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Background/Objectives: To date, not many studies have been conducted to examine the role of COVID-19 on gestation and fetal development. During COVID-19, pregnant women had difficulty accessing prenatal screening and care due to pandemics restrictions and lockdowns. In this retrospective study we aimed to assess the effect of the SARS-CoV-2 outbreak on fetal development in both prenatal and postnatal outcomes pre-and pre-COVID-19 pandemics in Northern Cyprus. Method(s): A total number of 61 aborted materials were karyotyped during the pre-pandemic period (January 2017 and March 2020) whereas 24 samples were analysed during the peripandemic period (March 2020-November 2021). On the other hand, 25 new-borns blood samples during the pre-pandemic and 44 samples during the pre-pandemic period were analysed. Result(s): No statistically significant difference found in health and abnormal aborted material karyotypes between two periods. On the other hand, a statistical significance was observed in postnatal chromosomal abnormalities (P = 0.04) after two long pandemic lockdowns, which are known as the first and the second waves, dramatically indicating that no baby with Down syndrome was between 2017-2020 whereas seven babies with Down Syndrome were born as consequences of without taking precaution against lockdowns. Conclusion(s): Overall, prenatal care is failed which resulting increased postnatal chromosomal abnormality due to heavy flight restrictions, economic inflation instability, limited access to medical services during COVID-19 pandemic lockdowns in Northern Cyprus.
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Purpose of Study: The regional NICU is an essential healthcare resource for families of newborns with serious life-threatening illnesses. Mechanical ventilation, cardiovascular therapies, therapeutic hypothermia, and neonatal surgeries are common life-sustaining interventions. Our NICU serves an underprivileged population in a resource poor environment and several ethical questions frequently emerge when facing extremes of innovative therapies. The pandemic and rapidly changing institutional protocols accentuated challenges faced by frontline NICU teams caring for newborns at risk for devastating illnesses and death. Concurrently, evolving paradigms in neonatal ethics required urgent and high quality palliative care in a background of racial and socioeconomic inequities, restrictive visitation policies, and limited healthcare resources. The purpose of this study was to ensure that neonates and their families receive ethically sound care, timely referrals for innovative therapies, and specialized palliative care in the strained and uncertain environment of the COVID-19 pandemic. Methods Used: The key steps consisted of structured and impromptu discussion forums for specialized palliative care and medical ethics, perinatal case conferences and pediatrics grand rounds on virtual platforms, educational webinars for interdisciplinary teams, and improved electronic communication. Online collaboration and innovative combinations of in-person and virtual meetings were utilized for urgently Incorporating clinical updates. Summary of Results: 1. A neonate with severe HIE and postnatally diagnosed congenital diaphragmatic hernia required emergent ECMO center referral. NICU providers utilized a structured bioethics and palliative care framework for providing family support and discussing the prognostication challenges of acute illnesses. 2. Many important bioethical questions emerged while caring for infants with life-threatening chromosomal abnormalities. Ethical tension was addressed by teaching tools, quality of life and pediatrics ethics conversations, mitigation of moral distress, contemporary clinical and surgical experience, community engagement, and family perspectives. 3. Ethical conflicts are central in the decision to resuscitate neonates born between 22 and 23 weeks of gestation. To provide urgent prenatal consultations and attend high risk deliveries, we collaborated across geographically distant healthcare systems, unified management strategies and analyzed outcomes data. 4. NEC in several extremely preterm babies had devastating outcomes and the team respected each family's voice with compassionate, shared decision-making for both curative care surgeries and palliative care. Conclusion(s): The new workflows, telephone and video conferences, and redirection to telehealth based family meetings did not change important outcomes during the pandemic. Advocacy and education for integrating bioethics and palliative care were vital facets of neonatal critical care in a resource poor and ever-changing pandemic environment.
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The article provides an overview of the most significant publications on the topic of male infertility. The main selection criteria were considered the practical significance of the article, as well as the impact factor of the journal in which it was published according to the SCImago Journal Rank (SJR). As a result, we formed a list of 10 articles published in the III quarter (July - September) of 2021. The review included articles concerning the following issues: the ability of oocytes to repair damaged DNA-chains of sperm cells, the effectiveness of ICSI in AZF-c microdeletions, the advanced paternal age, artificial intelligence in reproductive clinics, genetic causes of infertility, the effect of surgical treatment of varicocele concerning DNA fragmentation, the role of ICSI in the frequency of chromosomal abnormalities in offspring, the safety of COVID-19 vaccination for spermatogenesis, as well as the novel WHO 6 manual for semen investigation.Copyright © 2021 Vestnik Urologii. All rights reserved.
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Background: Data are limited regarding the safety of and antibody response to the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid vaccine in adolescents and young adults with underlying disease. Methods: This prospective observational study enrolled patients age 12–25 years with chronic underlying disease who received 2 doses of BNT162b2. A 18-item questionnaire was used to assess adverse events within 7 days post-vaccination, and data regarding severe adverse events were collected from electronic medical records. An antibody titer for the receptor-binding domain of the spike protein in SARS-CoV-2 was used to assess antibody response after the second vaccine dose. Results: Study participants were 429 patients (241 [56.2%] age 12–15 years;188 [43.8%] age 16–25 years). The most common underlying diseases were genetic or chromosomal abnormalities and/or congenital anomalies, followed by endocrine or metabolic diseases;32% of participants were immunocompromised. Severe adverse events were observed after the second dose in 1 (0.4%) patient age 12–15 years and in 2 (1.1%) patients age 16–25 years;all patients recovered. Seropositivity after the second vaccine dose was 99.0%. The geometric mean antibody titer was higher in patients age 12–15 years versus 16–25 years (1603.3 [1321.8–1944.7] U/mL vs. 949.4 [744.2–1211.0] U/mL). Compared with immunocompetent patients, immunocompromised patients had a lower antibody titer (2106.8 [1917.5–2314.7] U/mL vs. 467.9 [324.4–674.8] U/mL). Conclusions: Vaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
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Case Report: Initial History/Presentation: A term vaccinated 7-month-old male with a history of eczema presents with two hours of right-sided hemiplegia and hemidystonia. Parents deny loss of consciousness, altered mental status, or facial symptoms. He has no known history of recent or remote head trauma. Patient may have had COVID two months prior when he had upper respiratory symptoms, with his mother testing COVID+ at that time. Of note, he received a Moderna COVID vaccination one day prior to onset of symptoms. Physical Exam: Pertinent exam findings include CN II-XII intact, right-sided upper and lower extremity strength 3/5, sensation intact, and truncal ataxia while seated. Physical exam is otherwise unremarkable. Diagnostic Evaluation: Initial lab work revealed leukocytosis (20.9), but otherwise a reassuring CMP, triglycerides, HDL, and LDL. PTT was elevated, but normal on recheck. Protein C antigen and activity were low, but deemed non-concerning by hematology. All other hypercoagulable labs were normal. On imaging, CT Brain showed linear calcifications in bilateral basal ganglia suggestive of mineralizing angiopathy. HisCTA head/neckwas negative.MRI Brain revealed an acute infarct of the body/tail of the left caudate nucleus, posterior limb of internal capsule, and posterior putamen. Clinical Course/Follow-up: Our patient was started on Aspirin 4 mg/kg daily. Throughout the course of his 3-day inpatient stay, he had mild improvement of right-sided strength and function, and continued improvement upon follow-up with his pediatrician. Given the short interval between receiving his COVID vaccination and onset of symptoms, his case was reported to the Vaccine Adverse Event Reporting System. Conclusion(s): From a radiological perspective, mineralizing angiopathy is an uncommon but familiar finding seen in up to 5% of all neonatal head ultrasounds and increasing to nearly 20% in preterm infants. It is most commonly associated with infection, hypoxia, and chromosomal abnormalities but is usually of minimal clinical significance. However, there are numerous reports of basal ganglia and thalamic strokes following minor head trauma in children with mineralizing angiopathy. For radiologists, this association is important to recognize and relay to the primary team so targeted history and MRI, if indicated, may be obtained to expedite definitive diagnosis and initiation of treatment to preserve precious brain tissue. Without a history of head trauma, in this case, stroke provocation is unclear, and other infectious or inflammatory disorders could appear similarly if they induced vasospasm or blood pressure lability. A short-interval timeframe between COVID vaccine administration and symptom onset is likely incidental, but research to exclude or illicit any link may be of benefit. Findings of mineralizing angiopathy on CT in the appropriate clinical setting should prompt further evaluation with emergent MRI to determine the presence of basal ganglia or thalamic stroke. Copyright © 2023 Southern Society for Clinical Investigation.
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Background: The four-drug combo has becoming one of the main induction treatment for TE NDMM patients (pts). We conducted a phase 2 study to assess the safety and preliminary efficacy of Cyclophosphamide (C), thalidomide (T), dexamethasone (d)-(CTd) and Dara combination. MAXDARA study has shown in the primary analysis with 21 included patients (pts), 4 and 8 pts MRD negativity after four induction cycles and two consolidation cycles post transplant, respectively. (Crusoe E et al ASH 2020, 2416 poster presentation). In the present analysis we evaluate the effect of deep response rate on PFS. Method(s): This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the ECOG performance status = 0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. The MRD was evaluated by next-generation flow (NGF) 10-6 and PET-CT was performed when the patient obtained NGF negativity or finished consolidation. PFS outcome was estimated using Kaplan-Meier method and PFS analysis were performed based on the different response rates. (Data cut-off was April 2022) Results: A total of 24 pts were included. The median age being 58 (range 37- 67 years), 15 (62.5%) pts were female, 22 (92%) were non-white, 6 (25%) had an R-ISS = 1, 12 (50%) had an R-ISS = 2 and 4 (16%), an R-ISS = 3. Sixteen (66.7%) pts were IgG isotype and Six (25%) had high-risk chromosomal abnormalities [1q+, del17p, t(4;14) or t(14;16)]. To date, 23 pts have completed induction, 21 performed transplant and 14 are still in treatment after one year of dara maintenance. By ITT analysis, 22 pts (91.6%) achieved (> PR) after 4 induction cycles. One pts achieved SD, one MR and one sCR. Eleven (39%) pts achieved PR, and 10 (35.7%) VGPR. After two consolidation cycles, ORR was 68%, 8 (28.6%) and 11 (39.3%) pts obtained sCR and VGPR, respectively. The best response during any time of the treatment were PR in 3 (12.5%) pts, VGPR in 12 pts (50%) and sCR in 8 (33.3%) pts. In a ITT analysis, NGF MRD 10-6 negativity were observed in 4(16.6%) after four induction cycles, and in 17 (70.8%) pts after two consolidation cycles post-ASCT. In a ITT analysis, after a median follow up (FU) of 26 months, the PFS was 37months for the entire group. The median PFS comparing sCR vs < VGPR were 37m vs 27m (p = 0.021), respectively, and comparing MRD negative by NGF vs no, had impacted even more on PFS with a median of 37m vs 16m (p = 0.004), respectively. The OS was not yet achieved and 83% of the patients still alive after a median FU of 27m. Four pts died from infection, two of them related with covid infection (one before transplant and one during maintenance). Another case post-transplant, considered not related to the investigational agent and one after consolidation, related to the investigational agent. Summary/Conclusion: The Daratumumab - CTd protocol is an active and safe regimen capable of producing deep and sustainable responses. The deeper response rate impacted on PFS, confirm that MRD negativity is critical to patient outcome. Copyright © 2022
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Objective: About 70% of cases of Acute Lymphoblastic Leukemia (ALL) affect children aged 1- 4 years. The incidence increases slightly again in adults over 50 years, characterizing a poor prognosis. According to data from the National Cancer Institute, for the year 2020 leukemias present in men as the fifth most frequent neoplasm in the Northeast Region with a risk of 8.20/100,000 inhabitants, occupying the fifth position. In the case of women, the risk in the Northeast region is 4.42/100,000 inhabitants and ranks tenth. This study aimed to identify the molecular and epidemiological profile of adult patients with ALL in the state of Ceara. Methodology: Sample collection was performed in patients with ALL treated at the General Hospital of Fortaleza (GHF), considered the main and largest hematology outpatient clinic in the metropolitan region of Fortaleza, as well as the State of Ceara. All patients participating in this study read and signed the informed consent form. Patients with other types of leukemias or other hematological diseases were excluded. This study was approved by the Research Ethics Committee of the Federal University of Ceara under protocol no. 38680520.9.0000.5054. Result(s): From July 2021 to July 2022, 25 patients with ALL were treated, of whom 9 are women and 16 are men. The mean age observed was 42.5 years. 44% of patients live in the capital (Fortaleza), while the other 56% of patients live in rural areas. Through immunophenotyping it was possible to verify that there were 22 patients (88%) compatible with ALL-B presenting CD19, CD10, CD45, CD38, CD22, CD79a, CD34, CD81 and CD58 as the main markers, while only 3 patients (12%) were compatible with ALL-T, expressing mainly CD3, CD45, CD5, CD7, CD2, CD11c and CD1a. Eleven patients (44%) had abnormal and complex karyotypes. Five patients had the BCR-ABL p190 mutation and two had the E2A-PBX1 mutation. A total of 9 patients died due to septic shock, COVID-19, or refractoriness to treatment. Discussion(s): The literature indicates a new peak of ALL cases after 50 years of age, however the highest incidence observed in the study participants was between 30 and 50 years. Studies indicate that immunophenotyping findings in patients with ALL B line are almost always CD19, CD79a, CD10, CD20 and CD22 positive, while T-strain ALL usually present CD7, CD3, CD1a and CD10 as the main markers, corroborating what was observed in the results. In addition, depending on the alteration observed in the karyotype, it may confer poor or good prognosis to the patient. The BCR-ABL1 and E2A-PBX1 mergers, for example, are alterations that give worse prognosis to patients and, therefore, may be targeted for treatment in an attempt to improve the survival of these patients. TEL-AML1 fusion, on the other hand, represents a good prognosis, being more incident in pediatric ALL. Conclusion(s): Epidemiological data from this preliminary study indicate that in the state of Ceara ALL is more common in male patients aged 30-50 years living in rural regions. In addition, the use of targeted therapies for patients with abnormal karyotypes as well as the adoption of stricter measures to prevent hospital infections may increase patient survival. Copyright © 2022
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Objective: Acute myeloid leukemia (AML) is the second most common leukemia in adults and older patients represent most cases. The states of the Northeast of the country have stood out in the frequency of leukemia cases, and the frequencies are higher than the rate of 35% compared to other neoplasms, especially in the metropolitan regions of Fortaleza. In the State of Ceara, the number of cases of leukemia expected for the year 2020 is 6.17 cases/100,000 inhabitants in men and 4.29 cases/100,000 inhabitants in women. In view of this information, the aim of this study was to identify the molecular and epidemiological profile of patients with AML in the state of Ceara. Methodology: Sample collection was performed in patients with AML treated at the General Hospital of Fortaleza, considered the main and largest hematology outpatient clinic in the metropolitan region of Fortaleza, as well as the State of Ceara. All patients participating in this study read and signed the informed consent form. Patients with other types of leukemias or other hematological diseases were excluded. This study was approved by the Research Ethics Committee of the Federal University of Ceara under protocol no. 38680520.9.0000.5054. Result(s): From July 2021 to July 2022, 31 patients with AML were treated, of which 8 are women and 23 are men. The mean age observed was 50.4 years. 54.8% of patients live in the capital, while the other 45.2% of patients live in rural areas. Through immunophenotyping it was possible to verify that the main markers presented by LMA patients were CD33, CD13, CD117, CD45, MPO, CD34, CD64, HLA-DR, CD11c, CD11b e CD38. Thirteen patients (42%) had abnormal and complex karyotypes, of which six died. Five patients (16,1%) had the t(15;17)(q24;q21.3) corresponding to the PML-RARA fusion. Six patients (19,3%) had the FLT3 mutation that confers a poorer prognosis. During the clinical follow up, a total of 16 patients died due to septic shock, COVID-19, or refractoriness to treatment. Discussion(s): The incidence of cases of adults over 50 years of age with AML was 58%, as it corroborates the expected incidence of cases regarding the age described in the literature. Studies indicate that immunophenotyping is critical to the differential diagnosis among AML subtypes. AML is defined by the mainly expression of the markers MPO, CD117, CD13, CD33, HLA-DR and CD38, corroborating what was observed in the results. In addition, depending on the alteration observed in the karyotype, it may confer poor or good prognosis to the patient. The PML-RARA merger, for example, is known as M3 AML or acute promyelocytic leukemia (APL), a subtype of AML with a better prognosis for patients. The FLT3 mutation is present in 1 in 3 patients with AML. The presence of this altered gene may mean a worse prognosis and a greater possibility of recurrence but allows a specific and differentiated treatment. Conclusion(s): Epidemiological data from this preliminary study indicate that in the state of Ceara AML is more common in male patients aged 50-80 years. In addition, the use of targeted therapies for patients with abnormal karyotypes as well as the adoption of stricter measures to prevent hospital infections may increase patient survival. Copyright © 2022
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The proceedings contain 329 papers. The topics discussed include: Incidence of methamphetamine use in homicide victims - a retrospective study;the investigation of traumatic brain injury death during COVID-19 pandemic lockdown in Ulaanbaatar, Mongolia;what is the place of YouTube in general pathology learning?;clinical application of pathology in a blended online and in-person curriculum;can knowledge about how to learn pathology effectively influence student academic practice;the impact of the COVID-19 pandemic on fine-needle aspiration practice for cytopathology education;teaching and learning of pathology at undergraduate level: How does it impact postgraduate medical education in various specialities;spectrum of chromosomal abnormalities in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL);programmed death-ligand 1 expression in diffuse large B-cell lymphoma is associated with poor prognosis;clinicopathological study of plasma cell myeloma in Oman with special reference to its cytogenetic features;and an unusual case of extranodal Rosai-Dorfman disease presenting as a spinal cord compression.
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Background: Arterial thrombotic events (ATE) are important cause of noncancer-related deaths among patients with cancer. It is estimated that the prevalence of ATE among those patients is between 2-5%. However, data regarding acute myeloid leukemia (AML) related ATE are scarce and far less available than those related to venous thrombotic events. Aims: To determine the incidence of ATE in nonM3-AML patients and to underline the potential risk factors for ATE development. Methods: The single center, retrospective, cohort study was carried out in University Clinical Center of Serbia. Adult patients, who were diagnosed with nonM3-AML between January 2009. and December 2021. were included. In all patients the occurrence of ATE (e.g. a heart attack, a stroke, critical limb ischemia) was assessed during the active treatment and the three months following the last chemotherapy session. Diagnosis of ATE was established using clinical, laboratory and radiological methods. Patients who experienced venous thromboembolism during the treatment period were excluded. Demographic data, presence of obesity, smoking status, history of thrombosis, baseline laboratory findings (complete blood count, fibrinogen, D-dimer, PT, aPTT, LDH), leukemia-related parameters (cytogenetics (including ELN risk stratification), flow cytometry), Khorana score, ECOG PS, HCT CI score, concurrent COVID-19 were collected from patients' health records. The methods of descriptive (mean ± standard deviation, median (range), frequency (%)) and analytic statistics (Student's t-test, chi-squared test) were used. Results: A total of 545 patients (293 males (53.8%)) were included in the study. Median age of the study population was 58 (range: 18-81) years. ATE was noted in 18/545 (3.3%) subjects with following distribution: ischemic stroke 12/18 (66.7%), myocardial infarction 5/18 (27.8%), and acute lower extremity arterial thrombosis 1/18 (5.5%). ATE was diagnosed most commonly during the induction (8 (44.4%) patients), reinduction (3 (16.7%) patients) and consolidation (4 (22.2%) patients) cycles. However, cases of ATE were noted at diagnosis (1 (5.6%) patient), after transplantation (1 (5.6%) patient) or at relapse (1 (5.6%) patient) as well. ATE were significantly more frequent among patients with previous history of thromboembolic events (p = 0.016). Moreover, ATE were more common in patients with adverse cytogenetic abnormalities (p < 0.001). Other examined parameters did not significantly differ between those with and without ATE. Summary/Conclusion: The incidence of arterial thrombosis in our group was 3.3% which is in accordance with the previously published studies. Since the great number of already known risk factors for the arterial thrombosis are modifiable (e.g. smoking, diet, physical activity, excessive drinking?) it is important to actively work on the reduction on those risk factors, especially if the patient has the history of previous thromboembolic event and/or suffer from high risk AML. Prophylactic therapy with antiplatelet agents is aggravated due to the lack of firmer evidences and the presence of thrombocytopenia. Therefore further studies regarding this issue are needed.
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Background: Despite therapeutic strategies improvement, there is still a subgroup of NDMM patients (pts) that pose a clinical challenge, whose represents a <20%, we refer to HRC. HRC Pts are associated with a poor prognosis and aggressive course, although, recent studies propose different clinical evolution according to the cytogenetic alteration (CA). IMWG identified a 4-year progression free survival (PFS) of 12% and OS of 35%. Aims: Describe our clinical experience and therapeutic management, also the clinical-biochemical alterations at diagnosis in a heterogeneous NDMM HRC's cohort. Evaluate survival curves according to HRC. Methods: Descriptive and retrospective analysis, using clinical and analytical NDMM HRC patient's data from 2009 to 2022 at Guadalajara University Hospital. 61/201 pts were selected in the MM treatment (tto) protocols. FISH results were not found in <30% NDMM, due to lack of metaphases or no request. Pts with t(4;14), t(14;16), gain 1q, t(14;20), plasmablastic leukemia and/or del(17p13) were classified as HRC. Survival data and Pearson (P) correlation were used. P value <0.05 was considered significant. Results: Total HRC NDMM 61 pts were analyzed. 21 of 61 pts (35%) were diagnosed with stage monoclonal gammopathy of undetermined significance (MGUS) prior to HRC NDMM, with a mean 4 years (y) (IR 2-10 y), greater % representation of MGUS were del17p (38), gain 1q (48), t (14;16) (4,5) and del17p + gain1q (9,5). Clinical characteristics data at diagnosis according to HRC are shown in Table 1. Pts receiving 1st line were 100% (61), 90,2% of the pts received bortezomib (V) - based induction, of them 29% (n=16) were treated with alkylating agents, 49,1% (n=27) received IMIDs and 18,2% (n=10) V with dexamethasone (d), plus two of these pts received regimens composed of 3xVCd + 3xVPd and the other dara-VRd. 25 pts (40,98%) were transplant eligible (TPH). 2nd line, 32 pts (52,5%), (n=3) VTD-PACE, (n=6) daratumumab (n=1 alone, 3 R, 1 V, 1 K), (n=1) Kdexa, (n=1) Pocydex and (n=9) V plus 3 IMIDs, 2 alkylating, 2 P or 2 alone and (n=12) IMIDs and alkylatings in combination. 5 pts (8,2) were TPH (1 alogenic). 3rd line, 16 pts (26,2), just 3 pts were TPH. 4th line, 7 pts (11,4), 1 pts were TPH. 5th line, 4 pts (6,5). 6th line, 2pts (3,3). In the last lines, the use of triplets with pomalidomide, karfilzomib or intensive chemotherapy prevail. After a median follow-up of 3 y (IR 1,6-6,2) from diagnosis, pts had relapsed at least one time (60,6%) and more than 3 times (11,5%), and 25 had died (40,9%), 16 of them due to infections (14 bacteremia, 2 COVID), 5 cardiorespiratory arrest and 3 due to progression. (Image 1) represents PFS y OS for only 5 CA, as data were no representative in other CA. Correlation between ISS and ISS-R data were only able to execute in HRC gain1q, due to lack of sample in other CA. We found a P coefficient of 0.568399 or 56.83% (p- <0.00578, CI 95%). Summary/Conclusion: Our case series continues with a longer survival curve compared to those commented in other studies. As cytogenetic abnormalities (t(4;14), t(14;16), t(14;20) and gain1q), similar % of representation are described as Kumar. Nat Rev Clin Oncol. 2018, except for del(17p), 23% vs 10%. From the second line, the probability of receiving a new line, the duration of tto and the interval without tto decreased with each line of tto. As treatment lines progress, therapeutic combinations are more heterogeneous and less concordant. A further longer follow-up and higher HRC NDMM pts's recruitment will be necessary to clarify the response to tto regimens based on individual cytogenetic groups.
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Background: The bortezomib, lenalidomide, and dexamethasone (VRd) regimen is a SoC for NDMM. Belamaf, a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate, demonstrated durable responses in patients with relapsed/refractory multiple myeloma. Preclinical studies of belamaf in combination with bortezomib/ lenalidomide suggest enhanced antimyeloma activity. We report preliminary findings of belamaf + VRd for patients with TI NDMM. Materials and Methods: DREAMM-9 (NCT04091126) is an ongoing Phase I, open label, randomized, dose and schedule evaluation trial. Adults with TI NDMM and ECOG status 0-2 are eligible. VRd is administered Q3W until Cycle 8, followed by lenalidomide + dexamethasone (Rd) Q4W. Belamaf + VRd is administered until Cycle 8, and with Rd thereafter. The currently evaluated belamaf dose cohorts are: Cohort 1 (1.9 mg/kg Q3/4W), Cohort 2 (1.4 mg/kg Q6/8W), Cohort 3 (1.9 mg/ kg Q6/8W), Cohort 4 (1.0 mg/kg Q3/4W), and Cohort 5 (1.4 mg/kg Q3/4W). Primary endpoint is safety. Secondary endpoints include efficacy, tolerability, and pharmacokinetics (PK). Results: Overall 36 patients were treated across the 5 cohorts. The median (range) age was 74.0 (63-80) years;56% patients were male, 17 (47%) had stage 2 disease, 3 (8%) had extramedullary disease, 6 (17%) patients had high risk cytogenetic abnormalities;the median number of belamaf cycles ranged from 1-9. No new safety signals were observed. Across Cohorts 1-5, all patients experienced AEs related to study treatment;1 patient in Cohort 1 died due to COVID-19 infection. The most common AEs leading to dose modification were thrombocytopenia, neutropenia, and corneal events. Patients in Cohort 2 and 3 had the lowest number of Grade ≥3 corneal events (3 and 2 events, respectively). All 12 patients in Cohort 1, all 6 in Cohorts 3 and 5, and 5/6 patients in Cohorts 2 and 4 have responded to the treatment;≥half of patients in each cohort achieved very good partial response or better. As of data cut-off, 3/12 patients in Cohort 1, 2/6 in Cohort 4, and 1/6 patients each in Cohorts 3 and 5 remained in complete response. Belamaf PK profile was similar to that observed in patients with RRMM taking into consideration baseline patients characteristics. Conclusions: Preliminary data suggest addition of belamaf to VRd did not reveal new safety signals and demonstrates high response rates, albeit with short follow-up. The trial is ongoing to confirm safety and evaluate the efficacy of belamaf + VRd. .
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Current therapy for adults with B-cell acute lymphoblastic leukaemia (B-ALL) remains suboptimal, despite good initial remission rates. Adults with relapsed or refractory B-ALL (R/R B-ALL) represent a challenge with historically poor outcome;the introduction of targeted agents has expanded options but there is no consensus management. Blinatumomab is a bispecific T-cell engager antibody construct against CD19 (Scottish Medicine consortium, SMC, approval February 2020);inotuzumab is a monoclonal anti-CD22 antibody conjugated to calicheamicin (SMC approval May 2018). Trial data have shown both agents improved remission rates and survival when compared with standard chemotherapy with manageable toxicity profiles, although adverse events including neurological toxicity and cytokine release syndrome (CRS) have been reported. We describe the experience of blinatumomab and inotuzumab in a BCSH level three unit from February 2017 to August 2021. Eleven patients-six male, five female, mean age 41.5 years (range 22-55) received a monoclonal antibody;blinatumomab ( n = 8) and inotuzumab ( n = 3). Ten had B-ALL and one had mixed lineage leukaemia (MLL). All patients were Philadelphia negative. Cytogenetic abnormalities were present in four cases-Inv(20), trisomy 21 (patient with Down syndrome), tetraploidy with isochromosome 17q and one with a complex karyotype. Further molecular information was available for nine cases, and all were negative for TCF3-PBX1 t(1;19), ETV6-RUNX1 t(12;21) and KMT2A rearrangements (including the case with MLL). Four patients received blinatumomab due to refractory BALL. Two (50%) went on to receive an allogeneic transplant in CR1 (one MRD negative and the other MRD below limit of quantification). Both patients were able to maintain a performance status of 0-1 pretransplant. One patient (25%) died due to SARS-COV-2 infection and the fourth patient's care was lost to follow-up. Four patients received blinatumomab due to relapsed BALL, two had undergone allogeneic transplant in CR1. Two patients (50%) died of progressive B-ALL. One patient is currently on UKALL 2011 regimen B maintenance B2 (comorbidities preclude allogeneic transplant), the other patient remains in molecular remission having failed lymphocyte collection for chimeric antigen (CAR) T-cell therapy. Three patients received inotuzumab for relapsed B-ALL. Two (66%) had a previous allogeneic transplant in CR1-one of whom went on to receive donor lymphocyte infusion (DLI) postinotuzumab while the other patient went on to have a second allogeneic transplant. The third patient relapsed on maintenance chemotherapy and has been referred for allogeneic transplant. Infective episodes occurred in 45% (all received blinatumomab) including one death from SARS-COV-2 pneumonitis. Following blinatumomab CRS and neurotoxicity (tonic-clonic seizures) occurred (both n = 1). No significant toxicities were observed in the three patients who received inotuzumab, although this likely reflects small patient numbers rather than a true difference between the two agents. Despite improved responses in R/R B-ALL with these therapies as single agents for the majority they do not offer cure. While toxicity was recorded it did not negatively impact PS. CAR T-cell therapy has demonstrated high initial remission rates in heavily treated B-ALL patients, including previous targeted therapy. Optimal sequencing of therapies remains to be defined alongside depth of response and duration of measurement.
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International Myeloma Working group (IMWG) diagnostic criteria for myeloma (MM) requires the presence of ≥10% clonal plasma cells alongside a MM defining event-traditionally a CRAB feature (hypercalcaemia, renal impairment, anaemia, bone disease). In 2014, three biomarkers were added (≥60% plasma cells in the marrow, light chain ratio ≥100 and ≥2 focal lesions on MRI), each associated with around an 80% probability of developing CRAB features within 2 years. These biomarkers are the SLiM criteria and the recommendation is that such patients are treated. In March 2020 UK Myeloma Forum issued guidance for MM therapy during the Covid-19 pandemic, recommending patients who fulfil the SLiM part only of the SLiM/CRAB (SLiM positive) or who only have anaemia should be monitored. There is a lack of real-world data available to validate the recommendation to treat based on SLiM criteria. The impact of not treating these patients during the Covid-19 pandemic remains unknown. We conducted a retrospective analysis of the outcomes of SLiM positive patients at Nottingham University Hospitals (NUH) NHS Trust who underwent observation rather than treatment during the Covid-19 pandemic. SLiM positive patients were detected via the MM MDT min from 1st April 2020-30 Nov 2021. Time to progression (TTP) was defined as the time from diagnosis of SLiM positive MM until the time systemic therapy was initiated (day 1 cycle 1). Decision to treat was based on development of CRAB features, worsening of SLiM criteria and patient choice. 22 SLiM positive patients were identified. Patient characteristics and outcomes for the entire cohort and for those who did and did not progress are shown in Table 1. No patients were R-ISS stage III and 1q gain was the only high-risk cytogenetic abnormality detected. This may suggest higher risk patients are more likely to present with CRAB features and less likely to be SLiM positive. The median follow-up was 12 months. Forty-one percent of patients progressed to require therapy in keeping with the IMWG data suggesting 80% of SLiM positive patients will progress over a 2-year period. The median TTP was not reached. For those patients who did progress, the median TTP was 3.8 months. Reasons for progression are shown in Table 1. Overall survival (OS) was 100% hence no suggestion thus far that observation of SLiM positive patients during the Covid-19 pandemic increased MM-related mortality. The majority who remained under observation were SLiM positive on WBMRI alone. In contrast, the majority who did progress had been SLiM positive on SFLC ratio, marrow infiltrate or a combination of features. We acknowledge the small numbers and relatively short follow-up of this study. Results thus far are in keeping with the IMWG finding that SLiM positive patients have around an 80% chance of progression at 2 years. There is a suggestion that patients who present with SLiM criteria only may have genomically lower risk disease. OS has not been affected thus far by monitoring SLiM patients. Our results also suggest that patients SLiM positive due to SFLC ratio or BM infiltration are more likely to require early intervention than those positive on WBMRI. We recommend a future multicentre UK wide analysis of the outcome of SLiM positive patients during Covid-19. Results would help counsel UK MM patients regarding when to offer treatment and potentially help develop a UK-based biomarker model to predict risk of progression..
ABSTRACT
Background: Newly drugs access for MM treatment still a challenge in some countries. One of the most availableinductions for TE NDMM patients (pts) worldwide is cyclophosphamide (C), thalidomide (T) and dexamethasone (d)-(CTd). Dara the first anti- CD38, had been combined with VCd, VTd and VRd and markedly increased the depth andduration of the response. We hypothesized that the combination of Dara and CTd could be safe and allow deeper activityas an alternative protocol. Aims: The primary endpoint was to evaluate the VGPR after two consolidation cycles post-autologousstem cell transplantation (ASCT). Secondary endpoints were the overall response rate during alltreatment phases and minimal residual disease (MRD), based on the International Myeloma WorkingGroup (IMWG) criteria that includes the next-generation flow (NGF) by the EuroFlow®and PET-CTand the safety profile. Methods: This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TENDMM, creatinine clearance > 30 mL/min, normal cardiac, renal and liver function and the EasterCooperative Oncology Group (ECOG) performance status = 0 - 2. The protocol was Dara-CTd for upto four 28-day induction cycles: C-500 mg oral (PO) on days 1,8 and 15, T at 100-200 mg PO on days1 to 28, (d) at 40 mg PO on days 1,8,15 and 22 and Dara at 16 mg/kg/dose intravenous (IV) on days1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 – 4, followed by ASCT. All ptsreceived up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16 mg/kg and (d) at 40 mg every other week, associated with T at 100 mg PO on days 1 - 28. Dara at 16 mg/kg was used monthly as maintenance until progression or limiting toxicity. G-CSF was used forstem cell (SC) mobilization and plerixafor had been allowed whenever the pts need. All pts receivedantiviral, anti-pneumocystis and anti-thrombotic prophylaxis. Results: The first pts was enrolled in November 2018. A total of 21 pts were included, the median age being 56 (range 37– 67 years), 19 (90%) were non-white, 3 (14%) had an R-ISS = 1, 12 (57%) had an R-ISS = 2 and 3 (14%), an R-ISS = 3. Five (24%) pts had high-risk chromosomal abnormalities [del17p, t(4;14) or t(14;16)]. To date, all pts have completedinduction, 19 have received transplant and 17 have completed D+90 post-transplant assessment. No SC mobilizationfailure was observed, and five (26%) pts needed plerixafor use. In an intention to treatment analysis, after the end ofinduction (cycle 4), 19 (90%) of the pts obtained > PR and 8 (38%) obtained >VGPR, including three MRD negativity byNGF. 17 pts have completed two consolidation cycles after transplant and 94% obtained > VGPR as best response, 12(70%) obtained MRD negativity by NGF and nine (53%) had negative PET-CT. Seven (41%) pts had both flow and PETCTnegativity. Three pts died from infection, one before transplant because of Covid infection, on post-transplant, considered not related to the investigational agent, and another after consolidation, related to the investigational agent. The most common nonhematological adverse events (AEs) grades 3 and 4 before ASCT were neuropathy (n = 6), infusion reaction (n = 7), infection (n = 2), hypertension (n = 1) and rash (n = 1). Summary/Conclusion: This is the first study that combined Dara with CTd as induction for TE NDMM pts. This presentdata has shown that the association of Dara-CTd achieved the primary end point once > 90% of the pts achieved VGPRafter two consolidations cycles, and safety profile was acceptable. Clinical trial information: NCT03792620.
ABSTRACT
Background: Freeman-Sheldon syndrome [distal arthrogryposis type 2A (OMIM #193700), DA2A, Freeman-Burian syndrome] is a rare autosomal dominant multiple pterygium syndrome caused by alterations in MYH3. The phenotypic features, particularly of the face, are distinct and easily recognizable, and the diagnosis can be confirmed with molecular gene analysis. Fetal ultrasound imaging may provide important diagnostic clues to facilitate the diagnostic process. Informed consent and parental permission were provided by the parents. Case presentation: The infant’s mother presented for a Maternal Fetal Medicine genetic counseling telehealth appointment (due to COVID-19 pandemic restrictions) as a G7P2132, 32-year old female who had insulin-dependent diabetes and thrombocytosis. Her partner was a 24-year old male with a history of hearing loss, a V-shaped palate, and a lower lip cleft. Gestational age was 14 4/7 weeks and the indications were: increased nuchal translucency, paternal complex medical history, maternal G6PD heterozygote, and recurrent pregnancy loss. During the genetic counseling session, the following were addressed: 1) Maternal heterozygote status for G6PD indicated that if the fetus was male, there was a 50% chance he would be affected with G6PD-deficiency;2) Increased nuchal translucency on fetal ultrasound (US) with measurement at 98th percentile is associated with an increased risk of chromosomal abnormalities, microdeletion/duplications, and Noonan syndrome. The patient reportedly had low risk cell-free DNA but results were not available to the counselor at the time of consult. The option for additional genetic screening and diagnostic testing was declined;3) Three first trimester pregnancy losses with the father of this baby (FOB) were addressed, and parents deferred chromosome analyses at the time;4) Mother shared FOB’s complex history of bilateral sensorineural hearing loss, V-shaped cleft palate, lower lip cleft, and micrognathia. However, father was not present during the telehealth encounter. Mother was counseled regarding the possibility of an autosomal dominant condition with the potential risk to the pregnancy of up to 50%. It was recommended that the FOB have a clinical genetics evaluation, which could potentially provide a specific diagnosis and inform recurrence risk and management guidance. Follow-up MFM genetic counseling telephone visit occurred with the mother at 31 6/7 weeks gestation due to multiple congenital anomalies evident on fetal ultrasound. A 25 week fetal ultrasound revealed hypotelorism and a thickened nuchal translucency. A repeat study at 29 weeks revealed a V-shaped palate with a possible cleft, micrognathia, and midline mandibular cleft. FOB’s history was revisited. It was determined that he had 3 previous “no shows” to Genetics clinic appointments and did not pursue evaluation after the last counseling appointment. Again, it was emphasized that in order to best make a diagnosis for the family, an affected person would need to undergo a thorough evaluation, including medical and family history review, physical examination, and any indicated genetic testing. The parents were comfortable with the likelihood that the baby had the same condition as the father, but variable expressivity and broad range pf phenotypic presentation were explained. Recommendations for postnatal evaluation of the infant and pertinent genetic testing were provided. Consultative Genetics evaluation of the infant at 2 days of age revealed a short, broad forehead with supraorbital fullness leading to a horizontal brow indentation;mask-like facial appearance;hypotelorism;very deep set eyes with blepharophimosis;deep, creased nasal bridge;small, upturned nose with hypoplastic alae and narrow nares;microstomia with pursed lips;glossoptosis;micrognathia;2 deep vertical chin creases;short neck with excess nuchal skin;inverted and wide spaced nipples;clenched hands with 5th digits overlying 4th and 2nd overlying 3rd, bilaterally;bilateral vertical talus;2nd toes longer and overlying rd toes;clinodactyly of 4th and 5th toes bilaterally;and deep gluteal crease with no visible sinus. There were no evident contractures. The father has a complex history with no medical assessments prior to age 18. He reported that he did “not look like anyone else” in his family. He has a diagnosis of autistic spectrum disorder, a submucous cleft, vision issues, hearing loss necessitating a hearing aid on the left, and a history of cholesteatomas and of mastoidectomy. On brief examination, he had a mask-like face, blepharophimosis, left microphthalmia, left esotropia, narrowing of his midface, deep vertical crease on the mandibular region, microstomia, broad great toes, single flexor creases on the thumbs, and contracture of right thumb. Maxillofacial CT of the infant revealed hypoplastic mandibular body, ramus, and condyles bilaterally with micrognathia and retrognathia;hypoplastic maxilla bilaterally;and enophthalmos with retracted appearance of globes in the bony orbits bilaterally. Multiple facial bone abnormalities were seen, including microsomia, micrognathia, retrognathia, orbital hypotelorism and enophthalmos Genetic testing was performed via a custom Whole Exome Slice at GeneDx laboratories and included the MYH3 and TNNI2 genes. Results revealed a heterozygous pathogenic change in MYH3 (c.2015 G>A;p. R6724) consistent with the diagnosis of Freeman-Sheldon syndrome. Conclusion: The presentation of “midline mandibular cleft” on fetal ultrasound was the most specific prenatal finding. This is a very rare fetal finding. Thus, it should prompt further evaluation to assess for true clefting versus ridging or creasing. Additionally, targeted assessment for other findings or clinical clues for Freeman-Sheldon syndrome, such as contractures, “windmill vane” hand, and mouth size, could aid in the differential diagnosis considerations and the diagnostic process. Admittedly, these are position and quality dependent, and are challenging to assess even in ideal situations. The phenotype of the father was immediately recognizable. However, due to COVID-19 pandemic restrictions, prior to the infant’s birth, only telehealth visits were conducted and the father’s participation was by telephone. This limited the ability to narrow the differential diagnosis without visualization of his distinct phenotypic features. Finally, missed opportunities to diagnose the father prior to this pregnancy occurred. Many clinics send “no show” letters to referring providers and patients, as we do. Emphasizing the importance of diagnosis prior to pregnancy for individuals concerned about having a genetic disorder should be considered as part of the information shared in these letters.
ABSTRACT
Introduction: TG-1701 is a selective, covalent BTK inhibitor administered once daily (QD). Both the 'U2' combination (anti-CD20 mAb ublituximab+the PI3Kd-CK1e inhibitor umbralisib) and BTK inhibitors are highly efficacious in treatment- naïve (TN) and relapsed/refractory (R/R) CLL, each having previously demonstrated superiority over standard chemoimmunotherapy. Here, we report results for patients treated with TG-1701 alone or in combination with U2 from an ongoing Phase 1 study, with a focus on patients with CLL. Methods: Patients with R/R CLL and B-cell non-Hodgkin lymphoma were enrolled in an ongoing Phase 1 study initially evaluating dose escalation (DE) of oral TG-1701 QD continuously administered in 28-day cycles (100, 200, 300, and 400 mg). After characterizing the safety profile of TG-1701 monotherapy, we implemented a parallel DE arm of TG-1701+U2. Select dose levels of TG-1701 monotherapy were also expanded. All patients were treated until disease progression, unacceptable toxicity, or investigator/patient decision to withdraw. Safety was evaluated in all treated patients, and efficacy was evaluated in all treated patients with CLL who had at least 1 post-baseline assessment. Results: As of 30 April 2021, 125 patients were treated with TG-1701, 49 of whom had CLL. Enrollment was: 25 patients in the monotherapy DE arm (6 with CLL), 61 in the 200-mg disease-specific cohorts (20 CLL [5 TN], 21 mantle cell lymphoma [MCL, 4 TN], 20 Waldenström's macroglobulinemia [WM, 8 TN]), 20 in the 300-mg CLL cohort (4 TN), and 19 in the 1701+U2 DE arm (3 with CLL). Patients with MCL or WM in the 200-mg disease-specific cohorts were excluded from this analysis. The median # of prior therapies among CLL patients was 1 (range, 0-5) and all patients were BTKi-naïve. TG-1701 was well-tolerated and the maximum tolerated dose for monotherapy was not reached up to 400mg (near 100% saturation of the BTK at all dose levels studied). In the DE arms, the most common all-causality treatment-emergent adverse events (TEAE) were constipation (32%), increased ALT (28%), bruising (28%), and upper respiratory tract infection (28% of patients) with TG-1701 monotherapy;diarrhea (53%) and bruising (42%) with TG-1701+U2. Grade 3/4 AEs were limited. In the CLL-specific cohorts, the most common TEAE was increased ALT/AST (all grades, 17.5%;grade 3, 2.5%;grade ≥4, none), followed by diarrhea (all grades, 12.5%;grade ≥3, none), and COVID-19 (all grades, 12.5%;grade 3-4, none;grade 5, 7.5%). There were no cases of atrial fibrillation, major bleeding, or ventricular tachyarrhythmia in the CLL cohorts at a median follow-up of 10.5 months. TEAEs leading to TG-1701 dose reduction occurred in 7.5% of patients. TEAEs leading to treatment discontinuation occurred in 7.5% of patients (all COVID-19). At the data cut-off, 48 patients with CLL were evaluable for response, including nine in DE. ORR was 95.6% for TG-1701 monotherapy (all PR/PR-L) and 100% for TG-1701+U2 (all PR). The median duration of response has not been reached in either cohort. The best change from baseline in tumor burden in patients with CLL is presented in Figure 1, and treatment exposure and response duration data are presented in Figure 2 below. In patients with anemia and thrombocytopenia at baseline, sustained improvement in hematologic variables was observed in the 200- and 300-mg cohorts. Lymphocytosis was observed in 70% of the monotherapy patients, with a resolution to normal or <50% of baseline in 57.1%. Consistent response rates were observed across all subgroups, including age and high-risk genomic features, such as del17p/TP53, unmutated immunoglobulin heavy-chain variable-region (IGHV), and complex karyotype (defined as three or more cytogenetic abnormalities). Time to event data will be reported at the time of presentation. Conclusions: TG-1701 exhibits an encouraging safety and efficacy profile in patients with CLL, with promising activity and a manageable tolerability profile as monotherapy and in combination with U2 (Figure 1). Future registration trials ar being planned in CLL with TG-1701. Recruitment to this study (NCT03671590) continues.
ABSTRACT
Cytogenetic abnormalities involving chromosome 16 are found in 5– 8% of acute myeloid leukemia (AML). These are typically a pericentric inversion inv(16)(p13.1q22) or a translocation, t(16;16)(p13.1;q22), involving the MYH11 and CBFB genes localized to chromosome 16p13.1 and 16q22, respectively. In addition, less common rearrangements include deletion of the long arm of chromosome 16, del(16) (q22), and cryptic insertions involving the MYH11 and the CBFB genes with otherwise normal karyotypes. In this report, we present the first AML case with a new translocation involving the CBFB gene. The more common CBFB - MYH11 fusion product resulting from the inversion and/or translocation of chromosome(s) 16 leads to an AML with monocytic and granulocytic differentiation and abnormal eosinophil component with large, purple to violet color eosinophilic granules. This entity typically corresponds to the adult AML-M4Eo in French-American- British (FAB) Classification and now called AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH1 in the new 2017 WHO Classification. Patients may present with myeloid sarcoma at initial diagnosis or at relapse. We present a case of an 80-year-old male with a history of prostate cancer post radiotherapy who was referred for COVID-19 testing. A complete blood count with differential revealed neutropenia and a macrocytic anemia. A bone marrow biopsy and a bone marrow aspirate confirmed a diagnosis of AML with 33% blasts including myeloblasts and promonocytes. Interphase fluorescence in situ hybridization (FISH) analysis with a break-apart probe for CBFB showed an abnormal hybridization pattern consistent with rearrangement of CBFB in 66% of nuclei. Chromosome analysis revealed an abnormal karyotype with two related clones: 47,XY, t(10;16)(p13;q22),+22[4]/48,idem,+8[16]. Sequential GTG-FISH confirmed that the 3’ region of CBFB was translocated to 10p13 in the t(10;16) and the 5’ region remained on 16q. Based on the karyotype, the patient’s bone barrow exhibits clonal evolution having acquired additional chromosome abnormalities (trisomy 22 and trisomy 8). Molecular studies by next generation sequencing showed NRAS p.Gln61Lys mutation with a VAF of 11.21%. No genomic alterations were detected in KIT, KRAS or FLT3 genes. AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22) is associated with a high rate of complete remission and favorable overall survival when treated with intensive consolidation therapy. However, their prognostic advantage may be affected by additional cytogenetic abnormalities and/or other gene mutations. Specifically, trisomy 22, is a frequent abnormality additional to inv(16) detected as a secondary finding which has been associated with an improved outcome when compared to the prognosis associated with inv(16) alone. Furthermore, KIT (in 30–40%), FLT3 (in 14%), NRAS (in 45%) and KRAS (in 13%) mutations are common in this AML type. The prognostic implications of KIT mutation (especially involving exon 8) do not appear to be significantly poor prognostic compared to other AML types. On the other hand FLT3-TKD mutations and trisomy 8 are associated with a worse outcome. The patient is currently receiving Vidaza 75 mg/m2, days 1–7 of a 28 days cycle with Venetoclax mg daily of a 28-day cycle and his clinical prognosis is currently unclear. Further analysis by DNA sequencing may help to characterize the molecular nature of the fusion gene product resulting from the novel t(10;16)(p13;q22). To the best of our knowledge, this is the first reported case of an AML patient with translocation t(10;16)(p13;q22) involving the CBFB gene. Given the rarity and lack of additional information regarding the effects of this abnormality, the prognosis and survival cannot be predicted.
ABSTRACT
Background: Coronavirus disease 19 (COVID-19) tends to be milder in children, but severe cases have been reported. We described a case report of a toddler admitted to our department with additional findings, highlighting the importance of assessing the patient as a whole. Case Presentation: A previously healthy, 15-month-year-old girl presented with fever and dry cough for 10 days, respiratory distress and PCR SARS-CoV-2 was positive. At admission, she presented with hypoxemia (SpO2 89-90% in room air), global retraction and bilateral bronchospasm. She was treated with bronchodilators, methylprednisolone, remdesivir and also amoxicillin/clavulanic acid. Her complete blood count revealed leucocytosis 16,160x109/L, 41% lymphocytes, C-reactive protein 57,9 mg/L, procalcitonin 0,13 ng/mL, sedimentation rate 44 mm/h, ferritin 218,4 ng/mL. Chest computed tomography (CT) scan revealed bilateral peripheral areas of ground glass, coexisting consolidation areas at inferior lobes but also revealed a 6 cm supra-renal mass. Abdominal ultrasound and CT confirmed an heterogeneous right supra-renal gland mass of 5,5cm along the greatest diameter with diffuse calcifications, evolving the inferior vena cava and the renal vascular pedicle, no signs of liver, bone, cutaneous or ganglionic metastization. These features were suggestive of neuroblastoma in stage L2. Vanillylmandelic acid, normetanephrine/creatinine ratio and metanephrine/creatinine ratio were elevated. The metaiodobenzylguanidine (Mibg) scan showed a localized disease. The total excision of the tumour mass was performed, and the histology confirmed neuroblastoma with no N-myc oncogene amplification, nor other bad prognosis chromosomal abnormalities. She is currently under oncological surveillance, with no signs of recurrence. Learning Points Discussion: Neuroblastoma is the most common extracranial solid tumour of childhood. It is known for its broad spectrum of clinical behaviour and outcome. In this case, although this toddler was admitted due to COVID-19 pneumonia, it allowed to identify a localized tumour, perform excision and due to the favourable biology tumour, she has a very good chances of being cured and free of disease.