Brain MRI imaging markers associated with death in children with central nervous system involvement of hemophagocytic lymphohistiocytosis.

OBJECTIVES: To investigate the association of brain MRI and clinical variables with death in children with central nervous system involvement of hemophagocytic lymphohistiocytosis (CNS-HLH). METHODS: Clinical and brain MRI data of children with CNS-HLH from January 2012 to March 2022 were reviewed retrospectively. Patients were divided into the deceased group and the surviving group. The intergroup differences of seven brain MRI variables, twelve clinical variables, and underlying diseases were studied. RESULTS: One hundred and fourteen patients were included in this study, consisting of 59 who died and 55 who survived. The included clinical variables did not show statistically independent correlation with patients' deaths. For MRI variables, a multivariate analysis demonstrated restricted diffusion of lesion (OR = 9.64, 95% CI: 3.39-27.43, p < 0.001) and count of affected brain regions (CABR) (OR = 1.24, 95% CI: 1.03-1.49, p = 0.02) were independent risk factors for death. ROC curve showed CABR (AUC = 0.79, 95% CI: 0.70-0.87, p < 0.001) is highly predictive for mortality with an optimal cutoff value of 4.5 (sensitivity 76%, specificity 73%). For HLH subtypes, familial HLH (F-HLH, OR = 9.90, 95% CI: 2.01-48.87, p = 0.005) and immune-compromise-related HLH (IC-HLH, OR = 4.95, 95% CI: 1.40-17.46, p = 0.01) presented statistically stronger association with death than infection-related HLH. F-HLH and IC-HLH preferred to have large lesions, restricted diffusion, and more brain regions involved than other subtypes. CONCLUSION: Brain MRI features exhibit independent prediction for mortality in children with CNS-HLH, and HLH subtypes pose effects on patient outcomes and brain MRI findings. CLINICAL RELEVANCE STATEMENT: The number of affected brain regions and diffusion restriction of lesion exhibit significant correlation with mortality in children diagnosed with CNS-hemophagocytic lymphohistiocytosis, and may serve as candidate MRI markers for the prediction of the disorder's severity. KEY POINTS: • The brain MRI markers, restricted diffusion of lesion and count of affected brain regions, significantly correlated with death. • Familial and immune-compromise-related hemophagocytic lymphohistiocytosis presented statistically stronger association with death than infection-related subtype. • Brain MRI is potential in death-predicting for children with central nervous system involvement of hemophagocytic lymphohistiocytosis.

Spectrum of neuroradiological manifestations in primary hemophagocytic lymphohistiocytosis: a comparative study of EBV-induced versus non-EBV-induced forms in 75 genetically confirmed pediatric cases.

OBJECTIVES: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition affecting young children. It is potentially triggered by Epstein-Barr virus (EBV). This study describes the neuroradiological features observed in 75 children with genetically confirmed primary HLH, comparing EBV-induced with non-EBV-induced HLH forms. METHODS: Brain MRIs between 2007 and 2021 from 75 children with HLH according to the 2004 Histiocyte Society criteria and with a confirmed HLH-related mutation, were retrospectively reviewed by two pediatric neuroradiologists blinded to EBV status and to mutation status. At diagnosis, 17 children with EBV viremia above a threshold of 1000 copies/mL were included in the EBV-induced HLH group. The remaining 58 patients were included in the non-EBV-induced HLH group. RESULTS: Of the 75 children initially included, 21 had abnormal MRI (21/75 (28%); 9/17 in the EBV-induced HLH group and 12/58 in the non-EBV-induced HLH group). All patients with abnormal MRI had neurological symptoms. Abnormal MRIs showed white matter lesions; the posterior fossa was affected in all but one case. There was no significant difference between groups regarding the localization or morphology of white matter lesions. The striatum was more frequently affected in the EBV-induced HLH group (8/9 (89%) versus 1/12 (8%), p = 0.00037). All lesions, whether in the white matter or in the basal ganglia, presented increased ADC values on diffusion weighted imaging (DWI). CONCLUSION: In this study of 75 children with genetically confirmed HLH, only children with neurological signs had abnormal brain MRI. Bilateral striatum involvement suggested an EBV-induced form of HLH. KEY POINTS: • In children with genetically proven HLH, only those with neurological signs did have brain abnormalities at MRI. • All patients with abnormal brain MRI had multiple white matter lesions with increased ADC values, including in the posterior fossa in almost all cases. • Basal ganglia and in particular the striatum were bilaterally and symmetrically affected in almost all EBV-induced HLH patients, in contrast to the non-EBV-induced HLH patients.

Brain Magnetic Resonance Imaging Findings of Pediatric Hemophagocytic Lymphohistiocytosis Could Be Diagnostic and Life-Saving.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal disease and may also present with central nervous system findings at the beginning without specific diagnostic criteria. Brain magnetic resonance imaging (MRI) findings are diverse and can also be diagnostic. We aimed to emphasize the importance of brain MRI findings in the early diagnosis of this fatal disease. METHODS: MRI findings, clinical presentations, treatment response, and prognosis of seven patients with HLH were described. RESULTS: There were seven pediatric patients who were initially diagnosed with HLH with neurological findings without systemic signs of HLH: four as primary, two as secondary, and one as possible primary HLH. All patients had contrast-enhancing diffuse cerebellar and brainstem lesions; patchy periventricular and callosal cerebral lesions were observed. Thalamus involvement was found in three (42.8%), corpus callosum involvement in six (85.7%), and cervical spinal involvement in one (14.2%). Patients were followed up with these MRI findings, with prediagnoses of toxic, metabolic, infectious, vascular, and demyelinating diseases. Not all patients met the HLH diagnostic criteria due to incomplete systemic/laboratory findings; therefore, only two were immediately directed for hematopoietic stem cell therapy. Four died shortly after admission, one patient could not be followed up after HLH treatment, and two patients who fulfilled the HLH diagnostic criteria underwent hematopoietic stem cell transplantation and survived. CONCLUSIONS: Brain MRI findings, especially in the presence of neurological findings, allow for early diagnosis, which can be life-saving. These common features in brain MRI findings should be evaluated with this suspicion and included in HLH diagnostic criteria.

18F-FDG PET/CT for Identifying the Potential Primary Diseases and Predicting Prognosis of Secondary Hemophagocytic Lymphohistiocytosis in Children.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal illness, which can be divided into primary HLH (pHLH) and secondary HLH (sHLH). pHLH can be driven by genetic defections. Moreover, the sHLH is usually be triggered by malignancy or non-malignancy diseases. Sixty-two newly diagnosed sHLH patients with known etiology and those who underwent 18F-FDG PET/CT examination from July 2018 to December 2020 were retrospectively analyzed. They were divided into malignancy-associated HLH (M-HLH, n = 13) and non-malignancy-associated HLH (NM-HLH, n = 49). The metabolic parameters of the liver (Li), spleen (Sp), bone marrow (BM), lymph nodes (LN), and their ratios to the liver background (LiBG) and mediastinum (M) were compared between two groups. These metabolic parameters were evaluated for correlation with laboratory parameters and prognostic parameters. We found that the SUVmax-LN/Sp/Li and SUVmean-Sp in M-HLH were significantly higher than those in NM-HLH (P=0.031, 0.035, 0.016, and 0.032). The malignant disease should be considered when SUVmax-LN was higher than 4.41 (sensitivity 61.5%, specificity 81.6%). Hypermetabolic lesions in extranodal organs were more likely to occur in M-HLH than in NM-HLH (P=0.011). IFN- γ was positively correlated with SUVmax-BM/Li/Sp and SUVmean-BM/Li/Sp (P < 0.05). Ferritin, sCD25, IL-6, and IL-10 were positively correlated with SUVmax-Sp and SUVmean-Sp (P < 0.05). In Epstein-Barr virus-associated HLH (EBV-HLH), the SUV parameters of bone marrow were significantly correlated with a poor 2-week treatment response, overall survival, and event-free survival (P < 0.05). We conclude that some 18F-FDG PET/CT metabolic parameters can help identify the etiology of sHLH in children and provide directions for further inspection. The malignant disease should be considered when the SUVmax-LN is higher than 4.41 and hypermetabolic lesions occur in extranodal organs. In EBV-HLH, a higher SUV of bone marrow is associated with a poorer prognosis.

Development and Validation of 18F-FDG PET/CT-Based Multivariable Clinical Prediction Models for the Identification of Malignancy-Associated Hemophagocytic Lymphohistiocytosis.

OBJECTIVE: 18F-fluorodeoxyglucose (FDG) PET/CT is often used for detecting malignancy in patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH), with acceptable sensitivity but relatively low specificity. The aim of this study was to improve the diagnostic ability of 18F-FDG PET/CT in identifying malignancy in patients with HLH by combining 18F-FDG PET/CT and clinical parameters. MATERIALS AND METHODS: Ninety-seven patients (age ≥ 14 years) with secondary HLH were retrospectively reviewed and divided into the derivation (n = 71) and validation (n = 26) cohorts according to admission time. In the derivation cohort, 22 patients had malignancy-associated HLH (M-HLH) and 49 patients had non-malignancy-associated HLH (NM-HLH). Data on pretreatment 18F-FDG PET/CT and laboratory results were collected. The variables were analyzed using the Mann-Whitney U test or Pearson's chi-square test, and a nomogram for predicting M-HLH was constructed using multivariable binary logistic regression. The predictors were also ranked using decision-tree analysis. The nomogram and decision tree were validated in the validation cohort (10 patients with M-HLH and 16 patients with NM-HLH). RESULTS: The ratio of the maximal standardized uptake value (SUVmax) of the lymph nodes to that of the mediastinum, the ratio of the SUVmax of bone lesions or bone marrow to that of the mediastinum, and age were selected for constructing the model. The nomogram showed good performance in predicting M-HLH in the validation cohort, with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.686-0.971). At an appropriate cutoff value, the sensitivity and specificity for identifying M-HLH were 90% (9/10) and 68.8% (11/16), respectively. The decision tree integrating the same variables showed 70% (7/10) sensitivity and 93.8% (15/16) specificity for identifying M-HLH. In comparison, visual analysis of 18F-FDG PET/CT images demonstrated 100% (10/10) sensitivity and 12.5% (2/16) specificity. CONCLUSION: 18F-FDG PET/CT may be a practical technique for identifying M-HLH. The model constructed using 18F-FDG PET/CT features and age was able to detect malignancy with better accuracy than visual analysis of 18F-FDG PET/CT images.

Differential Diagnosis of Hemophagocytic Syndrome by 18F-FDG PET/CT: A Meta-Analysis.

Hemophagocytic syndrome (HPS) is a rare disease in clinical practice, and there are often cases of delayed diagnosis. At present, researchers have applied 18F-FDG PET/CT in the differential diagnosis of HPS, but no consensus has been formed. Therefore, this study aims to systematically evaluate the application value of 18F-FDG PET/CT in the diagnosis of HPS patients. PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wangfang database (Wangfang), and Chinese Biomedical Network (CBM) were searched to collect the relevant studies of 18F-FDG PET/CT in the diagnosis of HPS. Data from the articles were screened and extracted for meta-analysis using Stata16.0 software. A total of 10 retrospective studies, including 300 patients, were included in this meta-analysis. The meta-analysis results showed that the pooled sensitivity was 0.82 (95% CI: 0.67-0.95), specificity was 0.72 (95% CI: 0.51-0.86), positive likelihood ratio was 2.89 (95% CI: 1.46-5.75), positive likelihood ratio was 0.25 (95% CI: 0.12-0.54), diagnostic odds ratio was 2.89 (95% CI: 1.46-5.75), and AUC was 0.84 (95% CI: 0.81-0.87). The SUVmax in the liver, spleen, lymph nodes, and bone marrow of HPS patients was greater than 2.5, and the SUVmax in the spleen, lymph nodes, and bone marrow of malignant HPS patients was higher than that of benign HPS patients. The difference was statistically significant (P < 0.05). According to the existing literature evidence, 18F-FDG PET/CT is an effective method for diagnosing HPS.

MRI Patterns in Pediatric CNS Hemophagocytic Lymphohistiocytosis.

BACKGROUND AND PURPOSE: Neuroimaging has an important role in detecting CNS involvement in children with systemic or CNS isolated hemophagocytic lymphohistiocytosis. We characterized a cohort of pediatric patients with CNS hemophagocytic lymphohistiocytosis focusing on neuroradiologic features and assessed whether distinct MR imaging patterns and genotype correlations can be recognized. MATERIALS AND METHODS: We retrospectively enrolled consecutive pediatric patients diagnosed with hemophagocytic lymphohistiocytosis with CNS involvement treated at 2 pediatric neurology centers between 2010 and 2018. Clinical and MR imaging data were analyzed. RESULTS: Fifty-seven children (40 primary, 70%) with a median age of 36 months (interquartile range, 5.5-80.8 months) were included. One hundred twenty-three MR imaging studies were assessed, and 2 broad imaging patterns were identified. Pattern 1 (significant parenchymal disease, 32/57, 56%) was seen in older children (P = .004) with worse clinical profiles. It had 3 onset subpatterns: multifocal white matter lesions (21/32, 66%), brainstem predominant disease (5, 15%), and cerebellitis (6, 19%). All patients with the brainstem pattern failed to meet the radiologic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. An attenuated imaging phenotype (pattern 2) was seen in 25 patients (44%, 30 studies) and was associated with younger age. CONCLUSIONS: Distinct MR imaging patterns correlating with clinical phenotypes and possible genetic underpinnings were recognized in this cohort of pediatric CNS hemophagocytic lymphohistiocytosis. Disruptive mutations and missense mutations with absent protein expression correlate with a younger onset age. Children with brainstem and cerebellitis patterns and a negative etiologic work-up require directed assessment for CNS hemophagocytic lymphohistiocytosis.

Increased 68Ga-FAPI Uptake in Intramuscular Gluteal Hematoma in a Patient With Hemophagocytic Syndrome.

ABSTRACT: A 39-year-old man was diagnosed clinically with hemophagocytic syndrome, which was suspected to be secondary to a malignancy. Therefore, the patient underwent a 68Ga-FAPI PET/CT scan as part of an ongoing clinical trial (ChiCTR2100044131). Increased tracer uptake was noted the gluteal region. Medical history revealed recent iliac bone marrow aspiration on the same side. On further examination, the lesion was confirmed to be a hematoma. The present case highlights that puncture operations may result in intramuscular hematomas, which might potentially malignancy on a 68Ga-FAPI PET/CT.

Exploring the Intersection of Isolated-CNS Hemophagocytic Lymphohistiocytosis and Pediatric Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids.

CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is an extremely rare neurologic inflammatory condition. Fewer than 10 pediatric cases have been described.Debate persists as to whether it is a distinct disease or a clinical, radiologic, and histologic phenotype evolving into another disorder. We propose that CLIPPERS may be a clinical manifestation of an underlying state of immune-dysregulation.We describe the case of the youngest known report of CLIPPERS, an 18-month-old infant from Melbourne, Australia. Reviewing the literature for all reported pediatric cases, we identified that robust investigation and whole exome sequencing was underutilized and proposed diagnostic criteria were frequently unmet. Particular focus should be paid to genes known to cause familial hemophagocytic lymphohistiocytosis (HLH), with the CLIPPERS phenotype manifesting as a form of isolated central nervous system (CNS)-HLH in some patients. Curative treatment options such as hematopoietic stem cell transplantation may be appropriate for some patients and should be considered early.

Multiple-Organ Involvement in Familial Hemophagocytic Lymphohistiocytosis Type 2 Shown on FDG PET/CT.

ABSTRACT: FDG PET/CT in an 18-year-old man with known familial hemophagocytic lymphohistiocytosis (HLH) type 2 demonstrated abnormally in the brain, liver, and lymph nodes. Pathology showed no sign of lymphoproliferative disease. The patient underwent the chemotherapy of HLH. Six months after chemotherapy, a follow-up FDG PET/CT did not show any abnormal 18F-FDG activity, suggesting a complete response. The present case shows FDG PET/CT might not only be useful in staging the familial HLH but also able to evaluate the therapy response.

Central nervous system involvement in adult-onset relapsing hemophagocytic lymphohistiocytosis responsive to maintenance treatment with anakinra.

A 43 year-old male presented with a relapsing and progressive systemic inflammatory disorder with central nervous system (CNS) involvement. After a two years follow up, he was diagnosed with hemophagocytic lymphohistiocytosis (HLH), based on clinical, laboratory and radiological findings. Treatment was started with anakinra, a recombinant humanised interleukin-1 (IL-1) receptor antagonist. Clinical response was good. Laboratory and radiological findings showed no disease activity throughout a five years follow-up period. Several immunosuppressive agents have been used in HLH without any good outcomes. This is the first case report of HLH with CNS involvement responsive to chronic treatment with anakinra.

Central Nervous System Involvement of Hemophagocytic Lymphohistiocytosis: When 18F-FDG PET/CT Solves a Complex Diagnostic Investigation.

ABSTRACT: Hemophagocytic lymphohistiocytosis is rare life-threatening syndrome, hereditary or acquired, mainly affecting children. Hemophagocytic lymphohistiocytosis is an immune deficiency characterized by severe inflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages. The usual biological and clinical data may associate polyadenopathy, hepatosplenomegaly, fever, multivisceral damages, and cytopenias with potential multiorgan dysfunction and death. We report the case of a 4-year-old girl, hospitalized for recurrent cerebellar symptoms (ataxia) associated later with fever and pancytopenia. 18F-FDG PET/CT revealed a node pathological uptake, which was biopsied and confirmed a diagnosis of hemophagocytic lymphohistiocytosis.

Hemophagocytic Lymphohistiocytosis Associated with Disseminated Nontuberculous Mycobacterial Infection in a Patient with Mesenteric Panniculitis.

Mesenteric panniculitis is a chronic inflammatory disease characterized by non-specific inflammation of the adipose tissue in the mesentery. Hemophagocytic lymphohistiocytosis is a life-threating disease associated with aberrant macrophage overactivation, in which infections can be a leading cause in immunocompromised hosts. Here, we report a rare case of mesenteric panniculitis and hemophagocytic lymphohistiocytosis complicated by disseminated Mycobacterium intracellulare. A 71-year-old male with mesenteric panniculitis was admitted to our hospital for fever and pancytopenia. He was treated with oral prednisolone (15 mg/day) and cyclosporin A (150 mg/day) at presentation. Physical and laboratory examinations revealed disseminated infection with nontuberculous mycobacteria; Mycobacterium intracellulare was detected in cultures of cerebrospinal fluid, blood, sputum, and gastric fluid. Patient signs and symptoms fulfilled the five criteria for a diagnosis of hemophagocytic lymphohistiocytosis, including fever, cytopenia, hemophagocytosis, hyperferritinemia, and high soluble interleukin-2 receptor levels. Therefore, the diagnosis of nontuberculous mycobacteria-associated hemophagocytic lymphohistiocytosis was established. An anti-mycobacterial chemotherapy including chloramphenicol (800 mg/day), rifampin (450 mg/day) and ethambutol (750 mg/day) together with streptomycin (750 mg twice per week) was initiated at 30 days after admission; maintenance doses of prednisolone were increased to 60 mg/day. Fever and pancytopenia improved in response to anti-mycobacterial chemotherapy. The present case suggests that mesenteric panniculitis could be complicated with hemophagocytic lymphohistiocytosis caused by immunosuppressive therapy-associated infections as well as underlying disease activity. In conclusion, the possibility of disseminated nontuberculous mycobacteria infection with hemophagocytic lymphohistiocytosis should be considered if unexplained fever or hematological dyscrasia were presented in patients of mesenteric panniculitis.

Cytomegalovirus-Associated Hemophagocytic Syndrome Diagnosed by Liver Biopsy in a Kidney Transplant Recipient.

Hemophagocytic syndrome (HPS) is a rare but potentially life-threatening disease in kidney transplant recipients, and is caused by systemic proliferation of macrophages actively phagocytizing other blood cells in the bone marrow, lymph nodes, and the spleen. Here, we report a 40-year-old male kidney transplant recipient who presented with fever, bicytopenia, and elevated liver enzymes 2 months after transplantation. Given that cytomegalovirus antigenemia and real-time polymerase chain reaction tests were positive, liver biopsy was performed under an assumption of cytomegalovirus-induced hepatitis. Hepatic histology revealed multifocal microabscess with cytomegalovirus inclusion bodies, marked Kupffer cell hyperplasia, and erythrophagocytosis by activated macrophages. As laboratory findings such as hyperferritinemia, elevated serum lactate dehydrogenase, low natural killer cell activity, and high soluble interleukin-2 receptor were also compatible with HPS, the recipient was diagnosed as having cytomegalovirus-induced hepatitis combined with reactive HPS. Following intravenous ganciclovir therapy with continuous administration of tacrolimus and corticosteroid, the symptoms resolved and laboratory findings were normalized. As far as we know, this is the first report of cytomegalovirus-induced hepatitis combined with reactive HPS in a kidney transplant recipient that is diagnosed by liver biopsy.

Prognosis predicting value of semiquantitative parameters of visceral adipose tissue and subcutaneous adipose tissue of 18F-FDG PET/CT in newly diagnosed secondary hemophagocytic lymphohistiocytosis.

PURPOSE: The purpose of this study was to investigate the prognosis predicting value of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of 18F-FDG PET/CT, and clinical inflammatory cytokines in newly diagnosed secondary hemophagocytic lymphohistiocytosis (SHLH). METHODS: We retrospectively collected 58 patients with newly diagnosed SHLH from August 2016 to July 2019 in our hospital. All patients were followed up between 6 and 24 months. First, a comprehensive comparison of the general data between the death and the survival group was performed. Clinical lab indexes included were recorded and analyzed retrospectively. Second, the correlation between 18F-FDG PET/CT semiquantitative metabolic parameters of VAT, SAT and inflammatory cytokines was performed. 3D slicer software was used to get SUV and volume of VAT and SAT from 18F-FDG PET/CT. Third, overall survival (OS) analysis was performed. Finally, the prognosis predicting model was built based on risk factors to stratify SHLH patients. RESULTS: There was significant difference in WBC, PLT, FBG, IL-10, PCR tests of EBV-DNA loads, SCD25 between the death group and the survival group. There was significant correlation between SAT coefficient variance (CV) and CRP, the mean standardized uptake value (SUVmean) of SAT (SAT SUVmean) and TG, SAT SUVmean and ESR. In univariate analysis with Cox regression analysis, SUVmean of VAT (VAT SUVmean), SAT Volume, SUVmean of SAT, CV of SAT (SAT HU CV), plasma EBV-DNA, WBC, PLT, FBG showed significance with OS. In multivariate Cox regression analysis, SAT Volume, SUVmean of SAT, plasma EBV-DNA, were independent prognostic factors for OS. CONCLUSIONS: For newly diagnosed SHLH, SAT Volume, SUVmean of SAT, plasma EBV-DNA had significant relationship with poor prognosis. They were important independent predictors for overall survival for newly diagnosed SHLH.

Atypical neuroimaging characteristics of hemophagocytic lymphohistiocytosis in infants: a case series of hemorrhagic brain lesions in the deep grey matter.

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem condition associated with uncontrolled overproduction and infiltration of lymphocytes and histiocytes predominantly in liver, lymph nodes, spleen, and central nervous system. Neuroimaging findings on MRI are fairly nonspecific and classically include periventricular white matter signal abnormalities and diffuse atrophy. Focal parenchymal lesions may demonstrate post contrast ring or nodular enhancement and calcification. However, the MR imaging characteristics can be highly variable. Here, we present two cases of HLH in infants with multiple hemorrhagic lesions mostly depicted in both thalami and basal ganglia regions. Thalamic, basal ganglia, and brain stem involvement with hemorrhagic changes in HLH are rarely described in literature. Early diagnosis of HLH may be lifesaving. Awareness of the disease is necessary to investigate its characteristic findings and avoiding a delay in diagnosis.

SARS CoV 2 infection in chronic myelogenous leukemia: Severe hematological presentation.

Infection with SARS-CoV-2, the cause of coronavirus infectious disease-19 (COVID-19), has caused a pandemic. Few data are available about the risk of COVID-19 infection in persons with hematological cancer, but controversy whether these persons have the same clinical signs and outcomes. We describe a case of life-threatening COVID-19 infection complicated by severe anemia in patients affected also by chronic myelogenous leukemia. The screening for RBC antibodies and the direct antiglobulin test (DAT) turned positive. The identification of the antibodies, showed the presence of an alloantibody with anti-Lewis b specificity, which was reactive at room temperature, in the anti-human globulin phase (AGH) and with papain-treated red blood cells. At the same time hemophagocytic lymphohistiocytosis (HLH), on the basis of major laboratory findings including hyperferritnemia, increase of triglicerides levels and according to the HLH score was suspected. Patients received antiviral therapy, steroids and intravenous immunoglobulins. Hemolysis resolved and ferritin dramatically decreased after administration of Ig and a Afull recovery was achieved after viral infection resolution.This case highlights the novel and multifaceted hematological findings during sever COVID 19 infection. COVID 19-related pneumonia is mediated by hyper activation of effector T cells and excessive production of inflammatory cytokines, such as IL-6, IL-1, interferon-gamma, and TNF. This inflammatory process called "cytokine storm" is a life-threatening complication of COVID 19 infection. In this case severe immunohematological consequences are reported for the first time and recognition of this complications are probably underestimated.