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Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.
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From March 2020 to May 2022, when SARS-CoV2 pandemic started spreading in Italy, 15 consecutive patients with non-Hodgkin Lymphoma (NHL) have been treated at the Pediatric Unit of Fondazione IRCCS Istituto Nazionale dei Tumori. Three of 15 patients developed COVID19 while on treatment [1 Burkitt lymphoma (BL), 1 anaplastic large cell lymphoma, 1 lymphoblastic T-cell lymphoma (T-LL)] and one patient at diagnosis [gray zone lymphoma (GZL), previously misdiagnosed as Hodgkin lymphoma]. Median age at diagnosis was 12 years;3 were male. Median positivity time of the nasal swab was 58 days (range 9-107 days). All patients remained asymptomatic or paucisymptomatic (flu-like symptoms) while positive. The first positive patient with T-LL, was in the induction phase of the Euro-LB-02 protocol guidelines: he succeeded in completing the whole treatment during the 107 days of swab positivity, experiencing mild toxicities (grade 2 transaminases and grade 3 lipase increase, both reversible) without significant delays. For this reason, we reduced the total dose of the first HD-MTX (protocol M) and administer the subsequent doses in 6 hours infusion instead of 24 with no further toxicities. After this first experience, all the subsequent patients have been treated accordingly, without major deviations from the established protocols. Minor precautions: the patient with refractory GZL received IEP course instead of IGEV as second-line treatment to avoid severe subsequent immunosuppression;the patient with BL omitted the fourth course of Rituximab during the period of swab positivity. Overall, we did not observe outstanding toxicities except for a toxic MTX level with subsequent reversible acute renal failure. Main teaching from these pilot experiences, which may translate into guidelines: 1) SARS-CoV2 infection is not an absolute contraindication to the oncological treatments. This is of main importance for the patients affected by lymphoma whose dose-intensity has a prognostic value. 2)We need to pay caution during HD-MTX treatment;indeed, we observed unexpected similar toxicities in other patients treated with HD-MTX for other solid malignancies. 3) The clearance of SARS-CoV2 might be exceptionally prolonged with persistent positivity of the nasal swabs for a longer time than the matched healthy population due to the immunosuppression characterizing lymphoma patients. For this reason and given the importance of maintaining the dose-intensity, specific treatments aiming at speeding up the clearing process are warmly suggested. (Figure Presented) Figure 1: (: 091) ITHACA study design and blood sampling time points. (OHT = Orthotopic Heart Transplant).Copyright © 2022 Elsevier Ltd. All rights reserved.
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Hematologic malignancy is a risk factor for severe coronavirus disease 2019 (COVID-19) in adults;however, data specific to children with leukemia are limited. High-quality infectious adverse event data from the ongoing Children's Oncology Group (COG) standard-risk B acute lymphoblastic leukemia/lymphoma (ALL/LLy) trial, AALL1731, were analyzed to provide a disease-specific estimate of SARS-CoV-2 infection outcomes in pediatric ALL. Of 253 patients with reported infections, the majority (77.1%) were asymptomatic or mildly symptomatic (CTCAE grade 1/2) and there was a single COVID-19-related death. These data suggest SARS-CoV-2 infection does not confer substantial morbidity among young patients with B-lymphoblastic leukemia/lymphoma (B-ALL/LLy).Copyright © 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.
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Introduction: Use of hematopoietic cell transplantation (HCT) in patients with trisomy 21 (+21) is infrequent given concerns about increased toxicity with cytotoxic chemotherapy.1 Due to increasing evidence of benefit from post-HCT cyclophosphamide (PTCy) for graft-vs.-host disease (GVHD) prophylaxis and lack of prior descriptions in patients with +21,2-4 we report on 2 patients with +21 and acute lymphoblastic leukemia (ALL) who underwent HCT with PTCy. Method(s): Retrospective data were collected from 2 patients with ALL and +21 who underwent allogeneic HCT with PTCybased GVHD prophylaxis from 2019 to 2021. Data collected included age, disease risk, HCT-CI, GVHD incidence, and survival. Result(s): Patient 1 is a 22-year-old male and patient 2 a 25-year-old female. Both had Ph-negative, B-cell ALL. Patient 1 had ETV6/RUNX1 rearrangement, del 12p, gain of X, and he had recurrence of measurable residual disease (MRD) after initial MRD-negative CR with two lines of therapy pre-HCT. Patient 2 had normal cytogenetics and relapsed disease with 4 prior lines of therapy. Both achieved MRD-negativity pre-HCT. Both received fludarabine and melphalan conditioning, and patient 1 also received thiotepa 2.5 mg/kg. PTCy was given on days +3 and 4 at 50 mg/kg with sirolimus and tacrolimus for GVHD prophylaxis. Patient 1 had a haploidentical donor and received one dose of rabbit ATG (1 mg/kg) on day +5. Patient 2 had a matched unrelated donor. There was no significant delay in engraftment of ANC (day 16-19) or platelets (day 15-16). Patient 2 developed acute GVHD at day 30 (stage I skin, stage II GI) that resolved with steroids which were tapered off by day 96 without recurrence. Sirolimus stopped at day 79 (pt 1) and 103 (pt 2) and tacrolimus was stopped at day 274 (pt 1) and 469 (pt 2). Patient 1 developed a sirolimus-induced pericardial effusion at day 84 which did not recur after sirolimus discontinuation. Patient 2 developed moyamoya 8 months post-HCT during tacrolimus taper without other GVHD symptoms. Response to steroids was noted, so tacrolimus was restarted for residual neurological deficit. Neither patient developed chronic GVHD or left ventricular ejection fraction decline, and neither patient had disease relapse at follow-up of 30 and 16 months respectively. Patient 2 developed COVID pneumonia 16 months post-HCT and died while in CR. Patient 1 remains alive, in CR, and off immunosuppression nearly 3 years post HCT. Conclusion(s): Allogeneic HCT with PTCy at standard doses did not appear prohibitively toxic in patients with +21 when administered after reduced-intensity conditioning. In this case series, GVHD rates seemed consistent with larger series in patients without +21. Moyamoya development is associated with autoimmunity in patients with +21 and hence may have been GVHD-related5. Trisomy 21 should not be a barrier to patients otherwise eligible for HCT, even with PTCy prophylaxis.Copyright © 2023 American Society for Transplantation and Cellular Therapy
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Lactic acidosis is considered to be one of the most common causes of high anion gap metabolic acidosis in hospitalized patients. Warburg effect can present with type B lactic acidosis and is considered to be a rare but well-known complication of hematological malignancies. Here, we present the case of a 39-year-old male who had type B lactic acidosis and recurrent hypoglycemia secondary to newly diagnosed Burkitt lymphoma. This case highlights the importance of considering malignancy workup in any case of unexplained type B lactic acidosis with vague clinical presentation, which can aid in early diagnosis and management.
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Background: The COVID-19 pandemic severely impacted patients with acute lymphoblastic leukemia(ALL) in maintenance phase of chemotherapy. Teleconsultation was introduced to ensure continuity of care for these patients during the lock-down phase of the pandemic and was continued well after its end. Hence, we decided to analyze the impact of teleconsultation in a cohort of ALL patients. Method(s): Our study was a single-centre retrospective analysis of patients with ALL on maintenance chemotherapy. Thirty-five patients records were analyzed, comparison was made between absolute neutrophil counts (ANC) and frequency of consultations before and after the start of teleconsultation, which included 2-weekly phone calls, necessitating visit only once in 3 months as opposed to a monthly visit as required before. Hemograms were done twice a month and sent on WhatsApp. Consultations were done via phone calls and prescriptions sent via WhatsApp. Result(s): The median [IQR] age of our cohort was 7.5 [4.2;9.3] years and age at diagnosis was 5.4 [2.3;7.5] years;23/35 (66%) were male and 30/35 (88%) were phenotypically B-ALL;rest T-ALL/Lymphoma. All patients received chemotherapy as per the ICiCLE (Indian Collaborative Childhood Leukaemia group) protocol. A total of 437 teleconsultations were done (73/month). Before teleconsultation, the mean (SD) ANC was 2272 (644)//microL, and after teleconsultation it was 1754 (461)/microL (p value=0.0001). Teleconsultation improved target ANC (<2000/microL) attainment in our cohort of patients (31% vs 80%, p value=0.0002). Prior to teleconsultation, majority (27/35, 77%) visited the hospital once a month which reduced to once in 3 months, after teleconsultation. Conclusion(s): Teleconsultation is time saving, economical and reduces the gap in schooling in a child with ALL. It also helps optimize compliance during this maintenance phase of chemotherapy, a key in management of leukemia patients, contributing to the continuum of care and improvement in overall survival of these patients. Copyright © 2022
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These proceedings contains 114 articles that discuss building toward resilient health systems as the main topic of the first ASGCR plenary. Speakers stressed the significance of collaborations, adaptation, and innovation while highlighting crucial gaps that have appeared in the face of serious threats and emergencies like COVID-19, climate change, and political shifts. In order to close the gap between research and practice in cancer prevention and control in LMICs, this workshop covered evidence-based and cutting-edge solutions. The sometimes transient nature of many programs and initiatives was discussed, along with the difficulties of sustainability in the face of conflicting priorities and dangers to reliable health systems. Nevertheless, even as it discussed past failings, the event also recognised significant gains and started a conversation about resilient building patterns. The second plenary addressed equality in international cancer research, acknowledging the inequalities in the field's translational capacity. Research in LMICs has frequently led to important advances in cancer science, such as the early Burkitt lymphoma treatment trials in Uganda and the human papillomavirus immunisation trials in Costa Rica. The LMIC groups who contributed to these triumphs have frequently not received the rewards of this progress fairly. Inequities in cancer between high-income countries (HIC) and low- and middle-income countries (LMICs) also lead to research that fails to take into account the entire scientific worth of studies carried out in LMICs as well as the worldwide burden of disease. Established power imbalances that are frequently related to funding sources can hinder the development of HIC's career and local knowledge. To ensure the translation of research findings, suggestions included multisectoral stakeholder engagement across entire health systems, such as finance and education, as well as proper humility and listening on the part of HIC researchers and funders. Additionally, the chance for two-way information exchange and learning, respecting local knowledge, and developing trust to ensure successful relationships were noted. In turn, successful collaborations and active community involvement were considered as the way to effectively translate and disseminate research findings.
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Background: During the coronavirus pandemic, the risk of severe COVID-19 and mortality are higher in certain groups, in particular in patients with oncohematological diseases. Acute lymphoblastic leukemia (ALL) is a special group of oncohematological diseases in which mortality in the era of COVID-19 has increased 2-3 times. Currently, there is no consensus on the treatment of ALL during coronavirus infection. Aims: To determine the basic principles and features of the management of patients with ALL during COVID-19. Methods: 46 patients with ALL and COVID-19 (men 52.2%, women 47.8%) aged 18-74 years (median-44.5) were treated at the Moscow City Clinical Hospital 52 on 01.04.20-01.11.21. B-ALL was 58.7% (27 patients), T-ALL - 34.8% (16 patients), biphenotypic - 4.3% (2 patients), not defined - 2.2% (1 patient), Ph-positive ALL - 17.4% (8 patients). The status of the disease of patients upon admission to the Hospital differed: debut of ALL - 20 patients (43.5%), remission - 16 patients (34.8%), relapse and refractory course - 10 patients (21.7%). All patients were treated COVID-19 in accordance with the current guidelines for the prevention, diagnosis and treatment of COVID- 19 (interleukin 6 inhibitor, anticoagulant and antibacterial therapy, glucocorticoids (GCs), human immunoglobulin (IG) against COVID-19). According to vital indications and with stabilization of the patient's condition, 18 patients (39.1%) received chemotherapy (CT). Results: There were no deaths in the group of patients with remission of ALL. In patients with the debut of ALL, mortality was 45% (9 patients), in relapse and refractory course - 50% (5 patients) (p=0.005). Mortality in the group who did not receive CT was 35.7%, and in the group who received CT - 22.2%. 6 patients with Ph-positive ALL (75.0%) continued therapy with tyrosine kinase inhibitors (TKI). According to the protocol for the treatment of ALL, full doses of GCs (100%) and anthracyclines (ATC) (100%) were used, lumbar punctures (LP) and intrathecal (IT) injections of CT (100%) were continued. Due to the high risk of thrombotic complications in COVID-19 and asparaginase therapy, anticoagulant therapy was performed (100%). Prevention of pneumocystis pneumonia (PCP) (89.1%), antifungal (37.0%) and antibacterial (87.0%) therapy were carried out in the treatment of COVID-19. With the persistence of COVID-19 and the absence of antibodies to COVID-19, 2 patients received repeated transfusion of human IG against COVID-19. Summary/Conclusion: During the COVID-19 pandemic, patients in remission of ALL coronavirus infection are treated and controlled. Treatment of COVID-19 in patients with ALL is carried out according to general protocols for the treatment of COVID-19, taking into account the peculiarities of nosology (agranulocytosis, high risk of PCP and fungal infection with long-term therapy of GCs, persistence of COVID-19). When the patient's condition is stabilized, the issue of CT should be decided individually in each case, taking into account all the risks of ALL and COVID-19. During CT, use full doses of GCs, ATC. In patients with mild and moderate COVID-19, continue LP and IT injections of CT, therapy with TKI.
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Background: Recognized as an entity in the 2016 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, Pediatric-Type Follicular Lymphoma (PTFL) is a rare nodular follicular lymphoma that affects primarily children and young adults. The clinical presentation is characterized by the sudden appearance of an isolated lymphadenopathy, with a predilection for the head and neck region, without systemic symptoms. The incidence is higher in men. It has an excellent prognosis with the excision of the affected ganglion. By definition, diagnosis is histological, immunocytochemical and molecular. There are no known risk factors or any described association with immunodeficiency or viral infections. Aims: We report two clinical cases. Methods: Case 1 - a previously healthy 18-year-old boy with an isolated, non-painful, cervical lymphadenopathy of approximately 20 mm, which was incidentally found. Case 2 - a 13-year-old boy without relevant personal history, who, after the second dose of vaccination against COVID-19, developed multiple adenomegalies that spontaneously regressed. However, one month later, a right submandibular adenomegaly appeared. It was analysed by ultrasound and was described as suspicious. In both cases, a fine-needle lymph node biopsy was performed for cytological diagnosis and material was sent for immunophenotyping by flow cytometry and molecular cytogenetics by FISH. Results: Immunophenotyping suggested a large-cell B-lymphoma with a phenotype compatible with Burkitt's Lymphoma (BL). In the cytology of both cases, the population observed was more consistent with diffuse large B cell lymphoma (DLBCL) or possibly high-grade follicular lymphoma (FL). In the FISH study, no rearrangements in the MYC, BCL2, BCL6 or IRF4 genes were detected in the samples of the two cases. The lymphadenopathies were excised with a probable diagnosis of PTFL or DLBCL. Histological examination confirmed the PTFL diagnosis. Summary/Conclusion: We did not find in the literature any reference to clear causal relationship between vaccination against COVID-19 and the onset of lymphoproliferative diseases. The cytological/immunophenotypic/molecular approach of this entity in both cases seems to define a characteristic pattern, which may eventually allow, in a first approach, to suspect this diagnosis. More extensive studies will be needed to establish the role of these methodologies in the diagnosis of this pathology.
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Background: ERN-EuroBloodNet was established in 2017 as the European Reference Network on Rare Hematological Disorders (RHDs) bringing together nationally recognized centres of excellence with the goal of promoting EU best health care in RHDs. ERN-EuroBloodNet has been recently enlarged integrating 103 HCP from 24 EU-MS. Aims: ERN-EuroBloodNet was conceived to contribute to innovative, efficient and sustainable health systems and facilitate access to better and safer healthcare for EU citizens while decreasing the cross-border health barriers. Methods: Since 2017, ERN-EuroBloodNet established the state-of-the art of RHD allowing the implementation of transversal and disease-specific strategies, where actions on very rare RHD were prioritized. Results: Profile. 182 expert profiles were created freely accessible. Expert centers follow 65,000 RHD patients and treat 5,000 new patients per year, while 24 patients requested support for cross-border health assistance. Expertise. The need to improve access to next-generation sequencing for non-oncological RHD and bone marrow transplantation for sickle cell disease (SCD) was identified. Also, significant disparities in the clinical practice of primary vitreoretinal lymphoma were found and we demonstrated that less than 30% of children with SCD benefit from adequate annual stroke risk monitoring. Guidelines. A repository of 68 Clinical Practice Guidelines (CPG) classified on quality of evidence and consensus approach was created. Recommendations for diagnosis and treatment of methemoglobinemia was published in collaboration with EHA. A CPG on Adult Burkitt Lymphoma is under development. Next topics focus long-term complications in hemoglobinopathies and patients' pathways&summary. Education. ERN-EuroBloodNet Webinars were launched for professionals with 26 Thursdays Webinars and 3 EBAH accredited Topic on Focus on Cutaneous Lymphoma, Thrombotic Microangiopathies, and Bone Marrow Failures. A collaboration was established for EHA & ERN-EuroBloodNet Spotlight on Castleman Disease. For patients, 3 Topic on Focus were launched for Myelodysplastic syndromes, SCD, and Cutaneous lymphoma. Past webinars are available at EuroBloodNet EDU Youtube channel. Preceptorships on SCD will be launched soon. Telemedicine. 43 complex cases have been inter-professionally discussed in the Clinical Patient Management System with 21 outcome reports delivered. Registries. 184 Registries were identified through the European Rare Blood Diseases Platform (ENROL), endorsed by the EHA. The ENROL project, which includes rare anemias, dendritic cell leukemia and von Villebrand's disease pilots, aims to collect exhaustive and therefore epidemiological data for RHDs. The final objective is a possibility of EU health planningl and the promotion of research by identifying cohorts of patients. ERNEuroBloodNet launched the collaborative platform on patients with red blood cells and COVID-19 containing so far 373 patients. Collaborations. collaborative research projects were encouraged like EC-funded projects i.e., genomics and personalized medicine in hematological diseases (GenoMed4All) and the properties and viability of erythrocytes (EVIDENCE), or the International Hemoglobinopathy Research Network (INHERENT) for genomic and phenotypic correlations. Summary/Conclusion: The implementation of well-defined strategies but above all adapted to the specific and not yet covered needs of RHD has led to the realization of concrete projects. This has laid the foundations to strengthen health systems in the field of RHD and allow them to flourish under the new EU4Health programme.
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Background: Lymphoma is one of the most common primary malignancies of the hematopoietic system. Lymphoid neoplasms are classified into Hodgkin’s and Non-Hodgkin’s lymphoma. Non-Hodgkin lymphoma accounts for about 5% of all cases of malignancies, It is less predictable than Hodgkin lymphoma and more liable for extra-nodal spread. Males are slightly more affected than females with higher incidence in white population. B-cell lymphomas have higher incidence in adults while T-cell lymphomas have higher incidence in children. With many imaging modalities that can describe the morphological changes in lymph nodes, it’s almost exclusive for the PET/CT to describe the biological changes in those lymph nodes through their uptake of FDG which has a great value in determining whether those lymph nodes are affected or not, which in turn will play an important role in treatment & management plan. What gives PET/CT scan the upper hand is that it acts on the biological level of the cells which permit early discovering of the affected lymph nodes, much earlier than standard C.T or MRI scan.
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Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic stem cell therapy (HSCT) with incidence rates ranging from 10-35%. The predominant mechanism leading to TA-TMA is endothelial cell damage leading to complement dysregulation and microvascular hemolysis. Complement dysregulation is particularly important in the pathophysiology of TA-TMA as initial trials have shown response to complement blockade using eculizumab, a humanized monoclonal antibody targeting the terminal complement pathway. Ravulizumab is a longer acting monoclonal antibody with the same target as eculizumab that is increasingly used for treatment of atypical hemolytic uremic syndrome. Herein, we describe the case of an African American female with relapsed/refractory infantile B-cell acute lymphoblastic leukemia (B-ALL) who underwent 10/10 HLA-matched sibling donor allogeneic transplant (conditioning: busulfan/fludarabine/thiotepa;GVHD prophylaxis: tacrolimus/methotrexate) who developed TA-TMA marked by pericardial effusion, elevated LDH, proteinuria, hypertension, thrombocytopenia, anemia, and evidence of microangiopathy. Upon diagnosis, as ravulizumab was on formulary and readily available unlike eculizumab, she was treated with ravulizumab instead of eculizumab. Objectives: To describe the therapeutic response to ravulizumab in one patient diagnosed with TA-TMA. Design/Method: A retrospective chart review was performed regarding this patient's ravulizumab treatment course, and direct discussions were had with the patient's care team. Results: Ravulizumab (loading dose of 600 mg followed 2 weeks later by maintenance dosing of 600 mg every 4 weeks) was administered. Pre-treatment CH50 was >75 U/mL (range: 30-75 U/mL) with sC5b9 and C3 complement levels at the upper limit of normal at 220 ng/mL (range: ≤244 ng/mL) and 143 mg/dL (range: 72-164 mg/dL), respectively. Clinical normalization of the patient's TA-TMA was achieved two weeks after loading dose administration with normalization of LDH and blood pressure values, improved proteinuria, decreased transfusion requirements, absence of schistocytes on peripheral smear, and complete resolution of pericardial effusion. A total of 5 maintenance doses of ravulizumab were administered approximately every 4 weeks with CH50 ranging <3-33 U/mL during this time period. Five maintenance doses were administered as the optimal duration was unknown and the patient's TA-TMA treatment course was complicated by COVID-19 infection, for which there was concern could lead to TA-TMA reactivation (which did not occur). The ravulizumab was well tolerated throughout with amoxicillin used for meningococcal prophylaxis. Conclusion: While studies evaluating ravulizumab for treatment of TA-TMA are ongoing, ravulizumab successfully led to complement blockade and clinical improvement in this patient with TA-TMA.
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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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Introduction: While Covid-19 pandemic spreads around the world, there has been described different evolution in individuals according to risk groups. The onset of the disease, which is mainly associated with respiratory distress, has its classic imaging presentation as ground-glass opacities in computer tomography (CT), although there are plenty of other possible findings. In pediatrics, the infection has its own particularities, rarely presenting severe course. Since April 2020, even if uncommon and less prevalent than in adults, cases with worse outcome started being described, mainly associated with multisystem inflammatory syndrome. Oncologic patients have higher mortality rates, and in the hematologic malignancies, this risk factor is even more evident, where severe lymphopenia is frequent. Proportionally, there is still small data about pediatric leukemia patients during Covid-19 disease, as there is also lack of imaging descriptions. Objectives: Evaluation of pediatric patients under leukemia treatment that had Sars Cov 2 infection, correlating clinical and radiologic presentations. Material and methods: Data was collected from patients in the institution. Leukemia patients with molecular confirmation of Covid-19 were considered. Patients that didn't have confirmation of infection on RT-PCR test were excluded from analysis. Results: During the period from March 2020 to May 2021, there were 11 subjects with leukemia that had Sars Cov 2 proved infection. They were from 3 to 17 years old at Covid-19 diagnosis. From those, 6 had B ALL, 1 T ALL and 4 AML. 1 AML patient had previous allogeneic stem cell transplant. 6 patients had lymphocytes count < 550/mL. 6 patients underwent CT (5 with lymphopenia), and all presented radiologic signs. The main presentation was ground-glass opacity (GGO), present on all the 6 CTs. GGO was bilateral in 4 patients. The other findings were nodule (1), consolidation (1), interlobular septal thickening (1). The patient that presented consolidation had it localized, unilateral and perihilar. Regarding clinical evolution, 5 patients were classified as critical and transferred to ICU;all had a CT with GGO. 3 of them needed respiratory support and 1 needed only supplementary oxygen. This one had an atypical presentation, firstly suspected of transfusion-related acute lung injury, supported by clinical history. 2 patients had septic shock, renal failure and myocarditis combined. There was 1 decease (mortality 9% in the group), in a patient with severe respiratory presentation, associated with pulmonary Graft-versus-host disease. Discussion: This study showed that the main imaging finding in the group was GGO, which was present in all patients that had a CT performed. All the subjects that needed intensive care had imaging proof of pulmonary involvement, even if the complications were also due to multisystemic inflammation. CT has been described with a high sensitivity for symptomatic Covid-19, and when it is very typical, can be diagnostic also if a negative RT-PCR. Patients undergoing leukemia treatment are immunocompromised and have low anti-viral defense, which could lead to higher risk of worse onset. The exam was not done for all patients in this study, the choice for indicating CT was based on clinic presentation and laboratory, which could bring a bias on positivity for GGO. Conclusion: GGO is the main finding in CT scan in Covid-19, which was also found in this pediatric leukemia group.
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Introduction: The use of high-dose post-transplant cyclophosphamide (PTCY) has revolutionized graft-versus-host disease (GVHD) prophylaxis and allowed to successfully reconsider haplotransplant in recent years. As this strategy significantly reduces the incidence of both acute and chronic GVHD, PTCY has been thereafter considered not only in matched settings but also as sole GVHD prophylaxis, at least when considering myeloablative allotransplant using matched sibling (MSD) or unrelated (MUD) donors and bone marrow as source of graft. Here, PTCY, as a sole GVHD prophylaxis, was tested in a reduced-intensity conditioning (RIC) setting, using peripheral blood stem cells (PBSC) as source of graft considering that this platform is currently broadly used worldwide in adults. Methods: This prospective monocentric phase 2 study was designed with the main objective to demonstrate the feasibility and safety of using only PTCY (without cyclosporine A nor mycophenolate mofetyl after transplant) in adults (18-70 years old) eligible for a RIC PBSC transplant with MSD or MUD. The Baltimore platform with 2 days of PTCY 50mg/kg/day on days 3 and 4 post infusion was considered as conditioning regimen, using fludarabine for lymphoid disease or clofarabine for myeloid disease. The primary objective was to appreciate the incidence of corticosteroid-resistant acute grade 3-4 GVHD (CR 3-4 GVHD) within 100 days post-transplant. According to statistical rules, patients have to be included in a step by step fashion (3, 3, 6, 15, 15 and 17 patients) for a total of 59 evaluable patients (meaning having received PTCY), in order to stop the protocol soon enough in case of excessive rate of deleterious severe acute GVHD (graded according to Mount Sinai International Consortium). Thus, the trial had to be stopped in case of documentation of > 2 CR 3-4 GVHD for the first 3 patients, >3 CR 3-4 GVHD for the first 6 patients, > 4 CR 3-4 GVHD for the first 12 patients, > 6 3-4 CR GVHD for the first 27 patients, > 8 CR 3-4 GVHD for the first 42 patients and finally as soon as > 9 CR 3-4 GVHD for the last included patients. All patients gave informed consent. The trial was registered at ClinicalTrials.gov Identifier: NCT03263767. Results: The results of the first 27 first patients (males n=17 and female n=10;median age: 59 years old (yo), range: 26-70) are reported here. They were included between February 2018 and November 2020. Diagnoses were AML (N=8), MDS (N=5), CMML (N=2), myelofibrosis (N=5), CML (N=1), DLBCL (N=1), T-cell lymphoma (N=1), Philadelphia positive B-ALL (N=1), CLL (N=1), lymphoblastic lymphoma (N=1) and mixed phenotype acute leukemia (N=1). Donors were MSD in 10 cases and MUD in 17. Only one primary graft failure was documented in a 61 yo MDS patient with active disease at transplant. He is however still alive in response after autologous reconstitution. With a median follow-up of 17.6 months (range: 10-42) for alive patients at the time of analysis (July 2021), 1-year and 2-year survivals were 80.9+7% and 74.7+9%, respectively, for both OS et DFS. GVHD-free/relapse-free survival (GRFS) at 1-year and 2-year was 58.7+9% and 52.2+10%, respectively. Three relapses (11%) and 6 deaths occurred. Deaths were due to acute GVHD in 4 patients (including 1 with sepsis and 1 with SARS-COVID 19 infection) and relapse in 2. Grade 2, 3 and 4 acute GVHD occurred in 11, 1 and 4 patients, respectively, for a total of 59% of grade 2-4 acute GVHD. CR 3-4 GVHD was observed in all of 5 patients with acute grade 3-4 GVHD and 4 died related to GVHD. Moderate/severe chronic GVHD occurred in 5/22 (22.7%) evaluable patients, including 4 still on immunosuppressive therapy at 40, 28, 25 and 16 months post-transplant. Overall non-relapse mortality (NRM) was 14.8% and related to acute GVHD. However, the number of cases conducting to stop the protocol was not reached. Conclusion: PTCY as a sole GVHD prophylaxis is here demonstrated as possible and relatively safe for adults receiving a matched PBSC Baltimore-based RIC allograft. The very good survivals reported he e may be related to a strong GVL effect associated with the high incidence of acute GVHD. However, because of this high incidence and the fact that NRM was related to GVHD after this first analysis, we have now made an amendment to test the addition to PTCY of one day of anti-thymoglobulin (ATG) 2.5 mg/kg on day-2 for the next 32 patients to be included. This second cohort receiving PTCY+ATG as a sole prophylaxis is ongoing.
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BACKGROUND Digital pathology and artificial intelligence (AI) are areas of growing interest in pathology. A number of institutes have already integrated digital imaging into routine workflow, relying on AI algorithms for the detection of various cancers and mitotic activity quantification. Despite the use of whole slide imaging (WSI) for tissue evaluation, the field of hematology has lagged behind. While many hospitals rely on limited technologies for automated peripheral blood evaluation (e.g. CellavisionTM), the Scopio LabsTM X100 digital scanner provides high resolution oil-immersion level dynamic images of large scanned areas (https://scopiolabs.com/hematology/). With recent FDA-clearance and newly implemented AI capabilities, the Scopio Labs scanner allows for clear and accurate cytomorphologic characterization and cell quantification for peripheral blood smears (PBS). To this end, we aimed to be one of the few pioneering institutes in the United States to adopt early and implement this technology into our routine workflow as a 'hub and spoke' model for optimized case assessment, data sharing and result reporting across multiple satellite locations within our hospital health system. DESIGN A Scopio x100 digital scanner was deployed at our main hospital site, with an anticipated secondary scanner for installment at a satellite laboratory. PBS flagged for hematopathologist review from two satellite laboratories were scanned, and full-field digitalized slides were evaluated by hematopathologists following AI automated analyses. RESULTS 311 peripheral smears were scanned since April 2021 and representative slides were digitalized at 100x magnification (Figure 1, weblink: https://demo.scopiolabs.com/#/view-scan/9231acaf-f898-4649-950d-a41c26c2baaa) with rapid monolayer, monolayer, fullfield, and full-field cytopenia scan options available. The automated AI capabilities classified cells into lineage-specific categories with quantification based on cytomorphologic features (Figure 2). Other AI features include additional cell assignment, cell annotation and comments accessible to all users, finalized report PDF generation, export, upload into our current PowerPath TM software with linkage to the corresponding flow cytometry and bone marrow biopsy reports;and the ability to share digitalized slides with clinicians, laboratory personnel and trainees using uniquely generated weblinks. Images can be used for lectures and tumor boards. Additionally, an 80-case study set for PBS was created for medical students, residents and fellow teaching purposes, including cases displaying acute B-cell lymphoblastic leukemia (B-ALL), acute myelomonocytic leukemia (AMML), hypersegmented neutrophils in COVID-19(+) patients, myelodysplastic syndrome (MDS), atypical lymphocytes, hemoglobinopathies, platelet disorders and various lymphomas. Overall improvements were made to the following areas: CLINICAL WORK/DIAGNOSIS 1. Time-saving due to pre-categorization of cells into lineage-specific groups for pathologist review 2. Minimizes subjectivity in cell counting and cellularity assessment EDUCATION 1. Case-based collection with flow and molecular being maintained here 2. Efficient case retrieval with retained annotations/comments for teaching purposes 3. Wide array of digitalized images for hematology atlas and publications ARCHIVING 1. Collection of reference images (intra/inter departmental) for an array of morphological entities for clinical reference and refined diagnosis (e.g. Bethesda reference images for pap by ASC) 2. Digital catalogue for long-term case follow-up and retrospective review CONCLUSION The Scopio Labs X100 digital system provides an efficient and cost-effective web-based tool to streamline clinical workflow and enhance PBS evaluation. With its recent AI capabilities of cell quantification, lineage-assignment and report-generation, we aim to continue our efforts to fully integrate Scopio Labs into our routine daily clinical workflow for reviewing PBS specimens. CONFLICT OF INTEREST STATEMENT The authors have nothing to isclose with regard to the submitted work (Figure Presented).
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Background. The novel Corona virus disease 2019 (COVID-19) is currently a global threat. Cancer patients constitute a group that is at high risk of COVID-19 infection with a more severe disease course and higher mortality rate. Case description. We report a case of COVID-19 occurring concurrently with B-cell acute lymphoblastic leukemia (ALL) in a young male patient. After verification of the morphological and immunophenotypic profiles of leukemia, the patient received ALL treatment (ALL-2009 protocol) with concurrent administration of antiviral and antibacterial drugs, as well as immunoglobin replacement therapy. Neutropenia caused by cytostatic treatment led to the progression of lung damage and respiratory failure, which required the withdrawal of cytostatic drugs. The patient was transferred to the Intensive Care Department, where dexamethasone therapy as well as antibacterial and antifungal therapy was continued. Since the lung damage reached 75 % and respiratory failure began to increase, non-invasive ventilation of the lungs was started. Clinical and hematological remission with hematologic recovery and subsequent pneumonia regression was achieved. However, long-term persistence of the virus was observed, and therefore the strategy for treating acute lymphoblastic leukemia was revised. Maintenance therapy with mercaptopurine and methotrexate was administered. After elimination of the virus on the 56th day from the initial positive test, therapy according to the ALL-2009 protocol was continued. Conclusion. The tactics of treating cancer patients with hemoblastosis during a pandemic should be selected individually with an assessment of the potential benefits and risk of life-threatening complications.
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Introduction: Acute lymphoblastic leukemia in adults represent amajor therapeutic challenge even in modern era. Constantly evolvinggenomics has led to a better risk stratification and prognostication.Aims &Objectives: Here we present a novel mutation in calreticulingene in a patient with Precursor B lineage Acute lymphoblasticleukemia.Materials &Methods: A 19 year old boy presented with fever,jaundice and pancytopenia. Initial investigation revealed a hemoglobin of 5.8 g/dl with a total leukocyte count of 700 cells/mm3 andplatelet count of 11,000/mm3. Differential count showed 95% lymphocytes and 5% neutrophils and no blasts with mildanisopoikilocytosis on PBF. Bone marrow biopsy demonstartedreduction granulocytic and erythroid lineage with adequatemegakaryocytes and occasional collections of immature appearingcells, whose charcter was not able to be definitely ascertained. PETCT showed FDG avid lymph nodes on both sides of diaphragm, withPET guided biopsy was suggestive of non specific lymphocyticinflammatory infiltrate. A diagnosis of hemophagocytic lymphohistiocytosis (HLH) was made according to HLH 2004 criteria (Fever,cytopenias, hypertriglyceridemia, splenomegaly and elevated serumferritin levels). However workup for primary HLH and primaryimmune deficiencies were negative.Clinical exome sequencing forprim was postive for mvk transcript (c.808G >A). He was treatedwith IVIG and short course steroids. Repeat bone marrow was normocellular with mild erythroid prominence and adequaterepresentation of granulocytic and megakaryocytic lineage elements.He was under regular follow up thereafter.Result: He developed mild Covid illness a month after discharge. Amonth after recovery from illness, he presented with easy fatiguabilityand pancytopenia (Hb: 7.1 g/dl, TLC: 900 cells/mm3 and Plateletcount: 1.46 lakhs) with presence of occasional blast in PBF. Repeatbone marrow was markedly hypercellular with 76% blast.Megakaryocytes were relatively preserved. On flow cytometry, blastswere positive for CD 10, CD 19, CD 20, cyto CD 79a, CytoCD22, CD34, CD 45, HLA DR and TDT and negative for MPO CD 2 CD 3 CD13 aand CD 33 consistent with Precursor B Lineage acute lymphoblastic leukemia. Multiplex RT-PCR for recurrent geneticabnormalities (ALL) were negative. A never reported CALR (TYPE1) mutation was found in this patient. CALR plays an important rolein cell proliferation, apoptosis and immune responses. Patient wastreated with modified BFM regimen and Rituximab, attained CR postinduction and currently in consolidation phase of therapy.Conclusions: CALR mutation has never been reported before in acase of acute lymphoblastic leukemia. Long term follow up of patient is required to conclude whether the novel mutation has prognostic andtherapeutic implications.
ABSTRACT
Background: In pediatrics, acquired aplastic anemia (AA) is most commonly due to infection, particularly viruses, when a cause can be identified. Coronavirus disease 2019 (COVID-19) has affected more than 197 million people worldwide, and children typically experience a less severe disease course. COVID-19 is known to cause transient hematologic abnormalities, including leukopenia, lymphopenia, anemia and thrombocytosis or thrombocytopenia in severe cases. Objectives: Describe three cases of COVID-19 associated acquired aplastic anemia in immunocompetent pediatric patients. Design/Methods: Case series established by retrospective review of the electronic medical record. Results: Case 1: An 8-year-old Hispanic male presented with a three-week history of increased bruising and a one-week history of progressive exercise intolerance, shortness of breath, pallor and fatigue. Labs showed pancytopenia. Bone marrow aspirate and biopsy was markedly hypocellular at 5-10% consistent with aplastic anemia (Figure 1). Work-up for the etiology of his aplastic anemia was only significant for positive SARS-COV-2 antibodies and a SEC23B variant of unknown significance on a comprehensive bone marrow failure (BMF)/myelodysplastic syndrome (MDS)/leukemia panel from the Children's Hospital of Philadelphia (CHOP). He was treated with eltrombopag olamine and then proceeded to immunotherapy with cyclosporine (CsA) and horse antithymocyte globulin (ATG) when a sibling match was not identified for hematopoietic stem cell transplant (HSCT). Three months later, his peripheral blood counts have improved, and he is no longer transfusion-dependent. Repeat bone marrow aspirate and biopsy continues to show markedly hypocellularity at <5%. Case 2: A 5-year-old non-Hispanic white female presented with a two-week history of easy bruising, petechial rash, fatigue and bone pain. Labs showed pancytopenia, and bone marrow aspirate and biopsy showed marked hypocellularity at 5-10% consistent with aplastic anemia (Figure 2). Her aplastic anemia work-up was significant for positive SARS-COV-2 antibodies and subclinical RBC and WBC paroxysmal nocturnal hemoglobinuria (PNH) clones. She was started on eltrombopag olamine and then proceeded to immunotherapy with CsA and ATG when a matched sibling donor was not identified. Three months later, she continues to be severely neutropenic, anemic and thrombocytopenic requiring multiple transfusions. Repeat bone marrow aspirate and biopsy showed variable cellularity with some areas 10-20% and others 70% with an overall cellularity of 50%. Case 3: An 8-year-old non-Hispanic white female presented with a 10-day history of fatigue, bilateral leg pain and pallor. Labs showed pancytopenia, elevated inflammatory markers and elevated hemoglobin F. Bone marrow aspirate and biopsy demonstrated mild-moderate hypocellularity at 40-50%, left-shifted myelopoiesis and dyspoiesis in the erythroid and megakaryocytic cell lines (Figure 3). MDS and acute lymphoblastic leukemia (ALL) fluorescence in situ hybridization (FISH) panels were negative. Additional work-up revealed positive SARS-COV-2 antibodies. Her pancytopenia resolved within two weeks of her initial hospitalization. Four months later, she presented with increased bruising and fatigue. Labs showed leukocytosis, thrombocytopenia, anemia and circulating peripheral blasts. Bone marrow aspirate and biopsy was consistent with B-cell ALL. She is receiving chemotherapy on study COG AALL1732. Conclusion: Severe aplastic anemia (SAA) has high morbidity and mortality, and timely diagnosis is needed for appropriate treatment. Multiple different viral infections have been known to cause acquired aplastic anemia. Data on all the sequelae of COVID-19 infection is still emerging, but it is plausible that COVID-19 infection may cause SAA. All three patients were found to have positive COVID-19 antibodies but did not have any evidence of previous COVID-19 infection. Further research and follow-up is needed to determine if previous COVID-19 infection is indeed a risk factor for development of S A. [Formula presented] Disclosures: No relevant conflicts of interest to declare.