Patients Undergoing Bone Marrow Transplantation Research Articles

Evaluation of the bone marrow transplantat recipient patients regarding fever onset, fever permanence, risk factors, and underlying causes, during the pre-engraftment phase

Background: Patients undergoing bone marrow transplantation (BMT) are at higher risk of immune system deficiency. The immunosuppression, followed by pre-transplant chemotherapy makes patients vulnerable to a variety of infections, and fever is one of the first symptoms, which could develop as a result of infectious or non-infectious diseases. In the present study, the features of the fever during the pre-engraftment stage in BMT-receiving patients have been investigated.
 Materials and Methods: Sixty-four patients receiving BMT were prospectively evaluated during the pre-engraftment phase to evaluate the evidence of the febrile reaction. Data concerning the cause of fever, microbiological tests, the treatments and fever onset pattern, and treatment outcomes were recorded and analyzed.
 Results: 73.4% of the patients had autologous transplants, and the others received allogeneic. After transplantation, 75% of patients encountered fever during the pre-engraftment period. Of the 48 patients, 47.9% of the patients suffered from fever of unknown origin (FUO). Age, gender, underlying malignancy, type of transplantation, and acute phase reactants levels before transplantation were not associated with fever development. Among febrile patients, patients with autologous transplantation were significantly more likely to develop FUO (p-value = 0.036) There was also no significant difference in the onset of fever between patients with infectious fever and who suffered FUO
 Conclusions: During BMT, half of the patients developed a fever of unknown origin; nevertheless, it seems that patients undergoing autologous transplantation are at higher risk of FUO compared to patients who received an allogeneic transplant.

Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Plasma Busulfan.

Busulfan is an alkylating agent and functions as a myeloablative and anti-leukemic chemotherapy drug. It is widely used with cyclophosphamide for conditioning patients undergoing bone marrow transplantation for myeloid leukemia. Studies have shown that the busulfan plasma concentration correlates better with clinical efficacy and toxicity than the patient's administered dosage. Low concentrations predispose to disease recurrence and even graft rejection, and higher concentrations can increase the risk of hepatic toxicity. As a result, dosing levels can vary significantly from patient to patient. Therapeutic drug monitoring (TDM) of busulfan plasma concentration guides the dosage adjustment to optimally achieve complete bone marrow ablation while minimizing the dosage-dependent toxicity. The quick and precise (precision <10%) UPLC-MS/MS method described here for monitoring plasma busulfan levels between 50ng/mL and 5000ng/mL involves the addition of an organic solvent and deuterated internal standard (busulfan d-8) followed by a liquid-liquid extraction, injection of the extract onto a C18 column, and analysis by multiple reaction monitoring (MRM) in ESI-positive mode.

Analysis of Hospitalization Outcomes in Bone Marrow Transplant Patients with Graft-Versus-Host Disease: A Nationwide Study

Background: Graft-versus-host disease (GVHD) is a well-known complication in patients with bone marrow transplantation. There is a need for additional data on the in-patient outcomes of GVHD in patients who have undergone bone marrow transplantation. Our analysis aims to evaluate the outcomes of GVHD in hospitalized patients with bone marrow transplantation. Method: In this retrospective study, we utilized data from the National Inpatient Sample (NIS) database from 2016 to 2019. Using ICD-10 codes, we identified hospitalizations involving bone marrow transplantation and categorized them into two groups: those with GVHD and those without GVHD. To account for potential confounding variables, we considered a comprehensive set of factors, including age, sex, race, zip code-based income quartile, hospital region, hospital teaching status, hospital division, hospital bed size, insurance status, and the Charlson comorbidity index score. We performed univariable logistic regression analysis to calculate unadjusted odds ratios. Subsequently, we conducted a multivariable logistic regression analysis to account for potential confounding effects and calculated adjusted odds ratios.(see Figure), where the model included only variables that were found to be associated with the outcome of interest in the univariable regression analysis at a significance level of P &amp;lt; 0.2. Proportions were compared using the Fisher exact test for categorical variables, and continuous variables were compared using the Student t-test. All P-values were two-sided, and the significance level was set at P &amp;lt; 0.05, indicating statistical significance. Results: From 2016 to 2019, data were collected from 13,999 hospitalizations involving bone marrow transplants. Among these cases, 836 hospitalizations were linked to GVHD patients. A comparison of patient characteristics showed that individuals with GVHD had a mean age of 51.61 years, while those without GVHD had a slightly higher mean age of 55.55 years. There were slight variations in gender and race distributions between the two groups, with a higher percentage of males and whites observed in the GVHD group compared to the group without GVHD. The analysis of outcomes between the two groups revealed significant differences. Patients with GVHD experienced notably longer mean lengths of stay (41.40 days vs. 21.31 days, P = 0.000) and incurred higher mean total hospital charges ($824,058 vs. $335,765, P = 0.000). Furthermore, after adjusting for confounding factors, GVHD posed a substantial risk to patients undergoing bone marrow transplantation. The adjusted odds ratio (aOR) for mortality in those with GVHD was 7.20 (95% CI: 5.54 to 9.36, P = 0.000) compared to those without GVHD, indicating a considerably higher risk of death. The coefficient for the length of stay was 19.36 days (95% CI: 17.29 to 21.42), and the coefficient for total hospital charges was $453,733 (95% CI: $396,577 to $510,889) in patients with GVHD compared to those without GVHD hospitalizations. Moreover, the presence of GVHD in patients was associated with elevated risks of various medical conditions. The adjusted odds ratios (aORs) for sepsis, pneumonia, acute respiratory failure, intubation and mechanical ventilation, Clostridium difficile infection, and acute kidney injury (AKI) in patients with GVHD were 2.79 (95% CI: 2.28 to 3.41, P = 0.000), 3.30 (95% CI: 2.57 to 4.24, P = 0.000), 5.10 (95% CI: 4.01 to 6.49, P = 0.000), 4.88 (95% CI: 3.75 to 6.34, P = 0.000), 1.45 (95% CI: 1.13 to 1.86, P = 0.003), and 3.57 (95% CI: 2.97 to 4.29, P = 0.000), respectively (see Figure). Conclusion: Patients with GVHD in patients with bone marrow transplantation experience higher mortality rates, extended hospital stays, and increased hospital charges. Additionally, they are at a significantly higher risk of developing severe medical conditions, including sepsis, pneumonia, acute respiratory failure, Clostridium difficile infection, and acute kidney injury (AKI). These findings highlight the importance of closely monitoring and effectively managing GVHD to enhance patient outcomes and alleviate the burden of complications associated with bone marrow transplantation. Nevertheless, further prospective studies are necessary to gain a deeper understanding and more comprehensive evaluation of the outcomes in these hospitalized patients.

Dosimetric Advantages of VMAT TBI Plans: A Direct Comparison to Conventional TBI Plans.

Total body irradiation (TBI) continues to play an integral role in the conditioning of patients undergoing bone marrow transplantation. Historically, conventional TBI (C-TBI) has been delivered based on a clinical plan without CT simulation. However, volumetric modulated arc therapy TBI (V-TBI) is emerging as an alternative method to deliver TBI in a contemporary fashion. We aimed to compare these two methods of TBI delivery. Patients undergoing treatment with V-TBI were identified. C-TBI plans were created using their existing simulation CT images. Patient thickness was measured on the scan and compensators such as lead sheets to attenuate dose in areas with less separation and lung blocks drawn on digitally reconstructed radiographs (DRR) were added when necessary. A 3D dose distribution was then calculated allowing for the direct comparison between C-TBI and V-TBI on the same patient using the same CT image set. Dosimetric data from each plan including target volume coverage, dose homogeneity, absolute max dose, and dose to lungs were recorded. V-TBI and C-TBI plans for a total of four patients were preliminarily analyzed. Two patients were prescribed 200 cGy in a single fraction, while the other two were prescribed 1200 cGy in eight fractions. V-TBI resulted in a more favorable dosimetry for all four patients in most evaluated metrics including dose coverage, dose homogeneity, and lung dose (Table 1). V-TBI did result in an increased absolute maximum dose to all four patients compared to c-TBI, but still met the desired constraint of D0.03cc<125%. V-TBI resulted in more favorable dosimetry for all four patients compared to C-TBI. To our knowledge, this is the first direct dosimetric comparison between the two methods. Analysis of 8 more V-TBI cases is currently underway. In the future, we plan to design a prospective study to evaluate the clinical outcomes of patients undergoing V-TBI vs C-TBI.

COVID-19 Crisis: A Time for Practical Assessment of Hygienic Principles Observance

Simultaneously with COVID-19 pandemic, numerous protocols have been developed to prevent the infection. COVID-19 can be more fatal in the bone marrow transplant ward because patients admitted to these wards have a weakened immune system. Assessment of the protocol specified for this wards and practical evaluation of the hygienic principles observance by the medical staff during COVID-19 pandemic can be a step towards saving the lives of the patients. Coinciding with COVID-19 pandemic, 40 patients underwent bone marrow transplantation at Imam Reza Hospital of Kermanshah, Iran from February 2020 to June 2022. A follow-up program was performed to evaluate the possibility of COVID-19 transmission and the rate of hygiene practice by medical staff. The principles of hygienic protocols were scored as a questionnaire in which the observance/non-observance method were applied. Real time-polymerase chain reaction (RT-PCR) based on three genes of the virus was used to diagnose the COVID-19 patients. The results of RT-PCR tests were negative in all patients who were hospitalised during the study. The rate of observance of the hygienic principles by the staff in the studied ward was 100%.The obtained result in the present study was a reflection of the step-by-step implementation of the hygienic protocol specified for bone marrow transplantation ward by the staff. The protocol specified for the bone marrow transplantation ward was highly overlapped with COVID-19 general hygienic guidelines.

Financial toxicity and quality of life in patients undergoing bone marrow transplant evaluation: A single center analysis.

7052 Background: The impact of pre-transplant financial toxicity on quality of life (QOL) outcomes following bone marrow transplant (BMT) is unknown. We investigated the prevalence of financial toxicity in a population undergoing evaluation for BMT and its impact on post-transplant clinical and health-related QOL outcomes. Methods: This is a cross-sectional study in patients undergoing evaluation for allogeneic BMT between 1/1/2018 and 9/23/2020 at a large academic medical center. Financial health at baseline was measured via the comprehensive score for financial toxicity (COST) survey. The cohort was divided into three groups: none, mild, and moderate-high financial toxicity. QOL was measured using Functional Assessment of Cancer Therapy (FACT)-based questionnaires at multiple timepoints. Multivariate logistic regression analysis evaluated factors associated with financial toxicity. Kaplan-Meier curves and log-rank tests evaluated overall survival and non-relapse survival. Results: Of 245 patients evaluated for BMT, 176 (71.8%) completed both questionnaires with 63.1% male, 72.2% white, and median age 57 years. Common diagnoses were myelodysplastic syndrome (39.2%), leukemia (38.1%), and lymphoma (13.6%). Overall, 83 (47.2%) patients reported no financial toxicity, 51 (29.0%) mild, and 42 (23.9%) with moderate-high financial toxicity at initial evaluation for BMT. Compared to those with no financial toxicity, those with mild or moderate-high financial toxicity reported significantly reduced spending on leisure, food/clothing, used all or a portion of savings, borrowed money or accumulated debt using a credit card, and did not fill a prescription due to costs (p &lt; 0.0001 for all). In patients with baseline moderate-high financial toxicity, FACT-BMT scores were lower at 6 months (126 none vs 122 mild vs 92 moderate-high; p = 0.0007) and 1 year (133 none vs 117 mild vs 112 moderate-high; p = 0.0075) following BMT. Older age (&gt;62) (OR 0.4; 95% CI [0.17 – 0.94], p = 0.03) and income equal or greater than $60,000 (OR 0.16; 95% CI [0.07 – 0.36], p = &lt; 0.001) were associated with lower odds of financial toxicity. No association was noted between financial toxicity and selection for BMT, overall survival, or non-relapse mortality. Conclusions: Financial toxicity was highly correlated with patient-reported changes in behavior affecting their daily activities and transplant care, with notable impact on QOL following transplant for up to 1 year. Early interventions by physician and social work-led teams may benefit patients who are at risk for financial toxicity. [Table: see text]

Association of atrial fibrillation and outcomes in patients undergoing bone marrow transplantation.

Haematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for several malignant and non-malignant haematologic conditions. Patients undergoing HSCT are at an increased risk of developing atrial fibrillation (AF). We hypothesized that a diagnosis of AF would be associated with poor outcomes in patients undergoing HSCT. The National Inpatient Sample (2016-19) was queried with ICD-10 codes to identify patients aged >50 years undergoing HSCT. Clinical outcomes were compared between patients with and without AF. A multivariable regression model adjusting for demographics and comorbidities was used to calculate the adjusted odds ratio (aOR) and regression coefficients with corresponding 95% confidence intervals and P-values. A total of 50 570 weighted hospitalizations for HSCT were identified, out of which 5820 (11.5%) had AF. Atrial fibrillation was found to be independently associated with higher inpatient mortality (aOR 2.75; 1.9-3.98; P < 0.001), cardiac arrest (aOR 2.86; 1.55-5.26; P = 0.001), acute kidney injury (aOR 1.89; 1.6-2.23; P < 0.001), acute heart failure exacerbation (aOR 5.01; 3.54-7.1; P < 0.001), cardiogenic shock (aOR 7.73; 3.17-18.8; P < 0.001), and acute respiratory failure (aOR 3.24; 2.56-4.1; P < 0.001) as well as higher mean length of stay (LOS) (+2.67; 1.79-3.55; P < 0.001) and cost of care (+67 529; 36 630-98 427; P < 0.001). Among patients undergoing HSCT, AF was independently associated with poor in-hospital outcomes, higher LOS, and cost of care.

Can the Left Internal Mammary Artery Be Used During Coronary Artery Bypass Graft Surgery in Patients Undergoing Bone Marrow Transplant? A First Case Report

Introduction: With the improvements in neoplasm treatments and the increased survival of patients with neoplastic diseases, we have entered a new era of having to deal with the complications of senile patients. The issue of bone fusion or the side effects of its delay, such as malunion or infections, are among the concerns for any surgery in patients whose bone marrow is affected by treatment or whose bone marrow blood flow is impaired. The left internal mammary artery (LIMA) is used for coronary artery bypass graft (CABG) surgery with its 2 - 3 times longer lifespan compared to saphenous vein grafts, but its harvest from the sternum affects the sternum blood flow and the outcome of its use is still not identified in patients undergoing bone marrow transplant. This case report is the first report on this issue. Case Presentation: A 60-year-old man with diffuse large B cell lymphoma who had undergone bone marrow transplant a year before had then developed chest pain, which was diagnosed as vessel disease; he was selected for CABG surgery. The LIMA was harvested during the surgery and the left anterior descending artery (LAD) was anastomosed. The saphenous vein graft was also anastomosed to the diagonal artery, obtuse marginatus (OM), posterior descending artery (PDA), and posterior left ventricle (PLV). After the surgery, the patient was followed up for six months, during which time no specific incidents occurred and no sternum-related complications were observed either. Conclusions: In this case report, the use of LIMA in a patient who had undergone a bone marrow transplant and CABG surgery was not associated with any increase in sternum-related complications.

Challenges to allogeneic hematopoietic stem cell transplantation in a patient with GATA2 deficiency and persistent Epstein-Barr virus infection

The germline Guanine-adenine-thymine-adenine 2 (GATA2) heterozygous mutations (GATA2 deficiency) are identified as a complex immunodeficiency, which entails susceptibility to non-tuberculous mycobacterium (NTM), fungus, or Epstein-Barr virus (EBV) infection, and hematological disorders including myelodysplastic syndrome (MDS)/acute myelogenous leukemia, accompanied by characteristic sighs such as lymphedema or deafness. A 21-year-old woman with persistent EBV infection was diagnosed with GATA2 deficiency based on the onset of MDS and her family history. The patient underwent bone marrow transplantation from an unrelated donor. She developed steroid-resistant graft-versus-host disease (GVHD), leading to an NTM infection, the deterioration of lymphedema, and life-threatening gut bleeding caused by not only GVHD but also thrombotic microangiopathy. Although allogeneic hematopoietic stem cell transplantation is a potential therapeutic option in patients with GATA2 deficiency, GATA2 haploinsufficiency in non-hematopoietic cells may affect the post-transplant complications. Therefore, the establishment of treatment guidelines on donor and graft selection, the intensity of conditioning regimens, GVHD prophylaxis, and prevention of post-transplantation infections based on the history of infection and degree of organ damage is necessary for patients with GATA2 deficiency.

The Determining Factors for Outcome of Pediatric Intensive Care Admitted Children After Stem Cell Transplantation.

Requiring pediatric intensive care unit (PICU) admission relates to high mortality and morbidity in patients who received hematopoietic stem cell transplantation (HSCT). In this study, we aimed to evaluate the indications for PICU admission, treatments, and the determining risk factors for morbidity and mortality in patients who had allogeneic HSCT from various donors. In this retrospective study, we enrolled to patients who required the PICU after receiving allogeneic HSCT at our Pediatric Bone Marrow Transplantation Unit between 2005 and 2020. We evaluated to indication to PICU admission, applications, mortality rate, and the determining factors to outcomes. Thirty-three (7%) patients had 47 PICU admissions and 471 patients underwent bone marrow transplantation during 16-year study period. Also, 14 repeated episodes were registered in 9 different patients. The median age of PICU admitted patients was 4 (0.3 to 18) years and 29 (62%) were male. The main reasons for PICU admission were a respiratory failure, sepsis, and neurological event in 20, 8, and 7 patients, respectively. The average length of PICU stay was 14.5 (1 to 80) days, 14 (43%) of patients survived and the mortality rate was 57%. Multiple organ failure ( P =0.001), need for respiratory support ( P =0.007), inotrope agents ( P =0.001), and renal replacement therapy ( P =0.013) were found as significant risk factors for mortality. Allogeneic HSCT recipients need PICU admission because of its related different life-threatening complications. But there is a good chance of survival with quality PICU care and different advanced organ support methods.

Phenotype and Natural History of ELANE and NON ELANE Severe Congenital Neutropenia in Italy: Data from the National Registry

INTRODUCTION Severe Congenital Neutropenia includes several disorders characterized by absolute neutrophil count depletion appearing early in life, high propensity to potentially lethal infections and risk of myelodysplasia/acute leukemia. Mutations of ELANE and HAX 1 genes are often reported as the most frequent causes of SCN but many other genes are now recognized as causative of the disease. AIM of The STUDY. To describe the clinical history and the outcome of SCN patients included in the Italian Neutropenia Registry (INR) and to investigate differences between ELANE and non- ELANE mutated groups PATIENTS AND METHODS. Demographics, biochemical, clinical and genetic information were retrieved from the INR. OS probability was estimated by the Kaplan-Meier method. RESULTS from June 2000 to June 2022 844 patients were reported to the INR and 106 (52% females) were diagnosed with SCN. Median age at diagnosis was 1 year (IQR 0.4-4.1) and at last follow up was 11years (IQR 6.0-19.4). Subjects were Caucasian in 90% of cases and of other ethnicities in 10% . Consanguinity occurred in 4/49 (8%) of the patients in which data were available. Genetic testing performed in all patients, enabled a definite genetic diagnosis in 94% of the subjects whereas in the remaining 6% a genetic lesion was not found. Genetic lesions were distributed as follows: ELANE 54% of which 28% were cyclic , TAZ 10%, CXCR4 6%, SLC37A 4.6%, COH1 3%, JAGN1 3%, SDS 3%, G6PC3 3%, SRP54 2%, USB1 2%, HAX1 2%, CSFR3 1%, , GATA2 1%). Of 106 patients, 4 were also reported to specific Registries (SDS and GATA2) while 11% were lost to follow-up. The 15 and 20-year overall survival of the 94 patients in active follow-up were respectively 93 % (83.6%-97.0%) and 87.4% (69.2%-95.2%) without differences between the ELANE and non ELANE groups. In the whole cohort 7/106 (7%) patients died and of them 3/7 for infections due to non compliance to G-CSF therapy, 2/7 for organ damage associated to the disease and 2/7 for complication after bone marrow transplantation. The cumulative incidence of MDS/AL after 20 yrs after diagnosis was 10,9% (3,2%-34%) that favorably compares with that from other Registries. Total number of Infection episodes prior to SCN diagnosis, was 592 in 73 pts (42 in ELANE, 31 non- ELANE) and were: pharingytis and bronchitis (32%), skin and deep abscesses (22%), otitis/mastoidistis (17%), miscellaneous (29%) (enteritis, other upper respiratory , urinary tract infections and fever of unknown origin (14%), pneumonia (10%) and sepsis (5%)). In pre-diagnosis period otitis occurred more frequently in ELANE (64/316 episodes) vsnon ELANE (36/276) (p= 0,02). Sepsis were also more frequent, though non significantly in ELANE subset. On the contrary, urinary tract infections were more frequent in non-ELANE (27/35) vs ELANE (8/40) group ( p<0,001). The post-diagnosis frequency of infections by age (0-5yrs, 6-10yrs and 10-15 yrs) in the whole group is shown in fig 1. Apart from skin infections that increase in peri/pubertal period (11-15 years) we observed a progressive decrease of the number of all other infections with full disappearance of sepsis after the age of 5 years. No main differences was observed between ELANE and non- ELANE group. Eighty-six % of patients were on G-CSF; 27% required doses>7,5 mcg/kg/day (12 ELANE and 1 HAX1), 22% needed 5 mcg/kg/day (8 ELANE, 1 USB1, 1 HAX1) and 51% (11 ELANE, 4 SCL37A, 7 TAZ, 1 JAGN1, 2 G6PC3, 1 CSFR3) required lower than 5 mcg/kg/day. Doses higher than 5 mcg/kg/day were more frequently used in ELANE vs non-ELANE group ( p=0.01). Fourteen patients underwent bone marrow transplantation (12 ELANE, 1 SCN gene orphan, 1 HAX1 and 1 JAGN1) for leukemic transformation (3 patients), poor response to G-CSF (7) and center decision (4). The 10-year OS of transplanted subjects was 87.5% and was comparable with that of non-transplanted ones (93%) (p=0.21) CONCLUSIONS. A genetic diagnosis was achieved in almost all SCN patents of the INR. ELANE mutations are the major cause of SCN and are associated to a more severe phenotype requiring higher doses of G-CSF and more frequent need for transplant. The relatively low incidence of MDS/AL in the whole cohort is consistent with a high proportion (73%) of patients receiving G-CSF dose ≤ 5 mcg/kg/day. Infection pattern improves overtime after diagnosis with disappearance of sepsis in both ELANE and non-ELANE subsets possibly reflecting the tight monitoring received by patients reported to registries. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Demographic Disparities Related to Fertility Preservation Counseling in Patients Undergoing Bone Marrow Transplantation

Infertility is a well-documented adverse effect associated with certain chemotherapeutic agents and radiation therapy.1 High-dose chemotherapy and/or total body irradiation (TBI) are utilized in preparation for bone marrow transplant (BMT), with the intent of achieving complete myeloablation prior to transplant.2 BMT is commonly used as a curative treatment modality for both malignant and benign hematologic conditions. Given this necessary exposure to high-dose chemotherapy and TBI, both male and female patients undergoing BMT are therefore at extremely high risk of impaired fertility later in life. Discussions concerning fertility preservation are often psychologically challenging for patients preparing to undergo BMT. To address these concerns, many institutions have developed fertility preservation counseling programs that aim to provide patients and caregivers with the necessary information to make informed decisions regarding fertility preservation. As is the case with many resources in healthcare, certain populations have more access to these resources than others. The goal of this study was to gain insight into if demographic features such as age, race, socioeconomic status, and underlying diagnosis/indication for BMT impacted the likelihood that a patient received fertility preservation counseling prior to transplant. It was hypothesized that there would be statistically significant differences in the rates of fertility preservation counseling when patients are compared by age, gender, race, socioeconomic status, and underlying diagnosis. A pre-existing database of BMT patients treated at the University of Rochester Medical Center was used to generate a study population of 244 patients between the ages of 0-39 years old who underwent BMT between 2012-2020. Demographic features including age, gender, race, insurance type, zip code, and indication for transplant were extracted from the database. A retrospective chart review was then conducted to identify if patients had a visit with a reproductive endocrinology and infertility (REI) specialist or if any documented fertility preservation counseling occurred prior to transplant. Odds ratios were then calculated for each of the aforementioned independent demographic variables. The overall prevalence of documented fertility preservation counseling was low. Approximately 20% of patients had a documented REI visit, while 47% had any form of documented fertility preservation counseling. There were differences in the prevalence of fertility preservation counseling related to patient age at transplant and median county income. Adult patients (age >18) were more likely than pediatric patients (age <18) to have a documented visit with an REI specialist (OR 2.99, 95% CI 1.37-6.51, p=0.0059) and more likely to have any documented fertility preservation counseling (OR 3.49, 95% CI 1.97-6.16, p<0.0001). Patients living in counties where the median income was >$60,000/year were more likely than patients living in counties with a median income of <$60,000/year to have a visit with an REI specialist (OR 4.25, 95% CI 1.89-9.54, p=0.0005) or any documented fertility preservation counseling (OR 2.72, 95% CI 1.59-4.64, p=0.0002). There were no statistically significant disparities in the prevalence of fertility preservation counseling based on patient gender, race, insurance type, or indication for transplant. These findings demonstrates that there are statistically significant differences in the prevalence of documented fertility preservation counseling based on demographic features, specifically on the basis of age and socioeconomic status. It is unclear if these findings represent the true prevalence of fertility preservation counseling, as some counseling is likely not adequately documented in the electronic medical record. Future studies are needed to design and implement improved fertility preservation counseling mechanisms, and to ensure adequate documentation of this counseling. Footnotes: 1. Rodriguez-Wallberg KA. Principles of cancer treatment: impact on reproduction. Adv Exp Med Biol. 2012;732:1-8. doi:10.1007/978-94-007-2492-1_1 2. Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014;124(3):344-353. doi:10.1182/blood-2014-02-514778

ABCL-265 Hematologic Malignancies in Pediatrics Inborn Errors of Immunity

Inherited errors of immunity (IEI) or primary immunodeficiencies are a group of genetic rare diseases predisposing to severe infections, autoimmunity, and malignancies. The overall risk for malignancies in pediatric IEI-patients is estimated to range from 4-25%, of which 60% of cases are of hematological origin. Evaluation of hematological malignancies in pediatrics IEI. Were included 13 patients 3 of which developed hematological malignancies and were evaluated for demographics, clinical features, and prognosis. The prevalence of hematological malignancies among our patients was 23% (3/13). The male-to-female ratio was 2:1. The mean age at diagnosis of malignancy was 8.6 years (range 5-14). Non-Hodgkin lymphoma was the malignancy type diagnosed in all the pediatric patients (n=3, of which Wiskott-Aldrich-1, ataxia-telangiectasia-1, common variable immunodeficiency (CVID)-1. However, 2 patients (52.5%) died (1-during first line-chemotherapy, 1-NHL was established postmortem). 1 patient underwent bone marrow transplantation and is currently under supervision. In this study, we related an association between hematological malignancies and IEI. Lymphoid malignancies were the most common malignancy, this warns of the need for multidisciplinary monitoring of these patients.

An Overview of the Problems and Changes in Guidelines with a View to the Future of Bone Marrow Transplantation during an Outbreak of COVID-19

Background: Patients undergoing bone marrow transplantation (BMT) are high-risk during the Coronavirus disease 2019 (COVID-19) outbreak. Viral infections are a common complication in transplanted patients. Since BMT is a definitive line treatment for many hematological malignancies, the BMT unit should provide therapy services during the COVID-19 outbreak. According to studies over the past two years, following the COVID-19 prevention guidelines recommended by the World Health Organization (WHO) and European Group for Blood and Marrow Transplantation (EBMT) has made it possible to carry out this high-risk treatment. This review article presents the experiences and challenges of BMT centers during the outbreak of COVID-19.&#x0D; Methods: The present study is a review article based on searching in medical-scientific databases, including PubMed, Scopus, MEDLINE, and Google Scholar, from 2020 to 2021. All articles were evaluated, and 30 articles were selected as the primary sources of study.&#x0D; Conclusion: Regarding the stability and new strains emergence of coronavirus over the last two years, as well as the importance of BMT as the last-line treatment in some hematological malignancies, COVID-19 prevention is the first pivotal step for immunity of BMT donor and recipient. Training medical service personnel and patients will effectively prevent virus contagiousness and spread. Moreover, regular screening of medical staff can inhibit viral transmission to admitted patients. Stick to home quarantine in patients pre-and post-BMT restricts the risk of COVID-19 contamination.

Determinación de Streptococcus sp. y Candida albicans en la cavidad oral de pacientes sometidos a trasplante de médula ósea

Introduction: Chemotherapy can lead to an imbalance in the ecosystem of the oral cavity, allowing the development of mucositis in the immunosuppression phase due to interaction with microbial agents. The objective of this study was to identify bacterial and fungal species that contribute to oral complications in patients undergoing marrow trans-lantation and compare their susceptibility to various antimicrobial agents before and during the immunosuppression period. Material and Methods: This observational-longitudinal study was performed on 18 patients undergoing bone marrow transplantation from the Oncohematology Ser-vice of Sanatorio Allende (2018/2019), with buccal mucosa swabs before treatment (I) and mid-stage (M), fourteen days after transplantation. The samples were cultured in selective media for Streptococcus and fungal species and a susceptibility study was performed on Müller Hinton agar. Results: At (I), 82.30% of patients were found to be positive for Streptococcus mutans, 11.30% for Streptococcus salivarius, 5.50% for Streptococcus sobrinus and 9.40% grew mixed commensal microorganisms. At (M), 96.60% were positive for Streptococcus mutans and 23.10% for Streptococcus salivarius, without any growth of Streptococcus sobrinus or mixed microorganisms. In (I), a 27.00% incidence of Candida albicans was observed, while in (M) the incidence was 73.00%. The antibiotics to which the microorganisms were most sensitive in (I) were vancomycin (88.80%), amikacin (83.30%), amoxicillin + clavulanic acid (78.00%), ciprofloxacin (77.75%) and azithromycin (66.60%). In (M) sensitivity to amikacin was 92.30%, vancomycin, 76.90%; amoxicillin + clavulanic acid, 38.50%; azithromycin, 23.10%; and ciprofloxacin, 15.40%. A statistically significant prevalence of Streptococcus mutans was observed in comparison to other species. Conclusion: During the immunosuppression period, there was a significant increase in Candida albicans. The antibiotics to which the bacteria were most sensitive were amikacin and, to a lesser extent, vancomycin, showing significant resistance to ciprofloxacin, azithromycin and amoxicillin + clavulanic acid.

Impact of graft-versus-host disease prophylaxis on immune reconstitution in patients after allogeneic hematopoietic stem cell transplantation

The graft-versus-host disease (GVHD) is among the most common complications after hematopoietic stem cell transplantation (allo-HSCT). The main tools for GVHD prevention remain calcineurin inhibitors (cyclosporin A, tacrolimus), methotrexate, mycophenolate mofetil. Upon implementation of reduced-intensity conditioning regimens, antithymocyte globulin was widely introduced. However, negative effects upon reconstitution of T-cell immunity have been noted, thus increasing risk of severe infectious complications and disease relapse. With extended practice of HSCT from alternative (partially matched or haploidentical) donors, cyclophosphamide was increasingly used. Our aim was to study reconstitution of immune cell subpopulations in the patients undergoing bone marrow transplantation (BMT), when using different GVHD prophylaxis regimens, including the schedules with post-transplant CP usage. The study concerned 44 cases classified into 2 groups. The first one included patients with standard immunosuppressive therapy, antithymocyte therapy, cyclosporine A, methotrexate, mycophenolate mofetil. The second group included the patients who received CP as immunosuppressive drug combined with other treatments (cyclosporine A, methotrexate, mycophenolate mofetil). At specified control terms, (D+14, +30, +60, +90) the blood leukocyte subpopulations were assayed by means of multicolor flow cytometry. Absolute counts of CD4+ cells in HSCT recipients treated with CP post-BMT proved to be sufficiently lower at D+14 and +30, than in those treated with classical immunosuppressive therapy. However, at later terms, (D+60, +90), these differences were not observed. Moreover, in CP-treated bone marrow recipients, absolute numbers of CD8+cells was significantly higher, compared to the patients who received conventional GVHD prophylaxis. Reconstitution of the studied lymphocyte populations in hematopoietic cell recipients did not depend on the GVHD prophylaxis regimen. Usage of CP combined with bone marrow as a source of stem cells, brings about sufficient decrease of some cell populations (CD4+; CD8+; NK cells) at early terms post-transplant. Administration of CP combined with hematopoietic stem cells as the source of hematopoietic graft seems to be more reasonable.

Efficacy of Oral Cryotherapy in the Prevention of Oral Mucositis Associated with Cancer Chemotherapy: Systematic Review with Meta-Analysis and Trial Sequential Analysis.

Background: This review aimed to evaluate the efficacy of oral cryotherapy in the prevention of chemotherapy-induced oral mucositis using meta-analysis and trial sequential analysis, as well as to assess the quality of the results by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Methods: A comprehensive search of three databases including Medline, Embase and Central was performed to identify randomized controlled trials that used oral cryotherapy for the prevention of chemotherapy-induced oral mucositis. The primary outcome was the incidence of oral mucositis for trials employing oral cryotherapy as the intervention for the prevention of oral mucositis. The meta-analysis was performed using the random-effects model and random errors of the meta-analyses were detected by trial sequential analysis. Results: A total of 14 RCTs with 1577 participants were included in the present meta-analysis. Patients treated with oral cryotherapy were associated with a significantly lower risk of developing oral mucositis of any grade (risk ratio (RR), 0.67 (95% CI: 0.56–0.81, p < 0.05)). Findings from the subgroup analyses showed that oral cryotherapy significantly reduced the risk of oral mucositis in patients undergoing bone marrow transplantation (RR 0.69, CI: 0.54–0.89, p < 0.05) as well as chemotherapy (RR 0.66, CI: 0.58–0.75, p < 0.05). Findings from the trial sequential analysis suggested that the evidence on oral cryotherapy as a preventive intervention for oral mucositis in patients with solid malignancies receiving conventional chemotherapy was conclusive. Conclusion: Oral cryotherapy is effective in preventing oral mucositis in patients undergoing chemotherapy for the management of solid malignancies. The use of oral cryotherapy in preventing oral mucositis in bone marrow transplantation settings showed promising efficacy, but the evidence is not conclusive and requires more high-quality randomized controlled trials.

Validity and reliability of the Turkish version of the functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) quality of life questionnaire in patients undergoing bone marrow transplantation.

The Functional Assessment of Cancer Therapy-Bone Marrow Transplant Version 4 (FACT-BMT) is a widely used instrument to assess quality of life in individuals treated with bone marrow transplantation (BMT). Our aim was to determine the reliability and validity of the Turkish version of the FACT-BMT in patients undergoing BMT. Patients between the age of 20 and 65 years and who had undergone BMT at least 3 months before the study were included. Validity was determined using exploratory and confirmatory factor analysis. To determine convergent validity, the European Cancer Research and Treatment Organization Quality of Life Questionnaire-Cancer30 (EORTC QLQ-C30), the Brief Fatigue Inventory (BFI), and the Eastern Cooperative Oncology Group (ECOG) performance score were used. Cronbach's alpha, intra-class correlation coefficient (ICC), and item-total correlation (ITC) values were calculated to assess the reliability of the FACT-BMT. Totally, 114 patients (F/M: 47/67) treated with BMT (mean age: 49.50 ± 12.50 years) were included. Confirmatory and exploratory factor analysis revealed that the FACT-BMT and the Bone Marrow Transplantation Subscale (BMTS) had sufficient fit. The FACT-BMT was moderately to strongly correlated with the EORTC QLQ-C30, the BFI, and the ECOG performance score (p < 0.001). Cronbach's alpha and ICC values of the FACT-BMT were acceptable (0.925 and 0.956, respectively). The ITC values of each item of the FACT-BMT were also acceptable (ranged from 0.296 to 0.737). Patients undergoing autologous BMT had a significantly higher BMTS score than those undergoing allogeneic BMT (p < 0.05). The Turkish version of the FACT-BMT is valid, reliable, and sensitive to changes in quality of life in patients undergoing BMT.

Dose individualization of intravenous busulfan in pediatric patients undergoing bone marrow transplantation: impact and in vitro evaluation of infusion lag-time.

To apply therapeutic drug monitoring and dose-individualization of intravenous Busulfan to paediatric patients and evaluate the impact of syringe-pump induced Busulfan infusion lag-time after in vitro estimation. 76 children and adolescents were administered 2 h intravenous Busulfan infusion every 6 h (16 doses). Busulfan plasma levels, withdrawn by an optimized sampling scheme and measured by a validated HPLC-PDA method, were used to estimate basic PK parameters, AUC, Cmax, kel, t1/2, applying Non-Compartmental Analysis. In vivo infusion lag-time was simulated in vitro and used to evaluate its impact on AUC estimation. Mean (%CV) Busulfan AUC, Cmax, clearance and t1/2 for pediatric population were found 962.3 μm × min (33.1), 0.95 mg/L (41.4), 0.27 L/h/kg (33.3), 2.2 h (27.8), respectively. TDM applied to 76 children revealed 6 (7.9%) being above and 25 (32.9%) below therapeutic-range (AUC: 900-1350 μm × min). After dose correction, all patients were measured below toxic levels (AUC < 1500 μm × min), no patient below 900 μm × min. Incorporation of infusion lag-time revealed lower AUCs with 17.1% more patients and 23.1% more younger patients, with body weight <16 kg, being below the therapeutic-range. TDM, applied successfully to 76 children, confirmed the need for Busulfan dose-individualization in paediatric patients. Infusion lag-time was proved clinically significant for younger, low body-weight patients and those close to the lower therapeutic-range limit.

Isolated Myeloperoxidase Expression in Pediatric B/Myeloid Mixed Phenotype Acute Leukemia Is Associated with Improved Survival Using ALL-Only Regimens

Background: Mixed phenotype acute leukemia (MPAL) represents a heterogeneous group of leukemias accounting for 2-5% of all newly diagnosed acute leukemias. Diagnostic criteria for mixed phenotype MPAL have evolved over time, with the World Health Organization (WHO) 2016 criteria now being recognized as the more definitive standard. According to WHO classification, isolated expression of myeloperoxidase (MPO) allows for myeloid lineage assignment in patients with an otherwise typical B-acute lymphoblastic leukemia (B-ALL) phenotype, thus meeting criteria for MPAL B/myeloid. Our goal was to determine if there were differences in treatment and survival between this group of patients, classified as MPAL B/myeloid isoMPO, and other MPAL patients.Methods: Data was obtained through a retrospective chart review of pediatric MPAL patients treated between 2001 and 2016 at Children's Healthcare of Atlanta. Cases were identified through our institutional tumor registry and pathology department flow cytometry database. Cases were eligible if the patients were between ages of 1 and 21 years at diagnosis and the leukemia met the WHO 2016 MPAL criteria. We excluded therapy related cases, non-myeloid cases (rare B/T subtype), and cases with a t(9;22) translocation. Data were extracted from clinical records for patient, disease and treatment related variables. All flow cytometry reports were reviewed by study hematopathologists. Cases were divided into two groups - MPAL B/Myeloid isoMPO and other MPAL cases. MPAL B/myeloid cases were classified as MPAL B/Myeloid isoMPO if there was a single B-lineage blast population expressing MPO as the only WHO MPAL myeloid marker. An event was defined as treatment failure requiring therapy change prior to end of induction (EOI), induction failure, induction death, remission death, or relapse. Event-free survival (EFS) and overall survival (OS) were calculated using Kaplan-Meier survival curves. Groups were compared using the log rank test. Chi-squared test was used for sampling distribution analyses.Results: Of the 35 MPAL cases included in our study, 21 (60%) met criteria for MPAL B/myeloid isoMPO. 20 of these patients were treated with ALL chemotherapy alone. One patient underwent bone marrow transplantation (BMT) due to a low DNA index. None of these patients were switched to myeloid therapy during their treatment course. The other 14 MPAL cases consisted of 5 MPAL B/myeloid (non-isolated MPO), 7 MPAL T/myeloid and 2 MPAL patients with t(v;11q23); MLL rearranged. Of these 14 cases, 10 were treated at least in part with myeloid chemotherapy and 7 proceeded to BMT. 6 of 10 patients in this group who started with ALL induction were switched over to AML therapy, with 3 being changed prior to EOI due to treatment failure. Despite these treatment differences, those with MPAL B/myeloid isoMPO had better outcomes. 3-year EFS was significantly higher at 84% for the MPAL B/myeloid isoMPO group compared to 57% in the other MPAL group (p=0.027 log rank test, Fig 1A). 3-year overall survival was 100% and 68%, respectively (p=0.083 log rank test, Fig 1B).Conclusion: There continues to be no consensus as to how to treat MPAL and the changing definition of MPAL has contributed to the difficulty in treating this rare and heterogeneous disease. While the WHO 2016 criteria have simplified the definition of MPAL, it has created a group of patients as shown here, that may be falsely categorized as MPAL. Our results suggest that MPAL B/myeloid isoMPO patients behave clinically like typical B-ALL patients, and should be treated as such. Consideration should be given to redefining the current MPAL WHO criteria to explicitly exclude these cases. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.