Myeloproliferative Neoplasms (MPN) are characterized by the overproduction of blood cells (red blood cells, white blood cells, and/or platelets) or collagen in the bone marrow. Often the MPN will be identified because of a blood test for another condition, as some recipients are asymptomatic. Common symptoms found in the array of myeloproliferative disorders include fatigue and the enlargement of the spleen (splenomegaly).
Question 1: Date of diagnosis of primary disease for infusion
Report the date of the first pathological diagnosis (e.g., bone marrow or tissue biopsy) of the disease. Enter the date the sample was collected for examination. If the diagnosis was determined at an outside center, and no documentation of a pathological or laboratory assessment is available, the dictated date of diagnosis within a physician note may be reported. Do not report the date symptoms first appeared.
If the recipient’s MPN progressed to from a lower grade MPN to a higher grade MPN, report the diagnosis date of the original MPN diagnosis (i.e., the lower MPN grade). The transformation date (i.e., diagnosis of the higher grade) is captured below.
If the recipient’s MPN transformed to AML prior to infusion, report diagnosis date of AML and ensure the primary disease for infusion is reported as AML. The AML section of the Disease Classification (2402) form should be completed appropriately. The MPN diagnosis date is captured below.
If the exact diagnosis date is not known, use the process described in General Instructions, Guidelines for Completing Forms
Question 380: Specify systemic mastocytosis
Specify the systemic mastocytosis sub-type / variant.
Systemic Mastocytosis Diagnostic Criteria
The diagnosis of systemic mastocytosis can be made when the major criterion and at least one minor criterion are present, or when > three minor criteria are present.
- Major criterion
- Multifocal dense infiltrates of mast cells (> 15 mast cells in aggregates) detected in sections of bone marrow and/or other extracutaneous organs(s).
- Minor criteria
- In biopsy sections of bone marrow or other extracutaneous organs, >25% of the mast cells in the infiltrate are spindle-shaped or have atypical morphology; or >25% of all mast cells in bone marrow aspirate smears are immature or atypical.
- Detection of an activating point mutation at codon 816 of KIT in the bone marrow, blood or another extracutaneous organ.
- Mast cells in bone marrow, blood or another extracutaneous organ express CD25, with or without CD2, in addition to normal mast cell markers.
- Serum total tryptase is persistently >20 ng/ml, unless there is an associated myeloid neoplasm, in which case this parameter is not valid.
Systemic Mastocytosis Subtypes / Variants Diagnostic Criteria
The diagnostic criteria for the systemic mastocytosis subtypes / variants are as follows. Each sub-type / variant meets the general criteria for systemic mastocytosis with additional criteria for each.
- Indolent systemic mastocytosis (ISM): Low mast cell burden; no evidence of an associated hematologic neoplasm; skin lesions are almost invariably present; no “C” findings.
- Smoldering systemic mastocytosis (SSM): +>+2 “B” findings and no “C” findings; high mast cell burden; no evidence of an associated hematologic neoplasm; does not meet criteria for mast cell leukemia
- Systemic mastocytosis with an associated hematologic neoplasm SM-AHN): Meets the criteria for an associated hematologic neoplasm (i.e., MDS, MPN, AML, lymphoma or another hematological neoplasm classified as a distinct entity in the WHO classification).
- Aggressive systemic mastocytosis (ASM): +>+1 “C” findings; does not meet the criteria for mast cell leukemia; skin lesions are usually absent.
- Mast Cell leukemia (MCL): Bone marrow biopsy shows diffuse infiltration of atypical, immature mast cells; bone marrow aspirate smears show +>+20% mast cells. In classic cases, mast cells account for +>+10% of the peripheral blood WBC, but the aleukemic variant (in which mast cells account for <10%) is more common. Skin lesions are usually absent
- Bone marrow mastocytosis: Absence of skin lesions and B-findings. Additionally, the basal serum tryptase is < 125 ng / ml.
Systemic Mastocytosis Burden of Disease (B) and Cytoreduction-Requiring ( C ) Findings
- “B” findings
- BM biopsy showing +>+30% infiltration by MC (focal, dense aggregates) and/or serum total tryptase level >200 ng/mL
- Signs of dysplasia or myeloproliferation, in non‐MC lineage(s), but insufficient criteria for definitive diagnosis of a hematopoietic neoplasm (AHNMD), with normal or slightly abnormal blood counts.
- Hepatomegaly without impairment of liver function, and/or palpable splenomegaly without hypersplenism, and/or lymphadenopathy on palpation or imaging.
- “C” findings
- Bone marrow dysfunction manifested by one or more cytopenia(s) (ANC < 1.0 × 109/L, Hgb < 10 g/dL, or platelets < 100 × 109/L), but no obvious non-mast cell hematopoietic malignancy.
- Palpable hepatomegaly with impairment of liver function, ascites and/or portal hypertension.
- Skeletal involvement with large osteolytic lesions and/or pathological fractures.
- Palpable splenomegaly with hypersplenism.
- Malabsorption with weight loss due to gastrointestinal mast cell infiltrates.
Question 381: Did the recipient have constitutional symptoms in six months before diagnosis? (symptoms are > 10% weight loss in six months, night sweats, unexplained fever higher than 37.5°C)
Indicate if constitutional symptoms were present at diagnosis. Constitutional symptoms are often called “B” symptoms and include unexplained fever greater than 38°C (100.4°F), night sweats, or unexplained weight loss in the six months prior to diagnosis. Indicate if any constitutional symptoms were present at or six months prior to diagnosis.
If constitutional symptoms were not present at or prior to diagnosis or are not known, report No or Unknown, respectively. The Unknown option should be used if it is not possible to determine the presence or absence of constitutional symptoms at or six months prior to diagnosis.
Questions 382 – 383: Blasts in bone marrow (at diagnosis)
Indicate whether the percentage of blasts in the bone marrow was known at diagnosis. If Known, report the percentage documented on the laboratory report.
If the lab was assessed multiple times prior to starting treatment, report the values closest to the diagnosis date.
If multiple methods were used to detect the percentage of blasts in the bone marrow, the aspirate differential is the preferred method; followed by flow cytometry and IHC (immunohistochemical staining).
Questions 384 – 392: Complete blood count (CBC) results available (check all that apply) (at diagnosis)
These questions are intended to capture the laboratory studies performed at the initial diagnosis of MPN. Report the date of the CBC completed closest to the diagnosis date and select all lab values assessed on the reported date. All values must reflect testing performed prior to the start of the first treatment of the primary disease for infusion. If the recipient’s MPN transformed, report the studies from the original diagnosis. If labs were assessed multiple times prior to starting treatment, report the values closest to the diagnosis date.
- WBC: The white blood cell count is a value that represents all of the white blood cells in the blood. If the count is too high or too low, the ability to fight infection may be impaired. If known, specify the value and units of measurement as documented on the lab report.
- Neutrophils: Neutrophils are a subtype of white blood cell that fights infection. The value on the laboratory report may be a percentage or an absolute value. If an absolute value is reported, divide it by the white blood cell count for a percentage. Neutrophils are also known as polymorphonuclear leukocytes (PMNs). If known, specify the percentage as documented on the lab report.
- Blasts in blood: Blasts are not typically found in the peripheral blood; however, can appear for various reasons, including infection, blood cancer, or blood disorder. If known, report the percentage of blasts detected in the blood.
- If a differential was performed and the percentage of plasma cells are not listed, report 0%.
- Hemoglobin: Hemoglobin is a molecule in red blood cells that delivers oxygen to tissues throughout the body. A low hemoglobin count is considered “anemia” and blood transfusions, or growth factors may be required to increase the hemoglobin level. If known, specify the value and units of measurement as documented on the lab report. Additionally, indicate if red blood cells were transfused < 30 days prior to the CBC date reported above.
- Transfusions temporarily increase the red blood cell count, and it is important to distinguish between a recipient whose body is creating these cells and a recipient who requires transfusions to support the counts.
- Platelets: Platelets are formed elements within the blood that help with coagulation. A low platelet count, called thrombocytopenia, may lead to easy bleeding or bruising. Thrombocytopenia may require platelet transfusions. If known, specify the value and unites of measurement as documented on the lab report. Additionally, indicate if platelets were transfused < seven days prior to the CBC date reported above.
- Transfusions temporarily increase the platelet count, and it is important to distinguish between a recipient whose body is creating these cells and a recipient who requires transfusions to support the counts.
If a CBC was not completed at diagnosis or unknown if completed, select None.
If the exact sample collection date is not known, use the process described in General Instructions, Guidelines for Completing Forms.
Question 393: Were cytogenetics tested (karyotyping or FISH)? (at diagnosis)
Cytogenetics is the study of chromosomes. Cytogenetic assessment involves testing blood or bone marrow for the presence of known chromosomal abnormalities that reflect the recipient’s disease.
Testing methods include conventional chromosome analysis (karyotyping) or fluorescence in situ hybridization (FISH). For more information about cytogenetic testing and terminology, see Appendix C: Cytogenetics.
Indicate if cytogenetic studies were obtained at diagnosis. If cytogenetic studies were obtained, select Yes. If no cytogenetic studies were obtained, or it is unknown if chromosome studies were performed, select No or Unknown, respectively.
Question 394: Were cytogenetics tested via FISH? (at diagnosis)
Specify if FISH studies were performed at diagnosis. If FISH studies were not performed at diagnosis or FISH samples were inadequate, or the result ‘failed,’ report No. If it is not known if it was performed, report Unknown.
Report chromosomal microarrays / chromosomal genomic arrays as FISH assessments.
Question 395: Sample source
The cytogenetic sample source is important for MPN research. Indicate if the sample was from Bone marrow or from Blood. If FISH studies were performed on multiple samples at diagnosis, the bone marrow results are the preferred sample source to report.
Question 396: Results of tests
Specify if FISH abnormalities were detected at diagnosis.
Questions 397 – 400: Specify FISH abnormalities (at diagnosis)
Report the ISCN compatible string, if the data field is enabled. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.
If the ISCN compatible string is not reported, then select the number of abnormalities detected by FISH at diagnosis and select all abnormalities detected.
If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.
Question 401: Were cytogenetics tested via karyotyping? (at diagnosis)
Specify if karyotyping studies were performed at diagnosis. Report Yes even if there were no evaluable metaphase cells / failed (these results will be specified below).
If karyotyping studies were not performed at diagnosis or it is unknown if performed, report No or Unknown, respectively.
Question 402: Sample source
The cytogenetic sample source is important for MPN research. Indicate if the sample was from Bone marrow or from Blood. If karyotype analyses were performed on multiple samples at diagnosis, the bone marrow results are the preferred sample source to report.
Question 403: Results of tests
Specify if abnormalities were detected by karyotype at diagnosis.
If karyotyping failed or the sample was inadequate, select No evaluable metaphases.
Questions 404 – 407: Specify karyotype abnormalities (at diagnosis)
Report the ISCN compatible string, if applicable. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.
If the ISCN compatible string is not reported, then select the number of abnormalities detected by karyotype at diagnosis and select all abnormalities detected.
If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.
Questions 408 – 417: Were tests for driver mutations performed? (at diagnosis)
Testing for driver mutations may be performed by different methods including next generation sequencing (NGS), polymerase chain reaction (PCR), microarray, and fluorescence in situ hybridization (FISH). If testing was performed by any / all of these methods at diagnosis, report Yes and report the results for the most recent test(s) prior to the start of therapy.
If testing for driver mutations were not performed / sample failed or is not known if performed, report No or Unknown, respectively.
Questions 418 – 421: Specify positive molecular marker(s) identified (at diagnosis)
Testing for molecular markers is often performed by using PCR based methods to assess specific genetic sequences. Once a marker has been identified, these methods can be repeated to detect minimal residual disease (MRD) in the recipient’s blood, marrow, or tissue. Molecular assessments include polymerase chain reaction (PCR) amplification to detect single specific disease markers; however, molecular methods are evolving and now include Sanger sequencing, and next generation sequencing (e.g., Illumina, Roche 454, Proton / PGM, SOLiD).
Specify all positive molecular markers detected at diagnosis and the amino acid change, if known. If molecular markers were not detected at diagnosis, the sample failed, testing was not completed or unknown if completed at diagnosis report None. This option should also be selected if other molecular markers were tested and resulted as negative.
If a molecular marker was detected, but not listed as an option, select Other molecular marker and specify the abnormality, along with the amino acid change, if known.
Question 422: Did the recipient progress or transform to a different MPN subtype or AML between diagnosis and the start of the preparative regimen / infusion?
MPN subtypes may also transform / progress from one into another. Indicate if the recipient’s disease progressed to AML or transformed into a different MPN subtype between initial diagnosis and the start of the preparative regimen / infusion. Historically, progression to AML was defined by an increase in blood or bone marrow blasts > 20%. However, for some AML classifications, > 20% blasts in the blood or bone marrow are not required. Review Specify the AML classification above for more information.
Specify if the recipient’s disease progressed to AML or transformed into a different MPN subtype between diagnosis and the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). If a transformation or progression did not occur or it is unknown, select No.
Question 423: Specify the MPN subtype or AML after transformation
Indicate the recipient’s current MPN subtype after transformation. If the recipient experienced more than one transformation after diagnosis, report the most recent subtype.
If the disease progressed to AML, report the date of MPN diagnosis. If MPN progresses to AML and the recipient is on the CRF track, the AML Pre-Infusion (2010) form will also come due.
For all other progressions or transformations, continue with to specify the date of the most recent transformation.
Question 424: Specify the date of the most recent transformation
Report the date of assessment that determined the most recent disease transformation (i.e., if there were multiple transformations, report the most recent). Report the date of the pathological evaluation (i.e., bone marrow) or blood / serum assessment (i.e., CBC, peripheral blood smear). Enter the date the sample was collected for pathological and laboratory evaluations.
If the exact date is not known, use the process for reporting partial or unknown dates as described in General Instructions, Guidelines for Completing Forms.
Question 425: Date of MPN Diagnosis
If the recipient’s MPN transformed to AML prior to infusion, report the date of diagnosis of MPN. If the exact date is not known, use the process for reporting partial or unknown dates as described in General Instructions, Guidelines for Completing Forms.
Ensure the diagnosis date for AML has been reported as the diagnosis date of the primary disease for infusion and AML is reported as the primary disease for infusion. The AML section of the Disease Classification (2402) form must be completed appropriately.
Question 426: Specify transfusion dependence at the last evaluation prior to the start of the preparative regimen / infusion
Indicate the transfusion dependence for the recipient at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).
Select Non-transfused (NTD) if the recipient was without RBC transfusions as supportive care for the disease within a period of 16 weeks prior to the start of the preparative regimen / infusion.
Select Low-transfusion burden (LTB) if the recipient had 3 – 7 RBC transfusions within a period of 16 weeks in at least 2 transfusion episodes with a maximum of 3 RBC transfusions in 8 weeks prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).
Select High-transfusion burden (HTB) if the recipient had ≥ 8 RBCs transfusions within a period of 16 weeks or ≥ 4 within 8 weeks prior to the start the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).
Question 427: Did the recipient have constitutional symptoms in six months before last evaluation prior to the start of the preparative regimen / infusion? (symptoms are > 10% weight loss in 6 months, night sweats, or unexplained fever higher than 37.5°C)
Specify if constitutional symptoms were present within six months before the last evaluation prior to the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). Constitutional symptoms are often called “B” symptoms and include unexplained fever greater than 38°C (100.4°F), night sweats, or unexplained weight loss in the six months before the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).
Report No if constitutional symptoms were not present or unknown if present at this timepoint.
Question 428: Did the recipient have splenomegaly at last evaluation prior to the start of the preparative regimen / infusion?
Indicate if the recipient had splenomegaly at the last evaluation. Splenomegaly is often documented during the physician’s physical assessment of the recipient and represents an abnormal finding. Splenomegaly can also be detected by imaging techniques such as ultrasonography, CT or MRI.
Indicate if splenomegaly was present at the last evaluation prior to the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).
If splenomegaly was not present or is unknown if present at this timepoint, report No.
Select Not applicable if the question does not apply to the recipient (i.e., prior splenectomy).
Questions 429 – 431: Specify the method used to measure spleen size
Indicate the method used to measure the spleen size. If spleen size is measured using multiple methods, report the most accurate assessment. Ultrasound is the most specific, and preferred, assessment.
If the method selected is Physical assessment, specify the spleen size (in centimeters) below the left coastal margin as determined by the physical exam.
If the method selected is Ultrasound or CT / MRI, specify the spleen size (in centimeters) as determined by imaging.
Question 432: Did the recipient have hepatomegaly at last evaluation prior to the start of the preparative regimen / infusion?
Indicate if the recipient had hepatomegaly at the last evaluation prior to the start the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). Hepatomegaly is often documented during the physician’s physical assessment of the recipient and represents an abnormal finding.
Indicate if hepatomegaly was present at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).
If hepatomegaly was not present or is unknown if present at this timepoint, report No.
Questions 433 – 435: Specify the method used to measure liver size
Indicate the method used to measure the liver size. If liver size is measured using multiple methods, report the most accurate assessment. Ultrasound is the most specific, and preferred, assessment.
If the method selected is Physical assessment, report the liver size (in centimeters) below the left coastal margin as determined by the physical exam.
If the method selected is Ultrasound or CT / MRI, report the liver size (in centimeters) as determined by imaging.
Questions 436 – 437: Blasts in bone marrow (at last evaluation)
Indicate whether the percentage of blasts in the bone marrow was known at the last evaluation. If Known, report the percentage documented on the laboratory report.
If the lab was assessed multiple times, report the most recent values prior the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). Laboratory values obtained on the first date of the preparative regimen / lymphodepleting therapy may be reported as long as the sample was collected before any administration of systemic therapy or radiation.
If multiple methods were used to detect the percentage of blasts in the bone marrow, the aspirate differential is the preferred method; followed by flow cytometry and IHC (immunohistochemical staining).
Questions 438 – 444: Complete blood count (CBC) results available (check all that apply) (at last evaluation)
These questions are intended to capture the laboratory studies performed at the evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). Report the date of the CBC completed at the last evaluation and select all lab values assessed on the reported date. If labs were assessed multiple times prior to the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy), report the most recent lab.
Laboratory values obtained on the first date of the preparative regimen / lymphodepleting therapy may be reported as long as the sample was collected before any administration of systemic therapy or radiation.
- WBC: The white blood cell count is a value that represents all of the white blood cells in the blood. If the count is too high or too low, the ability to fight infection may be impaired. If known, specify the value and units of measurement as documented on the lab report.
- Neutrophils: Neutrophils are a subtype of white blood cell that fights infection. The value on the laboratory report may be a percentage or an absolute value. If an absolute value is reported, divide it by the white blood cell count for a percentage. Neutrophils are also known as polymorphonuclear leukocytes (PMNs). If known, specify the percentage as documented on the lab report.
- Blasts in blood: Blasts are not typically found in the peripheral blood; however, can appear for various reasons, including infection, blood cancer, or blood disorder. If known, report the percentage of blasts detected in the blood.
- If a differential was performed and the percentage of plasma cells are not listed, report 0%.
- Hemoglobin: Hemoglobin is a molecule in red blood cells that delivers oxygen to tissues throughout the body. A low hemoglobin count is considered “anemia” and blood transfusions, or growth factors may be required to increase the hemoglobin level. If known, specify the value and units of measurement as documented on the lab report. Additionally, indicate if red blood cells were transfused < 30 days prior to the CBC date reported above.
- Transfusions temporarily increase the red blood cell count, and it is important to distinguish between a recipient whose body is creating these cells and a recipient who requires transfusions to support the counts.
If a CBC was not completed at diagnosis or unknown if completed, select None.
If the exact sample collection date is not known, use the process described in General Instructions, Guidelines for Completing Forms.
Question 445: Were cytogenetics tested (karyotyping or FISH)? (at last evaluation)
Cytogenetics is the study of chromosomes. Cytogenetic assessment involves testing blood or bone marrow for the presence of known chromosomal abnormalities that reflect the recipient’s disease.
Testing methods include conventional chromosome analysis (karyotyping) or fluorescence in situ hybridization (FISH). For more information about cytogenetic testing and terminology, see Appendix C: Cytogenetics.
Indicate if cytogenetic studies were obtained at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). If cytogenetic studies were obtained, select Yes. If no cytogenetic studies were obtained or it is unknown if chromosome studies were performed, select No.
Question 446: Were cytogenetics tested via FISH? (at last evaluation)
Specify if FISH studies were performed at last evaluation prior to the start the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). If FISH studies were not performed at this time point, FISH sample was inadequate, the result ‘failed,’ or it is unknown if performed, report No.
Report chromosomal microarrays / chromosomal genomic arrays as FISH assessments.
Question 447: Sample source
The cytogenetic sample source is important for MPN research. Indicate if the sample was from Bone marrow or from Blood. If FISH studies were performed on multiple samples at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy), the bone marrow results are the preferred sample source to report.
Question 448: Results of tests
Specify if FISH abnormalities were detected at the last evaluation.
Questions 449– 452: Specify FISH abnormalities (at last evaluation)
Report the ISCN compatible string, if the data field is enabled. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.
If the ISCN compatible string is not reported, then select the number of abnormalities detected by FISH at the last evaluation and select all abnormalities detected.
If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.
Question 453: Were cytogenetics tested via karyotyping? (at last evaluation)
Specify if karyotyping studies were performed at the last evaluation prior to the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy). Report Yes even if there were no evaluable metaphase cells (these results will be specified below).
If karyotyping studies were not performed at this time point or it is unknown if performed, report No.
Question 454: Sample source
The cytogenetic sample source is important for MPN research. Indicate if the sample was from Bone marrow or from Blood. If karyotype analyses were performed on multiple samples at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy), the bone marrow results are the preferred sample source to report.
Question 455: Results of tests
Specify if abnormalities were detected by karyotype at the last evaluation.
If karyotyping failed or the sample was inadequate, select No evaluable metaphases.
Questions 456 – 459: Specify karyotype abnormalities (at last evaluation)
Report the ISCN compatible string, if applicable. Refer to Appendix C: Cytogenetics for more information on how to report using the ISCN functionality.
If the ISCN compatible string is not reported, then select the number of abnormalities detected by karyotype at the last evaluation and select all abnormalities detected.
If a clonal abnormality is detected, but not listed as an option, select Other abnormality and specify the abnormality. If multiple other abnormalities were detected, report “see attachment” and attach the final report(s) for any other abnormalities detected.
CALR Testing
If CALR testing was performed and positive but the lab report does not specify the type, select Not done for CALR 1 and CALR 2, and Positive for Not defined.
Questions 460 – 469: Were tests for driver mutations performed? (at last evaluation)
Testing for driver mutations may be performed by different methods including next generation sequencing (NGS), polymerase chain reaction (PCR), microarray, and fluorescence in situ hybridization (FISH). If testing was performed by any / all these methods at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy), report Yes and report the results for the most recent test(s).
If testing for driver mutations were not performed / sample was inadequate or is unknown, report No.
Questions 470 – 473: Specify positive molecular marker(s) identified (at last evaluation)
Testing for molecular markers is often performed by using PCR based methods to assess specific genetic sequences. Once a marker has been identified, these methods can be repeated to detect minimal residual disease (MRD) in the recipient’s blood, marrow, or tissue. Molecular assessments include polymerase chain reaction (PCR) amplification to detect single specific disease markers; however, molecular methods are evolving and now include Sanger sequencing, and next generation sequencing (e.g., Illumina, Roche 454, Proton / PGM, SOLiD).
Specify all positive molecular markers detected at the last evaluation prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy) and the amino acid change, if known. If molecular markers were not detected at this time point, the sample failed, testing was not completed or unknown if completed at diagnosis report None. This option should also be selected if other molecular markers were tested and resulted as negative.
If a molecular marker was detected, but not listed as an option, select Other molecular marker and specify the abnormality, along with the amino acid change, if known.
Question 474: What was the disease status? (at infusion)
This data field is intended to capture the pre-infusion disease status, based on clinical / hematologic and / or radiologic (if applicable) assessments. Refer to the MPN Response Criteria section for definitions of each disease response.
Report the disease status prior to the start of the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).
Question 475: Was an anemia response achieved?
Specify if an anemia response was achieved prior to he preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).
An anemia response is characterized by a ≥ 20 g/L (or ≥ 2.0 g/dL) increase in hemoglobin level (for transfusion-independent recipients).
Question 476: Was a spleen response achieved?
Specify if a spleen response has been achieved prior to the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).
A spleen response is achieved when a baseline splenomegaly that is palpable at 5 – 10 cm below the left costal margin (LCM) becomes not palpable or baseline splenomegaly that is palpable at > 10 cm below the LCM, decreases by ≥ 50%.
A baseline splenomegaly that is palpable at < 5 cm, below the LCM, is not eligible for spleen response.
A spleen response can be documented by a physician but should be confirmed by MRI / computed tomography showing ≥ 35% spleen volume reduction.
Question 477: Was a symptom response achieved?
The Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score ( MPN-SAF TSS) is used to evaluate the recipient’s symptom response. The MPN-SAF TSS is used to provide an accurate assessment of MPN symptom burden. The evaluation tool allows recipients with MPN to report their symptom severity at the worst level. They rate their symptom severity on a scale from zero to ten, zero being absent to ten being the worst imaginable. Adding the scores for all symptoms together will result in the recipient’s MPN-SAF TSS. See Table 1 below for an example of this assessment:
Table 1. Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
| Symptom | 1 to 10 (0 if absent) ranking – 1 is most favorable and 10 least favorable |
|---|---|
| Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your WORST level of fatigue during the past 24 hours | (No fatigue) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
| Circle the one number that describes how, during the past week how much difficulty you have had with each of the following symptoms. | — |
| Filling up quickly when you eat (early satiety) | (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
| Abdominal discomfort | (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
| Inactivity | (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
| Problems with concentration – Compared to prior to my MPD | (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
| Numbness / tingling (in my hands and feet) | (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
| Night sweats | (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
| Itching (pruritus) | (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
| Bone pain (diffuse not joint pain or arthritis) | (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
| Fever (>100 F) | (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
| Unintentional weight loss last 6 months | (Absent) 0 1 2 3 4 5 6 7 8 9 10 (Worst imaginable) |
A symptom response is achieved when there is a ≥ 50% reduction in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS).
Specify if a symptom response has been achieved prior to the preparative regimen / lymphodepleting therapy (or infusion if no preparative regimen / lymphodepleting therapy).
Question 478: Specify the cytogenetic response
Specify the recipient’s cytogenetic response prior to the start of the preparative regimen / infusion. Use the following guidelines when reporting the cytogenetic response:
- Complete response (CR): Eradication of the previously reported abnormality
- Partial response (PR): ≥ 50% reduction in abnormal metaphases
- No response: Mutation persists
- Re-emergence of pre-existing cytogenetic abnormality: Cytogenetic abnormality was eradicated and reemerged at the last evaluation.
- Not assessed: Cytogenetic response was not tested at the last evaluation
- Not applicable: Cytogenetic abnormalities were never identified
- None of the above: If the response was assessed at the last evaluation but does not meet the criteria for CR, PR, no response, re-emergence of pre-existing cytogenetic abnormality, and not applicable (e.g., if a new cytogenetic abnormality is identified but there is also eradication of a previous abnormality).
Review the example below for additional information:
- Example 1: A recipient had 10 abnormal metaphases (out of 20) at diagnosis. At the last evaluation prior to the start of the preparative regimen, they had 2 abnormal metaphases (out of 20). As this is a ≥ 50% reduction in abnormal metaphases, Partial response (PR) should be reported.
Question 479: Specify the molecular response
Specify the recipient’s molecular response prior to the start of the preparative regimen / infusion, based on the four drive mutations (JAK2, CALR, MPL, and CSF3R). Use the following guidelines when reporting the molecular response:
- Complete response (CR): Eradication of the previously reported driver mutation (JAK2, CALR, MPL, and/or CSF3R)
- Partial response (PR): ≥ 50% decrease in allele burden of the driver mutation (JAK2, CALR, MPL, and/or CSF3R). Refer to example 2 for more information.
- No response: Mutation persists (JAK2, CALR, MPL, and/or CSF3R)
- Re-emergence of pre-existing molecular abnormality: Molecular abnormality (JAK2, CALR, MPL, and/or CSF3R) was eradicated and reemerged at the last evaluation.
- Not assessed: Molecular response was not tested at the last evaluation
- Not applicable: JAK2, CALR, MPL, and CSF3R were never identified
- None of the above: If the response was assessed at the last evaluation but does not meet the criteria for CR, PR, no response, re-emergence of pre-existing molecular abnormality, and not applicable.
Review the example below for additional information:
- Example 2: A recipient was found to have a molecular mutation identified (JAK2, CALR, MPL, and/or CSF3R) in 80% of cells examined at diagnosis. At their last evaluation prior to transplant, the molecular mutation was only identified in 40% of cells examined. The number of cells with the molecular mutation identified decreased from 80% to 40%, which is a 50% reduction. In this case, Partial response (PR) should be reported as their molecular response.
Section Updates:
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