Table 4.

Characteristics of patients that developed subsequent malignancies after genetically modified IECs

PatientAge at enrollment (y)SexPrimary diseaseHSCTIEC typeSubsequent neoplasmTime from IEC therapy,
mo
Tissue transgene detectionRCRTime to LFU,
y
Outcome at last follow-up
Neuroblastoma Yes
(auto-HSCT) 
GD2 CAR T AML 1.5 Negative Negative Alive 
27 HL Yes
(auto-HSCT) 
DNR TGF-β EBVSTs MDS 24 Negative Negative Died of complications after allogeneic transplant 
17 Nasopharyngeal carcinoma No DNR TGF-β EBVSTs Spindle-cell neoplasm 24 Negative Negative 4.5 Alive 
62 CLL Yes
(allo-HSCT) 
CD19 CAR T Bladder cancer 48 Negative Negative Died of secondary infection 
11 Glioblastoma No HER2 CAR T T-cell lymphoma 36 Negative Negative Died of T-cell lymphoma 
60 CLL No CD19 CAR T BCCx2* 36 and 48 Unable to obtain Negative Alive 
47 HL Yes
(auto-HSCT) 
DNR TGF-β EBVSTs Breast ductal cell carcinoma 42 Negative Negative Alive 
55 NHL Yes
(auto-HSCT) 
CD19 CAR T BCC 36 Unable to obtain Negative 7.5 Alive 
56 NHL No CD19 and κ CAR T 1-Penile squamous cell carcinoma 72 Negative Negative 7.5 Died of MDS complications 
2-MDS 36 Negative Negative 
10 36 HL Yes
(auto-HSCT) 
Auto EBVSTs with NeoR 1-RCC 154 Unable to obtain Negative 15 Alive 
2-Meningioma 172 Unable to obtain Unable to obtain 
11 18 ALL and secondary AML Yes
(allo-HSCT) 
Allo EBVSTs with NeoR Nerve sheath tumor 96 Negative Negative 15 Died of unrelated accident 
12 AML Yes
(allo-HSCT) 
Allo EBVSTs with NeoR Thyroid adenoma 144 Unable to obtain Negative 15 Alive 
13 15 ALL Yes
(allo-HSCT) 
Allo EBVSTs with NeoR BCC 156 Negative Negative 15 Alive 
PatientAge at enrollment (y)SexPrimary diseaseHSCTIEC typeSubsequent neoplasmTime from IEC therapy,
mo
Tissue transgene detectionRCRTime to LFU,
y
Outcome at last follow-up
Neuroblastoma Yes
(auto-HSCT) 
GD2 CAR T AML 1.5 Negative Negative Alive 
27 HL Yes
(auto-HSCT) 
DNR TGF-β EBVSTs MDS 24 Negative Negative Died of complications after allogeneic transplant 
17 Nasopharyngeal carcinoma No DNR TGF-β EBVSTs Spindle-cell neoplasm 24 Negative Negative 4.5 Alive 
62 CLL Yes
(allo-HSCT) 
CD19 CAR T Bladder cancer 48 Negative Negative Died of secondary infection 
11 Glioblastoma No HER2 CAR T T-cell lymphoma 36 Negative Negative Died of T-cell lymphoma 
60 CLL No CD19 CAR T BCCx2* 36 and 48 Unable to obtain Negative Alive 
47 HL Yes
(auto-HSCT) 
DNR TGF-β EBVSTs Breast ductal cell carcinoma 42 Negative Negative Alive 
55 NHL Yes
(auto-HSCT) 
CD19 CAR T BCC 36 Unable to obtain Negative 7.5 Alive 
56 NHL No CD19 and κ CAR T 1-Penile squamous cell carcinoma 72 Negative Negative 7.5 Died of MDS complications 
2-MDS 36 Negative Negative 
10 36 HL Yes
(auto-HSCT) 
Auto EBVSTs with NeoR 1-RCC 154 Unable to obtain Negative 15 Alive 
2-Meningioma 172 Unable to obtain Unable to obtain 
11 18 ALL and secondary AML Yes
(allo-HSCT) 
Allo EBVSTs with NeoR Nerve sheath tumor 96 Negative Negative 15 Died of unrelated accident 
12 AML Yes
(allo-HSCT) 
Allo EBVSTs with NeoR Thyroid adenoma 144 Unable to obtain Negative 15 Alive 
13 15 ALL Yes
(allo-HSCT) 
Allo EBVSTs with NeoR BCC 156 Negative Negative 15 Alive 

ALL, acute lymphocytic leukemia; Allo, allogeneic; AML, acute myelocytic leukemia; auto, autologous; BCC, basal cell carcinoma; CLL, chronic lymphoid leukemia; LFU, last follow-up; MDS, myelodysplastic syndrome; NeoR, neomycin resistant marker gene; RCC, renal cell carcinoma; RCR, replication-competent retrovirus; TGF, transforming growth factor.

*

Patient was diagnosed with 2 basal cell carcinomas of the skin at 36 and 48 mo after infusion.

Patient received both CD-19 and κ CAR. Time to last follow-up and to secondary malignancy was calculated from time of his first infusion (CD19 CAR).

Patient with history of neurofibromatosis.

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