JCPyV miR-J1-5p in Urine of Natalizumab-Treated Multiple Sclerosis Patients

The use of Natalizumab in Multiple Sclerosis (MS) can cause the reactivation of the polyomavirus JC (JCPyV); this may result in the development of progressive multifocal leukoencephalopathy (PML), a rare and usually lethal disease. JCPyV infection is highly prevalent in worldwide population, but the detection of anti-JCPyV antibodies is not sufficient to identify JCPyV infection, as PML can develop even in patients with negative JCPyV serology. Better comprehension of the JCPyV biology could allow a better understanding of JCPyV infection and reactivation, possibly reducing the risk of developing PML. Here, we investigated whether JCPyV miR-J1-5p—a miRNA that down-regulates the early phase viral protein T-antigen and promotes viral latency—could be detected and quantified by digital droplet PCR (ddPCR) in urine of 25 Natalizumab-treated MS patients. A 24-month study was designed: baseline, before the first dose of Natalizumab, and after 1 (T1), 12 (T12) and 24 months (T24) of therapy. miR-J1-5p was detected in urine of 7/25 MS patients (28%); detection was possible in three cases at T24, in two cases at T12, in one case at T1 and T12, and in the last case at baseline and T1. Two of these patients were seronegative for JCPyV Ab, and viral DNA was never found in either urine or blood. To note, only in one case miR-J1-5p was detected before initiation of Natalizumab. These results suggest that the measurement of miR-J1-5p in urine, could be a biomarker to monitor JCPyV infection and to better identify the possible risk of developing PML in Natalizumab-treated MS patients.     

Absence of JC polyomavirus (JCPyV) viremia in early post‐transplant JCPyV nephropathy: A case report

JC polyomavirus (JCPyV)‐associated nephropathy (JCPyVAN) occurs in <3% of PVAN cases after renal transplantation. We report the first confirmed case to our knowledge of JCPyVAN diagnosed by kidney biopsy in the early 6 months post transplant in Thailand. In this case report, recovery of renal allograft function was not observed after reduction of immunosuppressive agents and administration of intravenous immunoglobulin and cidofovir. Despite persistent JCPyV viruria, no significant further decline in allograft function was documented at 15 months post transplant.     

Idiopathic granulomatous mastitis in seventy seven-female patients: Management,follow up of an overlooked immune-mediated disease,and review of literature

BackgroundIdiopathic granulomatous mastitis (IGM) cases have been increasingly recognized in the context of autoimmune diseases. Hence rheumatologists need to be acquainted with IGM detection and management. Although studies evaluating the response to the emerging immunosuppressive drugs were promising, prospective studies still remain scarce.Aim of the workThis prospective study aimed to evaluate previous immunosuppressive regimens in the management of IGM cases.Patients and methodsSeventy seven female IGM patients were followed up, and stratified into 2 groups based on the treatment modalities received: double therapy (Group D, n = 17) who received steroids and methotrexate (MTX), and triple therapy (Group T, n = 60) who received steroids, MTX and mycophenolate mofetil (MMF). Each group was followed up monthly till the end of treatment then every 3 months after stopping treatment for at least 2 years, and the patients' data were recorded on 3 visits (V1, V2, and V3).ResultsFemale patients mean age was 33.9±6.2 years. IGM lesions improved in the form of pain relief, resolution of lumps; replacement of inflammatory lesions by granulation tissue, with superiority of triple therapy group T over double therapy in group D regarding significantly shorter duration of treatment (26.5±3.1 vs 18.1±4.4 months)(p < 0.001), and decreased time needed to steroid tapering (14.1±3.6 vs 5.5±5.2 months)(p < 0.001). No recurrence was noticed.ConclusionsTreatment of IGM has been successful using MTX, or MTX and MMF besides to steroid therapy. Triple therapy was significantly superior with shorter duration of treatment and faster feasibility of steroid tapering.     

Progressive multifocal leukoencephalopathy,a review and an extended report of five patients with different immune compromised states

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the brain caused by the JC-virus. Both a decreased cellular or humoral immune response can increase the susceptibility for JC-virus induced PML. Not only HIV infected people are at risk, a wide range of otherwise immune compromised patients are a potential target for this virus. This report of five PML patients shows the importance of a clinician's familiarity with this disease and it's presenting symptoms. The presenting symptoms of PML can sometimes mimic worsening of the underlying disease. Although different therapeutic strategies have been tried, the outcomes remain very poor. In this series, treatment with cidofovir appears not to be effective in treating PML, neither in HIV positive nor HIV negative patients. Experimental therapy with leflunomide, after tapering of the immunosuppressive medication, did change the natural course of PML in one patient.     

Comparison of qPCR with ddPCR for the Quantification of JC Polyomavirus in CSF from Patients with Progressive Multifocal Leukoencephalopathy

Background: Lytic infection of oligodendrocytes by the human JC polyomavirus (JCPyV) results in the demyelinating disease called progressive multifocal leukoencephalopathy (PML). The detection of viral DNA in the cerebrospinal fluid (CSF) by PCR is an important diagnostic tool and, in conjunction with defined radiological and clinical features, can provide diagnosis of definite PML, avoiding the need for brain biopsy. The main aim of this study is to compare the droplet digital PCR (ddPCR) assay with the gold standard quantitative PCR (qPCR) for the quantification of JC viral loads in clinical samples. Methods: A total of 62 CSF samples from 31 patients with PML were analyzed to compare the qPCR gold standard technique with ddPCR to detect conserved viral DNA sequences in the JCPyV genome. As part of the validation process, ddPCR results were compared to qPCR data obtained in 42 different laboratories around the world. In addition, the characterization of a novel triplex ddPCR to detect viral DNA sequence from both prototype and archetype variants and a cellular housekeeping reference gene is described. Triplex ddPCR was used to analyze the serum from six PML patients and from three additional cohorts, including 20 healthy controls (HC), 20 patients with multiple sclerosis (MS) who had never been treated with natalizumab (no-NTZ-treated), and 14 patients with MS who were being treated with natalizumab (NTZ-treated); three from this last group seroconverted during the course of treatment with natalizumab. Results: JCPyV DNA was detected only by ddPCR for 5 of the 62 CSF samples (8%), while remaining undetected by qPCR. For nine CSF samples (15%), JCPyV DNA was at the lower limit of quantification for qPCR, set at <250 copies/mL, and therefore no relative quantitation could be determined. By contrast, exact copies of JCPyV for each of these samples were quantified by ddPCR. No differences were observed between qPCR and ddPCR when five standardized plasma samples were analyzed for JCPyV in 42 laboratories in the United States and Europe. JCPyV-DNA was undetected in all the sera from HC and MS cohorts tested by triplex ddPCR, while serum samples from six patients with PML tested positive for JCPyV. Conclusion: This study shows strong correlation between ddPCR and qPCR with increased sensitivity of the ddPCR assay. Further work will be needed to determine whether multiplex ddPCR can be useful to determine PML risk in natalizumab-treated MS patients.     

Clopidogrel tapering as a strategy to attenuate platelet rebound phenomenon in patients with bare-metal stents

Early clustering of adverse cardiovascular events after abrupt cessation of clopidogrel has been reported in patients with acute coronary syndromes. A platelet rebound phenomenon may contribute to this increased thrombotic risk and a gradual drug tapering may attenuate this proposed platelet effect. Accordingly, we aimed to assess the effect of clopidogrel tapering on platelet reactivity. Twenty patients who underwent elective percutaneous coronary interventions with bare metal stents receiving 3 months of clopidogrel therapy (75 mg daily) were randomized to either of two discontinuation strategies: (1) Off group–abrupt drug cessation or (2) Tapering group–receiving clopidogrel 75 mg every other day for 4 weeks duration. Light transmission aggregometry, induced by ADP (5 and 10 μM) and collagen, was measured at four time-points (at baseline and 2, 4 and 6 weeks after randomization). In the off group, there was an early rise in platelet reactivity at 2 weeks after abrupt drug cessation compared to baseline, as measured by ADP 5 μmol/l (39.6 ± 2.8 vs. 67.9 ± 6.0, P < 0.001). The tapering regimen suppressed this rebound platelet aggregation by ADP 5 μmol/l at 2 weeks (P = 0.001) and 4 weeks (P = 0.001). Similar results were found with ADP 10 μmol/l and collagen agonists. Abrupt cessation of clopidogrel results in an early rise in platelet aggregability in patients with BMS that is attenuated by a tapering regimen. Clopidogrel administration every other day may achieve similar levels of platelet inhibition as full dose therapy. Further investigations evaluating clopidogrel tapering strategies and their potential clinical impact are warranted.     

Progressive multifocal leukoencephalopathy as a cause of neurologic symptoms in Sharp syndrome]

Progressive multifocal leukencephalopathy (PML) is a very rare complication of immunosuppressive or cytostatic treatment of rheumatic diseases. We describe a patient with a mixed connective tissue disease (MCTD) existing for more than 15 years, who had polyarthritis, myositis, scleroderma-like symptoms, pulmonary involvement, and psychosis of undetermined origin. After a 12-year low-dose corticosteroid therapy and a 4-year azathioprin therapy a quickly progressive PML developed; symptoms included: difficulty in urinating, bladder, articulation, spastic hemiplegia, eye movement malfunction. The patient died after after a few months. PML is an important consideration in the differential diagnosis when a patient with MCTD develops neurologic symptoms.     

Progressive multifocal leukoencephalopathy associated with mycophenolate mofetil treatment in a woman with lupus and CD4+ T-lymphocyte deficiency

There is an increase in the number of patients with systemic lupus erythematosus (SLE) reported as developing progressive multifocal leukoencephalopathy (PML) while on intensive immunosuppressive therapy. A 39-year-old HIV-negative woman with a 10-year history of SLE presented with progressive left-side weakness while on maintenance therapy with oral prednisone and mycophenolate mofetil (MMF). On several occasions low CD4+ T-lymphocyte counts were found (68/μL). Brain magnetic resonance imaging (MRI) revealed a large lesion in the right subcortical fronto-parietal region and a smaller one in the left frontal subcortex, corresponding to the PML. In cerebrospinal fluid, polymerase chain reaction (PCR) for JC virus (JCV) was negative, but anti-JCV antibodies were highly positive. Diagnosis of probable PML was made and MMF was withdrawn. The patient's condition improved with marked reduction of left-side weakness and an increase in CD4(+) T-lymphocyte count (141/μL). Follow-up MRI showed regression of lesions and over the next 6 months the patient remained stable. In spite of the grave prognosis associated with PML, SLE patients can have an excellent outcome if immunosuppressants are discontinued as soon as the correct diagnosis is made. SLE patients with associated low CD4(+) T-lymphocyte counts should be monitored for the development of PML during immunosuppressive therapy in particular.     

Manejo farmacológico de pacientes con enfermedades hepáticas y pancreáticas que involucran terapias inmunosupresoras. Posicionamiento en el marco de la pandemia de SARS-CoV-2 (COVID-19)

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. COVID-19 affected more than 6 million persons worldwide in fewer than 4 months, after the report of the first cases in China in December 2019. The relation of the disease caused by SARS-Cov-2 to immunosuppressive treatment used in different gastrointestinal disorders is uncertain, resulting in debate with regard to suspending immunosuppressive therapy to improve infection outcome. Said suspension implies the inherent risk for graft rejection or autoimmune disease exacerbation that can potentially worsen the course of the infection. Based on the presently available evidence, a treatment stance has been established for patients with gastrointestinal diseases that require immunosuppressive therapy.     

Risk Assessment of Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patients during 1 Year of Ocrelizumab Treatment

Background: Progressive multifocal leukoencephalopathy (PML) caused by the JC virus is the main limitation to the use of disease modifying therapies for treatment of multiple sclerosis (MS). Methods: To assess the PML risk in course of ocrelizumab, urine and blood samples were collected from 42 MS patients at baseline (T0), at 6 (T2) and 12 months (T4) from the beginning of therapy. After JCPyV-DNA extraction, a quantitative-PCR (Q-PCR) was performed. Moreover, assessment of JCV-serostatus was obtained and arrangements’ analysis of non-coding control region (NCCR) and of viral capsid protein 1 (VP1) was carried out. Results: Q-PCR revealed JCPyV-DNA in urine at all selected time points, while JCPyV-DNA was detected in plasma at T4. From T0 to T4, JC viral load in urine was detected, increased in two logarithms and, significantly higher, compared to viremia. NCCR from urine was archetypal. Plasmatic NCCR displayed deletion, duplication, and point mutations. VP1 showed the S269F substitution involving the receptor-binding region. Anti-JCV index and IgM titer were found to statistically decrease during ocrelizumab treatment. Conclusions: Ocrelizumab in JCPyV-DNA positive patients is safe and did not determine PML cases. Combined monitoring of ocrelizumab’s effects on JCPyV pathogenicity and on host immunity might offer a complete insight towards predicting PML risk.     

Immunosuppressive therapy for myelodysplastic syndrome: efficacy of methylprednisolone pulse therapy with or without cyclosporin A

We investigated whether immunosuppressive therapy using methylprednisolone (mPSL) with or without cyclosporin A (CsA) could benefit patients with myelodysplastic syndrome (MDS). Eligibility criteria for this study were a clinical diagnosis of MDS with less than 5% blast in peripheral blood, less than 10% blast in bone marrow and advanced cytopenia. Among 73 patients with MDS, 18 eligible and consecutive patients (8 men and 10 women), aged 48 to 87 years (median: 66.5 years) were assigned to receive mPSL pulse therapy (1,000 mg daily for 3 consecutive days, followed by tapering oral prednisolone; n= 12) or mPSL pulse with CsA therapy (4 to 5 mg/kg administered twice daily; n= 6). Six of 18 patients (33.3%; 3 of 10 patients with RA, 2 of 6 patients with RAEB, 1 of 2 patients with CMMoL) responded to immunosuppressive therapy. Four patients responded to mPSL pulse alone, and two patients responded to mPSL pulse with CsA. One of 6 patients with hypocellular bone marrow and 5 of 12 patients with normocellular or hypercellular marrow responded to immunosuppressive therapy. No patient with myelofibrosis responded to the therapy. The duration of response ranged from 4 to 59 months (median: 14 months). Although a significant difference was observed between responders and nonresponders in the survival rate (P<0.05), no significant difference was found in clinical characteristics at entry between responders and nonresponders. In responders, mean hemoglobin levels were significantly increased (P<0.01), and the required red cell transfusion dose was significantly reduced (P<0.01). It is possible that immunosuppressive therapy might be effective for a certain subset of patients with MDS.     

Multicentric Castleman's disease and Kaposi's sarcoma in a cyclosporin treated,HIV-1 negative patient: case report

Background  

Multicentric Castleman's disease (MCD) is a rare disease, but is more frequent in AIDS patients. MCD has only been reported twice before in patients receiving immunosuppressive therapy after renal transplantation, and never in patients receiving immunosuppressive therapy without transplantation. About half of the cases of MCD are human herpesvirus 8 (HHV8) – related, in contrast to Kaposi's sarcoma, a more common complication arising after immunosuppression, where the virus is found in virtually all cases.     

Manejo de la inmunosupresión en pacientes trasplantados de riñón con COVID19. Estudio multicéntrico nacional derivado del registro COVID de la Sociedad Española de Nefrología

IntroductionSARS-CoV-2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient's clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated.ObjectivesEvaluate the management of immunosuppressive therapy made during SARS-CoV-2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID-19 diagnosis.Material and methodsRetrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis.Results615 renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years.The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased.Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 ± 0.8, 2.1 ± 1.2 and 1.8 ± 1 mg/dl respectively (p < 0.001).56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID-19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant.ConclusionsThe management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.     

Characteristics of interstitial lung disease in SS-A positive/Jo-1 positive inflammatory myopathy patients

The strongest predictive factor for the development of interstitial lung disease (ILD) in myositis (IIM) patients is the presence of different antisynthetase antibodies. The aim of this study was to compare the clinical characteristics, radiological findings and therapeutic response between the anti-SS-A positive and negative antisynthetase syndrome (ASS) patients. A prospective study of 315 IIM patients was conducted including 27 anti-Jo-1 positive ASS patients. Mean disease duration was 46.6 (range 4–198) months. All patients fulfilled the classification criteria for IIM. All patients underwent chest radiography, pulmonary function tests and HRCT at he time of diagnosis and 6 months after the immunosuppressive therapy. Routine laboratory tests, RF, ANA, anti-ENA, anti-SS-A, anti-histidyl-transfer RNA antibody (Jo-1) measurements were performed in all patients. ILD was found to be present in 70.4% of ASS patients. The anti-SS-A negative ASS group had a more frequent association with alveolitis and responded well to immunosuppressive therapy (p < 0.05). HRCT scan showed more fibrosis in the SS-A positive group. 15.8% of patients died due to pulmonary or cardiac complications. In conclusion, coexistence of anti-SS-A and anti-Jo-1 antibody may be a good predictor for a more coarse and severe ILD in IIM patients who require a more aggressive approach in therapy.     

Clinical features and renal outcome in lupus patients with diffuse crescentic glomerulonephritis

The objectives of the study are to investigate the clinical features and renal outcomes in lupus patients with diffuse crescentic glomerulonephritis (DCGN). Ninety-four DCGN lupus patients were enrolled. Their clinical features and renal outcomes were investigated. There were 84 females and 10 males, with a mean age of 27.9 ± 10.7 years old. They represented: hypertension in 73 cases (77.7%), rapidly progressive glomerulonephritis in 62 cases (66.0%), 46 cases (48.9%) with nephritic syndrome, 35 (37.2%) gross hematuria, and 14 cases (14.9%) with uremic syndrome needed dialysis therapy. There were 25 cases received repeated renal biopsy. Their histological examination showed the decreasing of active lesions and the increasing chronic lesions. All patients were more than 6 months follow-up, and 79 patients (84.0%) were more than 12 months follow-up. At the first time of follow-up (3 months), the renal function, proteinuria, and anemia were improved significantly in all of cases received intensive immunosuppressive therapy. At the last time of follow-up (56.1 ± 18.8 months), only four patients eventually developed to the end-stage renal failure and five died with normal renal function. The lupus patients with DCGN presented more severe clinical syndromes, which were similar to those patients of type II of DCGN. The relative good renal outcomes were observed in those lupus patients, to which may be contribute to the effective induction therapy.     

Incidence and risk factors for progressive multifocal leukoencephalopathy among patients with selected rheumatic diseases

Objective

To ascertain the incidence of progressive multifocal leukoencephalopathy (PML) in patients with selected rheumatic diseases, to describe the characteristics of PML cases occurring in this setting, and to evaluate the extent to which such cases occurred in the context of biologic therapies such as rituximab or tumor necrosis factor antagonists.

Methods

We conducted a large population‐based study to describe the incidence and risk factors for PML among patients with rheumatoid arthritis, psoriatic arthritis, psoriasis, juvenile idiopathic arthritis, inflammatory bowel disease, and ankylosing spondylitis using national inpatient and outpatient administrative data from the entire Center for Medicare and Medicaid Services from 2000–2009. Suspected PML cases were identified using hospital discharge diagnosis codes. Risk factors for PML were evaluated using outpatient data ≥6 months prior to PML diagnosis.

Results

Among 2,030,578 patients with autoimmune diseases of interest, a total of 53 PML cases were identified (2.6 per 100,000 patients). Most PML cases had human immunodeficiency virus (HIV) and/or cancer. Nine PML cases had evidence for biologic use prior to PML hospitalization, of which 3 had neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or 6 months (all other biologics) prior to PML diagnosis. PML occurred at an estimated incidence of 0.2 per 100,000 patients with autoimmune diseases who did not have HIV or malignancy.

Conclusion

PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy.     

Brucellosis in a renal transplant recipient

Brucellosis is one of the most common systemic zoonotic diseases transmitted by consumption of unpasteurized dairy products or by occupational contact with infected animals. Brucellosis is rare in renal transplant recipients. Only 3 cases have been reported in the literature. We report a case of brucellosis with hematologic and hepatobiliary complications in a patient 3 years after renal transplantation. The mean time from transplantation to the diagnosis of brucellosis in these 4 reported patients was 5.1 years (range 17 months to 13 years). All patients had fever and constitutional symptoms, and all attained clinical cure after combination antibiotic therapy. Given the small number of patients, further study is needed to identify the characteristics of brucellosis in renal transplant recipients. Drug interactions and acute renal failure developed in our patient during antibiotic treatment. Therefore, we should monitor the levels of immunosuppressive agents frequently. Several studies have shown in vitro susceptibilities of Brucella melitensis to tigecycline. In our patient, fever finally subsided after tigecycline administration. The minimum inhibitory concentration of tigecycline using Etest was 0.094 μg/mL. Tigecycline may be a potential option for treatment of brucellosis in the setting of transplantation.     

Leg weakness in a lung transplant patient

Progressive multifocal leukoencephalopathy (PML) is associated with JC polyomavirus (JCV) infection of central nervous system oligodendrocytes resulting in demyelinization and progressive focal neurologic deficits. Reactivation of dormant JCV occurs in the setting of immunosuppression, most commonly in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) or hematological malignancies. PML has also been reported in solid organ transplant recipients. We report the case of a 61‐year‐old man after bilateral lung transplantation for chronic hypersensitivity pneumonitis who presented with leg weakness, cognitive decline, and expressive aphasia at 5 months post transplantation. Magnetic resonance imaging and brain biopsy were consistent with PML. Treatment attempt with cytarabine was unsuccessful, and immunomodulation resulted in recurrent grade A3 rejection. The difficulty of managing PML in lung transplant patients is highlighted by the lack of directed therapy and risk of graft rejection or failure with attempts at decreasing immunosuppression.     

Progressive multifocal leukoencephalopathy in a patient with B-cell lymphoma during rituximab-containing chemotherapy: case report and review of the literature

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC polyomavirus. We describe a rare case of PML in a 48-year-old female patient with diffuse large B-cell lymphoma who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy. While she was undergoing five cycles of R-CHOP, she noticed gradually progressive neurological symptoms, such as slurred speech and gait disturbance, and she eventually developed high-grade fever. She also developed Pneumocystis jiroveci pneumonia. The neurological symptoms deteriorated thereafter, and she developed spastic quadriparesis and bulbar palsy. Magnetic resonance imaging showed hyperintensity within the right cerebellar hemisphere on T2-weighted images. Polymerase chain reaction-based tests of the cerebrospinal fluid revealed the presence of the JC virus. Despite intravenous and intrathecal cytarabine treatment, the patient died of PML 5 months after it was diagnosed. Retrospective analysis of her laboratory data showed that her CD4⁺ T-cell count before R-CHOP therapy had decreased to 68 μL⁻¹. Thus, when administering rituximab-containing chemotherapy, even to patients with no prior history of opportunistic infections, attention should be paid to the potential occurrence of PML, particularly in patients with low CD4⁺ T-cell counts.