Clinical and molecular features of patients with systemic and/or extracutaneous NTRK-rearranged histiocytosis
| Nr . | Gene fusion . | Sex . | Age at diagnosis . | Sites of disease . | First-line treatment . | Response . | Progression/relapse . | Second- and further-line treatment . | Outcome . | Follow-up . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Systemic | Infants with systemic disease with skin and liver involvement | ||||||||||
| PK 01 | SQSTM1:: NTRK1 | M | Newborn | Skin, hematopoietic system, liver, spleen, and kidney. Possible bone and GI involvement. | Chemotherapy: vinblastine and prednisone for 1 y | CR | No | No | Alive, NED | 8 y | This study |
| PK 02 | TPM3:: NTRK1 | F | Newborn | Skin, hematopoietic system, liver, and spleen. | Supportive care (platelet transfusions) | CR | No | No | Alive, NED | 7 mo | This study and Kemps et al6 |
| AP 24 | PRDX1:: NTRK1 | M | Newborn | Skin, liver, and spleen. | Supportive care (platelet transfusions) | CR | No | No | Alive, NED | 13 mo | This study |
| AP 27 | TPM3:: NTRK1 | F | Newborn | Skin, hematopoietic system, and liver. | Supportive care (platelet transfusions) | CR | No | No | Alive, NED | 7 mo | This study |
| Isolated | Patients with isolated extracutaneous disease | ||||||||||
| AP 32 | IRF2BP2::NTRK1 | M | 8 mo | Right main bronchus | Bronchoscopy with partial resection (4×) | PD | Yes | TRK inhibition (larotrectinib) | Alive, NED | 8 mo | This study |
| US 13 | ARHGEF2::NTRK1 | F | 15 y | Left temporal lobe of the brain | TRK inhibition (larotrectinib) during 19 mo | PR | No | No | Alive, NED | 26 mo | This study & Newman et al33 |
| Literature | Patients with systemic AND/OR extracutaneousNTRK-rearranged histiocytosis reported in the literature | ||||||||||
| L01 | IRF2BP2::NTRK1 | M | Newborn | Skin, ocular, and hematopoietic system. | Active monitoring | PD | Yes | TRK inhibition (larotrectinib) | Alive, NED | 18 months | Kim et al25 |
| L02 | TFG:: NTRK1 | M | 0.2 y | NR (ECD) | NR | NR | NR | NR | NR | NR | Taylor et al27 |
| L03 | TPR:: NTRK1 | M | 20 y | NR (IDCS) | NR | NR | NR | NR | NR | NR | Taylor et al27 |
| L04 | PLEKHA6::NTRK3 | M | 2.8 y | Bone, soft tissue (LCH) | Surgery and chemotherapy | CR | No | No | Alive, NED | 12 mo | Cai et al36 |
| Nr . | Gene fusion . | Sex . | Age at diagnosis . | Sites of disease . | First-line treatment . | Response . | Progression/relapse . | Second- and further-line treatment . | Outcome . | Follow-up . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Systemic | Infants with systemic disease with skin and liver involvement | ||||||||||
| PK 01 | SQSTM1:: NTRK1 | M | Newborn | Skin, hematopoietic system, liver, spleen, and kidney. Possible bone and GI involvement. | Chemotherapy: vinblastine and prednisone for 1 y | CR | No | No | Alive, NED | 8 y | This study |
| PK 02 | TPM3:: NTRK1 | F | Newborn | Skin, hematopoietic system, liver, and spleen. | Supportive care (platelet transfusions) | CR | No | No | Alive, NED | 7 mo | This study and Kemps et al6 |
| AP 24 | PRDX1:: NTRK1 | M | Newborn | Skin, liver, and spleen. | Supportive care (platelet transfusions) | CR | No | No | Alive, NED | 13 mo | This study |
| AP 27 | TPM3:: NTRK1 | F | Newborn | Skin, hematopoietic system, and liver. | Supportive care (platelet transfusions) | CR | No | No | Alive, NED | 7 mo | This study |
| Isolated | Patients with isolated extracutaneous disease | ||||||||||
| AP 32 | IRF2BP2::NTRK1 | M | 8 mo | Right main bronchus | Bronchoscopy with partial resection (4×) | PD | Yes | TRK inhibition (larotrectinib) | Alive, NED | 8 mo | This study |
| US 13 | ARHGEF2::NTRK1 | F | 15 y | Left temporal lobe of the brain | TRK inhibition (larotrectinib) during 19 mo | PR | No | No | Alive, NED | 26 mo | This study & Newman et al33 |
| Literature | Patients with systemic AND/OR extracutaneousNTRK-rearranged histiocytosis reported in the literature | ||||||||||
| L01 | IRF2BP2::NTRK1 | M | Newborn | Skin, ocular, and hematopoietic system. | Active monitoring | PD | Yes | TRK inhibition (larotrectinib) | Alive, NED | 18 months | Kim et al25 |
| L02 | TFG:: NTRK1 | M | 0.2 y | NR (ECD) | NR | NR | NR | NR | NR | NR | Taylor et al27 |
| L03 | TPR:: NTRK1 | M | 20 y | NR (IDCS) | NR | NR | NR | NR | NR | NR | Taylor et al27 |
| L04 | PLEKHA6::NTRK3 | M | 2.8 y | Bone, soft tissue (LCH) | Surgery and chemotherapy | CR | No | No | Alive, NED | 12 mo | Cai et al36 |
CR, complete response; GI, gastrointestinal; IDCS, interdigitating dendritic cell sarcoma; NED, no evidence of disease; NR, not reported; PD, progressive disease; PR, partial response.