failure time model aligned closely to standard linear regression can estimate summary features such as the mean and percentiles of the survival distribution as functions of x. However, a full specification of a parametric distribution is often needed to analyze a model for $$ E(\log T|{\mathbf{x}}) $$ . A different approach is to model the restricted mean survival time $$ E(\hbox{min} (T,\tau )|{\mathbf{x}}) $$ . The specified time horizon $$ \tau $$ is informed by applications. All approaches must account for censoring in event times. We review analyses for restricted mean survival time based on the method of inverse-probability of censoring weighting, and on pseudo observations and a discussion on specified parametric models. As illustration, we apply the methods to a data set on relapse-free survival time in patients who underwent bone marrow transplantation.

Spinal Cord Compression in Patients with Acute Myeloid and Lymphoid Leukemia

Introduction Acute leukemias can be divided into acute myeloid leukemia and acute lymphoblastic leukemia. Common presentations of acute leukemia include fever, symptoms of anemia, bleeding, bone pain palpable Lymph nodes or spleen and symptoms due inflation or leukocystasis. Extramedullary mass is rare and can be of myeloid tissue and known as Chloroma or myeloid (granulocytic) sarcoma which one of the WHO classifications for acute myeloid leukemia. Common sites of occurrence are skin, sinuses, bone and other. It's rarely involve central nervous system. Spinal cord involvement usually manifest as epidural mass causing cord compression. Spinal epidural tumor with acute leukemia and myeloid sarcoma is rare and can be found in 3-9% in patients with leukemia. In this review we decide to review the cases of spinal cord compression caused by acute myeloid leukemia (including Chloroma) and acute lymphoblastic leukemia due to the significance of such presentation in addition to reports that Myeloid sarcoma of the spine has very poor prognosis Methodology: We have reviewed the literature using: PubMed, google scholar, Scopus for patient with spinal cord compression and acute leukemia. We used the search term and synonyms : : acute myeloid leukemia , acute myelocytic leukemia , acute monocytic leukemia , acute lymphoblastic leukemia , acute lymphoid leukemia, chloroma , myeloid sarcoma ,granulocytic sarcoma, spinal cord compression .We included adult patients above 18 years old only cases we exclude pediatrics cases and cases of chronic leukemia's and other myeloproliferative disorders as well as cases of central nervous system involvement other than spinal cord Results We gathered the information from 98 cases with general demographics, presentation, image modality, cytogenetics and molecular in addition to management and outcome. We have found mean age for the patients is 38 years old with male predominance with 70% of the cases. The most presenting symptom was back pain in around 75% of the cases. Neurological findings showed sensory loss and parapreresis in most of the documented cases. MRI was most performed modality of imaging 63% followed by Computed tomography(CT) 15 % and then myelogram 13 %, which is least used due to invasive nature and before the era of MRI. The most common affected site on spinal cord were thoracic followed by lumbar. Cytogenetics and molecular data was not reported in most of the cases. Patients were treated with either steroids or surgery or radiotherapy and or chemotherapy while few underwent bone marrow transplant, but the most common approach was surgery+ radiotherapy + chemotherapy combination. Steroids used in most of the cases especially in the cases of acute lymphoblastic leukemia and dexamethasone was the steroids of the choice mainly. The outcome of the patients were variable, 30 % were alive at the time of the reports 30 % died and 30 % between relapse and complete remission. Conclusions Acute leukemia can be presented as mass causing spinal cord compression which is very serious. There are is no standardized management of patients with acute leukemia who presented with spinal cord compression nether guidelines or steps to follow. Some reports speculated also specific morphology and cytogenetics association with predisposition to have Extramedullary mass, however there lack of reporting of such a valuable information. Large studies including all adjusted variables required to determine if spinal cord compression presentation can be an independent risk facto or not Effective diagnosis and prompt action should take place. Figure Disclosures No relevant conflicts of interest to declare.

Analysis of New Pediatric Thalassemia Diagnoses between 2010-2019 in a University System and Comparisons with Statewide Demography of Minnesota

Introduction Thalassemias are common inherited hematologic disorders worldwide, and with increasing migration, its prevalence evolves in different countries. However, community prevalence across most of the United States is unknown. Minnesota, particularly Minneapolis/St. Paul, has a relatively large community of immigrant families, with focal ethnic clusters of Karen and Hmong individuals from Southeast Asia, Liberia, and neighboring countries in Western Sub-Saharan Africa. Statewide data show that these ethnic minority populations have grown in the past decade; it is unknown whether thalassemia prevalence mirrors these migration trends. This report aims to quantify the demography and disease characteristics of children with thalassemia mutations seen at University of Minnesota/M Health Fairview (MHF) diagnosed between January 1, 2010 and December 31, 2019. Methods An institutional review board-approved electronic medical record (EMR) review was undertaken. Patients born on or after January 1, 2001 were included if they received medical care within the MHF system and thalassemia status could be confirmed. The prevalence by thalassemia type, demography, language, treatment details, and specialist involvement were detailed. A patient's ethnicity determination was defaulted to "American" if the ethnicity and/or immigration country of origin going back at least two generations could not be confirmed via EMR. The trends of new diagnoses over the decade were reviewed and compared to available state demography data trends. Descriptive statistical analyses were performed for the full group and by thalassemia type. Results A total of 404 patients met inclusion criteria, representing 48 country or region-specific ethnicities, 17 known countries of birth, and 30 separate languages. The most prevalent immigrant ethnicities were Karen (15%), Hmong (10%), and Vietnamese (5%), representing the 14th, 2nd, and 6th-largest immigrant communities in the state, respectively (www.mncompass.org). In Minnesota, the Asian population grew by 32% (69,800 people) between 2010-2018 (Minnesota State Demographic Center, https://mn.gov/admin/demography/data-by-topic/age-race-ethnicity/). The overall number of thalassemia diagnoses also increased over the decade, with Karen patients representing the largest proportional increase over the available time frame (Figure 1). Including both trait and disease, alpha thalassemias were more frequently diagnosed than beta thalassemias (63% versus 37%). Of the alpha thalassemias, 79% were suspected or confirmed 1-2 gene deletions based on newborn screening. Eleven (2.7%) had hemoglobin (Hb) H disease and 2 (0.5%) had alpha thalassemia major. Beta thalassemia intermedia, beta thalassemia major, and HbE were collectively 5.4% of all patients, 59% of whom were transfusion-dependent. Genetic confirmation was performed for 10.4% of all thalassemias. Those with alpha thalassemias were more ethnically diverse. Aside from those categorized as "American", those with beta thalassemias were more likely to be Karen (25%), while those with alpha thalassemias were most likely to be Hmong (14.4%). Seven had chelation prescribed during the time frame and 5 underwent bone marrow transplant. Only 16% were seen by a hematologist in the MHF system, though the yearly trends of hematology care did not match the increased diagnostic rate (Figure 2). Conclusions The incidence of pediatric thalassemia diagnoses have increased over the past decade at MHF, somewhat reflecting the statewide demographic trends. However, most patients are never being seen by hematology. A caveat to the data described is the fact that MHF is 1 of 2 pediatric hospitals locally, with the other having the historically larger thalassemia patient population. Thus, while these data offer crucial insights into the potential frequency of thalassemia mutations in our state, they also are likely to significantly under-represent the local prevalence. Also, the data do not reflect the prevalence in youths diagnosed prior to 2010 or the adult prevalence, for which institutional investigations are currently ongoing. These data illuminate the need to ensure adequate educational resources and financial support for these primarily non-English-speaking communities to improve awareness for families and medical providers and offset substantial medical costs for life-saving therapies. Disclosures No relevant conflicts of interest to declare.