Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

Treating Lymphoma in the Pandemic Era: What We Learned from Our Experience at Fondazione Irccs Istituto Nazionale Dei Tumori

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.

Evaluating Photopheresis Regimens for Advanced CTCL: The Role of the SARS-CoV-2 Pandemic-A Single-Center Retrospective Study

Extracorporeal photopheresis (ECP) is an established, safe, and effective treatment for cutaneous T-cell lymphoma (CTCL). There is no published literature reviewing the clinical efficacy of ECP at varying frequencies or the ideal duration of therapy. The SARS-CoV-2 pandemic necessitated a reduced frequency of ECP for patients with CTCL at our center. We performed a retrospective chart review of patients with CTCL receiving ECP at the Penn Dermatology Photopheresis Service (PDPS) on March 1, 2020, and followed up their course until January 31, 2021. Our retrospective cohort study suggests that one day of ECP with extending duration between treatments can be considered an alternative maintenance regimen in appropriate patients with stable disease on concomitant multimodality immunomodulatory therapy.

TCL-458 Real-World Treatment Patterns in Patients With Sézary Syndrome in the United States and the Impact of Covid-19.

BACKGROUND: Sézary syndrome (SS) is an aggressive type of cutaneous T-cell lymphomas (CTCL). Due to its low prevalence, there are limited data on real-world treatment patterns of available SS therapies. Furthermore, recent approvals of new agents for patients with CTCL as well as COVID-19 likely impacted real-world treatment patterns. OBJECTIVE: To examine real-world treatment patterns and the impact of COVID-19 among SS patients treated in 2018-2020 in the United States. METHODS: Patients in the 2018-2020 Symphony Health Solutions database were classified into 3 groups: ≥1 diagnosis of SS (ICD-10-CM code: C84.1x) in 2018, 2019, and 2020, respectively. Patient characteristics and treatment patterns for National Comprehensive Cancer Network guideline 2.2021 recommended therapies were examined: systemic therapy (e.g., extracorporeal photopheresis (ECP), parenteral, oral agents), skin-directed therapy (SDT, e.g., topical, local radiation, total skin electron beam therapy, phototherapy) and bone marrow transplant. The impact of COVID-19 was assessed using quarterly analysis. RESULTS: The analyses included 869, 882, and 853 SS patients in 2018, 2019, and 2020, respectively (mean age: 66.3, 66.9 and 67.3 years; male: 54.4%, 54.8%, and 55.6%). Overall, systemic therapy increased from 2018-2020 (41.8% to 46.5%), with increased parenteral (20.7% to 28.7%) but decreased ECP (17.0% to 13.5%) usage. SDT increased from 2018-2020 (48.9% to 52.9%), with increased topical (42.3% to 48.3%) but decreased phototherapy (6.3% to 4.1%) usage. ECP, mogamulizumab, and bexarotene were the most prescribed systemic therapies in 2019-2020, with mogamulizumab being the only one with increased usage over time. Quarterly analysis showed decreasing ECP from Q1 to Q4 within each year, with a notable drop in Q2 2020. For parental systemics, there was an increasing trend in 2019 and 2020, but lower utilization in Q4 2020 than in Q3 2020. For oral systemic, there was a notable drop in Q2 2020 but an increased trend in Q3-Q4 2020. CONCLUSIONS: This claims analysis indicated increased use in systemic and SDT among SS patients in 2018-2020. The quarterly analysis indicated that the drop in ECP and oral systemic usage in Q2 2020 coincided with the onset of the pandemic, but there was a stable use of parenteral systemic during 2020.

COVID-related delays in care and illness anxiety for patients with cutaneous T-cell lymphoma

It is well known that the COVID-19 pandemic caused significant treatment delays for dermatology patients, and recent studies demonstrate poor outcomes for patients with cutaneous T-cell lymphoma (CTCL) during this time. However, not much is known about patient reported delays in management of this condition following the pandemic. This study sought to evaluate patient-reported illness anxiety and delays in management of CTCL. Fifty-two CTCL patients were recruited from clinic from October 2020 to October 2021. Patients were asked to complete a 22-question survey adapted from the United States Census Household Pulse Survey. Control data was extrapolated from published national data from the Household Pulse Survey. Of 52 patients surveyed, 28 were male (59.6%). 25 identified as white (54.3%), 18 as Black (39.1%), 8 as Asian (15.3%) and 1 as Native American (2.2%). Average age was 57 years, age range 24-89 years. Results demonstrate that 32.6% (n=15) of respondents had a household member experience loss of employment since March 2020 compared to 39.6% of the US population. 46.8% of respondents vs. 32.3% US population noted some level of difficulty in paying for household expenses including medical care. Only 4.3% of respondents noted that they delayed receiving medical care due to the coronavirus pandemic. When compared to the US population (59.8%), a lower proportion of respondents (48.9%) noted symptoms of nervousness or anxiety over the past week. 27.7% of respondents vs. 46.1% of US population reported feelings of hopelessness or depression over the past week. These results demonstrate a low number of patients reporting care delays, possible due to the interval when data was collected, several months after COVID-19 onset. It is also possible that telehealth contributed to lessening delays in care. Overall, the results of this study reinforce the significant physical, financial, and emotional impact of CTCL on the daily lives of patients, and the heightened impact of COVID-19 on this population.Copyright © 2023

Subcutaneous panniculitis-like T-cell lymphoma post-mRNA-1273 COVID-19 vaccination.

This is a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) was diagnosed by skin biopsy in a patient who presented with fever and erythema nodosum in the umbilicum following mRNA-1273 COVID-19 vaccination. COVID-19 vaccines may cause SPTCL and skin biopsy may help in the diagnosis of erythema nodosum.

Newly diagnosed extranodal NK/T-cell lymphoma, nasal type, at the injected left arm after BNT162b2 mRNA COVID-19 vaccination.

Anti-SARS-CoV-2 vaccines were developed in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the BNT162b2 mRNA vaccine is effective, adverse effects have been reported. Here, we report a case of extranodal NK/T-cell lymphoma, nasal type (ENKL), of the left arm following BNT162b2 mRNA vaccination. A 73-year-old male presented with a lump in the left arm, which was the site where he received the BNT162b2 mRNA vaccine 3 months prior. He was treated with topical corticosteroids and debridement, but the tumor progressed. Additionally, fever, night sweats, and general fatigue were observed. Laboratory findings included thrombocytopenia, elevated lactate dehydrogenase, and soluble interleukin-2 receptor levels. Skin biopsy led to a diagnosis of ENKL. The patient was treated with a 50% dose of SMILE therapy and radiotherapy, resulting in regression of the tumor. It seems that latent Epstein-Barr virus (EBV)-infected NK/T cells were reactivated by vaccination and contributed to the onset of ENKL. This is the first report of ENKL after BNT162b2 mRNA vaccination. The present case highlights the possible risk of development of malignant lymphoma, including ENKL at the injection site, after BNT162b2 COVID-19 vaccination.

A case of cerebral amyloid angiopathy related inflammation after vaccination against SARS-CoV-2

Background: Cerebral amyloid angiopathy related inflammation (CAA-RI) is a neuroinflammatory disease that is associated with perivascular amyloid- deposition. Case presentation: A middle-aged woman with a remote history of autoimmune disorders presented with unilateral migraine headaches, dizziness, unsteadiness, and fogginess 36 hours after administration of mRNA vaccine against SARS-CoV-2. Initially, unilateral leptomeningeal enhancement on MRI on the same side of headaches raised suspicion for leptomeningeal involvement of her known cutaneous T-cell lymphoma in remission. After two relatively unremarkable CSF analyses, she underwent a brain biopsy which showed amyloid deposits in vessels instead of lymphomatous infiltration. She was diagnosed with CAA-RI, and the headache and cognitive symptoms responded well to high-dose corticosteroids with a slow taper. Discussion/conclusion: We review the clinical literature of CAA-RI and its potential association with amyloid-related imaging abnormalities (ARIA) after administration of immunotherapy against amyloid.Copyright © 2022

An Unusual Case of Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type Masquerading as Dacryocystitis and Sinusitis.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NNKTL) is a rare and highly aggressive non-Hodgkin lymphoma originating from NK or γδ T cells infected by Epstein-Barr virus (EBV). In the United States, NNKTL is usually noted in people of Asian or Hispanic descent. Natural killer/T-cell lymphoma, nasal type commonly involves the upper aerodigestive tract, including the nasopharynx, nasal cavity, Waldeyer's ring, and oropharynx. Extensive local destruction and invasion has been noted, especially of the paranasal sinuses, hard palate, and central nervous system; involvement of the nasolacrimal duct with dacryocystitis is yet to be reported. We report a rare case of a Hispanic man with extranodal NNKTL masquerading as persistent dacryocystitis and necrotizing sinusitis unresponsive to antibiotics and surgical intervention. An extensive background of necrosis and inflammation was noted on pathology, and additional analysis with immunohistochemistry and in situ hybridization after repeat biopsy were necessary for accurate diagnosis.

Successful Diagnosis by Video-Assisted Thoracoscopic Surgical Lung Biopsy in a Case of Progressive Primary Pulmonary Extranodal Natural Killer/T-cell Lymphoma, Nasal Type: A Case Report.

Malignant pulmonary lymphoma is very rare and the majority of which are B-cell lymphomas. Since primary pulmonary extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) is difficult to diagnose and associated with poor prognosis and aggressive course, some cases are diagnosed at the postmortem autopsy. We report a case of a 53-year-old man with primary pulmonary ENKL diagnosed by video-assisted thoracoscopic surgery (VATS) lung biopsy. This case explains the importance of VATS lung biopsy and in-depth evaluation, including flow cytometry, chromosome, genetic, and immunostaining tests, when primary pulmonary malignant lymphoma is suspected.

Patients with B-cell malignancies experience reduced antibody responses with class switching defect following BNT162b2 SARS-CoV-2 vaccination

Vaccines having aided in escaping the majority of the population from immunological naïvety, our strategies are now shifting towards an increased focus on identifying and protecting the extremely vulnerable. We here describe the results of testing 12 patients, those with lymphoid malignancies having been targeted their B-cells for therapy with rituximab-containing regimens or a Bruton tyrosine kinase inhibitor, for anti-SARS-CoV-2 spike antibodies after receiving the BNT162b2 mRNA vaccine doses. The interval from last dosing of B-cell depletion therapy to SARS-CoV-2 vaccination was at median 5.3 (range 3.1–6.6) months. Using the ‘seroprotection' threshold of 775 [BAU/mL] for the anti-spike antibody titer, our finding points out the crucial unresponsiveness of the targeted population with 0/12 (0%) achieving ‘seroprotection'. Although IgG seroconversion was observed in 4/12 (33%), supporting the overall benefit of vaccination, the figures still point out a potential need for optimization of practice. IgA was further less responsive (unsuccessful ‘seroconversion' in 11/12 (92%)), implicating an underlying class switch defect. Those with depletion on B-cells are caught at a dilemma between, being too early and too late on receiving SARS-CoV-2 vaccines. They wish to get over their immunological naïvety at the earliest, while, in order to assure quality immune memory, are also required to hold the patience for their B-cells to repopulate. Although it remains an issue whether intensified vaccine schedules and/or regimens will lead to stronger immunogenicity or more effective boosters for non-responders, we shall take advantage of every increasing evidence in order to optimize current options. © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases

Two cases of challenging cutaneous lymphoid infiltrates presenting in the context of COVID-19 vaccination: a reactive lymphomatoid papulosis-like eruption and a bona fide lymphoma.

COVID-19 infection and vaccination may be associated with a wide variety of cutaneous and immune manifestations. Here, we describe two patients who presented with monoclonal cutaneous T-cell infiltrates that showed cytologic and immunophenotypic features concerning for lymphoma shortly following COVID-19 vaccination. In one case, the eruption completely resolved. The second patient showed initial resolution, but her disease recurred and progressed following a breakthrough SARS-CoV-2 infection. These cases suggest that immune stimulation following exposure to SARS-Cov-2 protein(s) in vaccine or infection may facilitate the development of a lymphoma or lymphoproliferative disorder in susceptible individuals. Moreover, they demonstrate that separating these cases from pseudolymphomatous reactive conditions is often challenging and requires close clinical correlation.

A rare case of lethal midline granuloma posing a diagnostic challenge in COVID times and the response to chemotherapy

Lethal midline granuloma is a rare aggressive, mutilating disorder of the upper airways. It is most likely secondary to natural killer/T-cell lymphoma and is difficult to diagnose owing to the varied and nonspecific symptoms. It is usually prevalent in the fourth decade of life and carries a poor prognosis. Our patient was a 19-year-old male with disease duration of 3 months, was diagnosed with lethal midline granuloma based on clinical examination, histopathology, and immunohistochemistry. The patient responded well to the first cycle of chemotherapy.

SIGNIFICANT INCREASE IN NEWLY DIAGNOSED HEMATOLOGICAL MALIGNANCIES FOLLOWING LOCKDOWN EASE IN CROATIA

Background: Special epidemiological measures aimed at suppressing SARS-CoV-2 outbreak were introduced in Croatia in March 2020, thus reducing regular work capacity in hematological outpatient and inpatient care. In our hospital, this included relocating the entire Hematology Department to a remote location, reduction of hospital beds in the Hematology Inpatient Unit by approximately 60%, Day Clinic operating at a reduced capacity, and a complete suspension of Hematology Polyclinic during first lockdown. Aims: Herein we report our observation of unusually high incidence of newly diagnosed malignant hematological diseases following first lockdown ease in May/June 2020. Methods: We collected data of patients hospitalized in Hematology Department for 4 periods: May 1 - June 15, 2020 for the test arm, and the same calendar period during previous 3 years (May 1 - June 15 of each of the calendar years 2017, 2018 and 2019), for the control arm. The rationale for such design was that a phenomenon of re-establishing regular work capacity, following temporary restriction, was only observed in the test arm. The study included patients of both sexes older than 18 who were diagnosed with either: Hodgkin lymphoma (C81.0 -C81.9 according to the 10th ICD Revision), different types of non-Hodgkin lymphoma (subsections C82.0 - C83.9 and C85.1-C85), as well as multiple myeloma and malignant plasma cell neoplasms (C90.0 - C90.3). Excluded from our study were diagnoses of T/NK cell lymphoma (C84.0- C84.9;C86.0 - C86.6), malignant immunoproliferative diseases (C88.0 - C88.9), leukemias and other specified malignant neoplasms of lymphatic, hematopoietic and related tissues (C91.0 - C96.9) as well as polycythemia vera and non-malignant hematological diseases (D45 and D50 - D89 in ICD-10). Results: In years 2017-2019, similar numbers of patients were diagnosed with a hematological malignancy in our Department (n=4 for 2017, n=8 for 2018, n=4 for 2019) whereas in 2020, a total of 28 patients were diagnosed during the same calendar period (Hodgkin lymphoma: n=5, NHL n=12, multiple myeloma n=7, CLL/SLL n=4). Statistical analysis revealed a significant increase (p ≤0.05) of newly diagnosed hematological malignancies in May and first half of June 2020, when compared to the same calendar periods during previous three years. Further statistical analysis has not established significant differences in outcome (difference in EFS statistically insignificant, p=0.86), as we had expected in the short follow-up period. (Table Presented) Summary/Conclusion: Facilitating treatment of patients affected by the novel coronavirus represented a welcome change in healthcare system in early 2020, in our country and abroad. At the same time, however, the reduction of tertiary health care capacity aimed at population with hematological diseases presented serious risks for successful diagnosis and treatment outcome, a subject that gained wide attention in literature. It has been reported that, also due to psychological reasons, a fraction of patients delayed seeking medical attention after noticing symptoms. In our study we aimed at analyzing the effects of lockdown ease on the number of newly diagnosed hematological malignancies. We were able to demonstrate the effect of pandemic-related measures on detecting new disease cases. It remains to be clarified if a sudden surge in new diagnoses was due to delayed first physician's appointments/hospitalizations, as is suggested by available literature. The results of our study suggest that longer follow-up period will be required in order to clarify the effects of possible late diagnoses on the treatment outcome.

PROGNOSTIC FACTORS IN PATIENTS IN THE TERMINAL PHASE OF HEMATOLOGICAL MALIGNANCIES WHO RECEIVED HOME MEDICAL CARE

Background: In the current global COVID-19 pandemic, terminal care in a patient's home has been expanded as a positive choice even for patients suffering from hematological malignancy (HM). Although there are many tools for predicting the prognosis of patients in the terminal phase of solid tumors, there is little information about prognostic factors in patients in the terminal phase of HM, especially patients receiving home medical care (HMC). In comparison to patients with solid tumors, those with HM are more likely to have acute diseases such as acute bleeding and acute infection leading to death. A previous report revealed that HM was a factor associated with aggressive end-of-life care. Because of the various complications associated with HM, it was reported to be difficult to predict the prognosis for patients with HM. Providing patients with accurate information about prognosis is important for them to consider how to spend their remaining life. Aims: In patients in the terminal phase of HM who received HMC, we aimed to validate the usefulness of two prognostic models: Palliative Prognostic Index (PPI), which is an established prognostic model for patients in the terminal phase of a solid tumor, and the prognostic model reported by Kripp et al., which is a prognostic model for patients with HM in a palliative care unit. In addition, we aimed to determine prognostic factors for patients in the terminal phase of HM who received HMC and to develop a more detailed prognostic scoring system. Methods: We retrospectively evaluated 136 patients in the terminal phase of HM who were receiving HMC provided by 6 clinics between 2008 and 2022. Medical records relevant to prognosis were collected by a chart review. The effects of possible factors associated with overall survival (OS) were determined by the Kaplan-Meier method and univariate and multivariate Cox regression models. This study was approved by the IRB of Hokkaido University Hospital. Results: Patients characteristics were as follows: male/female, 78/58;age, 25 to 94 years;median age, 79 years;AML, 50 patients;B-NHL, 32;MDS, 24;MM, 13;T-NHL 6;ALL, 5;ATL 2, CMML 2, and PV, 2. According to PPI, there was no significant difference in OS between the intermediate-risk group and the low-risk group (panel A;P = 0.15). By using the prognostic model reported by Kripp et al., we could stratify the patients into 3 risk groups with significantly different survival times (panel B;P < 0.01). However, there was a wide range of survival times in the high-risk group (OS, 0 to 125 days;median OS, 24 days). In our investigation of factors associated with OS, multivariate analyses revealed that there were 7 factors associated with poor OS (panel C). For the development of our prognostic scoring system, each variable was weighed according to the value of the hazard ratio (panel C) and 4 risk groups were shown to clearly discriminate survival (P < 0.01): low-risk group (n = 25, median OS of 434 days), intermediate-low risk group (n = 60, median OS of 112 days), intermediate-high risk group (n = 31, median OS of 31 days), and high-risk group (n = 20, median OS of 9 days). (Figure Presented ) Summary/Conclusion: This is the first investigation of prognostic factors that influence the overall survival of patients in the terminal phase of HM who received home medical care. In comparison to previously reported prognostic models, our scoring system could stratify patients in more detail. Providing patients and medical staff with accurate information about prognosis will lead to a higher quality of life in the terminal phase and better support by medical staff.

Rare Case of Refractory Hypoxia and Severe Multiorgan Failure from Secondary Lymphohistiocytosis Successfully Bridged to Treatment with Extracorporeal Membrane Oxygenation Support.

Introduction: Acute respiratory distress syndrome (ARDS) is an uncommon complication of hemophagocytic lymphohistiocytosis (HLH). Non-specific findings that mimic other diseases make timely diagnosis and treatment challenging. We present a rare case of severe ARDS and multiorgan failure from secondary HLH due to peripheral T-cell lymphoma. Case presentation: A middle-aged female presented with dry cough and fever for three days. On presentation, the patient was febrile to 105°F and hypoxic to 88% on room air. Chest X-ray showed bilateral interstitial infiltrates. Laboratory investigations showed lymphopenia and elevated inflammatory markers. The viral panel, including coronavirus disease-2019 (COVID-19), influenza, and respiratory syncytial virus (RSV), was negative. Her respiratory status progressively worsened, requiring invasive mechanical ventilation for ARDS. Despite lung-protective ventilation, prone positioning, and the use of paralytic agents, the patient continued to remain hypoxic, necessitating extracorporeal membrane oxygenation (ECMO) support. The patient was started on antibiotics and high-dose steroid. Thereafter, she developed a leukemoid reaction, and the ferritin level started rising; raising suspicion for lymphophagocytosis. During this time, she also developed acute liver and kidney failure and required multiple vasopressors and renal replacement therapy. Eventually, a diagnosis of mature peripheral T-cell lymphoma was established. Subsequently, her respiratory status and multiorgan failure significantly improved, and ECMO was explanted after 2 weeks. She was started on etoposide and steroid, and eventually discharged after 6 weeks. Discussion: This is the first case describing a successful implementation of ECMO in an adult diagnosed with ARDS secondary to mature peripheral T-cell lymphoma; allowing for recovery of respiratory status, which was compromised during the initial cytokine storm and provided time to establish the diagnosis and initiate appropriate treatment of secondary HLH mature due to peripheral T-cell lymphoma, and in the end, prevented a fatality. We believe that ECMO may be appropriately instituted in rapidly deteriorating patients with an unknown illness refractory to conventional therapy, to allow for end-organ recovery, to reach a diagnosis, and to administer appropriate therapy. How to cite this article: Hundal J, Bowers D, Gadela NV, Jaiswal A. Rare Case of Refractory Hypoxia and Severe Multiorgan Failure from Secondary Lymphohistiocytosis Successfully Bridged to Treatment with Extracorporeal Membrane Oxygenation Support. Indian J Crit Care Med 2022;26(8):970-973. Statement of Ethics: This is a case report and does not contain any images or patient identifying information.