Presentation, diagnosis, and management of solid tumor SMNs
| . | Cholangiocarcinoma11 . | Synovial sarcoma . | Melanoma . | Thyroid carcinoma . |
|---|---|---|---|---|
| Oncologic history | History of multiply relapsed B-ALL, initially diagnosed at age 18 y; received CD19 CAR T cells with subsequent consolidative HSCT from 10/10 matched sibling donor, with TBI -based myeloablative conditioning regimen (TBI and CTX) | History of multiply relapsed B-ALL, initially diagnosed at age 20 y; underwent haploidentical HSCT from parent, with TBI-based myeloablative conditioning regimen (TBI and CTX) in CR1 and CD19 CAR T-cell therapy in CR2 | History of multiply relapsed B-ALL, initially diagnosed at age 21 y; underwent double cord blood HSCT, with TBI-based myeloablative conditioning regimen (fludarabine, CTX, and TBI) in first relapse. Received CD19 CAR T cells in second relapse | History of multiply relapsed/refractory B-ALL, initially diagnosed at age 8 y; received CD19 CAR T cells with subsequent consolidative HSCT from 9/10 matched unrelated donor, with TBI-based myeloablative conditioning regimen (TBI, CTX, and thiotepa) |
| Total radiation exposure (TBI), cGy | 3600 | 1200 (plus 400 testicular boost) | 1320 | 1200 |
| Brief CAR T-cell therapy course | Received lymphodepleting chemotherapy with CTX and fludarabine before CD19 CAR T cells; achieved MRD− CR and proceeded directly to consolidative HSCT | Received lymphodepleting chemotherapy with CTX and fludarabine before CD19 CAR T cells; achieved MRD− CR; developed CD19− relapse 6 mo post–CD19 CAR T-cell therapy, and received ALL-directed therapy before SMN diagnosis | Received lymphodepleting chemotherapy with CTX and fludarabine before CD19 CAR T cells; achieved MRD− CR; continued B-cell aplasia (>7 y) | Received lymphodepleting chemotherapy with CTX and fludarabine before CD19 CAR T cells; achieved MRD− CR and proceeded directly to consolidative HSCT |
| CAR T-cell construct | CD19/28z | CD19/BB | CD19/BB (tisagenlecleucel/CTL019) | CD19/28z |
| HSCT (before/after CD19 CAR T-cell therapy) | Yes, after | Yes, before | Yes, before | Yes, after |
| SMN presenting symptoms | Presented at routine follow-up 3 y post–CD19 CAR T-cell therapy and post-HSCT at age 26 y with asymptomatic mild elevation of transaminases | Dental pain and swelling noted after wisdom teeth removal 5 y post–CD19 CAR T-cell therapy at age 29 y | Growing mole on right buttock 6 y post–CD19 CAR T-cell therapy | Presented for follow-up 8 y post–CD19 CAR T-cell therapy and post-HSCT with suspicious thyroid nodule |
| Diagnosis | MRI with MRCP: hilar biliary obstruction extending into left hepatic duct with no obstructing mass/stone identified ERCP: focal biliary stricturing in common and left hepatic ducts Diagnostic laparoscopy with exploration and resection: frozen section of left hepatic duct positive for carcinoma, with final surgical pathology results showing moderately differentiated cholangiocarcinoma | Biopsy: synovial sarcoma, biphasic type (FNCLCC grade 2) | Biopsy: malignant melanoma, superficial spreading type, in radial growth phase | Thyroidectomy: 1.5-cm nodule that contained papillary carcinoma of thyroid with extrathyroidal extension and microscopic strap muscle invasion |
| Management | Underwent left hepatectomy with extrahepatic bile duct resection and portal lymphadenectomy | Underwent partial left maxillary teeth extraction, left mandibular reconstruction, soft tissue flap, bilateral level 1 and left level 2-4 lymph node dissection as well as 660-cGy proton radiation therapy | Local resection with negative margins | Thyroidectomy and 131I radioactive iodine ablation |
| Outcome | Died on postoperative day 3 from fulminant hepatic failure | Continued remission from synovial sarcoma with active B-ALL | Continued remission from both B-ALL and malignant melanoma | Continued remission from both B-ALL and thyroid carcinoma |
| . | Cholangiocarcinoma11 . | Synovial sarcoma . | Melanoma . | Thyroid carcinoma . |
|---|---|---|---|---|
| Oncologic history | History of multiply relapsed B-ALL, initially diagnosed at age 18 y; received CD19 CAR T cells with subsequent consolidative HSCT from 10/10 matched sibling donor, with TBI -based myeloablative conditioning regimen (TBI and CTX) | History of multiply relapsed B-ALL, initially diagnosed at age 20 y; underwent haploidentical HSCT from parent, with TBI-based myeloablative conditioning regimen (TBI and CTX) in CR1 and CD19 CAR T-cell therapy in CR2 | History of multiply relapsed B-ALL, initially diagnosed at age 21 y; underwent double cord blood HSCT, with TBI-based myeloablative conditioning regimen (fludarabine, CTX, and TBI) in first relapse. Received CD19 CAR T cells in second relapse | History of multiply relapsed/refractory B-ALL, initially diagnosed at age 8 y; received CD19 CAR T cells with subsequent consolidative HSCT from 9/10 matched unrelated donor, with TBI-based myeloablative conditioning regimen (TBI, CTX, and thiotepa) |
| Total radiation exposure (TBI), cGy | 3600 | 1200 (plus 400 testicular boost) | 1320 | 1200 |
| Brief CAR T-cell therapy course | Received lymphodepleting chemotherapy with CTX and fludarabine before CD19 CAR T cells; achieved MRD− CR and proceeded directly to consolidative HSCT | Received lymphodepleting chemotherapy with CTX and fludarabine before CD19 CAR T cells; achieved MRD− CR; developed CD19− relapse 6 mo post–CD19 CAR T-cell therapy, and received ALL-directed therapy before SMN diagnosis | Received lymphodepleting chemotherapy with CTX and fludarabine before CD19 CAR T cells; achieved MRD− CR; continued B-cell aplasia (>7 y) | Received lymphodepleting chemotherapy with CTX and fludarabine before CD19 CAR T cells; achieved MRD− CR and proceeded directly to consolidative HSCT |
| CAR T-cell construct | CD19/28z | CD19/BB | CD19/BB (tisagenlecleucel/CTL019) | CD19/28z |
| HSCT (before/after CD19 CAR T-cell therapy) | Yes, after | Yes, before | Yes, before | Yes, after |
| SMN presenting symptoms | Presented at routine follow-up 3 y post–CD19 CAR T-cell therapy and post-HSCT at age 26 y with asymptomatic mild elevation of transaminases | Dental pain and swelling noted after wisdom teeth removal 5 y post–CD19 CAR T-cell therapy at age 29 y | Growing mole on right buttock 6 y post–CD19 CAR T-cell therapy | Presented for follow-up 8 y post–CD19 CAR T-cell therapy and post-HSCT with suspicious thyroid nodule |
| Diagnosis | MRI with MRCP: hilar biliary obstruction extending into left hepatic duct with no obstructing mass/stone identified ERCP: focal biliary stricturing in common and left hepatic ducts Diagnostic laparoscopy with exploration and resection: frozen section of left hepatic duct positive for carcinoma, with final surgical pathology results showing moderately differentiated cholangiocarcinoma | Biopsy: synovial sarcoma, biphasic type (FNCLCC grade 2) | Biopsy: malignant melanoma, superficial spreading type, in radial growth phase | Thyroidectomy: 1.5-cm nodule that contained papillary carcinoma of thyroid with extrathyroidal extension and microscopic strap muscle invasion |
| Management | Underwent left hepatectomy with extrahepatic bile duct resection and portal lymphadenectomy | Underwent partial left maxillary teeth extraction, left mandibular reconstruction, soft tissue flap, bilateral level 1 and left level 2-4 lymph node dissection as well as 660-cGy proton radiation therapy | Local resection with negative margins | Thyroidectomy and 131I radioactive iodine ablation |
| Outcome | Died on postoperative day 3 from fulminant hepatic failure | Continued remission from synovial sarcoma with active B-ALL | Continued remission from both B-ALL and malignant melanoma | Continued remission from both B-ALL and thyroid carcinoma |
CR1, first complete remission; CR2, second complete remission; CTX, cyclophosphamide; ERCP, endoscopic retrograde cholangiopancreatography; FNCLCC, Fédération Nationale des Centres de Lutte Contre Le Cancer; MRCP, magnetic resonance cholangiopancreatography; MRD, minimal residual disease; MRI, magnetic resonance imaging.