Question 143: Dosing weight used for preparative regimen orders
Report the dosing weight used for determining the preparative regimen orders. The intent of this question is to report the weight used to calculate the preparative regimen drug doses. Report the dosing weight as listed on the preparative regimen / chemotherapy orders. If dosing weight changes between chemotherapy orders and administration, report the new weight. Report weight to the nearest tenth of a kilogram or pound.
This weight may be the same weight reported above in Actual weight at start of the preparative regimen and / or could also be the same weight reported on the Recipient Baseline (2000) Form, if applicable.
Review the example below for additional information:
- Example 1: The recipient’s preparative regimen consisted of fludarabine and busulfan. The dosing weight to calculate the preparative regimen drug doses was 91.9 kg which was the same weight used for dosing weight of fludarabine. However, the dosing weight for busulfan was adjusted to 62.7 kg.
- The dosing weight used for the preparative regimen orders on the Pre-TED (2400) would be reported as 91.9 kg.
- The dosing weight of fludarabine and busulfan reported on the Recipient Baseline (2000) would be reported as 91.9 kg and 62.7 kg, respectively.
Question 144: Was a pre-HCT preparative regimen prescribed?
Recipients are generally transplanted under a specific protocol that defines the radiation and/or systemic therapy the recipient is intended to receive as a preparative regimen. This protocol, which may be either a research protocol or standard of care protocol, should be referred to when completing this section.
However, there are instances when a preparative regimen is not given. Examples may include, but are not limited to:
- Primary diagnosis of an immune deficiency.
- Subsequent allogeneic HCT due to loss of, or poor, neutrophil engraftment.
Specify if a preparative regimen is prescribed.
For more information regarding the recipient’s preparative regimen, consult a transplant physician or contact CIBMTR Center Support.
Question 145: Classify the recipient’s prescribed preparative regimen (Allogeneic HCTs only)
Myeloablative pre-transplant conditioning destroys bone marrow cells using high-dose radiation and/or systemic therapy. It is used to eliminate the recipient’s immune system and to leave space in the bone marrow niche for the donated cells. A myeloablative regimen is sometimes used for recipients with non-malignant diseases who require HCT for marrow reconstitution (i.e., immunodeficiencies) or to produce a complete donor chimerism.
Non-myeloablative stem cell transplant (NMA or NST) and Reduced-intensity conditioning (RIC) preparative regimens generally use lower doses of radiation and/or systemic therapy to prevent graft rejection and to suppress the recipient’s hematopoietic immune system, but not eliminate it completely. Non-myeloablative protocols rely on the immune cells of the donor to destroy the disease (called graft versus tumor or GVT effect), and typically produces mixed chimerism. NST is a common treatment option for recipients who are older or who have other health problems, as the lower radiation and/or systemic therapy doses are easier for the recipient to tolerate.
In general, RIC includes any regimen that does not meet the criteria for either myeloablative or non-myeloablative regimens.
The determination of the intent of the regimen should be based on the center’s protocol or the opinion of the physician overseeing the care of the recipient. However, if the intent is not specified, the regimen intensity may be reported based on CIBMTR operational guidelines below.
Indicate whether the intent of the preparative regimen was Myeloablative (to produce marrow ablation or pancytopenia), Non-myeloablative, or Reduced intensity.
Table 1. Examples of Myeloablative, Reduced Intensity, and Non-Myeloablative Regimens
| Myeloablative Regimens | Reduced Intensity Regimens | Non-Myeloablative Regimens |
|---|---|---|
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|
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Question 146: Was irradiation planned as part of the pre-HCT preparative regimen?
Specify if irradiation is planned as part of the preparative regimen.
Irradiation performed as previous treatment should not be reported in this section. Report irradiation performed as previous treatment on the appropriate Disease Specific Form. Additionally, “radiation boosts,” often given to smaller sites that may have residual malignant cells or to areas that were shielded (i.e., chest wall or lung), should not be reported in this section. Report irradiation boosts administered on the applicable Recipient Baseline Data (2000) Form.
Question 147: What was the prescribed radiation field?
Indicate if the planned irradiation was to Total body, Total body by intensity-modulated radiation therapy (IMRT), Total lymphoid or nodal regions, or Thoracoabdominal region.
Question 148: Total prescribed dose (dose per fraction x total number of fractions)
Enter the total dose of radiation prescribed. If radiation was prescribed as a single dose, the amount of radiation delivered in the single dose constitutes the total dose. If the radiation was prescribed in fractionated doses, multiply the dose per fraction by the total number of fractions to determine the total dose. Enter the total dose of radiation in either grays (Gy) or centigrays (cGy).
- Example 2: Radiation Order: TBI, 200 cGy/day for three days (3 doses)
- Total dose: 200 cGy x 3 doses = 600 cGy
- Report the total dose as 600 cGy
Question 149: Date started
Enter the date the single dose or first fraction of radiation was administered.
Question 150: Was the radiation fractionated?
Radiation is either delivered as a single dose or in several treatments (fractions). Radiation is fractionated to increase the loss of diseased cells, as they do not recover as quickly as disease-free cells.
Indicate if the radiation was fractionated.
Question 151: Total number of fractions
Enter the total number of fractions (treatments) of radiation that were administered. The recipient may receive more than one fraction per day (hyperfractionation).
The total number of fractions multiplied by the dose per fraction must be equal to the total dose reported above.
Questions 152 – 153: Drug
Select the preparative regimen drug. The form lists each drug by the generic name. The following website provides the trade names under which generic drugs are manufactured: http://www.rxlist.com/script/main/hp.asp.
Other drug should be used only if the drug is not one of the listed options. If selected, specify the name of the drug.
Additional information:
- Intrathecal drugs: Include any intrathecal drugs the recipient received for prophylaxis or treatment of CNS disease within 21 days prior to the start of the preparative regimen.
- Additional sites of radiation: Do not report additional sites of radiation (e.g., cranial boost).
- If the recipient is assigned to the Comprehensive Report Forms by the form selection algorithm, the additional sites of radiation will be reported on the Recipient Baseline Form (Form 2000). If the recipient is assigned to TED Forms by the form track selection algorithm, the additional sites of radiation will not be reported.
- GVHD prophylaxis: Do not report GVHD prophylaxis, such as Methotrexate, as preparative regimen.
- Pre-infusion treatment: Do not report pre-infusion treatment, such as Venetoclax, as preparative regimen.
- If the Pre-TED (2400) Form is being completed for a subsequent infusion, do not report therapy that was given to treat the recipient’s disease (between the previous and current planned infusions) in the preparative regimen section.
- Change in preparative regimen: If there is a change to the chemotherapy preparative regimen (e.g., from busulfan + fludarabine to melphalan + fludarabine) after the Pre-TED (2400) Form has been submitted, return to the form and make this correction directly in FormsNet3SM to ensure that the chemotherapy reported reflects the actual chemotherapy regimen given.
Question 154: Total prescribed dose
Report the total dose of each drug as prescribed in the preparative regimen section of the HCT protocol. Do not report the prescribed daily dose. Report the drug doses to the nearest tenth. For paper submission, do not modify the number of boxes or include decimal values. The pharmacy record or Medication Administration Record (MAR) should be used for determining the date the drug was started.
If the total prescribed dose is reported in a unit other than those listed, convert the dose to the appropriate unit. If drug doses cannot be converted to the unit listed, leave the unit field blank, override the error (using “unable to answer”), and attach a copy of the source document to the Pre-TED (2400) Form using the attachment feature in FormsNet3SM.
Pharmacokinetics
Pharmacokinetic testing can be used to determine whether the drug concentration in the bloodstream is appropriate to the dose given. This reflects the speed of absorption and elimination of the drug. These tests are usually performed using the first dose of systemic therapy, or a test dose, where multiple samples are drawn at specific time points following the first dose. The samples are sent to a laboratory that performs the testing to determine the drug concentration. If carboplatin was prescribed, indicate if pharmacokinetic testing was performed to determine the preparative regimen dosing. If it is not known whether this testing was performed, consult a transplant physician.
A common example of this situation occurs in the use of busulfan. When pharmacokinetic (pK) testing is performed, the ordered busulfan dose can be calculated from either the AUC dose or daily AUC. If an AUC dose is documented, this can be multiplied by the number of ordered doses in order to calculate the ordered busulfan dose. When a daily AUC is documented, this can be multiplied by the number of days in order to calculate the ordered busulfan dose. See the example below for more information.
- Example 3: Calculating the ordered dose of busulfan using AUC dose
- The AUC dose in the source document example below is 2842 uMol x Min, which was prescribed for a total of 5 doses. The total ordered dose of Busulfan in this scenario should be reported as 14,210 uMol x Min.
Pharmacokinetics and Test Dose
In some cases, a “test dose” of the drug is given before the actual preparative regimen is started, and this dose is used for acquiring drug levels that are used to adjust the dose that will be used in the preparative regimen. In other situations, the first dose of the drug is given in the usual fashion as part of the preparative regimen. After this first dose, serum drug levels are drawn and sent to a reference lab. The drug is continued at the starting dose until the lab results are reported and adjustment is made to later doses.
When a drug is used for the preparative regimen where pharmacokinetics will be tested, it is important to distinguish whether the testing will be done with a “test dose” before beginning the preparative regimen or using the first dose of the preparative regimen. The reporting of the dosing for CIBMTR forms depends upon this distinction. This helps distinguish whether the dose is part of the therapeutic regimen, or not.
- Example 4: A test dose was given > 24 hours prior to the intended therapeutic dosing
- A recipient with AML underwent allogeneic HCT from a sibling; busulfan and cyclophosphamide were used as the preparative regimen. The recipient presented to clinic 9 days before the HCT, where a dose of busulfan at 0.5 mg/kg was given intravenously. Blood samples were drawn for the next 6 hours, after which the patient left the clinic. His samples were sent to a lab, results were returned the next day, and an adjusted dose of busulfan was calculated. He returned to the hospital 6 days before HCT and began to receive busulfan at the adjusted dose intravenously for 4 days, followed by cyclophosphamide, and proceeded to receive his cells. Since he received 0.5 mg/kg as a “test dose,” this would not be reported in his total preparative regimen dose.
If a test dose was given, where the dose was distinct from the therapeutic dosing preparative regimen (often 1-2 or more days prior to the initiation of regular dosing), the following should be reported:- On the Pre-TED (2400) Form, the total prescribed dose per protocol would NOT include the test dose.
- On the Baseline (2000) Form, the start date of the chemotherapy agent should be reported as the date the first therapeutic dose was administered. The actual dose received would NOT include the test dose.
- A recipient with AML underwent allogeneic HCT from a sibling; busulfan and cyclophosphamide were used as the preparative regimen. The recipient presented to clinic 9 days before the HCT, where a dose of busulfan at 0.5 mg/kg was given intravenously. Blood samples were drawn for the next 6 hours, after which the patient left the clinic. His samples were sent to a lab, results were returned the next day, and an adjusted dose of busulfan was calculated. He returned to the hospital 6 days before HCT and began to receive busulfan at the adjusted dose intravenously for 4 days, followed by cyclophosphamide, and proceeded to receive his cells. Since he received 0.5 mg/kg as a “test dose,” this would not be reported in his total preparative regimen dose.
- Example 5: The first dose of therapeutic dosing is used for monitoring
- A recipient with MDS received an allogeneic HCT from an unrelated donor; busulfan and fludarabine were used as the preparative regimen. She was admitted to the hospital 7 days before her HCT and received a dose of busulfan at 0.8 mg/kg IV at 6:00 AM. Serum samples were drawn every 30 minutes until the next dose of Busulfan at 0.8 mg/kg IV was given at 12:00 noon. Her blood was sent to a reference lab, and she continued to receive busulfan every 6 hours. On day -6, the lab called with her drug levels, and it was determined that the current dose was correct. No adjustment was made, and she completed all 16 doses of busulfan. Since the dose of busulfan (0.8 mg/kg) that was used for drug testing was ALSO her first dose of the preparative regimen, it should be included in the amount of drug that was given for preparative regimen. The total prescribed dose per protocol should be reported as “13 mg/kg.” (0.8 mg/kg x 16 doses = 12.8 mg/kg rounded to 13 mg/kg).
If the first dose of the preparative regimen was used to determine pharmacokinetics, the following should be reported:- On the Pre-TED (2400) Form, the total prescribed dose per protocol would include the dose used for monitoring.
- On the Baseline (2000) Form, the start date of the chemotherapy agent should be reported as the date the first dose was administered. The actual dose received would include the dose used for monitoring.
- A recipient with MDS received an allogeneic HCT from an unrelated donor; busulfan and fludarabine were used as the preparative regimen. She was admitted to the hospital 7 days before her HCT and received a dose of busulfan at 0.8 mg/kg IV at 6:00 AM. Serum samples were drawn every 30 minutes until the next dose of Busulfan at 0.8 mg/kg IV was given at 12:00 noon. Her blood was sent to a reference lab, and she continued to receive busulfan every 6 hours. On day -6, the lab called with her drug levels, and it was determined that the current dose was correct. No adjustment was made, and she completed all 16 doses of busulfan. Since the dose of busulfan (0.8 mg/kg) that was used for drug testing was ALSO her first dose of the preparative regimen, it should be included in the amount of drug that was given for preparative regimen. The total prescribed dose per protocol should be reported as “13 mg/kg.” (0.8 mg/kg x 16 doses = 12.8 mg/kg rounded to 13 mg/kg).
Test doses must be reported consistently by the center. Since most centers follow a consistent approach to pharmacokinetic testing, it should be straightforward for the center to adopt a consistent approach to the reporting of test doses.
Question 155: Date started
Enter the date when the first dose of the preparative regimen drug was administered. The pharmacy record or Medication Administration Record (MAR) should be used for determining the date the drug was started.
Question 156: Specify administration (busulfan only)
Report the busulfan administration route as either Oral, IV, or Both.
Section Updates:
| Question Number | Date of Change | Add/Remove/Modify | Description | Reasoning (If applicable) |
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