Acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) are hematologic malignancies that occur most frequently in the sixth and seventh decades of life. Both disorders are associated with a poor prognosis, with median survival of one year or less. An overall five-year survival rate for both disorders, regardless of treatment, is less than 10%. A primary goal of treatment is to improve quality of life (QOL) because cure is improbable. The purpose of this longitudinal cohort study was to compare QOL between groups, intensive, non-intensive therapy, and supportive care. The sample consisted of 85 patients with high risk MDS and AML recruited from Moffitt Cancer Center. Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) was used to measure QOL. The aims for the study were to: 1) To compare the difference in QOL scores measured by the Functional Assessment of Cancer Therapy –Leukemia version for intensive chemotherapy, non-intensive therapy and supportive care within 7 days of new treatment and one month after initiation of treatment; 2) To determine QOL predictors of AML and high risk MDS from age, comorbidity, fatigue, and diagnosis; 3) To test the moderating effect of treatment with age, comorbidity, and fatigue on QOL. The first aim was analyzed with repeated measures analysis of variance (ANOVA). The supportive care group was not included in the analysis because of low accrual. Results indicated that there was a significant group by time interaction (with p=.040). Follow up tests revealed that the intensive treatment group had a significant improvement in their QOL scores at 1 month post treatment (p=.020). The second aim was conducted using Pearson’s correlations with age, comorbidity, fatigue, and diagnosis with significant correlations found between fatigue and QOL (r=-.693, p< .001). These findings identify an important relationship between fatigue and QOL. This was a negative correlation, showing that as fatigue increases QOL decreases. The third aim was explored using regression with Hayes (2013) application for moderation analysis. Scores for QOL for age, comorbidity, and fatigue were not moderated by treatment. These findings suggest that the most intensive treatment approach improves QOL. In addition, fatigue is a significant predictor of QOL. As fatigue increases, QOL scores decrease. Additional studies with a larger, more diverse sample is needed to explore the relationship between treatment approaches and QOL. In addition, intervention studies can be developed in AML and high risk MDS focused on fatigue management. It is anticipated that the results of this study will be used to inform patients and health care providers when making decisions concerning treatment based on QOL outcomes.

Burkitt lymphoma is a highly aggressive B cell non-Hodgkin lymphoma characterized by the translocation t(8,14) and deregulation of the MYC gene on chromosome 8. The endemic (African) form presents classically as an expanding mass in the jaw. The nonendemic (European/North American) form often presents with an abdominal mass. We present an interesting case of Burkitt’s Lymphoma with atypical features. A thirty-five-year-old lady with no significant medical history presented to the hospital with a three week complaint of vaginal bleeding and lower abdominal pain/cramps associated with night sweats and chills. She underwent gynecologic workup with an ultrasound revealing endometrial thickening followed by a hysteroscopic Dilatation and Curettage procedure. Laboratory workup revealed direct hyperbilirubinemia and elevated liver enzymes. MRCP showed gallbladder wall thickening but no biliary obstruction. A diagnosis of acalculous cholecystitis was considered and she underwent a laproscopic cholecystectomy and liver biopsy. Her initial complete blood count revealed mild leukocytosis. Follow up lab work revealed worsening leukocytosis and a hematology consultation was sought. A peak WBC of 81,000 with peripheral blood blasts as high as 31% was noted. Peripheral smear exam revealed moderate sized immature wbc precursors/blasts with high nuclear-cytoplasmic ratio. Further hematological work up including bone marrow aspirate and biopsy was expedited. Pathology resulted positive for Burkitt's lymphoma/leukemia, positive molecular studies, t(8,14), involving bone marrow, gallbladder, liver and endometrium. Patient was emergently treated with dexamethasone and nitrogen mustard as elevated bilirubin levels precluded standard treatment. She was started on Rituxan as this neoplasm is a CD 20+ B cell malignancy but could not tolerate it. HyperCVAD multi-agent chemotherapy was subsequently initiated along with intrathecal chemotherapy (cytarabine and methotrexate). CSF cytology remained negative for lymphoma. Patient’s clinical condition has improved after 2 cycles of chemotherapy and she is currently receiving on going therapy. Burkitt’s lymphoma is one of the most aggressive neoplasms with a tumor doubling time of a few days. The usual presentation is with constitutional symptoms and adenopathy or a mass lesion, and sometimes may manifest solely in the peripheral circulation as an L3 variant of acute lymphoblastic leukemia. Hepatic parenchymal involvement is rare, but reported. Gallbladder involvement with endoluminal deposits is even rarer. Simultaneous hepatic, gallbladder, uterine, nodal and leukemic involvement at presentation is unique. Treatment is primarily with systemic chemotherapy and multi agent regimens effective in acute lymphoblastic leukemia and/or aggressive lymphomas have been used successfully in this condition with a complete response rate of 80%-90% with a long-term survival rate of approximately 60%. Therapy is fraught with risks of fatal tumor lysis syndrome, pancytopenia, infection/sepsis, and bleeding. Potential progression/relapse in the CNS with the CSF serving as a sanctuary site has been well documented necessitating prophylactic intra thecal chemotherapy administration as in our patient. Aggressive biology of this disease required urgent treatment, as delay in institution of combination chemotherapy could result in poor outcome. This case highlights the need to maintain an open mind while evaluating apparently routine symptoms and the importance of rapid diagnosis and treatment of a hematologic-oncologic emergency.

Orientador: Claudia Regina Bonini-Domingos / Resumo: O “jabuti-piranga” (Chelonoidis carbonarius) é um jabuti brasileiro, amplamente distribuído entre os estados do Nordeste, ocorrendo em áreas de Cerrado e campo aberto, mas também presente em recintos de zoológicos e aquários, distribuídos por todo o território nacional. São animais ectotérmicos, cujo metabolismo e fisiologia são influenciados por condições ambientais (como temperatura, umidade relativa da atmosfera e luminosidade) em magnitudes superiores aos dos animais endotérmicos, como aves e mamíferos, por exemplo. O atual trabalho tem por objetivo avaliar como esses fatores ambientais influenciam no perfil hematológico e bioquímico de “jabuti-pirangas” em cativeiro durante o período de um ano. Foi observado que machos e fêmeas diferiram no perfil hematológico, em que os primeiros apresentaram maiores valores para hematócrito, hemoglobina e eritrócito; enquanto que no perfil bioquímico, machos obtiveram maiores valores para glicose e as fêmeas para colesterol e triglicérides. Entre os meses do ano, foi possível observar menores valores para concentração de hemoglobina circulante e correspondentes índices hematimétricos nos meses de outubro e dezembro; enquanto que a concentração de colesterol e triglicérides teve aumento significativo em dezembro e junho, para machos e apenas em dezembro, para as fêmeas. Foi possível concluir que: a variação sazonal dos fatores ambientais influencia diretamente nos parâmetros hematológicos, reduzindo a concentração de hemoglobinas circul... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The “red-footed tortoise” (Chelonoidis carbonarius) is a Brazilian tortoise, widely distributed among the states of the Northeast, occurring in areas of Cerrado and open fields, but also present in enclosures of zoos and aquariums, distributed throughout the national territory. They are ectotermal animals, whose metabolism and physiology are more influenced by environmental conditions (such as temperature, relative humidity and luminosity) than they are in endothermic animals, such as birds and mammals, for example. The aim of the current study is to evaluate how these environmental factors influence the hematological and biochemical profile of “redfooted tortoises” in captivity during the period of one year. It has been observed that males and females differed in the hematological profile, in which the former had higher values for hematocrit, hemoglobin and erythrocyte; whereas in the biochemical profile, males obtained higher values for glucose and females for cholesterol and triglycerides. Between the months of the year, it was possible to observe lower values for circulating hemoglobin concentration and corresponding hematimetric indices in the months of October and December; while the concentration of cholesterol and triglycerides increased significantly in December and June, in males and only in December, in females. It was possible to conclude the following: the seasonal variation of the environmental factors directly influences the hematological parameters, reducing t... (Complete abstract click electronic access below) / Mestre

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of requirements for the degree of Master of Science. Johannesburg, 17 May 1994. / Two black South African subjects presenting with hereditary elliptocytosis were investigated and the defect defined as Spol/74, a previously described spectrin variant leading to defective heterodimer self-association and instability of the erythrocyte membrane. [Abbreviated Abstract. Open document to view full version]

Acute Myeloid Leukemia (AML) is an aggressive hematopoietic neoplasm characterized by rapid clinical progression and universally fatal outcome if left untreated. The neoplastic cells are immature precursor cells that usually originate in the bone marrow and are often noted in the peripheral circulation. Myeloid sarcomas are rare abnormal collection of these cells in extramedullary sites and are now defined as a unique subset of AML as per the WHO classification. Here we describe a patient with AML presenting with a renal and testicular mass, which on biopsy revealed myeloid sarcoma in the absence of blood and bone marrow involvement. A 71 year old male was hospitalized with complaints of nausea, vomiting, confusion and jaundice associated with worsening pruritus in the absence of constitutional symptoms. Medical history notable for chronic kidney disease, Type 2 Diabetes Mellitus and history of localized prostate cancer treated with TURP. Family history of thyroid cancer in his mother. Clinical exam revealed small right testicular non tender mass. Labs revealed a total bilirubin of 11.5mg/dL, creatinine of 3.09 mg/dL, Hemoglobin 13.4g/dL, WBC 9.5k/uL and Platelet count of 283K/uL. Abdominal imaging studies demonstrated a biliary stricture, a 16mm right testicular lesion and a additional right renal mass measuring 4.0 x 3.9 x 2.4 cm. He underwent a right inguinal orchiectomy, which confirmed myeloid sarcoma. Histopathologically, numerous neoplastic cells with enlarged nuclei and mitotic figures were identified with immunohistochemical staining positive for CD45, MPO, CD117, CD68, CD71 and BCL2. A biopsy of the right renal mass also demonstrated myeloid sarcoma, with similar features. He had an ERCP with stent placement for his biliary stricture with negative cytology. Bone marrow biopsy was negative for AML. His challenging clinical presentation, advanced age, medical comorbidities, hyperbilirubinemia, and impaired kidney function, precluded aggressive treatment with standard acute myeloid leukemia induction chemotherapy regimens so a trial of hypomethylating agent (Azacitidine) was successfully initiated. AML is characterized by a rapid clonal proliferation of immature hematopoietic cells in the peripheral blood and bone marrow. It is a heterogeneous disease with regard to acquired genetic alterations, including cytogenetic aberrancies as well as gene mutations and changes in gene expression. The signs and symptoms of AML mostly reflect predominant cytopenias or cytoses and usually a short history (1 to 8 weeks) of constitutional complaints. Myeloid sarcomas are rare extramedullary solid tumors that have resulted in infiltration of organs such as gingiva, skin, lymph nodes and other organs with immature granulocytic precursor cells. The majority of cases are reported in association with coexisting acute myeloid leukemia and infrequently can present in isolation (a harbinger for future blood and marrow involvement). Treatment of myeloid sarcomas follows the AML paradigm. The overall survival of AML is dictated by cytogenetics/ molecular markers and age. Complete remission can be achieved in a group of patients. Relapses occur in the first two years. Leukemic infiltration of the kidney or testicle with myeloid sarcoma is extremely rare and the concurrent presentation is documented in isolated case reports only.

The day that I joined McMaster University and the Department of Health Research Methods, Evidence, and Impact as a Master student, I did not foresee the amazing journey I was embarking on or the impact of my academic achievements. I was continuously challenged to think critically and apply my ideas to real world problems. Seeing the opportunity to make a difference in clinical research and patient care inspired me to begin my PhD studies. Creating knowledge and applying it practically was a difficult task, however, the opportunities to share my research in a dynamic and complex field with the world fuelled my motivation. Completing a PhD has been an incredible privilege for which I will always be grateful. To my family – Mamma, Papa, Mark and Matthew – thank you for your undying and unconditional love, support, and encouragement. A pandemic forced us to come together, and having your support 24/7 (literally) made the journey more enjoyable. To my closest friends, thank you for being a part of my life and supporting my ambitions. We all recognized my ambitiousness would set me on a difficult path and completing a PhD was not my original plan. Thank you for inspiring me to take on the challenge and ensure my work was truly impactful. Thank you for encouraging mental strength, being understanding and willing to lend a hand, reminding me that I can achieve anything I set my mind to, and inspiring me to dare. To my supervisory committee members and independent study supervisor, thank you for your continued interest in my work and for always supporting my ambitions. I am grateful for your patience and belief that I would succeed in completing what I had sought to achieve. Thank you for the chance to work together, and for your constant support and mentorship throughout my PhD journey. To the faculty, staff and fellow students at the Department of Health Research Methods, Evidence, and Impact, and the McMaster Centre for Transfusion Research, thank you for providing the resources, friendship, and guidance I needed to achieve greatness. To the panel members of the ITP Emergency Management Guideline, thank you for believing in this project and making this work possible. I look forward to implementing the results of our efforts into clinical practice. To the ITP patient community, thank you for entrusting me with the task of improving patient care and supporting me along the way. You have enabled me to be a voice for change. To the rare disease community, I know the completion of my PhD journey will not be the end of our work together. To the funding agencies who allowed this project to be possible, the Canadian Institutes of Health Research and Platelet Disorder Support Association, thank you for supporting my PhD journey and the completion of this important work. To my doctoral supervisor, Dr. Donald Arnold, it has been an honour and privilege to have learned from you and received your guidance throughout my PhD journey. Since our initial meeting, when I hobbled into the McMaster Centre for Transfusion Research offices several minutes late, I felt that your kindness and honesty would be the perfect form of mentorship to push me towards success. Thank you for recognizing my ambition and reminding me to keep focused. I will continue to apply this lesson throughout my life and strive for ‘depth’. For many years, you have been my mentor who I reached out to for advice, support, honest feedback, and encouragement. Thank you for imparting your knowledge to me over my PhD journey and teaching me how to be an inspirational mentor who highlights the strengths of their students while simultaneously supporting their growth. Although I may have finally reached the destination in my PhD journey, I know that we will continue to collaborate for many years to come. / Developing clinical practice guidelines (CPGs) for rare diseases is methodologically challenging. As each disease has so few patients, published literature includes low-quality studies or studies that do not directly address the questions of interest. As a result, CPG panelists have limited evidence on which to base their recommendations. Historically, when no evidence was available, CPGs have relied on physician opinion. This does not align with the mandate of CPGs which transparently identifies, appraises, and relies on evidence. The challenges of developing CPGs for rare diseases are exemplified by immune thrombocytopenia (ITP), a rare autoimmune disease that affects approximately 1 in 8,000 people. It predominantly affects females and young adults, and is characterized by low blood platelets that increase the risk of bleeding. Bleeding emergencies in ITP patients are critical, life-threatening events that can cause life-long morbidity and associated health care costs. Treatment of ITP bleeding emergencies requires a rapid, coordinated approach that involves emergency department staff, hematologists, pharmacy, and the laboratory. However, there is no evidence-based CPG for the management of ITP bleeding emergencies. The objectives of my PhD thesis are (1) exploring the heterogeneity of ITP diagnosis using antiplatelet autoantibodies; (2) developing a standardized definition of ITP bleeding emergencies; (3) outlining the synthesis of existing evidence on the treatment of ITP bleeding emergencies through a systematic review; and (4) developing a novel methodology to address the lack of evidence in rare disease CPGs and applying it to develop a CPG for the management of ITP bleeding emergencies. / Thesis / Candidate in Philosophy / Guidelines for rare diseases can be hard to develop because of a lack of information. Doctors and researchers make decisions on rare disease management based on their experiences, which can be limited. Low blood platelets and emergency bleeding can be caused by a rare disease called immune thrombocytopenia (ITP). When emergency bleeds occur, patients need care from the Emergency Department immediately. The problem is that there is no standard way for doctors to treat these ITP bleeding emergencies. My PhD thesis project will fill an important gap for ITP emergency treatment. First, we will assess how ITP patients are diagnosed. Second, we will define an ITP bleeding emergency. Third, we will collect existing information about ITP bleeds. Fourth, we will overcome the challenge of not having enough information by collecting new data from patient records. The method we use to develop ITP guidelines can be used for other rare diseases.

Extracorporeal circulation damages blood and causes harmful side effects such as stroke and/or systemic inflammatory response in patients. Reactions of blood components to extracorporeal circulation include complement and inflammatory reactions, coagulation and thrombogenesis, frank hemolysis, and platelet activation and adhesion to the extracorporeal circuit. Non-physiologic pressure and flow produced by blood pumps contribute to blood injury. Two pump types, roller and centrifugal, are used for maintaining flow, with various models available from different manufacturers. This study compared the effects of these two pumps in identical, isolated, artificial circuits to a non-pumped control for a period of 24 hours on heparinized porcine blood. Hematology parameters were used to evaluate blood damage. Mean corpuscular volume, mean corpuscular hemoglobin, white blood cell count, platelet count, and mean platelet volume were affected by time of circulation. Mean corpuscular hemoglobin, platelet count, and red cell distribution width were different between circulated and non-circulated blood, however no differences were found between the pumping systems in any parameter. Red blood cell count, total hemoglobin, and hematocrit were not affected by time or treatment. The changes observed in this study have implications for the use of extracorporeal circulation in the clinical setting and in future use of blood as a potential organ perfusion medium. / Master of Science

In this study the researcher explored and described the utilization of Gestalt play therapy concepts and techniques in order to strengthen the sense of self of the pediatric hematology/oncology patient. Literature studies were compiled to examine the concepts of the pediatric hematology/oncology patient, sense of self and Gestalt play therapy. These literature studies provided the theoretical frame in which the study was executed. During the empirical study qualitative data was gathered by means of unstructured interviews within an instrumental case study. Eight therapy sessions were conducted with the participant in order to explore how Gestalt play therapy concepts and techniques could be utilized to strengthen the sense of self of the pediatric hematology/oncology patient. Following the analysis of the data the researcher was able to describe how the Gestalt play therapy concepts and techniques were utilized to strengthen the sense of self of the pediatric hematology/oncology patient. / Social Work / M. Diac. (Play Therapy)

In this study the researcher explored and described the utilization of Gestalt play therapy concepts and techniques in order to strengthen the sense of self of the pediatric hematology/oncology patient. Literature studies were compiled to examine the concepts of the pediatric hematology/oncology patient, sense of self and Gestalt play therapy. These literature studies provided the theoretical frame in which the study was executed. During the empirical study qualitative data was gathered by means of unstructured interviews within an instrumental case study. Eight therapy sessions were conducted with the participant in order to explore how Gestalt play therapy concepts and techniques could be utilized to strengthen the sense of self of the pediatric hematology/oncology patient. Following the analysis of the data the researcher was able to describe how the Gestalt play therapy concepts and techniques were utilized to strengthen the sense of self of the pediatric hematology/oncology patient. / Social Work / M. Diac. (Play Therapy)

Thesis (M.Med. (Paediatrics and Child Health)) -- University of Limpopo, 2022 / BACKGROUND Febrile neutropenia is a medical emergency that complicates the clinical course and treatment of both hematological and solid malignancies, potentially worsening the overall outcome and increasing the financial burden. The epidemiology of pathogens is varied, and determines the selection of empiric antibiotic therapy for febrile neutropenia. Empirically piperacillin/tazobactam plus amikacin has been recommended as the most suitable antibiotic for management of febrile neutropenia. There is a lack of local studies to provide advice for antibiotic choice in our setting. OBJECTIVE To identify causative organisms of infection and antibiotic susceptibility patterns in childhood cancer patients with chemotherapy related febrile neutropenia in Pietersburg Hospital Oncology Ward Limpopo Province. METHODS This is a retrospective cross-sectional study that reviewed all the febrile neutropenic episodes in children with cancer and with a positive blood culture during the febrile neutropenia episode. Data collected included patient demographics (date of birth, sex, date of diagnosis) diagnosis, organisms cultured and the antibiotic sensitivity profile. RESULTS There were 152 records of positive blood cultures identified of 348 episodes of febrile neutropenia for 413 patients. The median age of study population is 6years (mean age of 6.8years; range 3 to 11years) with male predominance at (61.2%). The most common cancer diagnosis was Acute Lymphoblastic Leukemia (ALL) (33.6%) followed by Nephroblastoma (15.8%), Acute myeloid leukemia (11.2%), Non- Hodgkin’s lymphoma (9.9%), Hodgkin’s lymphoma (5.9%) and other cancers (15.3%). The majority of causative organisms were gram-positive bacteria (45%) followed by gram-negative bacteria (32.4%) and fungi (6.1%). Gram-positive organisms were statistically significant pathogens causing bacteraemia more often in neutropenic patients than gram-negative organisms with a p value=0.016. The majority (n=102; 67.10%) were sensitive organisms with the minority being multidrug resistant organisms (n=23; 15.1%) and 17.8% were contaminants n=27. The most common gram-positive pathogens were Coagulase negative staphylococcus n=37; (21.6%). The most common multidrug resistant organisms were Klebsiella pneumoniae CRE (10.7 %;), followed by Enterococcus faecium VRE (1.9%), Klebsiella oxytoca CRE (1.3%), Enterococcus faecalis VRE (0.6%), and Staphylococcus aureus MRSA (0.6%). No multidrug resistant fungal organisms were cultured. The majority of organisms were sensitive to the first line empiric therapy piperacillin/tazobactam plus Amikacin (67.10%). Thirty patients died during these febrile neutropenic episodes and case fatality rate was 8.6%. CONCLUSION This study confirmed that the causative bacteria of febrile neutropenia in this study were susceptible to the first line empiric therapy piperacillin/tazobactam plus amikacin, and this regimen is therefore appropriate for this paediatric oncology unit.