Table 1.
Patient Age/Sex |
Underlying disease Immune suppressive treatment history |
Absolute values CD4/CD8/CD19 at baseline |
Donor Age/Sex Degree of HLA-match DonorJCV Ab status |
Clinical Course (Time 0=first PyVST infusion) |
Standardized Clinical Scale Scores (baseline → final visit) • mRS • KPS • MMSE |
JCV CSF copies per ml (baseline → last value) Time from first PyVST infusion to last value |
---|---|---|---|---|---|---|
1 62/F |
ICL/CVID/cyclic neutropenia Remote treatment with prednisone, methotrexate, TNF-inhibitor |
21/416/283 |
Donor 1: 39/F 6/10 match JCV Ab status unknown |
Neurological symptom onset: Month -6 Diagnosis of PML: Month -4 Died of complications of PML: Month 6 PML onset with rapid development of diplopia,severe truncal and appendicular ataxia, requiring bilateral assistive device for ambulation. Received 2 infusions of pembrolizumab, however symptoms continued to progress with worsening ataxia, cerebellar dysarthria, impaired eye movements, intractable hiccups; wheelchair-bound. Received two PyVST infusions from Donor 1 and one from Donor 2, with continued progression of symptoms. Withdrew from study and entered hospice care two months following last PyVST infusion. |
mRS 4→4 KPS 40→40 MMSE 26→28 |
27,429→77,774 Month 3 |
Donor 2: 64/F 2/10 match JC Ab negative | ||||||
2 61/F |
Microscopic polyangiitis Remote chronic prednisone Rituximab, last 2 months prior to PyVST |
706/101/0 | 40/F 5/10 match JCV Ab positive |
Neurological symptom onset: Month -1 Diagnosis of PML: Month -1 Survived PML: last communication > 36 months PML onset with progressive decline in memory and language over weeks, which developed into severe expressive aphasia, apraxia and mild right-sided weakness. Following first PyVST infusion, clinically stabilized. By Month 6 had improved use of right hand, further improved by Month 12. |
mRS 3→3 KPS 70→70 MMSE 22→28 |
609→Undetected Month 9 |
3 53/F |
CLL Remote rituximab, CFR, bendamustine, ibrutinib/obinutuzumab, CART, 2 months prior to PyVST |
45/19/0 | 58/F 10/10 match JCV Ab status unknown |
Neurological symptom onset: Month -2 Diagnosis of PML: Month -1 Died of complications of PML: Month 4 PML onset with progressive ataxia, abnormal eye movements with nystagmus, dysarthria with continued neurological deterioration following 2 PyVST infusions. By Day 14 post infusion 2, patient had developed severe bulbar dysfunction requiring NG tube and total care for ADL. Withdrew from study to enter hospice care within 1 month following second PyVST infusion. |
mRS 4→5 KPS 40→30 MMSE 28→4 |
62,963→109,880 Month 2 |
4 71/M |
Lymphoma (DLBC) Remote chemo (R-CHOP and intrathecal methotrexate; R-DICE x 3; R-BEAM) Autologous BMT |
217/426/53 | 44/M 5/10 match JCV Ab status unknown |
Neurological symptom onset: Month -2 Diagnosis of PML: Month -2 Presumed dead of complications of Stage IV lung cancer: > Month 12, date unknown PML onset with change in mental status, geographic disorientation with inability to find his way in his own home. Subsequently developed dense right sided weakness with inability to ambulate independently. Following first PyVST infusion, stabilized clinically. In the subsequent months, right hemiparesis improved such that by Month 6 follow-up was able to ambulate using a walker and had regained limited ability to use his right hand. At last communication, one year following completion of PyVST treatment, patient reported new diagnosis of Stage IV lung cancer and decision to enter hospice care. |
mRS 4→4 KPS 40→50 MMSE 14→18 |
333→18 Month 3 |
5 40/F |
SLE Remote azathioprine, prednisone, methotrexate, belimumab Rituximab, last 4 months prior to PyVST |
177/112/1 |
Donor 1: 39/M 5/10 match JCV Ab positive |
Neurological symptom onset: Month -2 Diagnosis of PML: Month -2 Died of complications of SLE: Month 14 PML onset with ataxia, slurred speech, right sided weakness and apraxia with rapid progression to being bed-bound, aphasic with cortical visual impairment. By three weeks after first PyVST infusion, clinical stabilization with subsequent improved cognition, vision and motor function following 2nd and 3rd infusions. By Month 6 following completion of PyVST treatment, able to ambulate using a walker, speech improved with recovery of limited reading and writing and use of tools. By Year 1, had experienced exacerbation of underlying SLE, leading to severe debilitation and inability to travel, and withdrew from study. |
mRS 4→4 KPS 50→50 MMSE 13→21 |
9564→1354 Month 7 |
Donor 2: 35/M 5/10 match JCV Ab positive | ||||||
6 40/F |
Follicular Lymphoma Bendamustine, Rituximab, last 6 months prior to PyVST |
230/134/0 | 64/F 6/10 match JCV Ab negative |
Neurological symptom onset: Month -6 Diagnosis of PML: Month -5 Died of complications of PML: Month 4 PML onset with progressive cortical visual impairment with quadrantopsia/alexia/simultag-nosia, developing into cortical blindness. Received a total of 3 PyVST infusions with no benefit and neurological symptoms progressed with left hemiparesis, bulbar symptoms and cognitive changes. One month following last PyVST infusion, withdrew from study and entered hospice care. |
mRS 3→4 KPS 60→40 MMSE 19→7 |
38,772→2,830,385 Month 2.5 |
7 60/M |
HBV/HDV Pegylated α interferon |
87/135/67 | 19/F 5/10 match JCV Ab positive |
Neurological symptom onset: Month -4 Diagnosis of PML: Month -3 Survived PML: last communication >24 months PML onset with right hand weakness and ataxia; symptoms progressed to dense right sided weakness, diplopia and dysarthria. Following first PyVST infusion, experienced initial worsening of symptoms with loss of ability to ambulate independently; following the 2nd and 3rd infusions, clinical stabilization and some improvement in speech and right sided weakness. By Month 6 after completion of PyVST treatment, experienced slight worsening of neurological symptoms, in context of progressive liver failure and ascites with no evidence of PML reactivation. Unable to return for Year 1 visit due to general medical debilitation. |
mRS 4→4 KPS 60→60 MMSE 25→28 |
782→Undetected Month 8 |
8 71/M |
CLL Remote ofatumumab, alemtuzumab, prednisone Rituximab, last 6 months prior to PyVST |
69/58/2 | 43/F 2/10 match JCV Ab positive |
Neurological symptom onset: Month -3 Diagnosis of PML: Month -2 Survived PML: last communication >16 months PML onset with progressive worsening dysarthric speech, left upper extremity weakness; dysphagia, requiring PEG. Received one PyVST infusion and withdrew from study 2 weeks later due to burden of trial participation. |
mRS 3→3 KPS 40→40 MMSE 28→29 |
362→533 Week 2 |
9 40/F |
SCID with spontaneous reversion mutation; hemolytic anemia Corticosteroids, rituximab, last 3 months prior to |
150/104/2 | 45/M 5/10 match JCV Ab positive |
Neurological symptom onset: Month -4 Diagnosis of PML: Month -3 Died of complications of PML: Month 2 PML onset with cognitive changes, apathy,slurred speech; progressive left hemiparesis and left hemianopsia; loss of ability to ambulate, decreased attentiveness, minimal to no verbalization. Received one PyVST infusion with no benefit; over subsequent weeks became increasingly less interactive with inability to take nutrition by mouth. By 2 months following PyVST infusion, withdrew from study and entered hospice care. |
mRS 4→4 KPS 40→40 MMSE 9→0 |
51,230→20,927 Month 1 |
10 35/F |
CVID untreated |
310/112/7 | 33/F 5/10 match JCV Ab negative |
Neurological symptom onset: Month -2 Diagnosis of PML: Month -1 Died of complications of PML: Month 2 PML onset with right UE weakness and expressive aphasia; progression to right hemiparesis and hemisensory loss. Received 2 infusions of PyVST with no benefit; neurological symptoms progressed to right hemiplegia, global aphasia and decreased attentiveness. By 2 weeks following 2nd PyVST infusion, withdrew from study and entered hospice care. |
mRS 4→4 KPS 50→40 MMSE 8→0 |
344,163→14,654 Month 2 |
11 57/M |
CLL untreated |
683/1,045/11,562 | 54/F 10/10 match JCV Ab negative |
Neurological symptom onset: Month -5 Diagnosis of PML: -3 Survived PML: last communication >24 months PML onset with left inferior quadrantopsia and subsequent development of cortical visual impairment; decreased dexterity left hand; partial complex seizures. Following first PyVST infusion, experienced progressive improvement in vision such that following second infusion regained limited ability to read. Progressive improvement in vision over following months. |
mRS 3→2 KPS 70→70 MMSE 28→29 |
74→32 Month 3 |
12 72/M |
CLL Remote obinutuzumab |
367/132/24 | 30/M 7/10 match JCV Ab positive |
Neurological symptom onset: Month -2 Diagnosis of PML: -1 Survived PML: last communication > 13 months PML onset with left sided ataxia, bulbar symptoms with dysarthria and dysphagia, ataxic gait. Continued slow worsening following first two PyVST infusions; by the third infusion, demonstrating improved strength and dysphagia. Withdrew from study following completion of PyVST treatment due difficulty with travel. At last communication, was neurologically stable13 months post PyVST treatment completion. |
mRS 2→3 KPS 70→50 MMSE 27→27 |
1,648→1,476 Month 2.5 |
Abbreviations: PyVST, polyomavirus specific T cells; M, male; F, female; Ab, antibody; MRS, Modified Rankin Scale (0 no signs or symptoms → 5 dead); KPS, Karnofsky Performance Scale (100 no signs or symptoms → 0 dead); MMSE, mini-mental status exam (30 best score → 0 worst score); CSF, cerebrospinal fluid; CLL, chronic lymphocytic leukemia; ICL, idiopathic lymphopenia; CVID, combined variable immunodeficiency; CAR, chimeric antigen receptor; NG, naso gastric; ADL, activities of daily living; DLBC, diffuse large B cell; RCHOP, rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisolone; R-DICE, rituximab, ifosfamide, carboplatin, etoposide phosphate; R-BEAM, rituximab, carmustine, etoposide, cytarabine, melphalan; BMT, bone marrow transplant; SLE, systemic lupus erythematosus; HBV, hepatitis B; HDV, hepatitis; PEG, percutaneous endoscopic gastrostomy.