Q74-148: Pre-HCT or Pre-Infusion Therapy

The FormsNet3^SM application allows questions 75-148 to be reported multiple times. Complete these questions for each line of therapy administered prior to the start of the preparative regimen (or prior to infusion if no preparative regimen was given). When submitting the paper version of the form for more than two lines of therapy, copy the “Pre-HCT or Pre-Infusion Therapy for Chronic Lymphocytic Leukemia” section and complete a “Line of Therapy” section for each line of therapy administered.

A single line of therapy refers to any agents administered during the same time period with the same intent (induction, consolidation, etc.). If a recipient’s disease status changes resulting in a change to treatment, a new line of therapy should be reported. Additionally, if therapy is changed because a favorable disease response was not achieved, a new line of therapy should be reported.

Question 74: Was therapy given between diagnosis and the start of the preparative regimen?

Indicate if the recipient received treatment for their primary disease between diagnosis and the start of the preparative regimen. If “yes,” continue with question 75. If “no” or “unknown,” skip questions 75-148.

Question 75: Systemic therapy

Systemic therapy is delivered via the blood stream and distributed throughout the body. Therapy may be injected into a vein or given orally. Common systemic therapies used to treat CLL include chemotherapy and monoclonal antibodies.

If systemic therapy was administered, report “yes” and continue with question 76. If not, report “no” and skip questions 76-108.

Question 76-77: Date therapy started

Indicate whether the therapy start date is “known” or “unknown.” If the therapy start date is known, report the date the recipient began this line of therapy in question 77. If the start date is partially known (e.g., the recipient started in mid-July 2010), use the process for reporting partial or unknown dates as described in the General Instructions, General Guidelines for Completing Forms.

Question 78-79: Date therapy stopped

Indicate if therapy stop date is “known” or “unknown.” If the therapy is being given in cycles, report the date the recipient started the last cycle for this line of therapy in question 79. Otherwise, report the final administration date for the therapy being reported. If the stop date is partially known, use the process for reporting partial or unknown dates as described in the General Instructions, General Guidelines for Completing Forms.

If the date therapy stopped is “unknown,” skip question 79.

Question 80-81: Number of cycles

Systemic therapy (e.g., chemotherapy, monoclonal Abs) is usually administered in cycles with rest periods in-between. This enables cancer cells to be attacked at vulnerable times and provides healthy cells adequate time to recover from the damage sustained during therapy. A cycle can last one or more days and can repeat weekly, bi-weekly, or monthly. A single systemic therapy course may consist of multiple cycles.

Indicate whether the number of cycles is “known” or “unknown.” If known, enter the number of cycles the recipient received in question 81. If “unknown,” continue with question 82.

If therapy is not being administered in cycles (e.g., daily chemotherapy), report “unknown” for question 80 and skip question 81.

Questions 82-107: Specify therapy given

Treatments vary based on protocol and in most cases are administered in the outpatient setting. A treatment may consist of a single drug or a combination of drugs. Additionally, the drugs may be administered on one day, over consecutive days, or continuously. For the line of therapy being reported, report “yes” for any drug administered. Report “no” for any drug(s) not given. Do not leave any responses blank. If the recipient received a systemic therapy which is not listed, report “yes” for “other treatment” and specify the treatment in question 107. Report the generic name of the agent, not the name brand.

Question 108: Was this line of therapy given for stem cell mobilization (priming)?

The release of stem cells from the bone marrow into the peripheral blood is called stem cell mobilization (priming). Chemotherapy agents (e.g., cyclophosphamide) may be used to stimulate the mobilization of these stem cells for future collections.

If this line of therapy was given for stem cell mobilization, report “yes.” If not, report “no.”

Question 109: Radiation therapy

Radiation therapy utilizes high-energy x-rays, gamma rays, electron beams, or proton beams to kill cancer cells. For CLL, radiation therapy may be used to kill cells that have invaded other tissues and lymph nodes. Radiation therapy may be given in conjunction with systemic chemotherapy or as a separate line of therapy.

If radiation therapy was given during or adjacent to administration of systemic therapy, report them together as single line of therapy on the form (i.e., one copy of questions 75-148). Otherwise, capture the radiation treatment as a separate line of therapy.

If the recipient received radiation therapy between the time of diagnosis and the start of the preparative regimen, report “yes” and continue with question 110. If not, report “no” and skip questions 110-116.

Question 110-111: Date therapy started

Indicate whether the start date for radiation therapy is “known” or “unknown.” If known, enter the date radiation therapy began in question 111. If the start date is partially known (e.g., the recipient started in mid-July 2010), use the process for reporting partial or unknown dates as described in the General Instructions, General Guidelines for Completing Forms.

Questions 112-113: Date therapy stopped

Indicate if the stop date for radiation therapy is “known” or “unknown.” If known, enter the final date radiation was administered in question 113. If the stop date is partially known, use the process described for reporting partial or unknown dates in General Instructions, General Guidelines for Completing Forms.

Question 114-116: Specify site(s) of radiation therapy

Report all sites of radiation therapy administered between the start and stop dates reported in questions 110-113. If “yes” is reported for “Other site,” specify all other sites in question 116.

Question 117: Surgery

If surgery was performed during or adjacent to administration of systemic therapy or a period of radiation therapy report them together as single line of therapy on the form (i.e., one copy of questions 75-148). Otherwise, capture the surgery as a separate line of therapy.

If the recipient underwent surgical treatment for their primary disease, report “yes,” continue with question 118. If not, report “no” and skip questions 118-121.

Question 118: Date of surgery

Enter the date the surgery occurred. If the date of surgery is partially known, use the process described for reporting partial or unknown dates in General Instructions, General Guidelines for Completing Forms.

Question 119-121: Specify surgery

Report all sites of surgery performed on the date reported in question 118. If “yes” is reported for “Other site,” specify all other sites in question 121.

Question 122: Best response to line of therapy

Indicate the best response to the line of therapy using the international working group criteria provided in CLL Response Criteria section of the Forms Instructions Manual. The best response is determined by a disease assessment, such as hematologic testing, pathology study, and/or physician assessment.

If the best response to the line of therapy was not evaluated, report “not assessed (NA)” and skip question 123-148.

If the best response to the line of therapy is unknown, report “unknown” and skip question 123-148.

Question 123: Date best response established

Report the date the best response to the line therapy was established. This should be the earliest date all international working group criteria were met for the response reported in question 122. Enter the date the sample was collected for pathologic evaluation (e.g., bone marrow biopsy) or blood/serum assessment (e.g., CBC, peripheral blood smear). If no pathologic, radiographic, or laboratory assessment was performed to establish the best response to the line of therapy, report the office visit in which the physician clinically evaluated the recipient’s response.

If the best response was achieved prior to starting the line of therapy being reported, indicate the date of the first assessment which was performed after initiating the current line of therapy and confirms the sustained response.

If the exact date is not known, use the process described for reporting partial or unknown dates in General Instructions, General Guidelines for Completing Forms.

Question 124-125: Were tests for molecular markers performed (e.g. PCR)?

Indicate whether testing for molecular markers was performed between the time the best response was achieved and starting a new line of therapy or the preparative regimen. If multiple tests were performed during this time period, report the testing performed closest to the date of best response (question 123). For further instructions on reporting testing for molecular markers, refer to questions 41-42.

If testing for molecular markers was done during this time period, report “yes” and indicate the sample collection date in question 125. If the exact date is not known, use the process described for reporting partial or unknown dates in General Instructions, General Guidelines for Completing Forms.

If testing for molecular markers was not during this time period, report “no” and skip questions 126-133.

Question 126-133: Specify results

For each molecular marker in questions 126-132, report whether testing was “positive,” “negative,” or “not done.” If tests identified a molecular marker other than those listed in questions 126-131, report the result in question 132 and specify the marker in question 133.

If multiple “other molecular markers” were tested at the time of best response, report “see attachment” in question 133 and attach the final reports for any other markers which were tested. For further instructions on how to attach documents in FormsNet3^SM, refer to the Training Guide. In this scenario, report “positive” in question 132 if any of the “other molecular markers” were detected.

Question 134-135: Was the disease status assessed via flow cytometry (minimum 4-color flow) (immunophenotyping)?

Indicate whether flow cytometry (immunophenotyping) was performed between the time the best response was achieved and starting a new line of therapy or the preparative regimen. If multiple tests were performed during this time period, report the testing performed closest to the date of best response (question 123).

If flow cytometry was done during this time period, report “yes” and indicate the sample collection date in question 135. If the exact date is not known, use the process described for reporting partial or unknown dates in General Instructions, General Guidelines for Completing Forms.

If flow cytometry was not during this time period, report “no” and skip questions 135-136.

Question 136: Was disease detected?

Indicate whether disease was detected by flow cytometry. If the findings are unclear, consult with a physician and have them document whether evidence of disease is present.

Question 137: Was the disease status assessed via cytogenetic testing (karyotyping or FISH)?

Indicate whether karyotyping or FISH assessments were performed between the time the best response was achieved and starting a new line of therapy or the preparative regimen. If multiple tests were performed during this time period, report the testing performed closest to the date of best response (question 123).

If karyotyping or FISH assessments were done during this time period, report “yes” and continue with question 138. If not, report “no” and skip questions 138-143.

Question 138-139: Was the disease status assessed via FISH?

Indicate whether FISH testing was performed between the time the best response was achieved and starting a new line of therapy or the preparative regimen. If multiple tests were performed during this time period, report the testing performed closest to the date of best response (question 123).

If FISH testing was done during this time period, report “yes” and indicate the sample collection date in question 139. If the exact date is not known, use the process described for reporting partial or unknown dates in General Instructions, General Guidelines for Completing Forms.

If FISH testing was not done during this time period, report “no” and skip questions 139-140. Examples of this include: no FISH study performed or FISH sample was inadequate.

Question 140: Was disease detected?

Indicate whether disease was detected by FISH. If the findings are unclear, consult with a physician and have them document whether evidence of disease is present.

Question 141-142: Was the disease status assessed via conventional cytogenetics (karyotyping)?

Indicate whether karyotyping was performed between the time the best response was achieved and starting a new line of therapy or the preparative regimen. If multiple tests were performed during this time period, report the testing performed closest to the date of best response (question 123).

If karyotyping was done during this time period, report “yes” and indicate the sample collection date in question 142. If the exact date is not known, use the process described for reporting partial or unknown dates in General Instructions, General Guidelines for Completing Forms.

If karyotyping was not done during this time period, report “no” and skip questions 135-136. Examples of this include: no conventional cytogenetics performed or conventional cytogenetic culture failed.

Question 143: Was disease detected?

Indicate if disease was detected by karyotyping. If the findings are unclear, consult with a physician and have them document whether evidence of disease is present.

Question 144-145: Was the disease status assessed by clinical/hematologic assessment?

Clinical and hematologic assessments are the least sensitive methods of establishing a patient’s disease status. Examples include: pathologic evaluation (e.g., bone marrow biopsy), radiographic examination (e.g., X-ray, CT scan, MRI scan, PET scan), and laboratory assessment (e.g., CBC, peripheral blood smear), in addition to clinician evaluation and physical examination.

Indicate whether clinical and/or hematologic assessments were performed between the time the best response was achieved and starting a new line of therapy or the preparative regimen. If “yes,” report the date of assessment in question 145. The date reported should be that of the most-disease specific assessment performed at the time of best response (question 123). When determining the most disease-specific assessment, only consider studies which have previously shown or currently show evidence of disease. If all assessments are negative, report the date of the most sensitive test performed (e.g., report a bone marrow biopsy rather than a CBC) within the appropriate time period. If assessments are positive for disease, report the first assessment confirming the best response (question 122). If the exact date is not known, use the process for reporting partial or unknown dates as described in the General Instructions, General Guidelines for Completing Forms.

If no clinical and/or hematologic assessments were performed during this time period, report “no” and skip questions 145-146. This option should rarely be reported given the inclusion of physician assessments.

Question 146: Was disease detected?

Indicate if disease was detected by clinical/hematologic assessment. If the findings are unclear, consult with a physician and have them document whether evidence of disease is present.

Question 147: Did disease relapse/progress following this line of therapy?

Refer to the international working group criteria provided in CLL Response Criteria section of the Forms Instructions Manual for more information on how to determine recurrence or progression of disease. Report “yes” if the recipient met the criteria for relapse or progression after starting this line of therapy and prior to starting a subsequent line of therapy.

Report “no” if the recipient never relapsed or progressed following this line of therapy. Also, report “no” if the recipient relapsed or progressed after beginning a subsequent line of therapy. This episode of relapse / progression will be captured in the instance (i.e., copy) of questions 75-148 completed for the subsequent line of therapy.

If this is the last line of therapy administered prior to HCT, only report “yes” if relapse or progression occurred prior to infusion. Relapse or progression occurring after the infusion date will be reported on the CLL Post-HCT Data Form (Form 2113).

Question 148: Date of relapse/progression

Enter the assessment date that relapse or progression was established following initiation of this line of therapy. Report the date of the pathologic evaluation (e.g., bone marrow) or blood/serum assessment (e.g., CBC, peripheral blood smear). Enter the date the sample was collected for pathologic and laboratory evaluations. If extranodal disease is detected upon radiographic examination (e.g., X-rays, CT scans, MRI scans, PET scans), enter the date the imaging took place. If the physician determines evidence of relapse following a clinical assessment during an office visit, report the date of assessment.