American Society of Hematology

Figure 4.

$RHOA mutations can be followed over time and correlate with radiological measures of response. Clonal tides representing mutation dynamics for RHOA and, where possible, TET2 and IDH2, during treatment of 5 PTCL cases. VAFs are plotted as indicated by the color key to the lower right. The dotted vertical lines indicate the points at which samples were taken. (A) PTCL_08 was treated with cyclophosphamide, Adriamycin, vincristine, and prednisolone (CHOP) chemotherapy and achieved a radiological complete response. Subsequent consolidation was with ifosfamide, epirubicin, and etoposide (IVE) followed by a lomustine, etoposide, cytarabine, melphalan (HDT/LEAM)–conditioned autologous stem cell transplant. Data were obtained from Ion Torrent sequencing. (B) PTCL_02 had disease refractory to 2 lines of chemotherapy (CHOP and IVE) before achieving a PET-negative response with gemcitabine, dexamethasone, and cisplatin (GDP). Treatment was then consolidated with an autologous followed by an allogeneic stem cell transplant. The data for the 4 timepoints indicated by black dotted lines are taken from Ion Torrent sequencing data and those indicated by red dotted lines from ddPCR. (C) PTCL_25 was treated with CHOP with etoposide (CHOEP) chemotherapy but did not respond and then received IVE followed by HDT/LEAM autologous stem cell transplant. PTCL recurred 2 years later, and reinduction chemotherapy with GDP achieved a transient partial response before further progression occurred and the patient died. Data were obtained from Ion Torrent sequencing. (D) PTCL_10 was treated with CHOP chemotherapy and achieved a partial remission on CT scan. The remission lasted ∼18 months, but she then represented with a rising peripheral blood lymphocyte count, pruritus, and skin lesions. CT scan (day 476) showed lung nodules. Lymph node biopsy confirmed relapsed lymphoma, and she was retreated with GDP. In this case, loss of mutant RHOA after GDP was associated with disease progression. Data were obtained from Ion Torrent sequencing. (E) PTCL_09 was treated with CHOP chemotherapy but progressed clinically and was treated with IVE, achieving a partial response. The response was consolidated with GDP and autologous stem cell transplantation. Data were obtained from ddPCR.$

RHOA mutations can be followed over time and correlate with radiological measures of response. Clonal tides representing mutation dynamics for RHOA and, where possible, TET2 and IDH2, during treatment of 5 PTCL cases. VAFs are plotted as indicated by the color key to the lower right. The dotted vertical lines indicate the points at which samples were taken. (A) PTCL_08 was treated with cyclophosphamide, Adriamycin, vincristine, and prednisolone (CHOP) chemotherapy and achieved a radiological complete response. Subsequent consolidation was with ifosfamide, epirubicin, and etoposide (IVE) followed by a lomustine, etoposide, cytarabine, melphalan (HDT/LEAM)–conditioned autologous stem cell transplant. Data were obtained from Ion Torrent sequencing. (B) PTCL_02 had disease refractory to 2 lines of chemotherapy (CHOP and IVE) before achieving a PET-negative response with gemcitabine, dexamethasone, and cisplatin (GDP). Treatment was then consolidated with an autologous followed by an allogeneic stem cell transplant. The data for the 4 timepoints indicated by black dotted lines are taken from Ion Torrent sequencing data and those indicated by red dotted lines from ddPCR. (C) PTCL_25 was treated with CHOP with etoposide (CHOEP) chemotherapy but did not respond and then received IVE followed by HDT/LEAM autologous stem cell transplant. PTCL recurred 2 years later, and reinduction chemotherapy with GDP achieved a transient partial response before further progression occurred and the patient died. Data were obtained from Ion Torrent sequencing. (D) PTCL_10 was treated with CHOP chemotherapy and achieved a partial remission on CT scan. The remission lasted ∼18 months, but she then represented with a rising peripheral blood lymphocyte count, pruritus, and skin lesions. CT scan (day 476) showed lung nodules. Lymph node biopsy confirmed relapsed lymphoma, and she was retreated with GDP. In this case, loss of mutant RHOA after GDP was associated with disease progression. Data were obtained from Ion Torrent sequencing. (E) PTCL_09 was treated with CHOP chemotherapy but progressed clinically and was treated with IVE, achieving a partial response. The response was consolidated with GDP and autologous stem cell transplantation. Data were obtained from ddPCR.

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