Statements pertinent to testing, prognostication, and staging of RT
| Statement number . | Grade . | Prognostication . |
|---|---|---|
| 2.1.1 | B | TP53 aberrations in either CLL or RT tissue are associated with shortened OS. |
| 2.1.2 | B | Therapy for CLL before the development of RT is associated with poorer RT outcomes. |
| rk | Insufficient data exist to determine whether the type of CLL therapy (chemoimmunotherapy vs targeted therapeutics) influences prognosis of RT. | |
| Statement number | Grade | Laboratory testing |
| 2.2.1 | G | Clonality should be determined by comparing immunoglobulin gene rearrangement from the RT tissue with the immunoglobulin gene rearrangement in the CLL cells. |
| rk | We understand that this means of testing for clonality is not universal. However, we believe this to be the gold standard. If tissue specimen attained does not allow for this analysis, appropriate analysis per tissue attained should be performed. An additional biopsy should not be performed if alternative testing is possible with the tissue available. | |
| 2.2.2 | R | At present, NGS of the RT tissue offers limited clinical value in determining prognosis. |
| 2.2.3 | G | No direct evidence supports testing of molecular resistance to BTK or BCL2 inhibitors in patients with RT. |
| rk | It is unclear whether “resistance mutations” confer resistance to BTKis or BCL2is in RT. However, clinical rational based on evidence in CLL suggests that RT harboring these mutations may not be amenable to treatment with these agents. | |
| 2.2.4 | R | If available, all attempts should be made to biobank RT samples for future characterization. |
| rk | Paired germ line tissue should be stored along with malignant tissue for use in future genetic sequencing. | |
| Statement number | Grade | Staging/pretreatment assessment |
| 2.3.1 | G | We recommend using a pretreatment PET-CT scan to establish the extent of the disease. |
| 2.3.2 | G | Unlike standard DLBCL, we recommend bone marrow biopsy at time of treatment to determine presence of bone marrow disease, and to assess status of CLL. |
| Statement number . | Grade . | Prognostication . |
|---|---|---|
| 2.1.1 | B | TP53 aberrations in either CLL or RT tissue are associated with shortened OS. |
| 2.1.2 | B | Therapy for CLL before the development of RT is associated with poorer RT outcomes. |
| rk | Insufficient data exist to determine whether the type of CLL therapy (chemoimmunotherapy vs targeted therapeutics) influences prognosis of RT. | |
| Statement number | Grade | Laboratory testing |
| 2.2.1 | G | Clonality should be determined by comparing immunoglobulin gene rearrangement from the RT tissue with the immunoglobulin gene rearrangement in the CLL cells. |
| rk | We understand that this means of testing for clonality is not universal. However, we believe this to be the gold standard. If tissue specimen attained does not allow for this analysis, appropriate analysis per tissue attained should be performed. An additional biopsy should not be performed if alternative testing is possible with the tissue available. | |
| 2.2.2 | R | At present, NGS of the RT tissue offers limited clinical value in determining prognosis. |
| 2.2.3 | G | No direct evidence supports testing of molecular resistance to BTK or BCL2 inhibitors in patients with RT. |
| rk | It is unclear whether “resistance mutations” confer resistance to BTKis or BCL2is in RT. However, clinical rational based on evidence in CLL suggests that RT harboring these mutations may not be amenable to treatment with these agents. | |
| 2.2.4 | R | If available, all attempts should be made to biobank RT samples for future characterization. |
| rk | Paired germ line tissue should be stored along with malignant tissue for use in future genetic sequencing. | |
| Statement number | Grade | Staging/pretreatment assessment |
| 2.3.1 | G | We recommend using a pretreatment PET-CT scan to establish the extent of the disease. |
| 2.3.2 | G | Unlike standard DLBCL, we recommend bone marrow biopsy at time of treatment to determine presence of bone marrow disease, and to assess status of CLL. |
B, background statement; G, good practice statement; R, research statement; rk, remark to earlier statement.